Prospective Validation of a Prediction Tool for Identifying Patients at High Risk for Chemotherapy-Induced Nausea and Vomiting

• George Dranitsaris, BPharm, PhD,

  

  Nathaniel Bouganim, MD,Carolyn Milano, Lisa Vandermeer, MSc, Susan Dent, MD, Paul Wheatley-Price, MD, Jenny Laporte, RN, Karen-Ann Oxborough, RN, Mark Clemons, MD

  Abstract

  Background

  Even with modern antiemetic regimens, up to 20% of cancer patients suffer from moderate to severe chemotherapy-induced nausea and vomiting (CINV) (≥ grade 2). We previously developed chemotherapy cycle–based risk predictive models for ≥ grade 2 acute and delayed CINV. In this study, the prospective validation of the prediction models and associated scoring systems is described.

  Objective

  Our objective was to prospectively validate prediction models designed to identify patients at high risk for moderate to severe CINV.

  Methods

  Patients receiving chemotherapy were provided with CINV symptom diaries. Prior to each cycle of chemotherapy, the acute and delayed CINV scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression was used to compare the occurrence of ≥ grade 2 CINV between patients considered by the model to be at high vs low risk. The external validity of each system was assessed via an area under the receiver operating characteristic (AUROC) curve analysis.

  Results

  Outcome data were collected from 97 patients following 401 cycles of chemotherapy. The incidence of ≥ grade 2 acute and delayed CINV was 13.5% and 21.4%, respectively. There was a significant correlation between the risk score and the probability of developing acute and delayed CINV following chemotherapy. Both the acute and delayed scoring systems had good predictive accuracy when applied to the validation sample (acute, AUROC = 0.70, 95% CI, 0.62–0.77; delayed, AUROC = 0.75, 95% CI, 0.69–0.80). Patients who were identified as high risk were 3.1 (P = .006) and 4.2 (P < .001) times more likely to develop ≥ grade 2 acute and delayed CINV than were those identified as low risk.

  Conclusion

  This study demonstrates that the scoring systems are able to accurately identify patients at high risk for acute and delayed CINV.

  
  

  *For a PDF of the full article click in the link to the left of this introduction.

Prospective Validation of a Prediction Tool for Identifying Patients at High Risk for Chemotherapy-Induced Nausea and Vomiting

• George Dranitsaris, BPharm, PhD,

  

  Nathaniel Bouganim, MD,Carolyn Milano, Lisa Vandermeer, MSc, Susan Dent, MD, Paul Wheatley-Price, MD, Jenny Laporte, RN, Karen-Ann Oxborough, RN, Mark Clemons, MD

  Abstract

  Background

  Even with modern antiemetic regimens, up to 20% of cancer patients suffer from moderate to severe chemotherapy-induced nausea and vomiting (CINV) (≥ grade 2). We previously developed chemotherapy cycle–based risk predictive models for ≥ grade 2 acute and delayed CINV. In this study, the prospective validation of the prediction models and associated scoring systems is described.

  Objective

  Our objective was to prospectively validate prediction models designed to identify patients at high risk for moderate to severe CINV.

  Methods

  Patients receiving chemotherapy were provided with CINV symptom diaries. Prior to each cycle of chemotherapy, the acute and delayed CINV scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression was used to compare the occurrence of ≥ grade 2 CINV between patients considered by the model to be at high vs low risk. The external validity of each system was assessed via an area under the receiver operating characteristic (AUROC) curve analysis.

  Results

  Outcome data were collected from 97 patients following 401 cycles of chemotherapy. The incidence of ≥ grade 2 acute and delayed CINV was 13.5% and 21.4%, respectively. There was a significant correlation between the risk score and the probability of developing acute and delayed CINV following chemotherapy. Both the acute and delayed scoring systems had good predictive accuracy when applied to the validation sample (acute, AUROC = 0.70, 95% CI, 0.62–0.77; delayed, AUROC = 0.75, 95% CI, 0.69–0.80). Patients who were identified as high risk were 3.1 (P = .006) and 4.2 (P < .001) times more likely to develop ≥ grade 2 acute and delayed CINV than were those identified as low risk.

  Conclusion

  This study demonstrates that the scoring systems are able to accurately identify patients at high risk for acute and delayed CINV.

  
  

  *For a PDF of the full article click in the link to the left of this introduction.

Prospective Validation of a Prediction Tool for Identifying Patients at High Risk for Chemotherapy-Induced Nausea and Vomiting

• George Dranitsaris, BPharm, PhD,

  

  Nathaniel Bouganim, MD,Carolyn Milano, Lisa Vandermeer, MSc, Susan Dent, MD, Paul Wheatley-Price, MD, Jenny Laporte, RN, Karen-Ann Oxborough, RN, Mark Clemons, MD

  Abstract

  Background

  Even with modern antiemetic regimens, up to 20% of cancer patients suffer from moderate to severe chemotherapy-induced nausea and vomiting (CINV) (≥ grade 2). We previously developed chemotherapy cycle–based risk predictive models for ≥ grade 2 acute and delayed CINV. In this study, the prospective validation of the prediction models and associated scoring systems is described.

  Objective

  Our objective was to prospectively validate prediction models designed to identify patients at high risk for moderate to severe CINV.

  Methods

  Patients receiving chemotherapy were provided with CINV symptom diaries. Prior to each cycle of chemotherapy, the acute and delayed CINV scoring systems were used to stratify patients into low- and high-risk groups. Logistic regression was used to compare the occurrence of ≥ grade 2 CINV between patients considered by the model to be at high vs low risk. The external validity of each system was assessed via an area under the receiver operating characteristic (AUROC) curve analysis.

  Results

  Outcome data were collected from 97 patients following 401 cycles of chemotherapy. The incidence of ≥ grade 2 acute and delayed CINV was 13.5% and 21.4%, respectively. There was a significant correlation between the risk score and the probability of developing acute and delayed CINV following chemotherapy. Both the acute and delayed scoring systems had good predictive accuracy when applied to the validation sample (acute, AUROC = 0.70, 95% CI, 0.62–0.77; delayed, AUROC = 0.75, 95% CI, 0.69–0.80). Patients who were identified as high risk were 3.1 (P = .006) and 4.2 (P < .001) times more likely to develop ≥ grade 2 acute and delayed CINV than were those identified as low risk.

  Conclusion

  This study demonstrates that the scoring systems are able to accurately identify patients at high risk for acute and delayed CINV.

