Sara Freeman

Major Finding: Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were other treatments.

Data Source: A 3-year follow-up from a Spanish trial comparing health-related quality of life outcomes after primary radical RRP, external beam radiotherapy (EBRT), and interstitial brachytherapy in 435 patients with localized (T1/2) prostate cancer not given hormonal treatment.

Disclosures: The Spanish National Health System funded the study. Dr. Guedea had no conflicts of interest.

BARCELONA – The 3-year results of a nonrandomized trial from Spain reveal different patterns of adverse events after three leading treatments for localized prostate cancer.

Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were external beam radiotherapy (EBRT) or brachytherapy, according to charts presented at the meeting.

Brachytherapy, however, was associated with far more irritative and obstructive urinary symptoms than were surgery or EBRT).

The trial was conducted in 11 hospitals throughout Spain, and originally enrolled 435 men with stage T1 and T2 prostate cancer who had received no prior surgical resection or hormonal treatment. The aim of the trial was to compare the health-related quality of life (HRQoL) impact of the three treatments.

Treatment decisions were made jointly by physicians and patients; the analysis covered 123 men who had RRP, 127 who had EBRT, and 123 who had brachytherapy.

HRQoL was assessed using validated questionnaires before and at 1, 3, 6, 12, 24, and 36 months after treatment. The questionnairesuincluded the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index.

This study is important because it takes into account the patients' quality of life before they had any treatment, Dr. Ferran Guedea said at a scientific press briefing. Previously published results showed that despite partial recovery from immediate deterioration in HRQoL, relevant differences persisted with 2 years' follow-up (Int. J. Radiat. Oncol. Biol. Phys. 2008; 72:421-32).

The 3-year results also show that in each treatment group, HRQoL deteriorated immediately after treatment, but then rose to varying degrees, said Dr. Guedea, a radiation oncologist at the Catalan Institute of Oncology, L'Hospitalet de Llobregat, near Barcelona.

SF-36 Physical Component scores decreased most dramatically after prostatectomy compared with either radiotherapy technique, but rose in the first 6 months after the procedure before gradually deteriorating over the 3-year follow-up.

EBRT produced lower scores than those for brachytherapy, and these gradually worsened during long-term follow-up, such that they were lower at 3 years than were scores in patients who had undergone surgery.

“RRP caused considerable urinary incontinence and sexual dysfunction,” Dr. Guedea observed. He added: “Brachytherapy and EBRT caused moderate urinary irritative-obstructive urinary symptoms and moderate adverse effects on sexual function, and finally, EBRT had very moderate bowel-related adverse events.”

Major Finding: Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were other treatments.

Data Source: A 3-year follow-up from a Spanish trial comparing health-related quality of life outcomes after primary radical RRP, external beam radiotherapy (EBRT), and interstitial brachytherapy in 435 patients with localized (T1/2) prostate cancer not given hormonal treatment.

Disclosures: The Spanish National Health System funded the study. Dr. Guedea had no conflicts of interest.

BARCELONA – The 3-year results of a nonrandomized trial from Spain reveal different patterns of adverse events after three leading treatments for localized prostate cancer.

Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were external beam radiotherapy (EBRT) or brachytherapy, according to charts presented at the meeting.

Brachytherapy, however, was associated with far more irritative and obstructive urinary symptoms than were surgery or EBRT).

The trial was conducted in 11 hospitals throughout Spain, and originally enrolled 435 men with stage T1 and T2 prostate cancer who had received no prior surgical resection or hormonal treatment. The aim of the trial was to compare the health-related quality of life (HRQoL) impact of the three treatments.

Treatment decisions were made jointly by physicians and patients; the analysis covered 123 men who had RRP, 127 who had EBRT, and 123 who had brachytherapy.

HRQoL was assessed using validated questionnaires before and at 1, 3, 6, 12, 24, and 36 months after treatment. The questionnairesuincluded the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index.

This study is important because it takes into account the patients' quality of life before they had any treatment, Dr. Ferran Guedea said at a scientific press briefing. Previously published results showed that despite partial recovery from immediate deterioration in HRQoL, relevant differences persisted with 2 years' follow-up (Int. J. Radiat. Oncol. Biol. Phys. 2008; 72:421-32).

The 3-year results also show that in each treatment group, HRQoL deteriorated immediately after treatment, but then rose to varying degrees, said Dr. Guedea, a radiation oncologist at the Catalan Institute of Oncology, L'Hospitalet de Llobregat, near Barcelona.

SF-36 Physical Component scores decreased most dramatically after prostatectomy compared with either radiotherapy technique, but rose in the first 6 months after the procedure before gradually deteriorating over the 3-year follow-up.

EBRT produced lower scores than those for brachytherapy, and these gradually worsened during long-term follow-up, such that they were lower at 3 years than were scores in patients who had undergone surgery.

“RRP caused considerable urinary incontinence and sexual dysfunction,” Dr. Guedea observed. He added: “Brachytherapy and EBRT caused moderate urinary irritative-obstructive urinary symptoms and moderate adverse effects on sexual function, and finally, EBRT had very moderate bowel-related adverse events.”

Major Finding: Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were other treatments.

Data Source: A 3-year follow-up from a Spanish trial comparing health-related quality of life outcomes after primary radical RRP, external beam radiotherapy (EBRT), and interstitial brachytherapy in 435 patients with localized (T1/2) prostate cancer not given hormonal treatment.

Disclosures: The Spanish National Health System funded the study. Dr. Guedea had no conflicts of interest.

BARCELONA – The 3-year results of a nonrandomized trial from Spain reveal different patterns of adverse events after three leading treatments for localized prostate cancer.

Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were external beam radiotherapy (EBRT) or brachytherapy, according to charts presented at the meeting.

Brachytherapy, however, was associated with far more irritative and obstructive urinary symptoms than were surgery or EBRT).

The trial was conducted in 11 hospitals throughout Spain, and originally enrolled 435 men with stage T1 and T2 prostate cancer who had received no prior surgical resection or hormonal treatment. The aim of the trial was to compare the health-related quality of life (HRQoL) impact of the three treatments.

Treatment decisions were made jointly by physicians and patients; the analysis covered 123 men who had RRP, 127 who had EBRT, and 123 who had brachytherapy.

HRQoL was assessed using validated questionnaires before and at 1, 3, 6, 12, 24, and 36 months after treatment. The questionnairesuincluded the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index.

This study is important because it takes into account the patients' quality of life before they had any treatment, Dr. Ferran Guedea said at a scientific press briefing. Previously published results showed that despite partial recovery from immediate deterioration in HRQoL, relevant differences persisted with 2 years' follow-up (Int. J. Radiat. Oncol. Biol. Phys. 2008; 72:421-32).

The 3-year results also show that in each treatment group, HRQoL deteriorated immediately after treatment, but then rose to varying degrees, said Dr. Guedea, a radiation oncologist at the Catalan Institute of Oncology, L'Hospitalet de Llobregat, near Barcelona.

SF-36 Physical Component scores decreased most dramatically after prostatectomy compared with either radiotherapy technique, but rose in the first 6 months after the procedure before gradually deteriorating over the 3-year follow-up.

EBRT produced lower scores than those for brachytherapy, and these gradually worsened during long-term follow-up, such that they were lower at 3 years than were scores in patients who had undergone surgery.

“RRP caused considerable urinary incontinence and sexual dysfunction,” Dr. Guedea observed. He added: “Brachytherapy and EBRT caused moderate urinary irritative-obstructive urinary symptoms and moderate adverse effects on sexual function, and finally, EBRT had very moderate bowel-related adverse events.”

MILAN – Early findings from the phase III ICON-7 study have shown that bevacizumab added to standard, first-line chemotherapy for advanced epithelial ovarian cancer improves progression-free survival to a greater extent than does standard chemotherapy alone.

Progression-free survival, the primary end point for the trial, was a median of 17.3 months in patients who received standard first-line chemotherapy for ovarian cancer, but 19 months for those who received additional therapy with bevacizumab (hazard ratio, 0.81; log rank P = .0041).

As ICON-7 is the second trial to show such a benefit for bevacizumab (Avastin), these new findings could help Roche to gain approval for using the antiangiogenic agent in the first-line treatment of advanced epithelial ovarian cancer.

The first trial to show a possible benefit of bevacizumab in first-line ovarian cancer treatment was the Gynecologic Oncology Group (GOG)-218 trial (J. Clin. Oncol. 2010 [June 20 suppl.] abstract LBA1), said Dr. Tim J. Perren, a consultant medical oncologist at the St. James’s Institute of Oncology in Leeds, England. At the American Society of Clinical Oncology meeting earlier this year, investigators reported a median progression-free survival of 14.1 months with the addition of bevacizumab to standard chemotherapy, compared with 10.3 months in control patients.

“Both trials looked at bevacizumab added to standard chemotherapy as first-line therapy for ovarian cancer,” he said in an interview at the annual Congress of the European Society for Medical Oncology. However, whereas ICON-7 used bevacizumab at a dose of 7.5 mg/kg (the dose used in metastatic colorectal cancer), GOG-218 used 15 mg/kg (the dose used in advanced breast cancer). ICON-7 was also a two- rather than three-arm study; it involved patients with both early and advanced disease rather than just stage III/IV, and had a slightly shorter bevacizumab maintenance phase: 12 cycles (36 weeks) rather than up to 22 cycles (66 weeks).

Patient recruitment into the ICON-7 study began in December 2006 and ended in February 2009 at 263 clinical sites, with 1,528 women with newly diagnosed, epithelial ovarian, primary, or fallopian tube cancer evenly randomized to treatment with paclitaxel (175 mg/m2) plus carboplatin (area under the curve = 6.0) given in six 21-day cycles with or without additional bevacizumab. Bevacizumab (7.5 mg/kg) was given during the chemotherapy, and continued in the experimental arm as maintenance therapy.

At a median follow-up of 19.4 months, two patients were still on treatment, and there had been 759 cases of disease progression or death, including 241 deaths – 16% of the 715 required for final outcome analysis.

An exploratory analysis of women who had FIGO stage III disease with suboptimal debulking and those who had stage IV disease with debulking showed an even greater difference in progression-free survival in favor of bevacizumab (15.9 vs. 10.5 months; HR, 0.68; P = .001).

“The biggest clinically significant effect we saw was hypertension,” Dr. Perren said, noting that this occurred in 25.9% of patients in the bevacizumab arm and 6.2% of the control arm, and that 18% and 2%, respectively, in each group required treatment with antihypertensives. Other well-known side effects of antiangiogenics and the chemotherapeutic agents used were also seen, including bleeding (39.6% vs. 11.6%) and neutropenia (28.3% vs. 29.1%).

“Bevacizumab undoubtedly has activity in ovarian cancer,” Dr. Perren said. “It’s a drug that we don’t fully know how to use yet and exactly which patients are going to benefit from it, but it will be central to future research trials in ovarian cancer.”

“ICON-7 validated and extends the observations of GOG-218,” said Dr. Michael A. Bookman, chief of the hematology-oncology section of the Arizona Cancer Center in Tucson, and an investigator of the GOG-218 trial.

“The improvement in progression-free survival has not yet been accompanied by improvements in overall survival and that does raise questions about the true clinical benefit,” Dr. Bookman observed. While there is still research to be done with bevacizumab in the first-line setting, he said that “there is no question that bevacizumab achieves clinical benefit in patients with recurrent disease.”

ICON-7 was a Gynaecologic Cancer Intergroup (GCIG) trial run through the U.K. Medical Research Council’s Clinical Trials Unit. Roche provided bevacizumab and grants to perform the ICON-7 study. Dr. Perren has accepted travel and accommodation costs but not consultancy fees to attend Roche-sponsored advisory boards. Dr. Bookman had no financial interests to disclose but has acted as an ad hoc advisor to various pharmaceutical companies and was also a GOG-218 trial investigator.

MILAN – Early findings from the phase III ICON-7 study have shown that bevacizumab added to standard, first-line chemotherapy for advanced epithelial ovarian cancer improves progression-free survival to a greater extent than does standard chemotherapy alone.

Progression-free survival, the primary end point for the trial, was a median of 17.3 months in patients who received standard first-line chemotherapy for ovarian cancer, but 19 months for those who received additional therapy with bevacizumab (hazard ratio, 0.81; log rank P = .0041).

As ICON-7 is the second trial to show such a benefit for bevacizumab (Avastin), these new findings could help Roche to gain approval for using the antiangiogenic agent in the first-line treatment of advanced epithelial ovarian cancer.

The first trial to show a possible benefit of bevacizumab in first-line ovarian cancer treatment was the Gynecologic Oncology Group (GOG)-218 trial (J. Clin. Oncol. 2010 [June 20 suppl.] abstract LBA1), said Dr. Tim J. Perren, a consultant medical oncologist at the St. James’s Institute of Oncology in Leeds, England. At the American Society of Clinical Oncology meeting earlier this year, investigators reported a median progression-free survival of 14.1 months with the addition of bevacizumab to standard chemotherapy, compared with 10.3 months in control patients.

“Both trials looked at bevacizumab added to standard chemotherapy as first-line therapy for ovarian cancer,” he said in an interview at the annual Congress of the European Society for Medical Oncology. However, whereas ICON-7 used bevacizumab at a dose of 7.5 mg/kg (the dose used in metastatic colorectal cancer), GOG-218 used 15 mg/kg (the dose used in advanced breast cancer). ICON-7 was also a two- rather than three-arm study; it involved patients with both early and advanced disease rather than just stage III/IV, and had a slightly shorter bevacizumab maintenance phase: 12 cycles (36 weeks) rather than up to 22 cycles (66 weeks).

Patient recruitment into the ICON-7 study began in December 2006 and ended in February 2009 at 263 clinical sites, with 1,528 women with newly diagnosed, epithelial ovarian, primary, or fallopian tube cancer evenly randomized to treatment with paclitaxel (175 mg/m2) plus carboplatin (area under the curve = 6.0) given in six 21-day cycles with or without additional bevacizumab. Bevacizumab (7.5 mg/kg) was given during the chemotherapy, and continued in the experimental arm as maintenance therapy.

At a median follow-up of 19.4 months, two patients were still on treatment, and there had been 759 cases of disease progression or death, including 241 deaths – 16% of the 715 required for final outcome analysis.

An exploratory analysis of women who had FIGO stage III disease with suboptimal debulking and those who had stage IV disease with debulking showed an even greater difference in progression-free survival in favor of bevacizumab (15.9 vs. 10.5 months; HR, 0.68; P = .001).

“The biggest clinically significant effect we saw was hypertension,” Dr. Perren said, noting that this occurred in 25.9% of patients in the bevacizumab arm and 6.2% of the control arm, and that 18% and 2%, respectively, in each group required treatment with antihypertensives. Other well-known side effects of antiangiogenics and the chemotherapeutic agents used were also seen, including bleeding (39.6% vs. 11.6%) and neutropenia (28.3% vs. 29.1%).

