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Donepezil fails to improve cognition after brain irradiation
CHICAGO – Donepezil proved no better than placebo at improving overall cognitive function among 198 patients who had undergone partial or whole brain irradiation for brain tumors, investigators reported at the annual meeting of the American Society of Clinical Oncology.
A randomized, double-blind, multicenter phase III trial found no significant differences between donepezil (Aricept) and placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory, said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest Baptist Medical Center in Winston-Salem, N.C.
Among patients with more cognitive problems at baseline, however, there was a significant benefit in verbal memory for patients on donepezil, compared with controls (P = .005), and a trend toward preservation of motor speed and dexterity, Dr. Rapp said.
"We have to continue looking for effective treatments for cognitive symptoms in this population. It has a big impact on patients," he said.
Previous studies indicated that more than half of patients who receive partial or whole brain irradiation for tumors will have cognitive deficits, and that about 12% will develop some form of dementia. Cognitive problems have a major impact on patient quality of life, and anything clinicians can do to preserve or improve patient mental faculties is important, Dr. Rapp said.
The study was designed to test whether donepezil, an acetylcholinesterase inhibitor indicated for treatment of mild-to-moderate cognitive decline from Alzheimer’s disease, could have a similar neuroprotective effect following whole brain irradiation.
Investigators enrolled 198 patients 6 months after they received at least 30 Gy of brain irradiation. Following a baseline evaluation, patients were randomized to receive either 5-10 mg daily of oral donepezil or placebo for 24 weeks, with an interim assessment performed at 12 weeks.
The study looked at the effect of the drug on cognitive functioning and on measures of fatigue, mood, and quality of life.
The patients were assessed at baseline for cognitive function, and at 12 and 24 weeks with the Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure-modified (a measure of visual spatial ability, memory, and planning ability), Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard (a measure of dexterity and motor control).
Both study arms showed significant improvement in cognitive composite scores over baseline (P less than .01 for both), but the degree of improvement did not differ significantly between arms. Similarly, there were no significant differences between the treatment arms in any of the test domains, Dr. Rapp said.
Among patients with greater baseline cognitive deficits, as measured by a score of less than 51 on the FACT Brain subscale, there was also significant improvement over baseline but no between-group difference, he reported.
Donepezil was significantly better than placebo control in this subgroup for improvement in performance on the recognition portion of the Hopkins Verbal Learning Test, which measures verbal memory, and donepezil danced on the edge of significance at preserving motor speed and dexterity as measured by the Grooved Pegboard-Dominant Hand test but never crossed the line (P = .06), he said.
Adverse events were similar between the groups, and the patients assigned to donepezil appeared to tolerate it well, Dr. Rapp said.
Dr. Robin Grant of the Center for Clinical Brain Sciences at the University of Edinburgh, the invited discussant, said that the study was very well designed. He noted, however, "that there was no specified level of cognitive deficit at the time of [study] entry, and I think if you look at moderate to severely affected patients then you’re more likely to be able to show a change there," he said.
He added that it would be interesting to see results from the Grooved Pegboard test performed with the contralateral rather than dominant hand.
The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.
CHICAGO – Donepezil proved no better than placebo at improving overall cognitive function among 198 patients who had undergone partial or whole brain irradiation for brain tumors, investigators reported at the annual meeting of the American Society of Clinical Oncology.
A randomized, double-blind, multicenter phase III trial found no significant differences between donepezil (Aricept) and placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory, said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest Baptist Medical Center in Winston-Salem, N.C.
Among patients with more cognitive problems at baseline, however, there was a significant benefit in verbal memory for patients on donepezil, compared with controls (P = .005), and a trend toward preservation of motor speed and dexterity, Dr. Rapp said.
"We have to continue looking for effective treatments for cognitive symptoms in this population. It has a big impact on patients," he said.