  
  

  *For a PDF of the full article click in the link to the left of this introduction.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

CHICAGO – Wearing a scalp-cooling cap can reduce hair loss in women receiving chemotherapy for breast cancer, the results of a small prospective cohort study suggest.

Among women who used the cooling headgear starting 20 minutes before chemotherapy and continuing for 60-90 minutes after the infusion, 24% did not wear a wig or headband upon completion of chemotherapy, compared with 4% of a control group that did not have access to the device, investigators reported.

Courtesy Dr. Julie Lemieux

Further, patient satisfaction scores were higher than these numbers in a blinded assessment, according to Dr. Julie Lemieux of Laval University in Quebec City and her coinvestigators.

To grade the results with and without the cooling device, a hairdresser looked at before and after photos of women in the study, and was not told which women were in the scalp-cooling group. The criteria for successful hair preservation was characterization of hair loss as "not at all," "a little," or "moderate" from the beginning to the end of chemotherapy. The procedure was deemed a failure if the reviewer rated hair loss as "a lot," or "all," or "hair shaved."

The hairdresser graded the hair loss intervention as successful in 34% of the scalp-cooling group – as did 49% of the women who wore the caps. Only 9% of the control group received a successful grade from the hairdresser; even fewer, 4%, agreed they had not had substantial hair loss.

In all, 69% of women who tried scalp cooling said the advantages outweighed the disadvantages, and 78% said they would recommend it to other women receiving the same chemotherapy for breast cancer.

"When you look at patient evaluations, they are ... more optimistic than the hairdresser evaluations. They were more satisfied," Dr. Lemieux said in a poster-side interview at the annual meeting of the American Society of Clinical Oncology, where she displayed the results.

Scalp-cooling systems are approved for the reduction of alopecia in Canada, she said, but controversy persists among oncologists over safety and impact, if any, on the effectiveness of chemotherapy.

"If you cool the scalp there is vasoconstriction, so there is less blood that goes in the scalp ... that is the main mechanism," Dr. Lemieux explained. One concern is that scalp metastases could increase; another is that patients might receive less chemotherapy as a result.

Dr. Lemieux and her colleagues reviewed seven randomized trials of hair-cooling studies and found no safety signals. In all, 260 women were enrolled, and the studies covered a variety of chemotherapy regimens, including at least one that is not known to cause alopecia.

They also did a retrospective cohort study, and found that the incidence of scalp metastases was about 1% whether women used scalp cooling or not (Breast Cancer Res. Treat. 2009;118:547-52). Subsequently, they reported on two cases where the scalp was the first metastatic site, with metastases occurring 7 and 9 years after cooling (Breast Cancer Res. Treat. 2011;128:563-6).

At the San Antonio Breast Cancer Symposium, Dr. Lemieux and her associates reported on a retrospective study that found no difference in survival between patients who used scalp cooling and those who did not.

For the current study, the researchers compared outcomes in 110 patients at Centre des Maladies du Sein Deschênes-Fabia in Quebec City, which uses scalp cooling routinely, with those in 26 patients at the Centre Hospitalier Universitaire de Montréal, where scalp cooling is not available. The median patient age was in the early 50s, and most of the women had stage I or II, hormone receptor–positive breast cancer. A variety of neoadjuvant and adjuvant regimens were used.

The system tested in the study used a cap that is placed in a freezer and changed every 20-30 minutes, starting 20 minutes before chemotherapy and continuing for 60-90 minutes afterward. A new generation of scalp-cooling systems uses a compressor that circulates cold fluid in the cap, and it does not have to be changed.

Dr. Lemieux said the researchers conceived the study as a pilot for a larger randomized controlled trial that will address efficacy, cost, and quality of life issues. They are seeking to raise funds, as the companies that make the systems are too small to sponsor a large trial.

Cost is a concern, she noted, because of the additional time the women spend in the infusion room. "So you have to have that time available in the chemotherapy room," she said. "We also want to look at the cost of the system, of the extra time that women are in hospital, and at quality of life, too."

The trial was funded by the Fondations des Hôpitaux Enfant-Jésus et Saint-Sacrement, the Canadian Breast Cancer Research Alliance, and Sanofi-Aventis. Dr. Lemieux received a research grant from the Fonds de la Recherche en Santé du Québec.

The clinical effectiveness agency for England and Wales has rejected a second bevacizumab combination for metastatic breast cancer, citing the treatment’s high cost, uncertain effect on quality of life, and lack of robust evidence for overall survival improvements.

Roche’s bevacizumab (Avastin) is a monoclonal antibody that works by inhibiting vascular endothelial growth factor (VEGF). It is licensed in the European Union in combination with Roche’s capecitabine (Xeloda) for metastatic breast cancer; however, the National Institute for Health and Clinical Excellence found that the treatment did not meet its cost-effectiveness criteria. NICE’s decision was widely expected after the agency issued negative draft guidance in April.

In 2010, NICE turned down bevacizumab in combination with a taxane for first-line treatment of metastatic breast cancer, its licensed indication at the time; the European Medicines Agency late that year limited the breast cancer indication to a combination with paclitaxel.

In April 2011, EMA said bevacizumab could also be used with capecitabine if other chemotherapy treatments are inappropriate, citing evidence from RIBBON-1, a randomized, placebo-controlled trial that showed average progression-free survival of 8.6 months in patients receiving the combination, compared with 5.7 months in those receiving capecitabine alone.

In a final appraisal published July 6, NICE acknowledged the statistically significant, 2.9-month gain in progression-free survival seen with bevacizumab in the trial. However, the agency said that quality-of-life data were not captured, and while median overall survival also improved by 2.9 months, this result was not statistically significant due in part to crossover.

The manufacturer’s submission to NICE included clinical trial evidence only for a subgroup of people who had been previously treated with a taxane, while the full indication includes both previously treated and treatment-naive patients.

The NICE reviewers said they found "no biologically plausible reason why bevacizumab plus capecitabine would be more effective" in the previously treated subgroup than in the broader population for which the combination is licensed. They also concluded that the incremental cost-effectiveness ratio for the treatment would be at least £82,000 (U.S.$127,000) per quality-adjusted life year (QALY).

Bevacizumab is administered by intravenous infusion at a recommended dose of 10 mg/kg of body weight once every 2 weeks or 15 mg/kg of body weight once every 3 weeks. The average price of bevacizumab treatment for breast cancer in the United Kingdom is £3,689 (U.S.$5,727) per month, according to NICE.

The clinical effectiveness agency for England and Wales has rejected a second bevacizumab combination for metastatic breast cancer, citing the treatment’s high cost, uncertain effect on quality of life, and lack of robust evidence for overall survival improvements.