“Bevacizumab undoubtedly has activity in ovarian cancer,” Dr. Perren said. “It’s a drug that we don’t fully know how to use yet and exactly which patients are going to benefit from it, but it will be central to future research trials in ovarian cancer.”

“ICON-7 validated and extends the observations of GOG-218,” said Dr. Michael A. Bookman, chief of the hematology-oncology section of the Arizona Cancer Center in Tucson, and an investigator of the GOG-218 trial.

“The improvement in progression-free survival has not yet been accompanied by improvements in overall survival and that does raise questions about the true clinical benefit,” Dr. Bookman observed. While there is still research to be done with bevacizumab in the first-line setting, he said that “there is no question that bevacizumab achieves clinical benefit in patients with recurrent disease.”

ICON-7 was a Gynaecologic Cancer Intergroup (GCIG) trial run through the U.K. Medical Research Council’s Clinical Trials Unit. Roche provided bevacizumab and grants to perform the ICON-7 study. Dr. Perren has accepted travel and accommodation costs but not consultancy fees to attend Roche-sponsored advisory boards. Dr. Bookman had no financial interests to disclose but has acted as an ad hoc advisor to various pharmaceutical companies and was also a GOG-218 trial investigator.

MILAN – Early findings from the phase III ICON-7 study have shown that bevacizumab added to standard, first-line chemotherapy for advanced epithelial ovarian cancer improves progression-free survival to a greater extent than does standard chemotherapy alone.

Progression-free survival, the primary end point for the trial, was a median of 17.3 months in patients who received standard first-line chemotherapy for ovarian cancer, but 19 months for those who received additional therapy with bevacizumab (hazard ratio, 0.81; log rank P = .0041).

As ICON-7 is the second trial to show such a benefit for bevacizumab (Avastin), these new findings could help Roche to gain approval for using the antiangiogenic agent in the first-line treatment of advanced epithelial ovarian cancer.

The first trial to show a possible benefit of bevacizumab in first-line ovarian cancer treatment was the Gynecologic Oncology Group (GOG)-218 trial (J. Clin. Oncol. 2010 [June 20 suppl.] abstract LBA1), said Dr. Tim J. Perren, a consultant medical oncologist at the St. James’s Institute of Oncology in Leeds, England. At the American Society of Clinical Oncology meeting earlier this year, investigators reported a median progression-free survival of 14.1 months with the addition of bevacizumab to standard chemotherapy, compared with 10.3 months in control patients.

“Both trials looked at bevacizumab added to standard chemotherapy as first-line therapy for ovarian cancer,” he said in an interview at the annual Congress of the European Society for Medical Oncology. However, whereas ICON-7 used bevacizumab at a dose of 7.5 mg/kg (the dose used in metastatic colorectal cancer), GOG-218 used 15 mg/kg (the dose used in advanced breast cancer). ICON-7 was also a two- rather than three-arm study; it involved patients with both early and advanced disease rather than just stage III/IV, and had a slightly shorter bevacizumab maintenance phase: 12 cycles (36 weeks) rather than up to 22 cycles (66 weeks).

Patient recruitment into the ICON-7 study began in December 2006 and ended in February 2009 at 263 clinical sites, with 1,528 women with newly diagnosed, epithelial ovarian, primary, or fallopian tube cancer evenly randomized to treatment with paclitaxel (175 mg/m2) plus carboplatin (area under the curve = 6.0) given in six 21-day cycles with or without additional bevacizumab. Bevacizumab (7.5 mg/kg) was given during the chemotherapy, and continued in the experimental arm as maintenance therapy.

At a median follow-up of 19.4 months, two patients were still on treatment, and there had been 759 cases of disease progression or death, including 241 deaths – 16% of the 715 required for final outcome analysis.

An exploratory analysis of women who had FIGO stage III disease with suboptimal debulking and those who had stage IV disease with debulking showed an even greater difference in progression-free survival in favor of bevacizumab (15.9 vs. 10.5 months; HR, 0.68; P = .001).

“The biggest clinically significant effect we saw was hypertension,” Dr. Perren said, noting that this occurred in 25.9% of patients in the bevacizumab arm and 6.2% of the control arm, and that 18% and 2%, respectively, in each group required treatment with antihypertensives. Other well-known side effects of antiangiogenics and the chemotherapeutic agents used were also seen, including bleeding (39.6% vs. 11.6%) and neutropenia (28.3% vs. 29.1%).

“Bevacizumab undoubtedly has activity in ovarian cancer,” Dr. Perren said. “It’s a drug that we don’t fully know how to use yet and exactly which patients are going to benefit from it, but it will be central to future research trials in ovarian cancer.”

“ICON-7 validated and extends the observations of GOG-218,” said Dr. Michael A. Bookman, chief of the hematology-oncology section of the Arizona Cancer Center in Tucson, and an investigator of the GOG-218 trial.

“The improvement in progression-free survival has not yet been accompanied by improvements in overall survival and that does raise questions about the true clinical benefit,” Dr. Bookman observed. While there is still research to be done with bevacizumab in the first-line setting, he said that “there is no question that bevacizumab achieves clinical benefit in patients with recurrent disease.”

ICON-7 was a Gynaecologic Cancer Intergroup (GCIG) trial run through the U.K. Medical Research Council’s Clinical Trials Unit. Roche provided bevacizumab and grants to perform the ICON-7 study. Dr. Perren has accepted travel and accommodation costs but not consultancy fees to attend Roche-sponsored advisory boards. Dr. Bookman had no financial interests to disclose but has acted as an ad hoc advisor to various pharmaceutical companies and was also a GOG-218 trial investigator.

MILAN – Balloon kyphoplasty significantly relieved the pain of vertebral compression fractures in the first randomized clinical trial looking at the safety and efficacy of the technique specifically in patients with cancer.

One month after surgery, a significant (P = .0001) 8.5-point decrease in Roland-Morris Disability Questionnaire (RMDQ) scores from baseline was seen, while a nonsignificant decrease of 0.2 occurred in the patients who used conventional methods of pain relief (P = .82).

Compression fractures can be very painful for patients and may be the result of a variety of causes, such as osteoporosis and trauma, as well as certain cancer treatments. Balloon kyphoplasty is a minimally invasive procedure during which a cannula is inserted into the compressed area. This allows a balloon to be inserted through it and inflated, which restores the height of the vertebra. After deflating and removing the balloon, the gap is filled with cement to ensure that the vertebral space cannot collapse again.

“The most important message for patients is that it is a safe procedure and there is improved quality of life, especially in terms of pain,” Dr. Leonard Bastian explained in an interview at the annual congress of the European Society for Medical Oncology.

Dr. Bastian, director of the department for orthopedics, trauma, hand, and reconstructive surgery at the Klinikum Leverkusen (Germany), said that the one-off intervention is usually performed at his clinic under general anesthesia but may be performed under local anesthesia to allow for outpatient treatment. Another unique feature of the method his clinic uses is that two balloons (rather than one) are inserted on either side of the fracture during the 30-minute procedure, enabling more cement to be used to fill the gap.

The international, multicenter, randomized Cancer Patient Fracture Evaluation (CAFE) study involved 134 patients with a mean age of 63-64 years. Seventy were treated with balloon kyphoplasty and 64 with nonsurgical management. The latter included the use of analgesics, bed rest, physical therapy, and, in some cases, a brace, but was dependent on the study center.

For inclusion, patients with cancer had to have one to three acute vertebral compression fractures (T5-L5), painful compression fractures, and a pain score of at four or higher on a scale of 0-10. Patients’ life expectancy had to be more than 3 months and they had to have no planned changes to their current chemotherapy regimen, except dosing, in the month prior to or after enrollment.

Crossover to the balloon kyphoplasty arm was allowed after 1 month, and Dr. Bastian reported that 38 patients from the nonsurgical arm decided to undergoing the technique at that time, with a further 28 patients deciding to have surgery at 12 months.

The primary end point was change in functional status from baseline to 1 month as assessed by the RMDQ, which rates patients’ back pain on a scale of 0-24. Respective scores in the balloon kyphoplasty group and the nonsurgical group were 17.6 and 18.2 at baseline and 9.10 and 18.00 at the 1-month follow-up. The difference in score between groups was statistically significant (P = .0001) and maintained during 12-month follow up.

Secondary measures, including the Short Form 36v2 physical and mental components, the Karnofsky Performance Scale (KPS), a 10-point back pain score, use of analgesics for back pain, and change in ambulation status and activities of daily living, all showed significant improvement in favor of surgery over nonsurgical management.

Although Dr. Bastian noted that the incidence of device-related adverse events was low, one patient who underwent kyphoplasty had an intra-operative myocardial infarction with intermittent atrial fibrillation and another with cement leakage to the disc had an adjacent fracture. One patient who crossed over to have surgery had a new fracture approximately 2 weeks later, although there was not any difference between the number of patients with clinical or radiographic new fractures at 1 month.

Balloon kyphoplasty is not without risk, said the official discussant, Dr. Fausto Roila, a medical oncologist from the Ospedale Santa Maria, Terni, Italy, who was not involved in the study. “Reported complications, such as soft-tissue damage and nerve-root pain and compression, are related to the leakage of bone cement,” he said.

Dr. Roila noted that the CAFE study lacked true blinding and a placebo effect could not be excluded. “More studies, especially double-blind studies, are necessary to identify the real role of balloon kyphoplasty,” he observed.

“When investigating the treatment effect on subjective symptoms, the only way to distinguish the effect of expectations by the patients from the intervention itself is to conceal the treatment from the patients,” he added.

Medtronic Spine LCC financially supported the study and helped with data analysis and presentation. Dr. Bastian has received consultancy fees from the company, and two of the study’s coauthors are employees and stockholders. Dr. Roila had no relevant conflicts of interest.

MILAN – Balloon kyphoplasty significantly relieved the pain of vertebral compression fractures in the first randomized clinical trial looking at the safety and efficacy of the technique specifically in patients with cancer.

One month after surgery, a significant (P = .0001) 8.5-point decrease in Roland-Morris Disability Questionnaire (RMDQ) scores from baseline was seen, while a nonsignificant decrease of 0.2 occurred in the patients who used conventional methods of pain relief (P = .82).

Compression fractures can be very painful for patients and may be the result of a variety of causes, such as osteoporosis and trauma, as well as certain cancer treatments. Balloon kyphoplasty is a minimally invasive procedure during which a cannula is inserted into the compressed area. This allows a balloon to be inserted through it and inflated, which restores the height of the vertebra. After deflating and removing the balloon, the gap is filled with cement to ensure that the vertebral space cannot collapse again.

“The most important message for patients is that it is a safe procedure and there is improved quality of life, especially in terms of pain,” Dr. Leonard Bastian explained in an interview at the annual congress of the European Society for Medical Oncology.

Dr. Bastian, director of the department for orthopedics, trauma, hand, and reconstructive surgery at the Klinikum Leverkusen (Germany), said that the one-off intervention is usually performed at his clinic under general anesthesia but may be performed under local anesthesia to allow for outpatient treatment. Another unique feature of the method his clinic uses is that two balloons (rather than one) are inserted on either side of the fracture during the 30-minute procedure, enabling more cement to be used to fill the gap.

The international, multicenter, randomized Cancer Patient Fracture Evaluation (CAFE) study involved 134 patients with a mean age of 63-64 years. Seventy were treated with balloon kyphoplasty and 64 with nonsurgical management. The latter included the use of analgesics, bed rest, physical therapy, and, in some cases, a brace, but was dependent on the study center.

For inclusion, patients with cancer had to have one to three acute vertebral compression fractures (T5-L5), painful compression fractures, and a pain score of at four or higher on a scale of 0-10. Patients’ life expectancy had to be more than 3 months and they had to have no planned changes to their current chemotherapy regimen, except dosing, in the month prior to or after enrollment.

Crossover to the balloon kyphoplasty arm was allowed after 1 month, and Dr. Bastian reported that 38 patients from the nonsurgical arm decided to undergoing the technique at that time, with a further 28 patients deciding to have surgery at 12 months.

The primary end point was change in functional status from baseline to 1 month as assessed by the RMDQ, which rates patients’ back pain on a scale of 0-24. Respective scores in the balloon kyphoplasty group and the nonsurgical group were 17.6 and 18.2 at baseline and 9.10 and 18.00 at the 1-month follow-up. The difference in score between groups was statistically significant (P = .0001) and maintained during 12-month follow up.

Secondary measures, including the Short Form 36v2 physical and mental components, the Karnofsky Performance Scale (KPS), a 10-point back pain score, use of analgesics for back pain, and change in ambulation status and activities of daily living, all showed significant improvement in favor of surgery over nonsurgical management.

Although Dr. Bastian noted that the incidence of device-related adverse events was low, one patient who underwent kyphoplasty had an intra-operative myocardial infarction with intermittent atrial fibrillation and another with cement leakage to the disc had an adjacent fracture. One patient who crossed over to have surgery had a new fracture approximately 2 weeks later, although there was not any difference between the number of patients with clinical or radiographic new fractures at 1 month.

Balloon kyphoplasty is not without risk, said the official discussant, Dr. Fausto Roila, a medical oncologist from the Ospedale Santa Maria, Terni, Italy, who was not involved in the study. “Reported complications, such as soft-tissue damage and nerve-root pain and compression, are related to the leakage of bone cement,” he said.

Dr. Roila noted that the CAFE study lacked true blinding and a placebo effect could not be excluded. “More studies, especially double-blind studies, are necessary to identify the real role of balloon kyphoplasty,” he observed.

“When investigating the treatment effect on subjective symptoms, the only way to distinguish the effect of expectations by the patients from the intervention itself is to conceal the treatment from the patients,” he added.

Medtronic Spine LCC financially supported the study and helped with data analysis and presentation. Dr. Bastian has received consultancy fees from the company, and two of the study’s coauthors are employees and stockholders. Dr. Roila had no relevant conflicts of interest.

MILAN – Balloon kyphoplasty significantly relieved the pain of vertebral compression fractures in the first randomized clinical trial looking at the safety and efficacy of the technique specifically in patients with cancer.

One month after surgery, a significant (P = .0001) 8.5-point decrease in Roland-Morris Disability Questionnaire (RMDQ) scores from baseline was seen, while a nonsignificant decrease of 0.2 occurred in the patients who used conventional methods of pain relief (P = .82).

Compression fractures can be very painful for patients and may be the result of a variety of causes, such as osteoporosis and trauma, as well as certain cancer treatments. Balloon kyphoplasty is a minimally invasive procedure during which a cannula is inserted into the compressed area. This allows a balloon to be inserted through it and inflated, which restores the height of the vertebra. After deflating and removing the balloon, the gap is filled with cement to ensure that the vertebral space cannot collapse again.

“The most important message for patients is that it is a safe procedure and there is improved quality of life, especially in terms of pain,” Dr. Leonard Bastian explained in an interview at the annual congress of the European Society for Medical Oncology.