Previous studies indicated that more than half of patients who receive partial or whole brain irradiation for tumors will have cognitive deficits, and that about 12% will develop some form of dementia. Cognitive problems have a major impact on patient quality of life, and anything clinicians can do to preserve or improve patient mental faculties is important, Dr. Rapp said.
The study was designed to test whether donepezil, an acetylcholinesterase inhibitor indicated for treatment of mild-to-moderate cognitive decline from Alzheimer’s disease, could have a similar neuroprotective effect following whole brain irradiation.
Investigators enrolled 198 patients 6 months after they received at least 30 Gy of brain irradiation. Following a baseline evaluation, patients were randomized to receive either 5-10 mg daily of oral donepezil or placebo for 24 weeks, with an interim assessment performed at 12 weeks.
The study looked at the effect of the drug on cognitive functioning and on measures of fatigue, mood, and quality of life.
The patients were assessed at baseline for cognitive function, and at 12 and 24 weeks with the Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure-modified (a measure of visual spatial ability, memory, and planning ability), Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard (a measure of dexterity and motor control).
Both study arms showed significant improvement in cognitive composite scores over baseline (P less than .01 for both), but the degree of improvement did not differ significantly between arms. Similarly, there were no significant differences between the treatment arms in any of the test domains, Dr. Rapp said.
Among patients with greater baseline cognitive deficits, as measured by a score of less than 51 on the FACT Brain subscale, there was also significant improvement over baseline but no between-group difference, he reported.
Donepezil was significantly better than placebo control in this subgroup for improvement in performance on the recognition portion of the Hopkins Verbal Learning Test, which measures verbal memory, and donepezil danced on the edge of significance at preserving motor speed and dexterity as measured by the Grooved Pegboard-Dominant Hand test but never crossed the line (P = .06), he said.
Adverse events were similar between the groups, and the patients assigned to donepezil appeared to tolerate it well, Dr. Rapp said.
Dr. Robin Grant of the Center for Clinical Brain Sciences at the University of Edinburgh, the invited discussant, said that the study was very well designed. He noted, however, "that there was no specified level of cognitive deficit at the time of [study] entry, and I think if you look at moderate to severely affected patients then you’re more likely to be able to show a change there," he said.
He added that it would be interesting to see results from the Grooved Pegboard test performed with the contralateral rather than dominant hand.
The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.
CHICAGO – Donepezil proved no better than placebo at improving overall cognitive function among 198 patients who had undergone partial or whole brain irradiation for brain tumors, investigators reported at the annual meeting of the American Society of Clinical Oncology.
A randomized, double-blind, multicenter phase III trial found no significant differences between donepezil (Aricept) and placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory, said Stephen R. Rapp, Ph.D., professor of psychiatry and behavioral medicine at Wake Forest Baptist Medical Center in Winston-Salem, N.C.
Among patients with more cognitive problems at baseline, however, there was a significant benefit in verbal memory for patients on donepezil, compared with controls (P = .005), and a trend toward preservation of motor speed and dexterity, Dr. Rapp said.
"We have to continue looking for effective treatments for cognitive symptoms in this population. It has a big impact on patients," he said.
Previous studies indicated that more than half of patients who receive partial or whole brain irradiation for tumors will have cognitive deficits, and that about 12% will develop some form of dementia. Cognitive problems have a major impact on patient quality of life, and anything clinicians can do to preserve or improve patient mental faculties is important, Dr. Rapp said.
The study was designed to test whether donepezil, an acetylcholinesterase inhibitor indicated for treatment of mild-to-moderate cognitive decline from Alzheimer’s disease, could have a similar neuroprotective effect following whole brain irradiation.
Investigators enrolled 198 patients 6 months after they received at least 30 Gy of brain irradiation. Following a baseline evaluation, patients were randomized to receive either 5-10 mg daily of oral donepezil or placebo for 24 weeks, with an interim assessment performed at 12 weeks.
The study looked at the effect of the drug on cognitive functioning and on measures of fatigue, mood, and quality of life.