Roche’s bevacizumab (Avastin) is a monoclonal antibody that works by inhibiting vascular endothelial growth factor (VEGF). It is licensed in the European Union in combination with Roche’s capecitabine (Xeloda) for metastatic breast cancer; however, the National Institute for Health and Clinical Excellence found that the treatment did not meet its cost-effectiveness criteria. NICE’s decision was widely expected after the agency issued negative draft guidance in April.

In 2010, NICE turned down bevacizumab in combination with a taxane for first-line treatment of metastatic breast cancer, its licensed indication at the time; the European Medicines Agency late that year limited the breast cancer indication to a combination with paclitaxel.

In April 2011, EMA said bevacizumab could also be used with capecitabine if other chemotherapy treatments are inappropriate, citing evidence from RIBBON-1, a randomized, placebo-controlled trial that showed average progression-free survival of 8.6 months in patients receiving the combination, compared with 5.7 months in those receiving capecitabine alone.

In a final appraisal published July 6, NICE acknowledged the statistically significant, 2.9-month gain in progression-free survival seen with bevacizumab in the trial. However, the agency said that quality-of-life data were not captured, and while median overall survival also improved by 2.9 months, this result was not statistically significant due in part to crossover.

The manufacturer’s submission to NICE included clinical trial evidence only for a subgroup of people who had been previously treated with a taxane, while the full indication includes both previously treated and treatment-naive patients.

The NICE reviewers said they found "no biologically plausible reason why bevacizumab plus capecitabine would be more effective" in the previously treated subgroup than in the broader population for which the combination is licensed. They also concluded that the incremental cost-effectiveness ratio for the treatment would be at least £82,000 (U.S.$127,000) per quality-adjusted life year (QALY).

Bevacizumab is administered by intravenous infusion at a recommended dose of 10 mg/kg of body weight once every 2 weeks or 15 mg/kg of body weight once every 3 weeks. The average price of bevacizumab treatment for breast cancer in the United Kingdom is £3,689 (U.S.$5,727) per month, according to NICE.

The clinical effectiveness agency for England and Wales has rejected a second bevacizumab combination for metastatic breast cancer, citing the treatment’s high cost, uncertain effect on quality of life, and lack of robust evidence for overall survival improvements.

Roche’s bevacizumab (Avastin) is a monoclonal antibody that works by inhibiting vascular endothelial growth factor (VEGF). It is licensed in the European Union in combination with Roche’s capecitabine (Xeloda) for metastatic breast cancer; however, the National Institute for Health and Clinical Excellence found that the treatment did not meet its cost-effectiveness criteria. NICE’s decision was widely expected after the agency issued negative draft guidance in April.

In 2010, NICE turned down bevacizumab in combination with a taxane for first-line treatment of metastatic breast cancer, its licensed indication at the time; the European Medicines Agency late that year limited the breast cancer indication to a combination with paclitaxel.

In April 2011, EMA said bevacizumab could also be used with capecitabine if other chemotherapy treatments are inappropriate, citing evidence from RIBBON-1, a randomized, placebo-controlled trial that showed average progression-free survival of 8.6 months in patients receiving the combination, compared with 5.7 months in those receiving capecitabine alone.

In a final appraisal published July 6, NICE acknowledged the statistically significant, 2.9-month gain in progression-free survival seen with bevacizumab in the trial. However, the agency said that quality-of-life data were not captured, and while median overall survival also improved by 2.9 months, this result was not statistically significant due in part to crossover.

The manufacturer’s submission to NICE included clinical trial evidence only for a subgroup of people who had been previously treated with a taxane, while the full indication includes both previously treated and treatment-naive patients.

The NICE reviewers said they found "no biologically plausible reason why bevacizumab plus capecitabine would be more effective" in the previously treated subgroup than in the broader population for which the combination is licensed. They also concluded that the incremental cost-effectiveness ratio for the treatment would be at least £82,000 (U.S.$127,000) per quality-adjusted life year (QALY).

Bevacizumab is administered by intravenous infusion at a recommended dose of 10 mg/kg of body weight once every 2 weeks or 15 mg/kg of body weight once every 3 weeks. The average price of bevacizumab treatment for breast cancer in the United Kingdom is £3,689 (U.S.$5,727) per month, according to NICE.

A 43-year-old woman who was BRCA1 and -2 negative presented initially in 2002, when she was 35 years old, with inflammatory breast carcinoma on the right side. She was 9 months post partum. A biopsy revealed that the tumor was estrogen-receptor (ER)/progesterone- receptor (PR) negative and HER2 (human epidermal growth factor receptor–2) positive. She received neoadjuvant chemotherapy with adriamycin plus docetaxel for 6 cycles, followed by right mastectomy and prophylactic left mastectomy. There was no residual disease in the breast. After mastectomy, the patient underwent CMF (cyclophosphamide, methotrexate, and fluorouracil) chemotherapy for 3 months, as well as radiation therapy to the chest wall. Adjuvant trastuzumab was started concurrently with the CMF chemotherapy, and was continued for 1 year.

*For a PDF of the full article, click on the link to the left of this introduction.

A 43-year-old woman who was BRCA1 and -2 negative presented initially in 2002, when she was 35 years old, with inflammatory breast carcinoma on the right side. She was 9 months post partum. A biopsy revealed that the tumor was estrogen-receptor (ER)/progesterone- receptor (PR) negative and HER2 (human epidermal growth factor receptor–2) positive. She received neoadjuvant chemotherapy with adriamycin plus docetaxel for 6 cycles, followed by right mastectomy and prophylactic left mastectomy. There was no residual disease in the breast. After mastectomy, the patient underwent CMF (cyclophosphamide, methotrexate, and fluorouracil) chemotherapy for 3 months, as well as radiation therapy to the chest wall. Adjuvant trastuzumab was started concurrently with the CMF chemotherapy, and was continued for 1 year.

*For a PDF of the full article, click on the link to the left of this introduction.

A 43-year-old woman who was BRCA1 and -2 negative presented initially in 2002, when she was 35 years old, with inflammatory breast carcinoma on the right side. She was 9 months post partum. A biopsy revealed that the tumor was estrogen-receptor (ER)/progesterone- receptor (PR) negative and HER2 (human epidermal growth factor receptor–2) positive. She received neoadjuvant chemotherapy with adriamycin plus docetaxel for 6 cycles, followed by right mastectomy and prophylactic left mastectomy. There was no residual disease in the breast. After mastectomy, the patient underwent CMF (cyclophosphamide, methotrexate, and fluorouracil) chemotherapy for 3 months, as well as radiation therapy to the chest wall. Adjuvant trastuzumab was started concurrently with the CMF chemotherapy, and was continued for 1 year.