Dr. Bastian, director of the department for orthopedics, trauma, hand, and reconstructive surgery at the Klinikum Leverkusen (Germany), said that the one-off intervention is usually performed at his clinic under general anesthesia but may be performed under local anesthesia to allow for outpatient treatment. Another unique feature of the method his clinic uses is that two balloons (rather than one) are inserted on either side of the fracture during the 30-minute procedure, enabling more cement to be used to fill the gap.

The international, multicenter, randomized Cancer Patient Fracture Evaluation (CAFE) study involved 134 patients with a mean age of 63-64 years. Seventy were treated with balloon kyphoplasty and 64 with nonsurgical management. The latter included the use of analgesics, bed rest, physical therapy, and, in some cases, a brace, but was dependent on the study center.

For inclusion, patients with cancer had to have one to three acute vertebral compression fractures (T5-L5), painful compression fractures, and a pain score of at four or higher on a scale of 0-10. Patients’ life expectancy had to be more than 3 months and they had to have no planned changes to their current chemotherapy regimen, except dosing, in the month prior to or after enrollment.

Crossover to the balloon kyphoplasty arm was allowed after 1 month, and Dr. Bastian reported that 38 patients from the nonsurgical arm decided to undergoing the technique at that time, with a further 28 patients deciding to have surgery at 12 months.

The primary end point was change in functional status from baseline to 1 month as assessed by the RMDQ, which rates patients’ back pain on a scale of 0-24. Respective scores in the balloon kyphoplasty group and the nonsurgical group were 17.6 and 18.2 at baseline and 9.10 and 18.00 at the 1-month follow-up. The difference in score between groups was statistically significant (P = .0001) and maintained during 12-month follow up.

Secondary measures, including the Short Form 36v2 physical and mental components, the Karnofsky Performance Scale (KPS), a 10-point back pain score, use of analgesics for back pain, and change in ambulation status and activities of daily living, all showed significant improvement in favor of surgery over nonsurgical management.

Although Dr. Bastian noted that the incidence of device-related adverse events was low, one patient who underwent kyphoplasty had an intra-operative myocardial infarction with intermittent atrial fibrillation and another with cement leakage to the disc had an adjacent fracture. One patient who crossed over to have surgery had a new fracture approximately 2 weeks later, although there was not any difference between the number of patients with clinical or radiographic new fractures at 1 month.

Balloon kyphoplasty is not without risk, said the official discussant, Dr. Fausto Roila, a medical oncologist from the Ospedale Santa Maria, Terni, Italy, who was not involved in the study. “Reported complications, such as soft-tissue damage and nerve-root pain and compression, are related to the leakage of bone cement,” he said.

Dr. Roila noted that the CAFE study lacked true blinding and a placebo effect could not be excluded. “More studies, especially double-blind studies, are necessary to identify the real role of balloon kyphoplasty,” he observed.

“When investigating the treatment effect on subjective symptoms, the only way to distinguish the effect of expectations by the patients from the intervention itself is to conceal the treatment from the patients,” he added.

Medtronic Spine LCC financially supported the study and helped with data analysis and presentation. Dr. Bastian has received consultancy fees from the company, and two of the study’s coauthors are employees and stockholders. Dr. Roila had no relevant conflicts of interest.

MILAN – Cetuximab in combination with a continuous or intermittently administered Nordic FLOX regimen for the first-line treatment of metastatic colorectal cancer conferred no advantage over the chemotherapy regimen alone, the first results of the Nordic VII study show.

The addition of cetuximab (Erbitux) did not improve response rates, progression-free survival, or overall survival. No better outcome was seen in patients with wild-type KRAS who received cetuximab, although the study was admittedly not powered to look specifically at KRAS subpopulations.

This is contrary to expectations and comes after a very thorough analysis, study investigator Dr. Kjell Magne Tveit of Oslo University Hospital said at the annual congress of the European Society for Medical Oncology. Investigators did not release data from the trial at the American Society of Clinical Oncology meeting earlier this year because they wanted to be sure of the disappointing results.

“Cetuximab has a documented beneficial effect in the later stages of metastatic colorectal cancer when given alone or together with chemotherapy,” Dr. Tveit said in a press release. “We expected that similar findings would be found in early stage [disease] when given together with the oxaliplatin regimen.”

Patient recruitment into the Nordic VII study began in May 2005 and ended in October 2007, with a total of 571 patients randomized to one of three arms: the standard FLOX (5- fluorouracil [5-FU], folinic acid, oxaliplatin) regimen used in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at the time; FLOX plus additional cetuximab, with both given until progression or toxicity; or FLOX plus continuous cetuximab, with chemotherapy given for 16 weeks and then stopped and reintroduced at progression.

The Nordic FLOX regimen consists of a 5-FU intravenous bolus dose of 500 mg/m2 plus 60 mg/m2 folinic acid on days 1–2 every second week and oxaliplatin (85 mg/m2) on day 1. Cetuximab was used at a dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly.

The primary end point was progression-free survival, and this did not significantly differ between the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms, at a median of 7.9, 8.3, and 7.3 months, respectively (P = .31 comparing FLOX-cetuximab vs. standard FLOX).

Overall response rates in the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms were 41%, 49%, and 47%, with an odds ratio of 1.35 (P = .15) comparing the first two arms in the intent-to-treat population of 566 evaluable patients. Overall survival was also similar between the groups, at a median of 20.4, 19.7, and 20.3 months, respectively.

“KRAS mutation status was not found to be predictive for cetuximab effect,” Dr. Tveit said, noting that BRAF mutation was “a strong negative prognostic factor.”

The addition of cetuximab also was associated with more grade 3/4 adverse events than the standard FLOX arm. “The Nordic VII study indicates that oxaliplatin may not be a good match for cetuximab in metastatic colorectal cancer,” he observed.

Commenting on the trial, Dr. Alberto Sobrero from the Ospedale San Martino in Genoa, Italy, said the most unexpected result was that cetuximab was of no benefit in patients with wild-type KRAS. Despite a high level of quality-control measures in the study, “only Nordic VII reported lower response rates and progression-free survival in KRAS wild-type than in mutants out of 11 trials,” he said.

The choice of the Nordic FLOX regimen as the “backbone” of chemotherapy was questionable, as it incorporates one of the least effective 5-FU regimens. “If you want to impact on practice, you really want to have your control arm to be what everybody else is using,” he said.

Furthermore, “data supporting cetuximab in combination with oxaliplatin is “shaky at best,” and “whenever irinotecan [Camptosar] is a partner of cetuximab you have fantastic results,” Dr. Sobrero said. Irinotecan-based regimens should therefore be the chemotherapy backbone when using cetuximab. “There is also another piece of evidence of continuing chemotherapy until progression,” he added.

Merck-Serono and Sanofi-Aventis financially supported the Nordic VII study. All study authors had no conflicts of interest. Dr. Sobrero disclosed that he has acted as an advisory board member and speaker for Sanofi-Aventis, Amgen, AstraZeneca, Roche, Merck-Serono, Pfizer, Onyx, Bayer, and Genentech.

MILAN – Cetuximab in combination with a continuous or intermittently administered Nordic FLOX regimen for the first-line treatment of metastatic colorectal cancer conferred no advantage over the chemotherapy regimen alone, the first results of the Nordic VII study show.

The addition of cetuximab (Erbitux) did not improve response rates, progression-free survival, or overall survival. No better outcome was seen in patients with wild-type KRAS who received cetuximab, although the study was admittedly not powered to look specifically at KRAS subpopulations.

This is contrary to expectations and comes after a very thorough analysis, study investigator Dr. Kjell Magne Tveit of Oslo University Hospital said at the annual congress of the European Society for Medical Oncology. Investigators did not release data from the trial at the American Society of Clinical Oncology meeting earlier this year because they wanted to be sure of the disappointing results.

“Cetuximab has a documented beneficial effect in the later stages of metastatic colorectal cancer when given alone or together with chemotherapy,” Dr. Tveit said in a press release. “We expected that similar findings would be found in early stage [disease] when given together with the oxaliplatin regimen.”

Patient recruitment into the Nordic VII study began in May 2005 and ended in October 2007, with a total of 571 patients randomized to one of three arms: the standard FLOX (5- fluorouracil [5-FU], folinic acid, oxaliplatin) regimen used in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at the time; FLOX plus additional cetuximab, with both given until progression or toxicity; or FLOX plus continuous cetuximab, with chemotherapy given for 16 weeks and then stopped and reintroduced at progression.

The Nordic FLOX regimen consists of a 5-FU intravenous bolus dose of 500 mg/m2 plus 60 mg/m2 folinic acid on days 1–2 every second week and oxaliplatin (85 mg/m2) on day 1. Cetuximab was used at a dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly.

The primary end point was progression-free survival, and this did not significantly differ between the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms, at a median of 7.9, 8.3, and 7.3 months, respectively (P = .31 comparing FLOX-cetuximab vs. standard FLOX).

Overall response rates in the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms were 41%, 49%, and 47%, with an odds ratio of 1.35 (P = .15) comparing the first two arms in the intent-to-treat population of 566 evaluable patients. Overall survival was also similar between the groups, at a median of 20.4, 19.7, and 20.3 months, respectively.

“KRAS mutation status was not found to be predictive for cetuximab effect,” Dr. Tveit said, noting that BRAF mutation was “a strong negative prognostic factor.”

The addition of cetuximab also was associated with more grade 3/4 adverse events than the standard FLOX arm. “The Nordic VII study indicates that oxaliplatin may not be a good match for cetuximab in metastatic colorectal cancer,” he observed.

Commenting on the trial, Dr. Alberto Sobrero from the Ospedale San Martino in Genoa, Italy, said the most unexpected result was that cetuximab was of no benefit in patients with wild-type KRAS. Despite a high level of quality-control measures in the study, “only Nordic VII reported lower response rates and progression-free survival in KRAS wild-type than in mutants out of 11 trials,” he said.

The choice of the Nordic FLOX regimen as the “backbone” of chemotherapy was questionable, as it incorporates one of the least effective 5-FU regimens. “If you want to impact on practice, you really want to have your control arm to be what everybody else is using,” he said.

Furthermore, “data supporting cetuximab in combination with oxaliplatin is “shaky at best,” and “whenever irinotecan [Camptosar] is a partner of cetuximab you have fantastic results,” Dr. Sobrero said. Irinotecan-based regimens should therefore be the chemotherapy backbone when using cetuximab. “There is also another piece of evidence of continuing chemotherapy until progression,” he added.

Merck-Serono and Sanofi-Aventis financially supported the Nordic VII study. All study authors had no conflicts of interest. Dr. Sobrero disclosed that he has acted as an advisory board member and speaker for Sanofi-Aventis, Amgen, AstraZeneca, Roche, Merck-Serono, Pfizer, Onyx, Bayer, and Genentech.

MILAN – Cetuximab in combination with a continuous or intermittently administered Nordic FLOX regimen for the first-line treatment of metastatic colorectal cancer conferred no advantage over the chemotherapy regimen alone, the first results of the Nordic VII study show.

The addition of cetuximab (Erbitux) did not improve response rates, progression-free survival, or overall survival. No better outcome was seen in patients with wild-type KRAS who received cetuximab, although the study was admittedly not powered to look specifically at KRAS subpopulations.

This is contrary to expectations and comes after a very thorough analysis, study investigator Dr. Kjell Magne Tveit of Oslo University Hospital said at the annual congress of the European Society for Medical Oncology. Investigators did not release data from the trial at the American Society of Clinical Oncology meeting earlier this year because they wanted to be sure of the disappointing results.

“Cetuximab has a documented beneficial effect in the later stages of metastatic colorectal cancer when given alone or together with chemotherapy,” Dr. Tveit said in a press release. “We expected that similar findings would be found in early stage [disease] when given together with the oxaliplatin regimen.”

Patient recruitment into the Nordic VII study began in May 2005 and ended in October 2007, with a total of 571 patients randomized to one of three arms: the standard FLOX (5- fluorouracil [5-FU], folinic acid, oxaliplatin) regimen used in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at the time; FLOX plus additional cetuximab, with both given until progression or toxicity; or FLOX plus continuous cetuximab, with chemotherapy given for 16 weeks and then stopped and reintroduced at progression.

The Nordic FLOX regimen consists of a 5-FU intravenous bolus dose of 500 mg/m2 plus 60 mg/m2 folinic acid on days 1–2 every second week and oxaliplatin (85 mg/m2) on day 1. Cetuximab was used at a dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly.

The primary end point was progression-free survival, and this did not significantly differ between the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms, at a median of 7.9, 8.3, and 7.3 months, respectively (P = .31 comparing FLOX-cetuximab vs. standard FLOX).

Overall response rates in the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms were 41%, 49%, and 47%, with an odds ratio of 1.35 (P = .15) comparing the first two arms in the intent-to-treat population of 566 evaluable patients. Overall survival was also similar between the groups, at a median of 20.4, 19.7, and 20.3 months, respectively.

“KRAS mutation status was not found to be predictive for cetuximab effect,” Dr. Tveit said, noting that BRAF mutation was “a strong negative prognostic factor.”

The addition of cetuximab also was associated with more grade 3/4 adverse events than the standard FLOX arm. “The Nordic VII study indicates that oxaliplatin may not be a good match for cetuximab in metastatic colorectal cancer,” he observed.

Commenting on the trial, Dr. Alberto Sobrero from the Ospedale San Martino in Genoa, Italy, said the most unexpected result was that cetuximab was of no benefit in patients with wild-type KRAS. Despite a high level of quality-control measures in the study, “only Nordic VII reported lower response rates and progression-free survival in KRAS wild-type than in mutants out of 11 trials,” he said.

The choice of the Nordic FLOX regimen as the “backbone” of chemotherapy was questionable, as it incorporates one of the least effective 5-FU regimens. “If you want to impact on practice, you really want to have your control arm to be what everybody else is using,” he said.

Furthermore, “data supporting cetuximab in combination with oxaliplatin is “shaky at best,” and “whenever irinotecan [Camptosar] is a partner of cetuximab you have fantastic results,” Dr. Sobrero said. Irinotecan-based regimens should therefore be the chemotherapy backbone when using cetuximab. “There is also another piece of evidence of continuing chemotherapy until progression,” he added.

Merck-Serono and Sanofi-Aventis financially supported the Nordic VII study. All study authors had no conflicts of interest. Dr. Sobrero disclosed that he has acted as an advisory board member and speaker for Sanofi-Aventis, Amgen, AstraZeneca, Roche, Merck-Serono, Pfizer, Onyx, Bayer, and Genentech.

MILAN – Cetuximab in combination with a continuous or intermittently administered Nordic FLOX regimen for the first-line treatment of metastatic colorectal cancer conferred no advantage over the chemotherapy regimen alone, the first results of the Nordic VII study show.

The addition of cetuximab (Erbitux) did not improve response rates, progression-free survival, or overall survival. No better outcome was seen in patients with wild-type KRAS who received cetuximab, although the study was admittedly not powered to look specifically at KRAS subpopulations.