The patients were assessed at baseline for cognitive function, and at 12 and 24 weeks with the Hopkins Verbal Learning Test-Revised, Rey-Osterreith Complex Figure-modified (a measure of visual spatial ability, memory, and planning ability), Trail Making Test, Digit Span, Controlled Oral Word Association, and Grooved Pegboard (a measure of dexterity and motor control).
Both study arms showed significant improvement in cognitive composite scores over baseline (P less than .01 for both), but the degree of improvement did not differ significantly between arms. Similarly, there were no significant differences between the treatment arms in any of the test domains, Dr. Rapp said.
Among patients with greater baseline cognitive deficits, as measured by a score of less than 51 on the FACT Brain subscale, there was also significant improvement over baseline but no between-group difference, he reported.
Donepezil was significantly better than placebo control in this subgroup for improvement in performance on the recognition portion of the Hopkins Verbal Learning Test, which measures verbal memory, and donepezil danced on the edge of significance at preserving motor speed and dexterity as measured by the Grooved Pegboard-Dominant Hand test but never crossed the line (P = .06), he said.
Adverse events were similar between the groups, and the patients assigned to donepezil appeared to tolerate it well, Dr. Rapp said.
Dr. Robin Grant of the Center for Clinical Brain Sciences at the University of Edinburgh, the invited discussant, said that the study was very well designed. He noted, however, "that there was no specified level of cognitive deficit at the time of [study] entry, and I think if you look at moderate to severely affected patients then you’re more likely to be able to show a change there," he said.
He added that it would be interesting to see results from the Grooved Pegboard test performed with the contralateral rather than dominant hand.
The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.
AT THE ASCO ANNUAL MEETING 2013
Major finding: There were no significant differences between donepezil or placebo in either cognitive composite scores after 12 or 24 weeks of therapy – the study’s primary end point – or in domains of attention/concentration, motor speed/dexterity, learning, or memory.
Data source: Randomized, double-blind, placebo-controlled trial of 198 patients after partial or whole brain irradiation.
Disclosures: The study was funded by the National Institutes of Health and by Eisai, maker of donepezil. Dr. Rapp disclosed receiving research funding from the company. Dr. Grant reported having no financial disclosures.
Ganetespib trial hints at survival benefit in lung adenocarcinoma
CHICAGO – A novel heat-shock protein inhibitor, ganetespib, showed glimmers of a survival benefit for lung cancer patients in a randomized phase II trial presented at the annual meeting of the American Society of Clinical Oncology.
Tested in combination with docetaxel, the experimental drug appeared to improve overall and progression-free survival, compared with docetaxel alone, as second-line therapy for patients with advanced non–small cell adenocarcinoma of the lung, Dr. Suresh Ramalingam reported.
Neither measure, however, was a primary end point of the study. Heat-shock protein 90 is a chaperone protein that activates other proteins binding to it so that they can perform their normal cellular function. Ganetespib binds to and inhibits Hsp90, causing oncoproteins to become inactivated and to degrade before they have had a chance to unfold into their functional configuration.
In the randomized phase II GALAXY-1 study, median progression-free survival reached 4.5 months among 125 patients assigned to ganetespib and docetaxel, compared with 3.2 months for 127 patients assigned to docetaxel and placebo (hazard ratio, 0.84; P = .038) in an unadjusted analysis.
However, after adjusting for sex, smoking status, lactate dehydrogenase (LDH), performance status, interval since diagnosis, and other common factors, the difference was no longer significant, said Dr. Ramalingam, chief of thoracic oncology and director of medical oncology, at Emory University in Atlanta.
Overall survival, in contrast, was not significantly different in an unadjusted analysis, at a median of 9.8 months for the combination and 7.4 months for docetaxel alone (HR, 0.82), but became significant after adjustment for potential confounders (adjusted HR, 0.73; P = .041).