*For a PDF of the full article, click on the link to the left of this introduction.

Concern over a relationship between in vitro fertilization (IVF) and subsequent breast cancer has been ameliorated by a large study conducted in Australia. The authors report no overall increase in the rate of breast cancer in women who undergo IVF. However, there does seem to be a higher risk of breast cancer in those who begin IVF treatment when in their mid-20s.

A population-based study from Western Australia studied the incidence rate of breast cancer in a large cohort (n=21,025) aged 20 to 44 years who underwent hospital-based treatment for infertility. Researchers compared the rate of breast cancer in women who had IVF with those who had fertility treatment but not IVF.

The study, published in Fertility and Sterility, reports that there is no overall increase in the risk of breast cancer for women who undergo hospital-based IVF (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.36).

“For younger women,” write the authors, “there is some cause for concern, because it appears that they may face an increased risk of breast cancer after IVF treatment.”

Women who began hospital infertility treatment at 24 years of age and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI, 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF.

When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI, 1.01–2.40).

“The results of this study will be reassuring to women who commence IVF treatment in their 30s and 40s because, for these women, there appears to be no direct association between IVF treatment and breast cancer risk,” write the authors. Risk was not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR, 0.87; 95% CI, 0.62–1.22).

“Nevertheless, women should be aware that delivering their first child late in reproductive life, whether assisted by IVF or not, is associated with an increased risk of breast cancer.”

Access to the full-text article is available at http://bit.ly/KiLvwh.

Concern over a relationship between in vitro fertilization (IVF) and subsequent breast cancer has been ameliorated by a large study conducted in Australia. The authors report no overall increase in the rate of breast cancer in women who undergo IVF. However, there does seem to be a higher risk of breast cancer in those who begin IVF treatment when in their mid-20s.

A population-based study from Western Australia studied the incidence rate of breast cancer in a large cohort (n=21,025) aged 20 to 44 years who underwent hospital-based treatment for infertility. Researchers compared the rate of breast cancer in women who had IVF with those who had fertility treatment but not IVF.

The study, published in Fertility and Sterility, reports that there is no overall increase in the risk of breast cancer for women who undergo hospital-based IVF (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.36).

“For younger women,” write the authors, “there is some cause for concern, because it appears that they may face an increased risk of breast cancer after IVF treatment.”

Women who began hospital infertility treatment at 24 years of age and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI, 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF.

When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI, 1.01–2.40).

“The results of this study will be reassuring to women who commence IVF treatment in their 30s and 40s because, for these women, there appears to be no direct association between IVF treatment and breast cancer risk,” write the authors. Risk was not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR, 0.87; 95% CI, 0.62–1.22).

“Nevertheless, women should be aware that delivering their first child late in reproductive life, whether assisted by IVF or not, is associated with an increased risk of breast cancer.”

Access to the full-text article is available at http://bit.ly/KiLvwh.

Concern over a relationship between in vitro fertilization (IVF) and subsequent breast cancer has been ameliorated by a large study conducted in Australia. The authors report no overall increase in the rate of breast cancer in women who undergo IVF. However, there does seem to be a higher risk of breast cancer in those who begin IVF treatment when in their mid-20s.

A population-based study from Western Australia studied the incidence rate of breast cancer in a large cohort (n=21,025) aged 20 to 44 years who underwent hospital-based treatment for infertility. Researchers compared the rate of breast cancer in women who had IVF with those who had fertility treatment but not IVF.

The study, published in Fertility and Sterility, reports that there is no overall increase in the risk of breast cancer for women who undergo hospital-based IVF (hazard ratio [HR], 1.10; 95% confidence interval [CI], 0.88–1.36).

“For younger women,” write the authors, “there is some cause for concern, because it appears that they may face an increased risk of breast cancer after IVF treatment.”

Women who began hospital infertility treatment at 24 years of age and required IVF had an unadjusted HR of breast cancer of 1.59 (95% CI, 1.05–2.42) compared with women of the same age who had infertility treatment but no IVF.

When adjusted for late age at first delivery, which is associated with an increased rate of breast cancer, and delivery of twins and higher-order multiples, which is associated with a decreased rate of breast cancer, the HR remained elevated at 1.56 (95% CI, 1.01–2.40).

“The results of this study will be reassuring to women who commence IVF treatment in their 30s and 40s because, for these women, there appears to be no direct association between IVF treatment and breast cancer risk,” write the authors. Risk was not elevated in women who commenced treatment at age 40 and required IVF (adjusted HR, 0.87; 95% CI, 0.62–1.22).

“Nevertheless, women should be aware that delivering their first child late in reproductive life, whether assisted by IVF or not, is associated with an increased risk of breast cancer.”

Access to the full-text article is available at http://bit.ly/KiLvwh.

The European Medicines Agency said June 22 that it had recommended an extension of indication for the cancer drug everolimus to treat hormone receptor–positive, HER2–negative advanced breast cancer.

Everolimus (Afinitor, Novartis), already recommended by the EMA to treat pancreatic and renal cell cancers, is now recommended throughout the European Union in combination with exemestane as a second-line treatment in postmenopausal women in whom aromatase inhibitors have failed.

EMA also extended indications of agents used to treat two rheumatic diseases.

Etanercept (Enbrel), marketed by Pfizer and already licensed in Europe to treat rheumatic arthritis in adults, is now recommended as a treatment for polyarthritis (rheumatoid factor positive or negative), extended oligoarthritis, and psoriatic arthritis in children and adolescents in whom methotrexate has failed or is inappropriate. The indication for etanercept also was extended to treatment of enthesitis-related arthritis in adolescents 12 years and older not responding to conventional therapy.

Adalimumab (Humira), marketed by Abbott and licensed in Europe to treat a range of rheumatic diseases, will now be indicated for the treatment of adults with severe axial spondyloarthritis who have had an inadequate response to, or are intolerant of, nonsteroidal anti-inflammatory drugs. The new indication covers patients without radiographic evidence of axial spondyloarthritis but with evidence of inflammation determined by MRI or elevated C-reactive protein.

Also at its June meeting, the agency recommended a new six-in-one combination vaccine developed for use outside the European Union. Hexaxim, marketed by Sanofi Pasteur, will be used in children aged 6 weeks to 2 years old to inoculate against diphtheria, tetanus, pertussis, hepatitis B, polio, and diseases caused by Haemophilus influenzae type B, including meningitis. The vaccine is administered as three doses 4 or more weeks apart.