This is contrary to expectations and comes after a very thorough analysis, study investigator Dr. Kjell Magne Tveit of Oslo University Hospital said at the annual congress of the European Society for Medical Oncology. Investigators did not release data from the trial at the American Society of Clinical Oncology meeting earlier this year because they wanted to be sure of the disappointing results.

“Cetuximab has a documented beneficial effect in the later stages of metastatic colorectal cancer when given alone or together with chemotherapy,” Dr. Tveit said in a press release. “We expected that similar findings would be found in early stage [disease] when given together with the oxaliplatin regimen.”

Patient recruitment into the Nordic VII study began in May 2005 and ended in October 2007, with a total of 571 patients randomized to one of three arms: the standard FLOX (5- fluorouracil [5-FU], folinic acid, oxaliplatin) regimen used in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at the time; FLOX plus additional cetuximab, with both given until progression or toxicity; or FLOX plus continuous cetuximab, with chemotherapy given for 16 weeks and then stopped and reintroduced at progression.

The Nordic FLOX regimen consists of a 5-FU intravenous bolus dose of 500 mg/m2 plus 60 mg/m2 folinic acid on days 1–2 every second week and oxaliplatin (85 mg/m2) on day 1. Cetuximab was used at a dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly.

The primary end point was progression-free survival, and this did not significantly differ between the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms, at a median of 7.9, 8.3, and 7.3 months, respectively (P = .31 comparing FLOX-cetuximab vs. standard FLOX).

Overall response rates in the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms were 41%, 49%, and 47%, with an odds ratio of 1.35 (P = .15) comparing the first two arms in the intent-to-treat population of 566 evaluable patients. Overall survival was also similar between the groups, at a median of 20.4, 19.7, and 20.3 months, respectively.

“KRAS mutation status was not found to be predictive for cetuximab effect,” Dr. Tveit said, noting that BRAF mutation was “a strong negative prognostic factor.”

The addition of cetuximab also was associated with more grade 3/4 adverse events than the standard FLOX arm. “The Nordic VII study indicates that oxaliplatin may not be a good match for cetuximab in metastatic colorectal cancer,” he observed.

Commenting on the trial, Dr. Alberto Sobrero from the Ospedale San Martino in Genoa, Italy, said the most unexpected result was that cetuximab was of no benefit in patients with wild-type KRAS. Despite a high level of quality-control measures in the study, “only Nordic VII reported lower response rates and progression-free survival in KRAS wild-type than in mutants out of 11 trials,” he said.

The choice of the Nordic FLOX regimen as the “backbone” of chemotherapy was questionable, as it incorporates one of the least effective 5-FU regimens. “If you want to impact on practice, you really want to have your control arm to be what everybody else is using,” he said.

Furthermore, “data supporting cetuximab in combination with oxaliplatin is “shaky at best,” and “whenever irinotecan [Camptosar] is a partner of cetuximab you have fantastic results,” Dr. Sobrero said. Irinotecan-based regimens should therefore be the chemotherapy backbone when using cetuximab. “There is also another piece of evidence of continuing chemotherapy until progression,” he added.

Merck-Serono and Sanofi-Aventis financially supported the Nordic VII study. All study authors had no conflicts of interest. Dr. Sobrero disclosed that he has acted as an advisory board member and speaker for Sanofi-Aventis, Amgen, AstraZeneca, Roche, Merck-Serono, Pfizer, Onyx, Bayer, and Genentech.

MILAN – Cetuximab in combination with a continuous or intermittently administered Nordic FLOX regimen for the first-line treatment of metastatic colorectal cancer conferred no advantage over the chemotherapy regimen alone, the first results of the Nordic VII study show.

The addition of cetuximab (Erbitux) did not improve response rates, progression-free survival, or overall survival. No better outcome was seen in patients with wild-type KRAS who received cetuximab, although the study was admittedly not powered to look specifically at KRAS subpopulations.

This is contrary to expectations and comes after a very thorough analysis, study investigator Dr. Kjell Magne Tveit of Oslo University Hospital said at the annual congress of the European Society for Medical Oncology. Investigators did not release data from the trial at the American Society of Clinical Oncology meeting earlier this year because they wanted to be sure of the disappointing results.

“Cetuximab has a documented beneficial effect in the later stages of metastatic colorectal cancer when given alone or together with chemotherapy,” Dr. Tveit said in a press release. “We expected that similar findings would be found in early stage [disease] when given together with the oxaliplatin regimen.”

Patient recruitment into the Nordic VII study began in May 2005 and ended in October 2007, with a total of 571 patients randomized to one of three arms: the standard FLOX (5- fluorouracil [5-FU], folinic acid, oxaliplatin) regimen used in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at the time; FLOX plus additional cetuximab, with both given until progression or toxicity; or FLOX plus continuous cetuximab, with chemotherapy given for 16 weeks and then stopped and reintroduced at progression.

The Nordic FLOX regimen consists of a 5-FU intravenous bolus dose of 500 mg/m2 plus 60 mg/m2 folinic acid on days 1–2 every second week and oxaliplatin (85 mg/m2) on day 1. Cetuximab was used at a dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly.

The primary end point was progression-free survival, and this did not significantly differ between the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms, at a median of 7.9, 8.3, and 7.3 months, respectively (P = .31 comparing FLOX-cetuximab vs. standard FLOX).

Overall response rates in the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms were 41%, 49%, and 47%, with an odds ratio of 1.35 (P = .15) comparing the first two arms in the intent-to-treat population of 566 evaluable patients. Overall survival was also similar between the groups, at a median of 20.4, 19.7, and 20.3 months, respectively.

“KRAS mutation status was not found to be predictive for cetuximab effect,” Dr. Tveit said, noting that BRAF mutation was “a strong negative prognostic factor.”

The addition of cetuximab also was associated with more grade 3/4 adverse events than the standard FLOX arm. “The Nordic VII study indicates that oxaliplatin may not be a good match for cetuximab in metastatic colorectal cancer,” he observed.

Commenting on the trial, Dr. Alberto Sobrero from the Ospedale San Martino in Genoa, Italy, said the most unexpected result was that cetuximab was of no benefit in patients with wild-type KRAS. Despite a high level of quality-control measures in the study, “only Nordic VII reported lower response rates and progression-free survival in KRAS wild-type than in mutants out of 11 trials,” he said.

The choice of the Nordic FLOX regimen as the “backbone” of chemotherapy was questionable, as it incorporates one of the least effective 5-FU regimens. “If you want to impact on practice, you really want to have your control arm to be what everybody else is using,” he said.

Furthermore, “data supporting cetuximab in combination with oxaliplatin is “shaky at best,” and “whenever irinotecan [Camptosar] is a partner of cetuximab you have fantastic results,” Dr. Sobrero said. Irinotecan-based regimens should therefore be the chemotherapy backbone when using cetuximab. “There is also another piece of evidence of continuing chemotherapy until progression,” he added.

Merck-Serono and Sanofi-Aventis financially supported the Nordic VII study. All study authors had no conflicts of interest. Dr. Sobrero disclosed that he has acted as an advisory board member and speaker for Sanofi-Aventis, Amgen, AstraZeneca, Roche, Merck-Serono, Pfizer, Onyx, Bayer, and Genentech.

MILAN – Cetuximab in combination with a continuous or intermittently administered Nordic FLOX regimen for the first-line treatment of metastatic colorectal cancer conferred no advantage over the chemotherapy regimen alone, the first results of the Nordic VII study show.

The addition of cetuximab (Erbitux) did not improve response rates, progression-free survival, or overall survival. No better outcome was seen in patients with wild-type KRAS who received cetuximab, although the study was admittedly not powered to look specifically at KRAS subpopulations.

This is contrary to expectations and comes after a very thorough analysis, study investigator Dr. Kjell Magne Tveit of Oslo University Hospital said at the annual congress of the European Society for Medical Oncology. Investigators did not release data from the trial at the American Society of Clinical Oncology meeting earlier this year because they wanted to be sure of the disappointing results.

“Cetuximab has a documented beneficial effect in the later stages of metastatic colorectal cancer when given alone or together with chemotherapy,” Dr. Tveit said in a press release. “We expected that similar findings would be found in early stage [disease] when given together with the oxaliplatin regimen.”

Patient recruitment into the Nordic VII study began in May 2005 and ended in October 2007, with a total of 571 patients randomized to one of three arms: the standard FLOX (5- fluorouracil [5-FU], folinic acid, oxaliplatin) regimen used in the five Nordic countries (Denmark, Finland, Iceland, Norway, and Sweden) at the time; FLOX plus additional cetuximab, with both given until progression or toxicity; or FLOX plus continuous cetuximab, with chemotherapy given for 16 weeks and then stopped and reintroduced at progression.

The Nordic FLOX regimen consists of a 5-FU intravenous bolus dose of 500 mg/m2 plus 60 mg/m2 folinic acid on days 1–2 every second week and oxaliplatin (85 mg/m2) on day 1. Cetuximab was used at a dose of 400 mg/m2 on day 1, then 250 mg/m2 weekly.

The primary end point was progression-free survival, and this did not significantly differ between the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms, at a median of 7.9, 8.3, and 7.3 months, respectively (P = .31 comparing FLOX-cetuximab vs. standard FLOX).

Overall response rates in the standard FLOX, FLOX-cetuximab, and “stop/go” FLOX-cetuximab arms were 41%, 49%, and 47%, with an odds ratio of 1.35 (P = .15) comparing the first two arms in the intent-to-treat population of 566 evaluable patients. Overall survival was also similar between the groups, at a median of 20.4, 19.7, and 20.3 months, respectively.

“KRAS mutation status was not found to be predictive for cetuximab effect,” Dr. Tveit said, noting that BRAF mutation was “a strong negative prognostic factor.”

The addition of cetuximab also was associated with more grade 3/4 adverse events than the standard FLOX arm. “The Nordic VII study indicates that oxaliplatin may not be a good match for cetuximab in metastatic colorectal cancer,” he observed.

Commenting on the trial, Dr. Alberto Sobrero from the Ospedale San Martino in Genoa, Italy, said the most unexpected result was that cetuximab was of no benefit in patients with wild-type KRAS. Despite a high level of quality-control measures in the study, “only Nordic VII reported lower response rates and progression-free survival in KRAS wild-type than in mutants out of 11 trials,” he said.

The choice of the Nordic FLOX regimen as the “backbone” of chemotherapy was questionable, as it incorporates one of the least effective 5-FU regimens. “If you want to impact on practice, you really want to have your control arm to be what everybody else is using,” he said.

Furthermore, “data supporting cetuximab in combination with oxaliplatin is “shaky at best,” and “whenever irinotecan [Camptosar] is a partner of cetuximab you have fantastic results,” Dr. Sobrero said. Irinotecan-based regimens should therefore be the chemotherapy backbone when using cetuximab. “There is also another piece of evidence of continuing chemotherapy until progression,” he added.

Merck-Serono and Sanofi-Aventis financially supported the Nordic VII study. All study authors had no conflicts of interest. Dr. Sobrero disclosed that he has acted as an advisory board member and speaker for Sanofi-Aventis, Amgen, AstraZeneca, Roche, Merck-Serono, Pfizer, Onyx, Bayer, and Genentech.

BARCELONA – Although the risk of locoregional recurrence is undoubtedly reduced by the use of radiotherapy, uncertainty remains over the risk of second malignancies resulting from such treatment, according to two studies presented at the biennial meeting of the European Society for Therapeutic Radiation and Oncology.

New long-term data from the Stockholm mastectomy trial confirm that a major reduction in locoregional recurrence can be achieved with adjuvant radiotherapy of the breast, with no increased risk of contralateral or second malignancies.

Data from the European ALLEGRO project show, however, that the 20-year risk of second primary malignancies is higher in irradiated vs. nonirradiated women, with sites near the delivery of radiation being the most affected.

The Stockholm Mastectomy Trial

Radiotherapy is associated with a threefold decrease in the risk of locoregional recurrence in breast cancer, “but there is concern about the potential increase in non–breast cancer mortality,” said Dr. Rodrigo Arriagada, professor of oncology-pathology at the Karolinska Institute and University Hospital, Stockholm.

Dr. Arriagada presented findings from a median of 32 years’ follow-up of the Stockholm mastectomy trial in which 960 women with breast cancer were treated with pre- or postoperative radiotherapy or with modified radical mastectomy alone. Patients in the trial were recruited in 1971-1976, and those who received radiotherapy were treated with doses of 45 Gy given in 25 fractions over a 5-week period (J. Clin. Oncol. 1995;13:2869-78). The Swedish Tumor Registry reported second malignancies systematically.

When women in the radiotherapy arms were compared with those who were given no radiotherapy, the hazard ratio for overall survival was 0.90 (P = .16) and the HR for event-free survival was 0.79 (P less than .001). Locoregional recurrence was significantly reduced (HR, 0.29; P less than .001), with a nonsignificant trend for fewer distant metastases (HR, 0.87; P = .18) with radiotherapy vs. no radiotherapy.

In node-positive patients given radiotherapy, the hazard ratios for locoregional recurrence (0.24; P less than .0001) and distant metastases (0.65; P = .009) were significant. The HR for overall death in node-positive patients was 0.82 (P = .17).

Considering all patients, the risks of contralateral breast cancer and second malignancies were not significantly different between the patients who had received pre- or postoperative radiotherapy and those who had mastectomy alone.

“Adjuvant radiotherapy significantly decreases the risk of locoregional recurrences,” Dr. Arriagada said. “In high-risk patients with positive nodes, it may also decrease the incidence of distant metastases, and then have a positive impact on overall survival.”

Although later side effects, such as cardiovascular complications, may compromise the potential overall survival benefit, Dr. Arriagada concluded that long-term follow-up of oncology trials is essential in order to obtain complete information on likely complications of therapy.

The ALLEGRO Project

“The ALLEGRO project aims to address many of the early and late health risks to normal health tissue from the use of existing and emerging techniques in radiation therapy,” Trine Grantzau, a Ph.D. candidate from Aarhus (Denmark) University Hospital, said at the meeting. She noted that ALLEGRO involves collaboration by 13 institutions in eight European countries.

Linking data supplied by the Danish Breast Cancer Cooperative Group to the Danish Cancer Registry, the investigators were able to identify 47,518 women who were treated for early breast cancer in 1982-2007 and for whom follow-up data at 1 year after diagnosis were available. Of these, 24,316 had received postoperative radiotherapy whereas the remaining 23,202 had not.

In all, 2,958 second primary malignancies occurred, of which 1,187 were potentially related to the use of postoperative radiotherapy. Second malignancies occurred in a variety of locations, but mostly affected the respiratory, digestive, or genitourinary organs.

“All of these sites are within or close to the treatment field,” Ms. Grantzau said. “We have selected these sites out of an a priori assumption that these sites have received [radiotherapy] doses that could be potentially carcinogenic.”