"This is a first-in-class study showing the potential efficacy of this compound, and I think it presents a potential advance in an area of lung cancer where we haven’t had advances in a long time, and we’re all eagerly awaiting the outcome of the phase III trial," said Dr. Marjorie Zauderer, a medical oncologist and lung cancer specialist at Memorial Sloan-Kettering Cancer Center, New York.
Dr. Zauderer was not involved in the study, but commented on it in a briefing held prior to the presentation of data later in the day.
Overall survival and progression-free survival were secondary end points in the trial. The co-primary end points were progression-free survival in patients with elevated LDH levels or tumors with mutations in KRAS, but these data were not reported. According to Synta Pharmaceuticals, maker of ganetespib, neither KRAS nor epidermal growth factor receptor (EGFR) mutations correlated with an overall survival benefit for the experimental arm of the trial.
When the investigators looked at only those patients who had been diagnosed more than 6 months before being enrolled in the trial (the "6-month population") they found that, in both unadjusted and adjusted analyses, the ganetespib and docetaxel combination was superior to docetaxel and placebo, with median overall survival of 10.7 vs. 6.4 months (unadjusted HR, 0.61; P = .0093; adjusted HR, 0.55; P = .0036), and median progression-free survival of 5.4 vs. 3.4 months (unadjusted HR, 0.61, P = .0041; adjusted HR, 0.62, P = .0075).
About 70% of the patients in the trial were included in the 6-month population. The follow-on GALAXY-2 phase III trial will enroll only those patients who have lived with an adenocarcinoma diagnosis for at least 6 months, the population that derived the greatest benefit in the current study.
The ganetespib and docetaxel combination was generally well tolerated, with manageable mild-to-moderate diarrhea being the most common adverse event.
The study was sponsored by Synta Pharmaceuticals. Dr. Ramalingam said that his institution receives research support from the company but that he had no personal financial disclosures. Dr. Zauderer reported having no conflicts of interest.
CHICAGO – A novel heat-shock protein inhibitor, ganetespib, showed glimmers of a survival benefit for lung cancer patients in a randomized phase II trial presented at the annual meeting of the American Society of Clinical Oncology.
Tested in combination with docetaxel, the experimental drug appeared to improve overall and progression-free survival, compared with docetaxel alone, as second-line therapy for patients with advanced non–small cell adenocarcinoma of the lung, Dr. Suresh Ramalingam reported.
Neither measure, however, was a primary end point of the study. Heat-shock protein 90 is a chaperone protein that activates other proteins binding to it so that they can perform their normal cellular function. Ganetespib binds to and inhibits Hsp90, causing oncoproteins to become inactivated and to degrade before they have had a chance to unfold into their functional configuration.
In the randomized phase II GALAXY-1 study, median progression-free survival reached 4.5 months among 125 patients assigned to ganetespib and docetaxel, compared with 3.2 months for 127 patients assigned to docetaxel and placebo (hazard ratio, 0.84; P = .038) in an unadjusted analysis.
However, after adjusting for sex, smoking status, lactate dehydrogenase (LDH), performance status, interval since diagnosis, and other common factors, the difference was no longer significant, said Dr. Ramalingam, chief of thoracic oncology and director of medical oncology, at Emory University in Atlanta.
Overall survival, in contrast, was not significantly different in an unadjusted analysis, at a median of 9.8 months for the combination and 7.4 months for docetaxel alone (HR, 0.82), but became significant after adjustment for potential confounders (adjusted HR, 0.73; P = .041).
"This is a first-in-class study showing the potential efficacy of this compound, and I think it presents a potential advance in an area of lung cancer where we haven’t had advances in a long time, and we’re all eagerly awaiting the outcome of the phase III trial," said Dr. Marjorie Zauderer, a medical oncologist and lung cancer specialist at Memorial Sloan-Kettering Cancer Center, New York.
Dr. Zauderer was not involved in the study, but commented on it in a briefing held prior to the presentation of data later in the day.