Five of the active substances in the vaccine have been used in other vaccines and have been previously combined in Pentaxim, also manufactured by Sanofi Pasteur. The new vaccine adds Hansenula polymorpha-derived recombinant hepatitis B surface antigen. Clinical trials in Argentina, Mexico, Peru, Turkey, Thailand, and South Africa found the new vaccine to be as effective and safe as Pentaxim plus a monovalent hepatitis B vaccine, EMA said.

EMA recommended three additional new medications:

• Teduglutide (Revestive, Nycomed), a subcutaneous injection to treat short-bowel syndrome, a condition in which nutrients are not absorbed as a result of severe intestinal disease or the surgical removal of a large portion of the small intestine.

• Glycopyrronium bromide (Enurev, Novartis), a maintenance bronchodilator treatment for symptom relief in adults with chronic obstructive pulmonary disease.

• Ceftaroline fosamil (Zinforo, AstraZeneca), an infusion for treatment of adults with complicated skin and soft-tissue infections and community-acquired pneumonia.

The agency also announced that it was restricting indications for two medications on safety concerns. Following reports from Germany of hypersensitivity reactions, the agency advised clinicians not to prescribe tolperisone for indications other than poststroke spasticity and to use oral formulations in place of injectable ones. Tolperisone is a muscle relaxant used in Europe since the 1960s and only available in a handful of countries.

EMA recommended restricting the use of trimetazidine to second-line, add-on therapy after reports from France of movement disorders including Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Trimetazidine-containing medicines have been available since the 1970s in Europe and are used in the treatment of patients with angina pectoris. Clinicians are also advised not to prescribe in patients with these and related movement disorders, or those who have severe renal impairment.

All EMA recommendations require European Commission approval to be final.

The European Medicines Agency said June 22 that it had recommended an extension of indication for the cancer drug everolimus to treat hormone receptor–positive, HER2–negative advanced breast cancer.

Everolimus (Afinitor, Novartis), already recommended by the EMA to treat pancreatic and renal cell cancers, is now recommended throughout the European Union in combination with exemestane as a second-line treatment in postmenopausal women in whom aromatase inhibitors have failed.

EMA also extended indications of agents used to treat two rheumatic diseases.

Etanercept (Enbrel), marketed by Pfizer and already licensed in Europe to treat rheumatic arthritis in adults, is now recommended as a treatment for polyarthritis (rheumatoid factor positive or negative), extended oligoarthritis, and psoriatic arthritis in children and adolescents in whom methotrexate has failed or is inappropriate. The indication for etanercept also was extended to treatment of enthesitis-related arthritis in adolescents 12 years and older not responding to conventional therapy.

Adalimumab (Humira), marketed by Abbott and licensed in Europe to treat a range of rheumatic diseases, will now be indicated for the treatment of adults with severe axial spondyloarthritis who have had an inadequate response to, or are intolerant of, nonsteroidal anti-inflammatory drugs. The new indication covers patients without radiographic evidence of axial spondyloarthritis but with evidence of inflammation determined by MRI or elevated C-reactive protein.

Also at its June meeting, the agency recommended a new six-in-one combination vaccine developed for use outside the European Union. Hexaxim, marketed by Sanofi Pasteur, will be used in children aged 6 weeks to 2 years old to inoculate against diphtheria, tetanus, pertussis, hepatitis B, polio, and diseases caused by Haemophilus influenzae type B, including meningitis. The vaccine is administered as three doses 4 or more weeks apart.

Five of the active substances in the vaccine have been used in other vaccines and have been previously combined in Pentaxim, also manufactured by Sanofi Pasteur. The new vaccine adds Hansenula polymorpha-derived recombinant hepatitis B surface antigen. Clinical trials in Argentina, Mexico, Peru, Turkey, Thailand, and South Africa found the new vaccine to be as effective and safe as Pentaxim plus a monovalent hepatitis B vaccine, EMA said.

EMA recommended three additional new medications:

• Teduglutide (Revestive, Nycomed), a subcutaneous injection to treat short-bowel syndrome, a condition in which nutrients are not absorbed as a result of severe intestinal disease or the surgical removal of a large portion of the small intestine.

• Glycopyrronium bromide (Enurev, Novartis), a maintenance bronchodilator treatment for symptom relief in adults with chronic obstructive pulmonary disease.

• Ceftaroline fosamil (Zinforo, AstraZeneca), an infusion for treatment of adults with complicated skin and soft-tissue infections and community-acquired pneumonia.

The agency also announced that it was restricting indications for two medications on safety concerns. Following reports from Germany of hypersensitivity reactions, the agency advised clinicians not to prescribe tolperisone for indications other than poststroke spasticity and to use oral formulations in place of injectable ones. Tolperisone is a muscle relaxant used in Europe since the 1960s and only available in a handful of countries.

EMA recommended restricting the use of trimetazidine to second-line, add-on therapy after reports from France of movement disorders including Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Trimetazidine-containing medicines have been available since the 1970s in Europe and are used in the treatment of patients with angina pectoris. Clinicians are also advised not to prescribe in patients with these and related movement disorders, or those who have severe renal impairment.

All EMA recommendations require European Commission approval to be final.

The European Medicines Agency said June 22 that it had recommended an extension of indication for the cancer drug everolimus to treat hormone receptor–positive, HER2–negative advanced breast cancer.

Everolimus (Afinitor, Novartis), already recommended by the EMA to treat pancreatic and renal cell cancers, is now recommended throughout the European Union in combination with exemestane as a second-line treatment in postmenopausal women in whom aromatase inhibitors have failed.

EMA also extended indications of agents used to treat two rheumatic diseases.

Etanercept (Enbrel), marketed by Pfizer and already licensed in Europe to treat rheumatic arthritis in adults, is now recommended as a treatment for polyarthritis (rheumatoid factor positive or negative), extended oligoarthritis, and psoriatic arthritis in children and adolescents in whom methotrexate has failed or is inappropriate. The indication for etanercept also was extended to treatment of enthesitis-related arthritis in adolescents 12 years and older not responding to conventional therapy.

Adalimumab (Humira), marketed by Abbott and licensed in Europe to treat a range of rheumatic diseases, will now be indicated for the treatment of adults with severe axial spondyloarthritis who have had an inadequate response to, or are intolerant of, nonsteroidal anti-inflammatory drugs. The new indication covers patients without radiographic evidence of axial spondyloarthritis but with evidence of inflammation determined by MRI or elevated C-reactive protein.