Standardized incidence ratios (SIRs) were calculated for second primary cancers occurring from the 1-year follow-up to 20 or more years post diagnosis. The SIR “estimates the occurrence of cancer in a cohort relative to what would be expected in the general population – in this case, the general female Danish population,” the investigator explained.

For all 47,518 women who were identified as 1-year cancer survivors, SIRs at 1-4, 10-14, and 20 or more years after a breast cancer diagnosis were 1.0, 1.3, and 1.3, respectively. The respective SIRs for these time points for the nonirradiated women were 1.0, 1.2, and 1.2, and for the irradiated women were 1.0, 1.5, and 1.8. The difference in SIRs at 20 or more years following diagnosis between irradiated and nonirradiated women did not reach statistical significance (P = .08).

However, when SIRs for potentially radiotherapy-induced vs. nonpotentially radiotherapy-induced sites were compared, significant differences for irradiated vs. nonirradiated women were observed at 10-14 years (1.6 vs. 1.2; P = .03) and 20 or more years (2.6 vs. 0.9; P = .001).

SIRs for various tumor sites were also compared, showing that at 20 or more years after breast cancer diagnosis, irradiated women had a higher SIR ratio for second lung, bronchus, and tracheal malignancies than did the nonirradiated women, at 4.3 vs. 0.7 (P = .0001). Higher SIRs were seen for esophageal and colorectal cancers as well, but the differences did not reach statistical significance.

“There is an increased risk of developing potentially induced cancer, and the risk increases over time since treatment,” Ms. Grantzau said. The ALLEGRO project team will now use a dose-planning system to identify the radiation levels associated with the increased risk.

ALLEGRO is funded under the EURATOM Work Program. Dr. Arriagada and Ms. Grantzau reported no conflicts of interest.

BARCELONA – Although the risk of locoregional recurrence is undoubtedly reduced by the use of radiotherapy, uncertainty remains over the risk of second malignancies resulting from such treatment, according to two studies presented at the biennial meeting of the European Society for Therapeutic Radiation and Oncology.

New long-term data from the Stockholm mastectomy trial confirm that a major reduction in locoregional recurrence can be achieved with adjuvant radiotherapy of the breast, with no increased risk of contralateral or second malignancies.

Data from the European ALLEGRO project show, however, that the 20-year risk of second primary malignancies is higher in irradiated vs. nonirradiated women, with sites near the delivery of radiation being the most affected.

The Stockholm Mastectomy Trial

Radiotherapy is associated with a threefold decrease in the risk of locoregional recurrence in breast cancer, “but there is concern about the potential increase in non–breast cancer mortality,” said Dr. Rodrigo Arriagada, professor of oncology-pathology at the Karolinska Institute and University Hospital, Stockholm.

Dr. Arriagada presented findings from a median of 32 years’ follow-up of the Stockholm mastectomy trial in which 960 women with breast cancer were treated with pre- or postoperative radiotherapy or with modified radical mastectomy alone. Patients in the trial were recruited in 1971-1976, and those who received radiotherapy were treated with doses of 45 Gy given in 25 fractions over a 5-week period (J. Clin. Oncol. 1995;13:2869-78). The Swedish Tumor Registry reported second malignancies systematically.

When women in the radiotherapy arms were compared with those who were given no radiotherapy, the hazard ratio for overall survival was 0.90 (P = .16) and the HR for event-free survival was 0.79 (P less than .001). Locoregional recurrence was significantly reduced (HR, 0.29; P less than .001), with a nonsignificant trend for fewer distant metastases (HR, 0.87; P = .18) with radiotherapy vs. no radiotherapy.

In node-positive patients given radiotherapy, the hazard ratios for locoregional recurrence (0.24; P less than .0001) and distant metastases (0.65; P = .009) were significant. The HR for overall death in node-positive patients was 0.82 (P = .17).

Considering all patients, the risks of contralateral breast cancer and second malignancies were not significantly different between the patients who had received pre- or postoperative radiotherapy and those who had mastectomy alone.

“Adjuvant radiotherapy significantly decreases the risk of locoregional recurrences,” Dr. Arriagada said. “In high-risk patients with positive nodes, it may also decrease the incidence of distant metastases, and then have a positive impact on overall survival.”

Although later side effects, such as cardiovascular complications, may compromise the potential overall survival benefit, Dr. Arriagada concluded that long-term follow-up of oncology trials is essential in order to obtain complete information on likely complications of therapy.

The ALLEGRO Project

“The ALLEGRO project aims to address many of the early and late health risks to normal health tissue from the use of existing and emerging techniques in radiation therapy,” Trine Grantzau, a Ph.D. candidate from Aarhus (Denmark) University Hospital, said at the meeting. She noted that ALLEGRO involves collaboration by 13 institutions in eight European countries.

Linking data supplied by the Danish Breast Cancer Cooperative Group to the Danish Cancer Registry, the investigators were able to identify 47,518 women who were treated for early breast cancer in 1982-2007 and for whom follow-up data at 1 year after diagnosis were available. Of these, 24,316 had received postoperative radiotherapy whereas the remaining 23,202 had not.

In all, 2,958 second primary malignancies occurred, of which 1,187 were potentially related to the use of postoperative radiotherapy. Second malignancies occurred in a variety of locations, but mostly affected the respiratory, digestive, or genitourinary organs.

“All of these sites are within or close to the treatment field,” Ms. Grantzau said. “We have selected these sites out of an a priori assumption that these sites have received [radiotherapy] doses that could be potentially carcinogenic.”

Standardized incidence ratios (SIRs) were calculated for second primary cancers occurring from the 1-year follow-up to 20 or more years post diagnosis. The SIR “estimates the occurrence of cancer in a cohort relative to what would be expected in the general population – in this case, the general female Danish population,” the investigator explained.

For all 47,518 women who were identified as 1-year cancer survivors, SIRs at 1-4, 10-14, and 20 or more years after a breast cancer diagnosis were 1.0, 1.3, and 1.3, respectively. The respective SIRs for these time points for the nonirradiated women were 1.0, 1.2, and 1.2, and for the irradiated women were 1.0, 1.5, and 1.8. The difference in SIRs at 20 or more years following diagnosis between irradiated and nonirradiated women did not reach statistical significance (P = .08).

However, when SIRs for potentially radiotherapy-induced vs. nonpotentially radiotherapy-induced sites were compared, significant differences for irradiated vs. nonirradiated women were observed at 10-14 years (1.6 vs. 1.2; P = .03) and 20 or more years (2.6 vs. 0.9; P = .001).

SIRs for various tumor sites were also compared, showing that at 20 or more years after breast cancer diagnosis, irradiated women had a higher SIR ratio for second lung, bronchus, and tracheal malignancies than did the nonirradiated women, at 4.3 vs. 0.7 (P = .0001). Higher SIRs were seen for esophageal and colorectal cancers as well, but the differences did not reach statistical significance.

“There is an increased risk of developing potentially induced cancer, and the risk increases over time since treatment,” Ms. Grantzau said. The ALLEGRO project team will now use a dose-planning system to identify the radiation levels associated with the increased risk.

ALLEGRO is funded under the EURATOM Work Program. Dr. Arriagada and Ms. Grantzau reported no conflicts of interest.

BARCELONA – Although the risk of locoregional recurrence is undoubtedly reduced by the use of radiotherapy, uncertainty remains over the risk of second malignancies resulting from such treatment, according to two studies presented at the biennial meeting of the European Society for Therapeutic Radiation and Oncology.

New long-term data from the Stockholm mastectomy trial confirm that a major reduction in locoregional recurrence can be achieved with adjuvant radiotherapy of the breast, with no increased risk of contralateral or second malignancies.

Data from the European ALLEGRO project show, however, that the 20-year risk of second primary malignancies is higher in irradiated vs. nonirradiated women, with sites near the delivery of radiation being the most affected.

The Stockholm Mastectomy Trial

Radiotherapy is associated with a threefold decrease in the risk of locoregional recurrence in breast cancer, “but there is concern about the potential increase in non–breast cancer mortality,” said Dr. Rodrigo Arriagada, professor of oncology-pathology at the Karolinska Institute and University Hospital, Stockholm.

Dr. Arriagada presented findings from a median of 32 years’ follow-up of the Stockholm mastectomy trial in which 960 women with breast cancer were treated with pre- or postoperative radiotherapy or with modified radical mastectomy alone. Patients in the trial were recruited in 1971-1976, and those who received radiotherapy were treated with doses of 45 Gy given in 25 fractions over a 5-week period (J. Clin. Oncol. 1995;13:2869-78). The Swedish Tumor Registry reported second malignancies systematically.

When women in the radiotherapy arms were compared with those who were given no radiotherapy, the hazard ratio for overall survival was 0.90 (P = .16) and the HR for event-free survival was 0.79 (P less than .001). Locoregional recurrence was significantly reduced (HR, 0.29; P less than .001), with a nonsignificant trend for fewer distant metastases (HR, 0.87; P = .18) with radiotherapy vs. no radiotherapy.

In node-positive patients given radiotherapy, the hazard ratios for locoregional recurrence (0.24; P less than .0001) and distant metastases (0.65; P = .009) were significant. The HR for overall death in node-positive patients was 0.82 (P = .17).

Considering all patients, the risks of contralateral breast cancer and second malignancies were not significantly different between the patients who had received pre- or postoperative radiotherapy and those who had mastectomy alone.

“Adjuvant radiotherapy significantly decreases the risk of locoregional recurrences,” Dr. Arriagada said. “In high-risk patients with positive nodes, it may also decrease the incidence of distant metastases, and then have a positive impact on overall survival.”

Although later side effects, such as cardiovascular complications, may compromise the potential overall survival benefit, Dr. Arriagada concluded that long-term follow-up of oncology trials is essential in order to obtain complete information on likely complications of therapy.

The ALLEGRO Project

“The ALLEGRO project aims to address many of the early and late health risks to normal health tissue from the use of existing and emerging techniques in radiation therapy,” Trine Grantzau, a Ph.D. candidate from Aarhus (Denmark) University Hospital, said at the meeting. She noted that ALLEGRO involves collaboration by 13 institutions in eight European countries.

Linking data supplied by the Danish Breast Cancer Cooperative Group to the Danish Cancer Registry, the investigators were able to identify 47,518 women who were treated for early breast cancer in 1982-2007 and for whom follow-up data at 1 year after diagnosis were available. Of these, 24,316 had received postoperative radiotherapy whereas the remaining 23,202 had not.

In all, 2,958 second primary malignancies occurred, of which 1,187 were potentially related to the use of postoperative radiotherapy. Second malignancies occurred in a variety of locations, but mostly affected the respiratory, digestive, or genitourinary organs.

“All of these sites are within or close to the treatment field,” Ms. Grantzau said. “We have selected these sites out of an a priori assumption that these sites have received [radiotherapy] doses that could be potentially carcinogenic.”

Standardized incidence ratios (SIRs) were calculated for second primary cancers occurring from the 1-year follow-up to 20 or more years post diagnosis. The SIR “estimates the occurrence of cancer in a cohort relative to what would be expected in the general population – in this case, the general female Danish population,” the investigator explained.

For all 47,518 women who were identified as 1-year cancer survivors, SIRs at 1-4, 10-14, and 20 or more years after a breast cancer diagnosis were 1.0, 1.3, and 1.3, respectively. The respective SIRs for these time points for the nonirradiated women were 1.0, 1.2, and 1.2, and for the irradiated women were 1.0, 1.5, and 1.8. The difference in SIRs at 20 or more years following diagnosis between irradiated and nonirradiated women did not reach statistical significance (P = .08).

However, when SIRs for potentially radiotherapy-induced vs. nonpotentially radiotherapy-induced sites were compared, significant differences for irradiated vs. nonirradiated women were observed at 10-14 years (1.6 vs. 1.2; P = .03) and 20 or more years (2.6 vs. 0.9; P = .001).

SIRs for various tumor sites were also compared, showing that at 20 or more years after breast cancer diagnosis, irradiated women had a higher SIR ratio for second lung, bronchus, and tracheal malignancies than did the nonirradiated women, at 4.3 vs. 0.7 (P = .0001). Higher SIRs were seen for esophageal and colorectal cancers as well, but the differences did not reach statistical significance.

“There is an increased risk of developing potentially induced cancer, and the risk increases over time since treatment,” Ms. Grantzau said. The ALLEGRO project team will now use a dose-planning system to identify the radiation levels associated with the increased risk.

ALLEGRO is funded under the EURATOM Work Program. Dr. Arriagada and Ms. Grantzau reported no conflicts of interest.

Adding regional hyperthermia to neoadjuvant chemotherapy produced significantly higher progression-free and disease-free survival rates in patients who had undergone macroscopically complete resection of high-risk, nonextremity soft tissue sarcomas in a phase III trial, according to a study that was presented at the meeting in Barcelona.

At 2 years post treatment, the progression-free survival rate was 70% and the disease-free survival rate was 56% in patients who were treated with regional hyperthermia plus neoadjuvant chemotherapy, according to a subgroup analysis of patients with nonextremity disease. Corresponding rates for neoadjuvant chemotherapy alone were 54% and 39% in this population.

Hyperthermia’s advantage held at 5 years, with rates of 54% for progression-free survival vs. 43% in the control group, and 35% vs. 24% for disease-free survival, Dr. Rolf D. Issels reported at the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

“The rationale for using regional hyperthermia is to make tumors more sensitive to chemotherapeutic agents and radiotherapy,” Dr. Issels of the Klinikum Grosshadern at the Ludwig-Maximilians University of Munich said in an interview.

“Besides sensitization to other treatment modalities, hyperthermia also kills tumors in a temperature range between 40° and 43° C [104°-109.4° F], and we know from preclinical and early clinical data that it seems to activate the immune system by delivering stress or danger signals,” he explained.

The main findings of the ESHO/EORTC–Soft Tissue and Bone Sarcoma Group (STBSG) 62962 trial were published recently in the Lancet (2010;11:561-70). Of the 341 recruited patients (median age, 51-52 years), more than half had nonextremity tumors that were predominantly located in the abdomen, pelvis, or trunk, which led to the question of whether macroscopically complete surgical resection in these patients could potentially abrogate the beneficial effects of regional hyperthermia that was observed in the trial.

The new data that Dr. Issels presented at the meeting involved only those patients with nonextremity sarcomas who had macroscopically complete surgical resection. In total, 73 patients with R0/1 resection received neoadjuvant chemotherapy alone, and 76 had received neoadjuvant chemotherapy together with regional hyperthermia.

Neoadjuvant chemotherapy consisted of etoposide, ifosfamide, and doxorubicin (Adriamycin) – a regimen abbreviated as EIA – and was given for four cycles with or without additional regional hyperthermia before definitive surgery and postoperative radiotherapy. This was followed by four more cycles of postinduction chemotherapy with or without regional hyperthermia, according to randomization. Regional hyperthermia was delivered via the BSD-2000/3D Hyperthermia System, in which the patient lies down inside the deep-heating device while receiving intravenous chemotherapy.