Overall survival and progression-free survival were secondary end points in the trial. The co-primary end points were progression-free survival in patients with elevated LDH levels or tumors with mutations in KRAS, but these data were not reported. According to Synta Pharmaceuticals, maker of ganetespib, neither KRAS nor epidermal growth factor receptor (EGFR) mutations correlated with an overall survival benefit for the experimental arm of the trial.
When the investigators looked at only those patients who had been diagnosed more than 6 months before being enrolled in the trial (the "6-month population") they found that, in both unadjusted and adjusted analyses, the ganetespib and docetaxel combination was superior to docetaxel and placebo, with median overall survival of 10.7 vs. 6.4 months (unadjusted HR, 0.61; P = .0093; adjusted HR, 0.55; P = .0036), and median progression-free survival of 5.4 vs. 3.4 months (unadjusted HR, 0.61, P = .0041; adjusted HR, 0.62, P = .0075).
About 70% of the patients in the trial were included in the 6-month population. The follow-on GALAXY-2 phase III trial will enroll only those patients who have lived with an adenocarcinoma diagnosis for at least 6 months, the population that derived the greatest benefit in the current study.
The ganetespib and docetaxel combination was generally well tolerated, with manageable mild-to-moderate diarrhea being the most common adverse event.
The study was sponsored by Synta Pharmaceuticals. Dr. Ramalingam said that his institution receives research support from the company but that he had no personal financial disclosures. Dr. Zauderer reported having no conflicts of interest.
CHICAGO – A novel heat-shock protein inhibitor, ganetespib, showed glimmers of a survival benefit for lung cancer patients in a randomized phase II trial presented at the annual meeting of the American Society of Clinical Oncology.
Tested in combination with docetaxel, the experimental drug appeared to improve overall and progression-free survival, compared with docetaxel alone, as second-line therapy for patients with advanced non–small cell adenocarcinoma of the lung, Dr. Suresh Ramalingam reported.
Neither measure, however, was a primary end point of the study. Heat-shock protein 90 is a chaperone protein that activates other proteins binding to it so that they can perform their normal cellular function. Ganetespib binds to and inhibits Hsp90, causing oncoproteins to become inactivated and to degrade before they have had a chance to unfold into their functional configuration.
In the randomized phase II GALAXY-1 study, median progression-free survival reached 4.5 months among 125 patients assigned to ganetespib and docetaxel, compared with 3.2 months for 127 patients assigned to docetaxel and placebo (hazard ratio, 0.84; P = .038) in an unadjusted analysis.
However, after adjusting for sex, smoking status, lactate dehydrogenase (LDH), performance status, interval since diagnosis, and other common factors, the difference was no longer significant, said Dr. Ramalingam, chief of thoracic oncology and director of medical oncology, at Emory University in Atlanta.
Overall survival, in contrast, was not significantly different in an unadjusted analysis, at a median of 9.8 months for the combination and 7.4 months for docetaxel alone (HR, 0.82), but became significant after adjustment for potential confounders (adjusted HR, 0.73; P = .041).
"This is a first-in-class study showing the potential efficacy of this compound, and I think it presents a potential advance in an area of lung cancer where we haven’t had advances in a long time, and we’re all eagerly awaiting the outcome of the phase III trial," said Dr. Marjorie Zauderer, a medical oncologist and lung cancer specialist at Memorial Sloan-Kettering Cancer Center, New York.
Dr. Zauderer was not involved in the study, but commented on it in a briefing held prior to the presentation of data later in the day.
Overall survival and progression-free survival were secondary end points in the trial. The co-primary end points were progression-free survival in patients with elevated LDH levels or tumors with mutations in KRAS, but these data were not reported. According to Synta Pharmaceuticals, maker of ganetespib, neither KRAS nor epidermal growth factor receptor (EGFR) mutations correlated with an overall survival benefit for the experimental arm of the trial.