Also at its June meeting, the agency recommended a new six-in-one combination vaccine developed for use outside the European Union. Hexaxim, marketed by Sanofi Pasteur, will be used in children aged 6 weeks to 2 years old to inoculate against diphtheria, tetanus, pertussis, hepatitis B, polio, and diseases caused by Haemophilus influenzae type B, including meningitis. The vaccine is administered as three doses 4 or more weeks apart.

Five of the active substances in the vaccine have been used in other vaccines and have been previously combined in Pentaxim, also manufactured by Sanofi Pasteur. The new vaccine adds Hansenula polymorpha-derived recombinant hepatitis B surface antigen. Clinical trials in Argentina, Mexico, Peru, Turkey, Thailand, and South Africa found the new vaccine to be as effective and safe as Pentaxim plus a monovalent hepatitis B vaccine, EMA said.

EMA recommended three additional new medications:

• Teduglutide (Revestive, Nycomed), a subcutaneous injection to treat short-bowel syndrome, a condition in which nutrients are not absorbed as a result of severe intestinal disease or the surgical removal of a large portion of the small intestine.

• Glycopyrronium bromide (Enurev, Novartis), a maintenance bronchodilator treatment for symptom relief in adults with chronic obstructive pulmonary disease.

• Ceftaroline fosamil (Zinforo, AstraZeneca), an infusion for treatment of adults with complicated skin and soft-tissue infections and community-acquired pneumonia.

The agency also announced that it was restricting indications for two medications on safety concerns. Following reports from Germany of hypersensitivity reactions, the agency advised clinicians not to prescribe tolperisone for indications other than poststroke spasticity and to use oral formulations in place of injectable ones. Tolperisone is a muscle relaxant used in Europe since the 1960s and only available in a handful of countries.

EMA recommended restricting the use of trimetazidine to second-line, add-on therapy after reports from France of movement disorders including Parkinsonian symptoms, restless leg syndrome, tremors and gait instability associated with the medicine. Trimetazidine-containing medicines have been available since the 1970s in Europe and are used in the treatment of patients with angina pectoris. Clinicians are also advised not to prescribe in patients with these and related movement disorders, or those who have severe renal impairment.

All EMA recommendations require European Commission approval to be final.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

GAITHERSBURG, MD. – A novel radiofrequency probe is one step closer to the operating room to help surgeons ensure that lumpectomy margins are benign.

At a meeting on June 21, the Food and Drug Administration’s General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee voted 10-1 that the benefits of the MarginProbe system outweigh risks when used as an adjunctive diagnostic tool for the identification of cancerous tissue at the margins of the ex vivo lumpectomy specimen following primary excision in women previously diagnosed with breast cancer.

"I think that it has the potential to be beneficial to women to reduce their chances of going back to the operating room," said panel member Dr. A. Marilyn Leitch, an oncologic surgeon at the University of Texas Southwestern Medical Center in Dallas. "The sponsor has demonstrated that the device can detect tumor in the margins."

The system uses electromagnetic waves to characterize human tissue in real time, providing surgeons with intraoperative information on the malignancy of the margins of an ex vivo lumpectomy specimen. It is intended for use on freshly excised tissue within 20 minutes of excision. The probe is designed to characterize tissue, based on the principles of dielectric spectroscopy, according to a written statement by the company that sponsors the MarginProbe system, Dune Medical Devices Inc.

The sensor generates radiofrequency electromagnetic fields and measures a slice of tissue 7 mm in diameter, a few mm deep and adjacent to the sensor. The resonance characteristics are dependent on tissue properties – malignant tissue has been shown to have different characteristics compared with benign tissue.

The system is intended for intraoperative use in conjunction with standard methods, such as intraoperative imaging and palpation, to increase the likelihood that patients will undergo intraoperative re-excision of the lumpectomy cavity. The locations of re-excision will correspond to the margins of the ex vivo specimen that have less than 1-mm separation of the excision surface of the margin and the primary breast cancer, according to a statement by the company.

Dune Medical Devices is seeking premarket approval of the device based on data from several clinical trials and intended-use trials conducted primarily in Israel but also in the United States.

The FDA asked the General and Plastic Surgery Devices Panel of the Medical Devices Advisory Committee to vote on three questions:

• Is there reasonable assurance that the MarginProbe system is safe for use in patients who meet the criteria specified in the proposed indication?

• Is there reasonable assurance that the MarginProbe is effective for use in for patients who meet the criteria specified in the proposed indication?

• Do the benefits of the MarginProbe for use in patients who meet the specified criteria outweigh the risks for use in this patient populations?

Eleven panel members voted that the device is safe; there was one abstention. Eight panel members voted that the device was effective with regard to the proposed indication; one member voted no and there were two abstentions.

The agency also posed a number of questions to the panel regarding the adequacy of end points of key trials submitted; device sensitivity/specificity; the effect of specimen volume on future cosmesis; the appropriateness of applying the design dataset (based primarily on Israeli patients) to a U.S. population; and suggestions for the sponsor’s proposed postapproval study.

The FDA usually follows the recommendations of its advisory panels, which are not binding.

CHICAGO – Vitamin D₃ can relieve the aches and pains associated with aromatase inhibitor therapy for breast cancer, according to the results of a randomized, double-blind, placebo-controlled trial.

Six months of vitamin D at 30,000 IU per week proved safe and was associated with "less worsening" of musculoskeletal events and fewer overall adverse quality of life events in women starting adjuvant letrozole (Femara) for hormone receptor–positive breast cancer, Dr. Qamar J. Khan reported at the annual meeting of the American Society of Clinical Oncology.

© Kaspri/Fotolia.com

Aromatase inhibitors are often discontinued prematurely because of new or worsening musculoskeletal pain reported in as many as half of women and fatigue in 15%-30%, said Dr. Khan of the University of Kansas Medical Center in Kansas City.

Vitamin D deficiency is thought to contribute to musculoskeletal symptoms, he said, explaining the rationale for the study. It is prevalent in breast cancer patients who have these aches and pains, and in women receiving adjuvant chemotherapy, even with supplementation. A similar syndrome is seen in people with severe vitamin D deficiency, he noted.

A prior pilot study conducted by the investigators suggested that vitamin D at 50,000 IU/wk for 12 weeks may be effective in reducing these symptoms (Breast Cancer Res. 2010;119:111-8).