The primary end point was local progression-free survival, which remained significantly improved by the addition of regional hyperthermia to EIA chemotherapy, compared with EIA chemotherapy alone. The hazard ratio for local progression free-survival was 0.60, favoring the use of regional hyperthermia and EIA over EIA chemotherapy alone (log rank P = .034). Median local progression-free survival was not reached with regional hyperthermia; it was 30 months with chemotherapy alone.

The hazard ratio for disease-free survival (0.65; log rank P = .031) also favored the use of regional hyperthermia and EIA. Median disease-free survival was 32 months with the intervention vs. 17 months in the control group.

The clinical implications of the research are clear, said Dr. Issels: The combination of regional hyperthermia with neoadjuvant chemotherapy can improve outcomes in patients with high-risk sarcoma. “Unfortunately, we only have a few centers in the world to perform regional hyperthermia together with chemotherapy,” he noted, urging other centers that refer patients to consider the approach used at his institution.

Together with earlier preclinical work, the completed phase III trial provides not only proof of concept, but also proof of efficacy, Dr. Issels added.

“We are going to transfer the knowledge to advanced pancreatic cancer,” he said. “We have an open study to deliver gemcitabine plus cisplatin as second-line therapy combined with regional hyperthermia in locally advanced or metastatic pancreatic cancer.”

Dr. Issels and associates are also looking at the use of thermosensitive liposomes containing chemotherapeutic agents in early preclinical studies.

Disclosures: The study was funded by Deutsche Krebshilfe, the Helmholtz Association of German Research Centres (HDF), the European Organisation for Research and Treatment of Cancer (EORTC), the European Society for Hyperthermic Oncology (ESHO), and the U.S. National Institutes of Health. Dr. Issels has received research and educational grants from Amgen, Baxter, BSD Medical, and PharmaMar, together with honoraria and consulting fees from GSK and MedTherm.

Adding regional hyperthermia to neoadjuvant chemotherapy produced significantly higher progression-free and disease-free survival rates in patients who had undergone macroscopically complete resection of high-risk, nonextremity soft tissue sarcomas in a phase III trial, according to a study that was presented at the meeting in Barcelona.

At 2 years post treatment, the progression-free survival rate was 70% and the disease-free survival rate was 56% in patients who were treated with regional hyperthermia plus neoadjuvant chemotherapy, according to a subgroup analysis of patients with nonextremity disease. Corresponding rates for neoadjuvant chemotherapy alone were 54% and 39% in this population.

Hyperthermia’s advantage held at 5 years, with rates of 54% for progression-free survival vs. 43% in the control group, and 35% vs. 24% for disease-free survival, Dr. Rolf D. Issels reported at the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

“The rationale for using regional hyperthermia is to make tumors more sensitive to chemotherapeutic agents and radiotherapy,” Dr. Issels of the Klinikum Grosshadern at the Ludwig-Maximilians University of Munich said in an interview.

“Besides sensitization to other treatment modalities, hyperthermia also kills tumors in a temperature range between 40° and 43° C [104°-109.4° F], and we know from preclinical and early clinical data that it seems to activate the immune system by delivering stress or danger signals,” he explained.

The main findings of the ESHO/EORTC–Soft Tissue and Bone Sarcoma Group (STBSG) 62962 trial were published recently in the Lancet (2010;11:561-70). Of the 341 recruited patients (median age, 51-52 years), more than half had nonextremity tumors that were predominantly located in the abdomen, pelvis, or trunk, which led to the question of whether macroscopically complete surgical resection in these patients could potentially abrogate the beneficial effects of regional hyperthermia that was observed in the trial.

The new data that Dr. Issels presented at the meeting involved only those patients with nonextremity sarcomas who had macroscopically complete surgical resection. In total, 73 patients with R0/1 resection received neoadjuvant chemotherapy alone, and 76 had received neoadjuvant chemotherapy together with regional hyperthermia.

Neoadjuvant chemotherapy consisted of etoposide, ifosfamide, and doxorubicin (Adriamycin) – a regimen abbreviated as EIA – and was given for four cycles with or without additional regional hyperthermia before definitive surgery and postoperative radiotherapy. This was followed by four more cycles of postinduction chemotherapy with or without regional hyperthermia, according to randomization. Regional hyperthermia was delivered via the BSD-2000/3D Hyperthermia System, in which the patient lies down inside the deep-heating device while receiving intravenous chemotherapy.

The primary end point was local progression-free survival, which remained significantly improved by the addition of regional hyperthermia to EIA chemotherapy, compared with EIA chemotherapy alone. The hazard ratio for local progression free-survival was 0.60, favoring the use of regional hyperthermia and EIA over EIA chemotherapy alone (log rank P = .034). Median local progression-free survival was not reached with regional hyperthermia; it was 30 months with chemotherapy alone.

The hazard ratio for disease-free survival (0.65; log rank P = .031) also favored the use of regional hyperthermia and EIA. Median disease-free survival was 32 months with the intervention vs. 17 months in the control group.

The clinical implications of the research are clear, said Dr. Issels: The combination of regional hyperthermia with neoadjuvant chemotherapy can improve outcomes in patients with high-risk sarcoma. “Unfortunately, we only have a few centers in the world to perform regional hyperthermia together with chemotherapy,” he noted, urging other centers that refer patients to consider the approach used at his institution.

Together with earlier preclinical work, the completed phase III trial provides not only proof of concept, but also proof of efficacy, Dr. Issels added.

“We are going to transfer the knowledge to advanced pancreatic cancer,” he said. “We have an open study to deliver gemcitabine plus cisplatin as second-line therapy combined with regional hyperthermia in locally advanced or metastatic pancreatic cancer.”

Dr. Issels and associates are also looking at the use of thermosensitive liposomes containing chemotherapeutic agents in early preclinical studies.

Disclosures: The study was funded by Deutsche Krebshilfe, the Helmholtz Association of German Research Centres (HDF), the European Organisation for Research and Treatment of Cancer (EORTC), the European Society for Hyperthermic Oncology (ESHO), and the U.S. National Institutes of Health. Dr. Issels has received research and educational grants from Amgen, Baxter, BSD Medical, and PharmaMar, together with honoraria and consulting fees from GSK and MedTherm.

Adding regional hyperthermia to neoadjuvant chemotherapy produced significantly higher progression-free and disease-free survival rates in patients who had undergone macroscopically complete resection of high-risk, nonextremity soft tissue sarcomas in a phase III trial, according to a study that was presented at the meeting in Barcelona.

At 2 years post treatment, the progression-free survival rate was 70% and the disease-free survival rate was 56% in patients who were treated with regional hyperthermia plus neoadjuvant chemotherapy, according to a subgroup analysis of patients with nonextremity disease. Corresponding rates for neoadjuvant chemotherapy alone were 54% and 39% in this population.

Hyperthermia’s advantage held at 5 years, with rates of 54% for progression-free survival vs. 43% in the control group, and 35% vs. 24% for disease-free survival, Dr. Rolf D. Issels reported at the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

“The rationale for using regional hyperthermia is to make tumors more sensitive to chemotherapeutic agents and radiotherapy,” Dr. Issels of the Klinikum Grosshadern at the Ludwig-Maximilians University of Munich said in an interview.

“Besides sensitization to other treatment modalities, hyperthermia also kills tumors in a temperature range between 40° and 43° C [104°-109.4° F], and we know from preclinical and early clinical data that it seems to activate the immune system by delivering stress or danger signals,” he explained.

The main findings of the ESHO/EORTC–Soft Tissue and Bone Sarcoma Group (STBSG) 62962 trial were published recently in the Lancet (2010;11:561-70). Of the 341 recruited patients (median age, 51-52 years), more than half had nonextremity tumors that were predominantly located in the abdomen, pelvis, or trunk, which led to the question of whether macroscopically complete surgical resection in these patients could potentially abrogate the beneficial effects of regional hyperthermia that was observed in the trial.

The new data that Dr. Issels presented at the meeting involved only those patients with nonextremity sarcomas who had macroscopically complete surgical resection. In total, 73 patients with R0/1 resection received neoadjuvant chemotherapy alone, and 76 had received neoadjuvant chemotherapy together with regional hyperthermia.

Neoadjuvant chemotherapy consisted of etoposide, ifosfamide, and doxorubicin (Adriamycin) – a regimen abbreviated as EIA – and was given for four cycles with or without additional regional hyperthermia before definitive surgery and postoperative radiotherapy. This was followed by four more cycles of postinduction chemotherapy with or without regional hyperthermia, according to randomization. Regional hyperthermia was delivered via the BSD-2000/3D Hyperthermia System, in which the patient lies down inside the deep-heating device while receiving intravenous chemotherapy.

The primary end point was local progression-free survival, which remained significantly improved by the addition of regional hyperthermia to EIA chemotherapy, compared with EIA chemotherapy alone. The hazard ratio for local progression free-survival was 0.60, favoring the use of regional hyperthermia and EIA over EIA chemotherapy alone (log rank P = .034). Median local progression-free survival was not reached with regional hyperthermia; it was 30 months with chemotherapy alone.

The hazard ratio for disease-free survival (0.65; log rank P = .031) also favored the use of regional hyperthermia and EIA. Median disease-free survival was 32 months with the intervention vs. 17 months in the control group.

The clinical implications of the research are clear, said Dr. Issels: The combination of regional hyperthermia with neoadjuvant chemotherapy can improve outcomes in patients with high-risk sarcoma. “Unfortunately, we only have a few centers in the world to perform regional hyperthermia together with chemotherapy,” he noted, urging other centers that refer patients to consider the approach used at his institution.

Together with earlier preclinical work, the completed phase III trial provides not only proof of concept, but also proof of efficacy, Dr. Issels added.

“We are going to transfer the knowledge to advanced pancreatic cancer,” he said. “We have an open study to deliver gemcitabine plus cisplatin as second-line therapy combined with regional hyperthermia in locally advanced or metastatic pancreatic cancer.”

Dr. Issels and associates are also looking at the use of thermosensitive liposomes containing chemotherapeutic agents in early preclinical studies.

Disclosures: The study was funded by Deutsche Krebshilfe, the Helmholtz Association of German Research Centres (HDF), the European Organisation for Research and Treatment of Cancer (EORTC), the European Society for Hyperthermic Oncology (ESHO), and the U.S. National Institutes of Health. Dr. Issels has received research and educational grants from Amgen, Baxter, BSD Medical, and PharmaMar, together with honoraria and consulting fees from GSK and MedTherm.

BARCELONA – Mitomycin C proved as effective and well tolerated as cisplatin when used as part of a chemoradiation schedule for locally advanced stage IV head and neck cancer, but it was associated with more distant metastases at 3 years.

Results of a randomized, phase III trial indicate that “classical concurrent chemoradiation using cisplatin or MMC [mitomycin C] can still be considered the standard of care,” said study investigator Dr. Volker Budach, head of the radiation oncology department at Charité Medical University Berlin.

“This trial has established, for the first time, level Ib evidence for a concurrent, once-weekly cisplatin/[5-fluorouracil] regimen with a moderate, accelerated, radiation strategy,” he added, addressing the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

An invited discussant of the trial, Dr. Hans Langendijk noted that it was “the first phase III study in head and neck cancer that compared two different chemotherapy regimens in combination with a hypofractionated accelerated radiation schedule.”

Platinum-based, concomitant chemoradiation is considered the standard of care, but it is associated with considerable toxicity, and this has prompted the search for suitable alternative strategies, commented Dr. Langendijk, professor of radiotherapy at the University Medical Center Groningen (the Netherlands), who was not involved in the trial.

In the German Clinical Trials Cooperative Group’s ARO/AHMO 04-01 trial, 364 patients with stage IV head and neck cancer were randomized to receive chemoradiation consisting of 72-Gy hyperfractionated accelerated radiation therapy (HART) plus either concurrent cisplatin and 5-fluorouracil (5-FU) or MMC/5-FU for 6 weeks.

At 3 years’ follow-up, more patients who received weekly chemoradiation with cisplatin than MMC were free of distant metastases (hazard ratio, 0.622; P = .02). The primary end point of the trial (an improvement in overall survival) was not reached at 2 or 3 years, however, and cisplatin with 5-FU was not superior to MMC/5-FU in terms of any of the other end points assessed, which included progression-free survival, local control, regional control, and locoregional recurrence.

The local control rate was about 70%, as Dr. Budach reported, with regional and locoregional control rates of approximately 80% and 60%, respectively. “These are excellent values, and can easily compare” with those in other published trials, he said.

Acute hematologic or radiation-related toxicities were also not significantly different between the two study arms, although Dr. Budach highlighted that cisplatin-treated patients had higher creatinine levels than did those who were treated with MMC (P = .001).

“The cost:efficiency ratio is excellent due to the off-license use of all involved drugs, and far better than competitive regimens,” which include cetuximab (Erbitux) as well as the TPF (docetaxel [Taxotere], cisplatin, and 5-FU) regimen, Dr. Budach said.

Commenting on the data in an interview, ESTRO president Dr. Jean Bourhis said, “It’s interesting, because when you compare the two regimens, they are not too different except for the effects on distant metastases.” Dr. Bourhis, chairman of the radiation oncology department at the Institut Gustave Roussy in Villejuif, France, added that this finding could sway some clinicians toward the use of cisplatin rather than MMC.

However, considering that there was no difference in efficacy findings and fewer renal failures, “HART plus MMC/5-FU could be considered as a standard of care,” said Dr. Langendijk. He suggested that cetuximab plus radiotherapy could also be considered as a standard of care in patients for whom platinum-based chemotherapy is not an option.

“Further analysis is needed on specific subsets of patients,” Dr. Langendijk said, notably to see whether HPV status makes any difference in the effects of the MMC/5-FU combination.

Disclosures: Deutsche Krebshilfe (German Cancer Aid) funded the study. The investigators, Dr. Bourhis, and Dr. Langendijk had no conflicts of interest.

BARCELONA – Mitomycin C proved as effective and well tolerated as cisplatin when used as part of a chemoradiation schedule for locally advanced stage IV head and neck cancer, but it was associated with more distant metastases at 3 years.

Results of a randomized, phase III trial indicate that “classical concurrent chemoradiation using cisplatin or MMC [mitomycin C] can still be considered the standard of care,” said study investigator Dr. Volker Budach, head of the radiation oncology department at Charité Medical University Berlin.

“This trial has established, for the first time, level Ib evidence for a concurrent, once-weekly cisplatin/[5-fluorouracil] regimen with a moderate, accelerated, radiation strategy,” he added, addressing the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

An invited discussant of the trial, Dr. Hans Langendijk noted that it was “the first phase III study in head and neck cancer that compared two different chemotherapy regimens in combination with a hypofractionated accelerated radiation schedule.”

Platinum-based, concomitant chemoradiation is considered the standard of care, but it is associated with considerable toxicity, and this has prompted the search for suitable alternative strategies, commented Dr. Langendijk, professor of radiotherapy at the University Medical Center Groningen (the Netherlands), who was not involved in the trial.