When the investigators looked at only those patients who had been diagnosed more than 6 months before being enrolled in the trial (the "6-month population") they found that, in both unadjusted and adjusted analyses, the ganetespib and docetaxel combination was superior to docetaxel and placebo, with median overall survival of 10.7 vs. 6.4 months (unadjusted HR, 0.61; P = .0093; adjusted HR, 0.55; P = .0036), and median progression-free survival of 5.4 vs. 3.4 months (unadjusted HR, 0.61, P = .0041; adjusted HR, 0.62, P = .0075).
About 70% of the patients in the trial were included in the 6-month population. The follow-on GALAXY-2 phase III trial will enroll only those patients who have lived with an adenocarcinoma diagnosis for at least 6 months, the population that derived the greatest benefit in the current study.
The ganetespib and docetaxel combination was generally well tolerated, with manageable mild-to-moderate diarrhea being the most common adverse event.
The study was sponsored by Synta Pharmaceuticals. Dr. Ramalingam said that his institution receives research support from the company but that he had no personal financial disclosures. Dr. Zauderer reported having no conflicts of interest.
AT THE ASCO ANNUAL MEETING 2013
Major finding: The ganetespib and docetaxel combination was superior to docetaxel and placebo, with median overall survival of 10.7 vs. 6.4 months and median progression-free survival of 5.4 vs. 3.4 months.
Data source: Randomized controlled phase II trial in 252 patients with advanced non–small cell adenocarcinoma of the lung.
Disclosures: The study was sponsored by Synta Pharmaceuticals. Dr. Ramalingam said that his institution receives research support from the company but that he had no personal financial disclosures. Dr. Zauderer reported having no conflicts of interest.
After HCV treatment failure, some success with boceprevir-IFN-ribavirin
ORLANDO – Adding a protease inhibitor to pegylated interferon and ribavirin increased the rate of sustained virologic responses in patients with chronic hepatitis C infections for whom prior interferon/ribavirin therapy had failed, an investigator reported at the annual Digestive Disease Week.
Among patients with hepatitis C virus (HCV) infections who received only pegylated interferon and ribavirin (peg-IFN/RBV) in the control arms of phase II and III studies of boceprevir (Victrelis), more than 90% of those who had relapsed had a sustained virologic response for at least 24 weeks after therapy (SVR24) with combined boceprevir and peg-IFN/RBV, reported Dr. John Vierling, chief of hepatology at Baylor College of Medicine in Houston.
"Overall, the data from this final analysis lead to the conclusion that boceprevir combined with pegylated interferon/ribavirin therapy is efficacious in subjects with all three categories of nonresponse: relapsers, partial responders, and most importantly, null responders," Dr. Vierling said.
The PROVIDE study Included 168 patients (mean age, 52 years) in an intention-to-treat analysis whose peg-IFN/RBV therapy was considered a failure. The cohort included treatment-experienced patients with detectable HCV RNA after 12 weeks of peg-IFN/RBV and treatment-naive patients after 24 weeks of therapy, as well as those who had experienced virological breakthrough or relapse after having an end-of-treatment response.
Patients who had completed peg-IFN/RBV therapy within the previous 2 weeks were enrolled for 44 weeks. Those patients who had completed peg-IFN/RBV more than 2 weeks earlier were assigned to a 4-week lead-in phase with peg-IFN/RBV prior to starting on the study combination.
All participants were given boceprevir 800 mg orally three times daily with food, pegylated interferon-alpha-2b (Intron A) 1.5 mcg/kg subcutaneously once weekly, and weight-based ribavirin 600-1,400 mg daily divided into two oral doses.
Four patients dropped out of the study during the lead-in phase and thus did not receive any boceprevir, leaving 164 for a prespecified full-analysis set. A total of 60 patients discontinued therapy (including the 4 who dropped out in the lead-in phase). Of these patients, 14 stopped due to adverse events, 33 had treatment failure, and 13 dropped out for nonmedical reasons.