The current double-blind VITAL (Vitamin D for Arthralgias From Letrozole) trial evenly randomized 160 postmenopausal women with stage I-III hormone receptor–positive invasive breast cancer and a serum vitamin D level of 40 ng/mL or less. All patients received letrozole 2.5 mg daily and the standard daily recommended daily allowance (RDA) of vitamin D 600 IU and calcium 1,200 mg. One cohort also received 30,000 IU of oral vitamin D₃ weekly for 24 weeks; the other was given a placebo.

The two arms were well matched with regard to age, race, body mass index, vitamin D level at baseline, adjuvant chemotherapy, and radiation therapy.

The per-protocol primary end point was the incidence of a musculoskeletal event, defined as worsening of pain using a simple pain intensity scale, worsening disability from musculoskeletal pain using the Health Assessment Questionnaire II, or discontinuation of letrozole because of pain at 6 months. The primary end point also was measured, substituting the quantitative Brief Pain Inventory for the simple pain intensity scale, Dr. Khan said.

Thirteen patients did not complete the study for reasons unrelated to study agents and/or musculoskeletal events, leaving 147 evaluable for efficacy.

At 6 months, 37% of women receiving 30,000 IU vitamin D weekly experienced a per-protocol musculoskeletal event, compared with 51% on placebo (P = .069), based on the simple scale. When the more robust Brief Pain Inventory was used, 61% of controls and 38% of those on vitamin D reported a musculoskeletal event, a difference that reached statistical significance (P = .008), he said.

A significantly higher proportion of women on placebo also had an adverse quality of life event, defined as a musculoskeletal event plus worsening of fatigue (72% vs. 42%; P less than .001).

The median vitamin D level at baseline was 25.1 ng/mL in the control arm and 22.5 ng/mL in the vitamin D group. It hovered at 32 ng/mL at 12 weeks and 31 ng/mL at 24 weeks in the control group, but rose to 53 ng/mL at 12 weeks and 57 ng/mL at 24 weeks in the vitamin D arm (P = .001 at both 12 and 24 weeks).

Baseline levels had little influence on the final level achieved. The sharp rise followed by relatively little gain in the active treatment arm suggests a plateau in the effect of continued vitamin D supplementation, Dr. Khan observed.

One patient in the control arm developed mild hypercalcemia, and three patients in the control arm discontinued early because of a musculoskeletal adverse event. There were no severe adverse events.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) Medical Center, said that the trial used well-validated measures and showed no discernable toxicity with 30,000 IU weekly, which is beyond the current RDA. "Therefore it may be promising for helping with these musculoskeletal symptoms and possibly fatigue," she said.

Dr. Mustian asked whether the time needed to achieve a benefit poses a potential problem in terms of patient adherence and whether data are available on the sustainability of the improvements in musculoskeletal symptoms and fatigue.

Dr. Khan said that aromatase inhibitor–induced adverse events tend to peak at about 6 months and that only one study has looked at using higher doses of vitamin D beyond 6 months. The observation that the effect of vitamin D supplementation plateaus at 3-6 months, however, is consistent with other studies.

"After you load the body with vitamin D and ... you keep on giving the same dose, the body just maintains the levels," he said.

Dr. Khan said that additional studies are needed to address long-term sustainability, and that the investigators have proposed a trial to the Southwest Oncology Group for the same intervention for 1-2 years to study a longer-term effect.

Dr. Khan reports honoraria from Abraxis BioScience and Genentech, and research funding from Abraxis and Novartis Roche/Genentech. His coauthors and Dr. Mustian report no disclosures.

CHICAGO – Vitamin D₃ can relieve the aches and pains associated with aromatase inhibitor therapy for breast cancer, according to the results of a randomized, double-blind, placebo-controlled trial.

Six months of vitamin D at 30,000 IU per week proved safe and was associated with "less worsening" of musculoskeletal events and fewer overall adverse quality of life events in women starting adjuvant letrozole (Femara) for hormone receptor–positive breast cancer, Dr. Qamar J. Khan reported at the annual meeting of the American Society of Clinical Oncology.

© Kaspri/Fotolia.com

Aromatase inhibitors are often discontinued prematurely because of new or worsening musculoskeletal pain reported in as many as half of women and fatigue in 15%-30%, said Dr. Khan of the University of Kansas Medical Center in Kansas City.

Vitamin D deficiency is thought to contribute to musculoskeletal symptoms, he said, explaining the rationale for the study. It is prevalent in breast cancer patients who have these aches and pains, and in women receiving adjuvant chemotherapy, even with supplementation. A similar syndrome is seen in people with severe vitamin D deficiency, he noted.

A prior pilot study conducted by the investigators suggested that vitamin D at 50,000 IU/wk for 12 weeks may be effective in reducing these symptoms (Breast Cancer Res. 2010;119:111-8).

The current double-blind VITAL (Vitamin D for Arthralgias From Letrozole) trial evenly randomized 160 postmenopausal women with stage I-III hormone receptor–positive invasive breast cancer and a serum vitamin D level of 40 ng/mL or less. All patients received letrozole 2.5 mg daily and the standard daily recommended daily allowance (RDA) of vitamin D 600 IU and calcium 1,200 mg. One cohort also received 30,000 IU of oral vitamin D₃ weekly for 24 weeks; the other was given a placebo.

The two arms were well matched with regard to age, race, body mass index, vitamin D level at baseline, adjuvant chemotherapy, and radiation therapy.

The per-protocol primary end point was the incidence of a musculoskeletal event, defined as worsening of pain using a simple pain intensity scale, worsening disability from musculoskeletal pain using the Health Assessment Questionnaire II, or discontinuation of letrozole because of pain at 6 months. The primary end point also was measured, substituting the quantitative Brief Pain Inventory for the simple pain intensity scale, Dr. Khan said.

Thirteen patients did not complete the study for reasons unrelated to study agents and/or musculoskeletal events, leaving 147 evaluable for efficacy.

At 6 months, 37% of women receiving 30,000 IU vitamin D weekly experienced a per-protocol musculoskeletal event, compared with 51% on placebo (P = .069), based on the simple scale. When the more robust Brief Pain Inventory was used, 61% of controls and 38% of those on vitamin D reported a musculoskeletal event, a difference that reached statistical significance (P = .008), he said.

A significantly higher proportion of women on placebo also had an adverse quality of life event, defined as a musculoskeletal event plus worsening of fatigue (72% vs. 42%; P less than .001).

The median vitamin D level at baseline was 25.1 ng/mL in the control arm and 22.5 ng/mL in the vitamin D group. It hovered at 32 ng/mL at 12 weeks and 31 ng/mL at 24 weeks in the control group, but rose to 53 ng/mL at 12 weeks and 57 ng/mL at 24 weeks in the vitamin D arm (P = .001 at both 12 and 24 weeks).