In the German Clinical Trials Cooperative Group’s ARO/AHMO 04-01 trial, 364 patients with stage IV head and neck cancer were randomized to receive chemoradiation consisting of 72-Gy hyperfractionated accelerated radiation therapy (HART) plus either concurrent cisplatin and 5-fluorouracil (5-FU) or MMC/5-FU for 6 weeks.

At 3 years’ follow-up, more patients who received weekly chemoradiation with cisplatin than MMC were free of distant metastases (hazard ratio, 0.622; P = .02). The primary end point of the trial (an improvement in overall survival) was not reached at 2 or 3 years, however, and cisplatin with 5-FU was not superior to MMC/5-FU in terms of any of the other end points assessed, which included progression-free survival, local control, regional control, and locoregional recurrence.

The local control rate was about 70%, as Dr. Budach reported, with regional and locoregional control rates of approximately 80% and 60%, respectively. “These are excellent values, and can easily compare” with those in other published trials, he said.

Acute hematologic or radiation-related toxicities were also not significantly different between the two study arms, although Dr. Budach highlighted that cisplatin-treated patients had higher creatinine levels than did those who were treated with MMC (P = .001).

“The cost:efficiency ratio is excellent due to the off-license use of all involved drugs, and far better than competitive regimens,” which include cetuximab (Erbitux) as well as the TPF (docetaxel [Taxotere], cisplatin, and 5-FU) regimen, Dr. Budach said.

Commenting on the data in an interview, ESTRO president Dr. Jean Bourhis said, “It’s interesting, because when you compare the two regimens, they are not too different except for the effects on distant metastases.” Dr. Bourhis, chairman of the radiation oncology department at the Institut Gustave Roussy in Villejuif, France, added that this finding could sway some clinicians toward the use of cisplatin rather than MMC.

However, considering that there was no difference in efficacy findings and fewer renal failures, “HART plus MMC/5-FU could be considered as a standard of care,” said Dr. Langendijk. He suggested that cetuximab plus radiotherapy could also be considered as a standard of care in patients for whom platinum-based chemotherapy is not an option.

“Further analysis is needed on specific subsets of patients,” Dr. Langendijk said, notably to see whether HPV status makes any difference in the effects of the MMC/5-FU combination.

Disclosures: Deutsche Krebshilfe (German Cancer Aid) funded the study. The investigators, Dr. Bourhis, and Dr. Langendijk had no conflicts of interest.

BARCELONA – Mitomycin C proved as effective and well tolerated as cisplatin when used as part of a chemoradiation schedule for locally advanced stage IV head and neck cancer, but it was associated with more distant metastases at 3 years.

Results of a randomized, phase III trial indicate that “classical concurrent chemoradiation using cisplatin or MMC [mitomycin C] can still be considered the standard of care,” said study investigator Dr. Volker Budach, head of the radiation oncology department at Charité Medical University Berlin.

“This trial has established, for the first time, level Ib evidence for a concurrent, once-weekly cisplatin/[5-fluorouracil] regimen with a moderate, accelerated, radiation strategy,” he added, addressing the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

An invited discussant of the trial, Dr. Hans Langendijk noted that it was “the first phase III study in head and neck cancer that compared two different chemotherapy regimens in combination with a hypofractionated accelerated radiation schedule.”

Platinum-based, concomitant chemoradiation is considered the standard of care, but it is associated with considerable toxicity, and this has prompted the search for suitable alternative strategies, commented Dr. Langendijk, professor of radiotherapy at the University Medical Center Groningen (the Netherlands), who was not involved in the trial.

In the German Clinical Trials Cooperative Group’s ARO/AHMO 04-01 trial, 364 patients with stage IV head and neck cancer were randomized to receive chemoradiation consisting of 72-Gy hyperfractionated accelerated radiation therapy (HART) plus either concurrent cisplatin and 5-fluorouracil (5-FU) or MMC/5-FU for 6 weeks.

At 3 years’ follow-up, more patients who received weekly chemoradiation with cisplatin than MMC were free of distant metastases (hazard ratio, 0.622; P = .02). The primary end point of the trial (an improvement in overall survival) was not reached at 2 or 3 years, however, and cisplatin with 5-FU was not superior to MMC/5-FU in terms of any of the other end points assessed, which included progression-free survival, local control, regional control, and locoregional recurrence.

The local control rate was about 70%, as Dr. Budach reported, with regional and locoregional control rates of approximately 80% and 60%, respectively. “These are excellent values, and can easily compare” with those in other published trials, he said.

Acute hematologic or radiation-related toxicities were also not significantly different between the two study arms, although Dr. Budach highlighted that cisplatin-treated patients had higher creatinine levels than did those who were treated with MMC (P = .001).

“The cost:efficiency ratio is excellent due to the off-license use of all involved drugs, and far better than competitive regimens,” which include cetuximab (Erbitux) as well as the TPF (docetaxel [Taxotere], cisplatin, and 5-FU) regimen, Dr. Budach said.

Commenting on the data in an interview, ESTRO president Dr. Jean Bourhis said, “It’s interesting, because when you compare the two regimens, they are not too different except for the effects on distant metastases.” Dr. Bourhis, chairman of the radiation oncology department at the Institut Gustave Roussy in Villejuif, France, added that this finding could sway some clinicians toward the use of cisplatin rather than MMC.

However, considering that there was no difference in efficacy findings and fewer renal failures, “HART plus MMC/5-FU could be considered as a standard of care,” said Dr. Langendijk. He suggested that cetuximab plus radiotherapy could also be considered as a standard of care in patients for whom platinum-based chemotherapy is not an option.

“Further analysis is needed on specific subsets of patients,” Dr. Langendijk said, notably to see whether HPV status makes any difference in the effects of the MMC/5-FU combination.

Disclosures: Deutsche Krebshilfe (German Cancer Aid) funded the study. The investigators, Dr. Bourhis, and Dr. Langendijk had no conflicts of interest.

BARCELONA – The 3-year results of a nonrandomized trial from Spain reveal different patterns of adverse events after three leading treatments for localized prostate cancer.

Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were external beam radiotherapy or brachytherapy, according to charts presented at the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

Brachytherapy, however, was associated with far more irritative and obstructive urinary symptoms than were surgery or external beam radiotherapy (EBRT).

The trial was conducted in 11 hospitals throughout Spain, and originally enrolled 435 men with stage T1 and T2 prostate cancer who had received no prior surgical resection or hormonal treatment. The aim of the trial was to compare the health-related quality of life (HRQoL) impact of the three most commonly used primary treatments in men who were followed from before treatment to 3 years after intervention.

Treatment decisions were made jointly by physicians and patients; the analysis covered 123 men who underwent RRP, 127 who had EBRT, and 123 who had brachytherapy.

During the study, HRQoL was assessed using several validated questionnaires before and at 1, 3, 6, 12, 24, and 36 months after treatment. The questionnaires used included the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index.

“This is a very important study because it takes into account the previous stage in quality of life of our patients,” before they received any treatment, Dr. Ferran Guedea said at a scientific press briefing.

“We also have the results of 3-years of follow-up. That is a very long follow-up for different types of treatment,” added Dr. Guedea, a radiation oncologist at the Catalan Institute of Oncology, L’Hospitalet de Llobregat, near Barcelona.

Previously published results showed that despite partial recovery from immediate deterioration in HRQoL, relevant differences persisted with 2 years’ follow-up (Int. J. Radiat. Oncol. Biol. Phys. 2008; 72:421-32). The 3-year results also show that in each treatment group, HRQoL deteriorated immediately after receiving any of the prostate cancer treatments, but rose after the interventions to varying degrees.

SF-36 Physical Component scores decreased most dramatically after prostatectomy compared with either radiotherapy technique, but rose in the first 6 months after the procedure before gradually deteriorating over the 3 years’ follow-up. EBRT produced lower scores than those for brachytherapy, and these gradually worsened during long-term follow up, such that they were lower at 3 years than were scores in the patients who had undergone surgery.

“RRP caused considerable urinary incontinence and sexual dysfunction,” Dr. Guedea observed. He added: “Brachytherapy and EBRT caused moderate urinary irritative-obstructive urinary symptoms and moderate adverse effects on sexual function, and finally, EBRT had very moderate bowel-related adverse events.”

These results are useful to consider when discussing treatment options with patients, Dr. Guedea suggested, particularly in light of other studies showing the significant benefits of all treatments in terms of tumor control and improved overall survival.

Disclosures: The Spanish National Health System funded the study. Dr. Guedea had no conflicts of interest.

BARCELONA – The 3-year results of a nonrandomized trial from Spain reveal different patterns of adverse events after three leading treatments for localized prostate cancer.

Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were external beam radiotherapy or brachytherapy, according to charts presented at the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

Brachytherapy, however, was associated with far more irritative and obstructive urinary symptoms than were surgery or external beam radiotherapy (EBRT).

The trial was conducted in 11 hospitals throughout Spain, and originally enrolled 435 men with stage T1 and T2 prostate cancer who had received no prior surgical resection or hormonal treatment. The aim of the trial was to compare the health-related quality of life (HRQoL) impact of the three most commonly used primary treatments in men who were followed from before treatment to 3 years after intervention.

Treatment decisions were made jointly by physicians and patients; the analysis covered 123 men who underwent RRP, 127 who had EBRT, and 123 who had brachytherapy.

During the study, HRQoL was assessed using several validated questionnaires before and at 1, 3, 6, 12, 24, and 36 months after treatment. The questionnaires used included the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index.

“This is a very important study because it takes into account the previous stage in quality of life of our patients,” before they received any treatment, Dr. Ferran Guedea said at a scientific press briefing.

“We also have the results of 3-years of follow-up. That is a very long follow-up for different types of treatment,” added Dr. Guedea, a radiation oncologist at the Catalan Institute of Oncology, L’Hospitalet de Llobregat, near Barcelona.

Previously published results showed that despite partial recovery from immediate deterioration in HRQoL, relevant differences persisted with 2 years’ follow-up (Int. J. Radiat. Oncol. Biol. Phys. 2008; 72:421-32). The 3-year results also show that in each treatment group, HRQoL deteriorated immediately after receiving any of the prostate cancer treatments, but rose after the interventions to varying degrees.

SF-36 Physical Component scores decreased most dramatically after prostatectomy compared with either radiotherapy technique, but rose in the first 6 months after the procedure before gradually deteriorating over the 3 years’ follow-up. EBRT produced lower scores than those for brachytherapy, and these gradually worsened during long-term follow up, such that they were lower at 3 years than were scores in the patients who had undergone surgery.

“RRP caused considerable urinary incontinence and sexual dysfunction,” Dr. Guedea observed. He added: “Brachytherapy and EBRT caused moderate urinary irritative-obstructive urinary symptoms and moderate adverse effects on sexual function, and finally, EBRT had very moderate bowel-related adverse events.”

These results are useful to consider when discussing treatment options with patients, Dr. Guedea suggested, particularly in light of other studies showing the significant benefits of all treatments in terms of tumor control and improved overall survival.

Disclosures: The Spanish National Health System funded the study. Dr. Guedea had no conflicts of interest.

BARCELONA – The 3-year results of a nonrandomized trial from Spain reveal different patterns of adverse events after three leading treatments for localized prostate cancer.

Radical retropubic prostatectomy (RRP) was associated with significantly more urinary incontinence and sexual dysfunction than were external beam radiotherapy or brachytherapy, according to charts presented at the biennial meeting of the European Society for Therapeutic Radiation and Oncology (ESTRO 29).

Brachytherapy, however, was associated with far more irritative and obstructive urinary symptoms than were surgery or external beam radiotherapy (EBRT).

The trial was conducted in 11 hospitals throughout Spain, and originally enrolled 435 men with stage T1 and T2 prostate cancer who had received no prior surgical resection or hormonal treatment. The aim of the trial was to compare the health-related quality of life (HRQoL) impact of the three most commonly used primary treatments in men who were followed from before treatment to 3 years after intervention.

Treatment decisions were made jointly by physicians and patients; the analysis covered 123 men who underwent RRP, 127 who had EBRT, and 123 who had brachytherapy.

During the study, HRQoL was assessed using several validated questionnaires before and at 1, 3, 6, 12, 24, and 36 months after treatment. The questionnaires used included the Medical Outcomes Study 36-Item Short Form, the Functional Assessment of Cancer Therapy (General and Prostate Specific), the Expanded Prostate Cancer Index Composite (EPIC), and the American Urological Association Symptom Index.

“This is a very important study because it takes into account the previous stage in quality of life of our patients,” before they received any treatment, Dr. Ferran Guedea said at a scientific press briefing.

“We also have the results of 3-years of follow-up. That is a very long follow-up for different types of treatment,” added Dr. Guedea, a radiation oncologist at the Catalan Institute of Oncology, L’Hospitalet de Llobregat, near Barcelona.

Previously published results showed that despite partial recovery from immediate deterioration in HRQoL, relevant differences persisted with 2 years’ follow-up (Int. J. Radiat. Oncol. Biol. Phys. 2008; 72:421-32). The 3-year results also show that in each treatment group, HRQoL deteriorated immediately after receiving any of the prostate cancer treatments, but rose after the interventions to varying degrees.

SF-36 Physical Component scores decreased most dramatically after prostatectomy compared with either radiotherapy technique, but rose in the first 6 months after the procedure before gradually deteriorating over the 3 years’ follow-up. EBRT produced lower scores than those for brachytherapy, and these gradually worsened during long-term follow up, such that they were lower at 3 years than were scores in the patients who had undergone surgery.

“RRP caused considerable urinary incontinence and sexual dysfunction,” Dr. Guedea observed. He added: “Brachytherapy and EBRT caused moderate urinary irritative-obstructive urinary symptoms and moderate adverse effects on sexual function, and finally, EBRT had very moderate bowel-related adverse events.”

These results are useful to consider when discussing treatment options with patients, Dr. Guedea suggested, particularly in light of other studies showing the significant benefits of all treatments in terms of tumor control and improved overall survival.

Disclosures: The Spanish National Health System funded the study. Dr. Guedea had no conflicts of interest.

BARCELONA – Malnutrition remains a significant problem in cancer treatment, with a study reporting that all of nearly 1,000 cancer patients evaluated in Spanish hospitals were malnourished, more than 70% of them at levels ranging from moderate to severe.

New data from Portugal suggest, however, that individualized nutritional counseling not only improves patients’ nutritional status, but can also prolong their overall survival after they undergo radiotherapy.

Long-term follow-up (median, 6.5 years) of 111 colorectal cancer patients in a prospective trial revealed that the shortest survival (4.1 years) and highest mortality rate (30%) occurred in patients who were not given any nutritional intervention. Patients who were given high-protein liquid supplements had a median survival of 6.5 years and a mortality rate of 22%, but the longest survival (7.3 years) and lowest mortality (8%) were observed in patients who received personalized nutritional advice.

Both studies were presented at the biennial meeting of the European Society of Therapeutic Radiation and Oncology (ESTRO 29). “Malnutrition and its clinical consequences still remain as a major problem in our daily practice,” despite the more active care of patients, said Dr. Albert Biete, who reported on the NUTRIDIS study from Spain.

The NUTRIDIS Study

The cross-sectional NUTRIDIS study aimed to assess the impact of malnutrition and its clinical consequences in patients treated for primary cancer. Data were collected from April 2006 to April 2007 on 1,069 patients who were treated within the radiation oncology, medical oncology, and palliative care departments of 40 Spanish hospitals.

Nutritional status was determined at study entry by a variety of measures, including laboratory tests and calculation of the body mass index. Patients’ oncological treatments as well as nutritional and other drug support measures were recorded, and their effects on nutrition status assessed.

Nearly two-thirds (63.8%) of the 922 patients that could be evaluated were male; the median age of all patients was 63.8 years. During the preceding 6 months, patients lost a median of 10.1 kg, which was associated with a median decrease in weight of 8.7%. Fewer than half (45%) of patients had metastatic disease, and 49.1% had a performance status of 1.

All patients with cancer were found to have some level of malnutrition, with almost one-fifth (18.1%) being severely malnourished, 53.5% suffering from moderate malnutrition, and the remainder having ‘light’ malnutrition.

“We found a statistically significant relationship between the severity of malnutrition and the treatment response,” said Dr. Biete of the radiation oncology department at the Hospital Clinic i Provincial de Barcelona.

He reported that malnutrition was associated with a host of complications, including weight loss (48.7%), asthenia (47.1%), anorexia (37.2%), hypoproteinemia (33.3%), anemia (32.2%), depression (13.7%), anxiety (9.5%), infections (8.8%), mucositis (8.8%), taste disorders (6.9%), delayed wound closure (6.5%), and impaired capability to concentrate (6.1%).

These complications significantly affected patients’ ability to undertake their normal daily activities, said Dr. Biete. In a large percentage of patients, the received treatment had affected the nutritional status (64.1%), whereas malnutrition influenced the response to treatment in 43.1%, causing problems with completing treatment and delaying the end of treatment.

Dr. Biete noted that supportive nutritional measures were used in 60.8% of patients, and that megestrol acetate was the most commonly prescribed drug aimed at improving patients’ appetite.

Personal Counseling More Effective

The Portuguese study presented by Dr. Paula Ravasco suggests, however, that nutritional counseling can be a far more effective means of improving patient outcomes than are nutritional supplements alone, at least in patients undergoing radiotherapy. In addition to improving overall survival, dietary counseling improved patients’ quality of life to a greater extent than did protein supplements or no nutritional intervention.

“Early and timely individualized nutritional intervention had a sustained effect on outcomes,” said Dr. Ravasco, a clinical expert in nutrition at the University of Lisbon.

“What our data clearly demonstrate is that nutritional advice has to be individualized,” she added in an interview.

Between 2000 and 2003, 111 patients undergoing radiotherapy for colorectal cancer were evenly randomized to dietary counseling, protein supplements, or what the investigators called ad libitum intake. Investigators reported previously that counseling and supplements improved outcomes during radiotherapy, but only counseling results in sustained benefits 3 months later (J. Clin. Oncol. 2005;23:1431-8).

Dr. Ravasco advised that evidence-based nutritional counseling should always be based on an initial assessment of patients’ nutritional status and intake via a structured questionnaire. Patients’ dietary preferences, habits, and intolerances need to be considered, along with their psychological status and whether they are likely to be cooperative or might need help to feed themselves. Identifying any symptoms or conditions (such as gastrointestinal, anorexia, or pain) that might interfere with nutritional support is also important before a diet is prescribed.

“We are entering a new era in cancer management,” said Dr. Ravasco. Considering the clinical evidence now available, adjuvant nutritional intervention is an essential addition to the multidisciplinary care of patients with cancer, she added.

She and her associates are planning a larger, four-arm trial to look at the combined effects of nutritional counseling and supplements vs. counseling alone, supplements alone, and no intervention. This will initially involve patients with high-risk cancers, including colorectal, gastric, esophageal, and head and neck cancers, but could eventually be expanded to include patients with any solid tumor.

Disclosures: The NUTRIDIS study was supported by a grant from PRASFARMA SA in Barcelona. The randomized trial received a grant from N?cleo Regional do Sul da Liga Portuguesa contra o Cancro–Terry Fox Foundation. Dr. Biete and Dr. Ravasco reported no conflicts of interest.

BARCELONA – Malnutrition remains a significant problem in cancer treatment, with a study reporting that all of nearly 1,000 cancer patients evaluated in Spanish hospitals were malnourished, more than 70% of them at levels ranging from moderate to severe.

New data from Portugal suggest, however, that individualized nutritional counseling not only improves patients’ nutritional status, but can also prolong their overall survival after they undergo radiotherapy.

Long-term follow-up (median, 6.5 years) of 111 colorectal cancer patients in a prospective trial revealed that the shortest survival (4.1 years) and highest mortality rate (30%) occurred in patients who were not given any nutritional intervention. Patients who were given high-protein liquid supplements had a median survival of 6.5 years and a mortality rate of 22%, but the longest survival (7.3 years) and lowest mortality (8%) were observed in patients who received personalized nutritional advice.

Both studies were presented at the biennial meeting of the European Society of Therapeutic Radiation and Oncology (ESTRO 29). “Malnutrition and its clinical consequences still remain as a major problem in our daily practice,” despite the more active care of patients, said Dr. Albert Biete, who reported on the NUTRIDIS study from Spain.

The NUTRIDIS Study

The cross-sectional NUTRIDIS study aimed to assess the impact of malnutrition and its clinical consequences in patients treated for primary cancer. Data were collected from April 2006 to April 2007 on 1,069 patients who were treated within the radiation oncology, medical oncology, and palliative care departments of 40 Spanish hospitals.

Nutritional status was determined at study entry by a variety of measures, including laboratory tests and calculation of the body mass index. Patients’ oncological treatments as well as nutritional and other drug support measures were recorded, and their effects on nutrition status assessed.

Nearly two-thirds (63.8%) of the 922 patients that could be evaluated were male; the median age of all patients was 63.8 years. During the preceding 6 months, patients lost a median of 10.1 kg, which was associated with a median decrease in weight of 8.7%. Fewer than half (45%) of patients had metastatic disease, and 49.1% had a performance status of 1.

All patients with cancer were found to have some level of malnutrition, with almost one-fifth (18.1%) being severely malnourished, 53.5% suffering from moderate malnutrition, and the remainder having ‘light’ malnutrition.

“We found a statistically significant relationship between the severity of malnutrition and the treatment response,” said Dr. Biete of the radiation oncology department at the Hospital Clinic i Provincial de Barcelona.

He reported that malnutrition was associated with a host of complications, including weight loss (48.7%), asthenia (47.1%), anorexia (37.2%), hypoproteinemia (33.3%), anemia (32.2%), depression (13.7%), anxiety (9.5%), infections (8.8%), mucositis (8.8%), taste disorders (6.9%), delayed wound closure (6.5%), and impaired capability to concentrate (6.1%).

These complications significantly affected patients’ ability to undertake their normal daily activities, said Dr. Biete. In a large percentage of patients, the received treatment had affected the nutritional status (64.1%), whereas malnutrition influenced the response to treatment in 43.1%, causing problems with completing treatment and delaying the end of treatment.

Dr. Biete noted that supportive nutritional measures were used in 60.8% of patients, and that megestrol acetate was the most commonly prescribed drug aimed at improving patients’ appetite.

Personal Counseling More Effective

The Portuguese study presented by Dr. Paula Ravasco suggests, however, that nutritional counseling can be a far more effective means of improving patient outcomes than are nutritional supplements alone, at least in patients undergoing radiotherapy. In addition to improving overall survival, dietary counseling improved patients’ quality of life to a greater extent than did protein supplements or no nutritional intervention.

“Early and timely individualized nutritional intervention had a sustained effect on outcomes,” said Dr. Ravasco, a clinical expert in nutrition at the University of Lisbon.

“What our data clearly demonstrate is that nutritional advice has to be individualized,” she added in an interview.

Between 2000 and 2003, 111 patients undergoing radiotherapy for colorectal cancer were evenly randomized to dietary counseling, protein supplements, or what the investigators called ad libitum intake. Investigators reported previously that counseling and supplements improved outcomes during radiotherapy, but only counseling results in sustained benefits 3 months later (J. Clin. Oncol. 2005;23:1431-8).

Dr. Ravasco advised that evidence-based nutritional counseling should always be based on an initial assessment of patients’ nutritional status and intake via a structured questionnaire. Patients’ dietary preferences, habits, and intolerances need to be considered, along with their psychological status and whether they are likely to be cooperative or might need help to feed themselves. Identifying any symptoms or conditions (such as gastrointestinal, anorexia, or pain) that might interfere with nutritional support is also important before a diet is prescribed.

“We are entering a new era in cancer management,” said Dr. Ravasco. Considering the clinical evidence now available, adjuvant nutritional intervention is an essential addition to the multidisciplinary care of patients with cancer, she added.

She and her associates are planning a larger, four-arm trial to look at the combined effects of nutritional counseling and supplements vs. counseling alone, supplements alone, and no intervention. This will initially involve patients with high-risk cancers, including colorectal, gastric, esophageal, and head and neck cancers, but could eventually be expanded to include patients with any solid tumor.

Disclosures: The NUTRIDIS study was supported by a grant from PRASFARMA SA in Barcelona. The randomized trial received a grant from N?cleo Regional do Sul da Liga Portuguesa contra o Cancro–Terry Fox Foundation. Dr. Biete and Dr. Ravasco reported no conflicts of interest.

BARCELONA – Malnutrition remains a significant problem in cancer treatment, with a study reporting that all of nearly 1,000 cancer patients evaluated in Spanish hospitals were malnourished, more than 70% of them at levels ranging from moderate to severe.

New data from Portugal suggest, however, that individualized nutritional counseling not only improves patients’ nutritional status, but can also prolong their overall survival after they undergo radiotherapy.

Long-term follow-up (median, 6.5 years) of 111 colorectal cancer patients in a prospective trial revealed that the shortest survival (4.1 years) and highest mortality rate (30%) occurred in patients who were not given any nutritional intervention. Patients who were given high-protein liquid supplements had a median survival of 6.5 years and a mortality rate of 22%, but the longest survival (7.3 years) and lowest mortality (8%) were observed in patients who received personalized nutritional advice.

Both studies were presented at the biennial meeting of the European Society of Therapeutic Radiation and Oncology (ESTRO 29). “Malnutrition and its clinical consequences still remain as a major problem in our daily practice,” despite the more active care of patients, said Dr. Albert Biete, who reported on the NUTRIDIS study from Spain.

The NUTRIDIS Study

The cross-sectional NUTRIDIS study aimed to assess the impact of malnutrition and its clinical consequences in patients treated for primary cancer. Data were collected from April 2006 to April 2007 on 1,069 patients who were treated within the radiation oncology, medical oncology, and palliative care departments of 40 Spanish hospitals.

Nutritional status was determined at study entry by a variety of measures, including laboratory tests and calculation of the body mass index. Patients’ oncological treatments as well as nutritional and other drug support measures were recorded, and their effects on nutrition status assessed.

Nearly two-thirds (63.8%) of the 922 patients that could be evaluated were male; the median age of all patients was 63.8 years. During the preceding 6 months, patients lost a median of 10.1 kg, which was associated with a median decrease in weight of 8.7%. Fewer than half (45%) of patients had metastatic disease, and 49.1% had a performance status of 1.

All patients with cancer were found to have some level of malnutrition, with almost one-fifth (18.1%) being severely malnourished, 53.5% suffering from moderate malnutrition, and the remainder having ‘light’ malnutrition.

“We found a statistically significant relationship between the severity of malnutrition and the treatment response,” said Dr. Biete of the radiation oncology department at the Hospital Clinic i Provincial de Barcelona.

He reported that malnutrition was associated with a host of complications, including weight loss (48.7%), asthenia (47.1%), anorexia (37.2%), hypoproteinemia (33.3%), anemia (32.2%), depression (13.7%), anxiety (9.5%), infections (8.8%), mucositis (8.8%), taste disorders (6.9%), delayed wound closure (6.5%), and impaired capability to concentrate (6.1%).

These complications significantly affected patients’ ability to undertake their normal daily activities, said Dr. Biete. In a large percentage of patients, the received treatment had affected the nutritional status (64.1%), whereas malnutrition influenced the response to treatment in 43.1%, causing problems with completing treatment and delaying the end of treatment.

Dr. Biete noted that supportive nutritional measures were used in 60.8% of patients, and that megestrol acetate was the most commonly prescribed drug aimed at improving patients’ appetite.

Personal Counseling More Effective

The Portuguese study presented by Dr. Paula Ravasco suggests, however, that nutritional counseling can be a far more effective means of improving patient outcomes than are nutritional supplements alone, at least in patients undergoing radiotherapy. In addition to improving overall survival, dietary counseling improved patients’ quality of life to a greater extent than did protein supplements or no nutritional intervention.

“Early and timely individualized nutritional intervention had a sustained effect on outcomes,” said Dr. Ravasco, a clinical expert in nutrition at the University of Lisbon.

“What our data clearly demonstrate is that nutritional advice has to be individualized,” she added in an interview.

Between 2000 and 2003, 111 patients undergoing radiotherapy for colorectal cancer were evenly randomized to dietary counseling, protein supplements, or what the investigators called ad libitum intake. Investigators reported previously that counseling and supplements improved outcomes during radiotherapy, but only counseling results in sustained benefits 3 months later (J. Clin. Oncol. 2005;23:1431-8).

Dr. Ravasco advised that evidence-based nutritional counseling should always be based on an initial assessment of patients’ nutritional status and intake via a structured questionnaire. Patients’ dietary preferences, habits, and intolerances need to be considered, along with their psychological status and whether they are likely to be cooperative or might need help to feed themselves. Identifying any symptoms or conditions (such as gastrointestinal, anorexia, or pain) that might interfere with nutritional support is also important before a diet is prescribed.

“We are entering a new era in cancer management,” said Dr. Ravasco. Considering the clinical evidence now available, adjuvant nutritional intervention is an essential addition to the multidisciplinary care of patients with cancer, she added.

She and her associates are planning a larger, four-arm trial to look at the combined effects of nutritional counseling and supplements vs. counseling alone, supplements alone, and no intervention. This will initially involve patients with high-risk cancers, including colorectal, gastric, esophageal, and head and neck cancers, but could eventually be expanded to include patients with any solid tumor.

Disclosures: The NUTRIDIS study was supported by a grant from PRASFARMA SA in Barcelona. The randomized trial received a grant from N?cleo Regional do Sul da Liga Portuguesa contra o Cancro–Terry Fox Foundation. Dr. Biete and Dr. Ravasco reported no conflicts of interest.