Baseline levels had little influence on the final level achieved. The sharp rise followed by relatively little gain in the active treatment arm suggests a plateau in the effect of continued vitamin D supplementation, Dr. Khan observed.

One patient in the control arm developed mild hypercalcemia, and three patients in the control arm discontinued early because of a musculoskeletal adverse event. There were no severe adverse events.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) Medical Center, said that the trial used well-validated measures and showed no discernable toxicity with 30,000 IU weekly, which is beyond the current RDA. "Therefore it may be promising for helping with these musculoskeletal symptoms and possibly fatigue," she said.

Dr. Mustian asked whether the time needed to achieve a benefit poses a potential problem in terms of patient adherence and whether data are available on the sustainability of the improvements in musculoskeletal symptoms and fatigue.

Dr. Khan said that aromatase inhibitor–induced adverse events tend to peak at about 6 months and that only one study has looked at using higher doses of vitamin D beyond 6 months. The observation that the effect of vitamin D supplementation plateaus at 3-6 months, however, is consistent with other studies.

"After you load the body with vitamin D and ... you keep on giving the same dose, the body just maintains the levels," he said.

Dr. Khan said that additional studies are needed to address long-term sustainability, and that the investigators have proposed a trial to the Southwest Oncology Group for the same intervention for 1-2 years to study a longer-term effect.

Dr. Khan reports honoraria from Abraxis BioScience and Genentech, and research funding from Abraxis and Novartis Roche/Genentech. His coauthors and Dr. Mustian report no disclosures.

CHICAGO – Vitamin D₃ can relieve the aches and pains associated with aromatase inhibitor therapy for breast cancer, according to the results of a randomized, double-blind, placebo-controlled trial.

Six months of vitamin D at 30,000 IU per week proved safe and was associated with "less worsening" of musculoskeletal events and fewer overall adverse quality of life events in women starting adjuvant letrozole (Femara) for hormone receptor–positive breast cancer, Dr. Qamar J. Khan reported at the annual meeting of the American Society of Clinical Oncology.

© Kaspri/Fotolia.com

Aromatase inhibitors are often discontinued prematurely because of new or worsening musculoskeletal pain reported in as many as half of women and fatigue in 15%-30%, said Dr. Khan of the University of Kansas Medical Center in Kansas City.

Vitamin D deficiency is thought to contribute to musculoskeletal symptoms, he said, explaining the rationale for the study. It is prevalent in breast cancer patients who have these aches and pains, and in women receiving adjuvant chemotherapy, even with supplementation. A similar syndrome is seen in people with severe vitamin D deficiency, he noted.

A prior pilot study conducted by the investigators suggested that vitamin D at 50,000 IU/wk for 12 weeks may be effective in reducing these symptoms (Breast Cancer Res. 2010;119:111-8).

The current double-blind VITAL (Vitamin D for Arthralgias From Letrozole) trial evenly randomized 160 postmenopausal women with stage I-III hormone receptor–positive invasive breast cancer and a serum vitamin D level of 40 ng/mL or less. All patients received letrozole 2.5 mg daily and the standard daily recommended daily allowance (RDA) of vitamin D 600 IU and calcium 1,200 mg. One cohort also received 30,000 IU of oral vitamin D₃ weekly for 24 weeks; the other was given a placebo.

The two arms were well matched with regard to age, race, body mass index, vitamin D level at baseline, adjuvant chemotherapy, and radiation therapy.

The per-protocol primary end point was the incidence of a musculoskeletal event, defined as worsening of pain using a simple pain intensity scale, worsening disability from musculoskeletal pain using the Health Assessment Questionnaire II, or discontinuation of letrozole because of pain at 6 months. The primary end point also was measured, substituting the quantitative Brief Pain Inventory for the simple pain intensity scale, Dr. Khan said.

Thirteen patients did not complete the study for reasons unrelated to study agents and/or musculoskeletal events, leaving 147 evaluable for efficacy.

At 6 months, 37% of women receiving 30,000 IU vitamin D weekly experienced a per-protocol musculoskeletal event, compared with 51% on placebo (P = .069), based on the simple scale. When the more robust Brief Pain Inventory was used, 61% of controls and 38% of those on vitamin D reported a musculoskeletal event, a difference that reached statistical significance (P = .008), he said.

A significantly higher proportion of women on placebo also had an adverse quality of life event, defined as a musculoskeletal event plus worsening of fatigue (72% vs. 42%; P less than .001).

The median vitamin D level at baseline was 25.1 ng/mL in the control arm and 22.5 ng/mL in the vitamin D group. It hovered at 32 ng/mL at 12 weeks and 31 ng/mL at 24 weeks in the control group, but rose to 53 ng/mL at 12 weeks and 57 ng/mL at 24 weeks in the vitamin D arm (P = .001 at both 12 and 24 weeks).

Baseline levels had little influence on the final level achieved. The sharp rise followed by relatively little gain in the active treatment arm suggests a plateau in the effect of continued vitamin D supplementation, Dr. Khan observed.

One patient in the control arm developed mild hypercalcemia, and three patients in the control arm discontinued early because of a musculoskeletal adverse event. There were no severe adverse events.

Discussant Karen Mustian, Ph.D., of the University of Rochester (N.Y.) Medical Center, said that the trial used well-validated measures and showed no discernable toxicity with 30,000 IU weekly, which is beyond the current RDA. "Therefore it may be promising for helping with these musculoskeletal symptoms and possibly fatigue," she said.

Dr. Mustian asked whether the time needed to achieve a benefit poses a potential problem in terms of patient adherence and whether data are available on the sustainability of the improvements in musculoskeletal symptoms and fatigue.

Dr. Khan said that aromatase inhibitor–induced adverse events tend to peak at about 6 months and that only one study has looked at using higher doses of vitamin D beyond 6 months. The observation that the effect of vitamin D supplementation plateaus at 3-6 months, however, is consistent with other studies.

"After you load the body with vitamin D and ... you keep on giving the same dose, the body just maintains the levels," he said.

Dr. Khan said that additional studies are needed to address long-term sustainability, and that the investigators have proposed a trial to the Southwest Oncology Group for the same intervention for 1-2 years to study a longer-term effect.

Dr. Khan reports honoraria from Abraxis BioScience and Genentech, and research funding from Abraxis and Novartis Roche/Genentech. His coauthors and Dr. Mustian report no disclosures.