In the full analysis set, 27 of 28 (96%) patients who had had a relapse after prior peg-IFN/RBV had an SVR24, the primary endpoint, as did 57 of 85 (67%) prior partial responders and 20 of 49 (41%) prior null responders. Overall, 65% of patients in the full-analysis population and 63% of those in an intention-to-treat population had an SVR24.
In a breakdown by baseline characteristics of patients who had an SVR24, the authors found that SVR occurred more frequently in men than in women, in nonblack vs. black patients, among those with a viral load of 800,000 copies/mL or fewer, HCV genotype 1a vs. 1b (except among those with prior relapse), and patients with platelet counts of 200,000/mcL.
The most frequently reported adverse events were anemia in 45% of patients, dysgeusia in 35%, and neutropenia in 23%. The safety profile was similar to that reported for the combination in phase II and III studies, Dr. Vierling said.
The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
ORLANDO – Adding a protease inhibitor to pegylated interferon and ribavirin increased the rate of sustained virologic responses in patients with chronic hepatitis C infections for whom prior interferon/ribavirin therapy had failed, an investigator reported at the annual Digestive Disease Week.
Among patients with hepatitis C virus (HCV) infections who received only pegylated interferon and ribavirin (peg-IFN/RBV) in the control arms of phase II and III studies of boceprevir (Victrelis), more than 90% of those who had relapsed had a sustained virologic response for at least 24 weeks after therapy (SVR24) with combined boceprevir and peg-IFN/RBV, reported Dr. John Vierling, chief of hepatology at Baylor College of Medicine in Houston.
"Overall, the data from this final analysis lead to the conclusion that boceprevir combined with pegylated interferon/ribavirin therapy is efficacious in subjects with all three categories of nonresponse: relapsers, partial responders, and most importantly, null responders," Dr. Vierling said.
The PROVIDE study Included 168 patients (mean age, 52 years) in an intention-to-treat analysis whose peg-IFN/RBV therapy was considered a failure. The cohort included treatment-experienced patients with detectable HCV RNA after 12 weeks of peg-IFN/RBV and treatment-naive patients after 24 weeks of therapy, as well as those who had experienced virological breakthrough or relapse after having an end-of-treatment response.
Patients who had completed peg-IFN/RBV therapy within the previous 2 weeks were enrolled for 44 weeks. Those patients who had completed peg-IFN/RBV more than 2 weeks earlier were assigned to a 4-week lead-in phase with peg-IFN/RBV prior to starting on the study combination.
All participants were given boceprevir 800 mg orally three times daily with food, pegylated interferon-alpha-2b (Intron A) 1.5 mcg/kg subcutaneously once weekly, and weight-based ribavirin 600-1,400 mg daily divided into two oral doses.
Four patients dropped out of the study during the lead-in phase and thus did not receive any boceprevir, leaving 164 for a prespecified full-analysis set. A total of 60 patients discontinued therapy (including the 4 who dropped out in the lead-in phase). Of these patients, 14 stopped due to adverse events, 33 had treatment failure, and 13 dropped out for nonmedical reasons.
In the full analysis set, 27 of 28 (96%) patients who had had a relapse after prior peg-IFN/RBV had an SVR24, the primary endpoint, as did 57 of 85 (67%) prior partial responders and 20 of 49 (41%) prior null responders. Overall, 65% of patients in the full-analysis population and 63% of those in an intention-to-treat population had an SVR24.
In a breakdown by baseline characteristics of patients who had an SVR24, the authors found that SVR occurred more frequently in men than in women, in nonblack vs. black patients, among those with a viral load of 800,000 copies/mL or fewer, HCV genotype 1a vs. 1b (except among those with prior relapse), and patients with platelet counts of 200,000/mcL.
The most frequently reported adverse events were anemia in 45% of patients, dysgeusia in 35%, and neutropenia in 23%. The safety profile was similar to that reported for the combination in phase II and III studies, Dr. Vierling said.
The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
ORLANDO – Adding a protease inhibitor to pegylated interferon and ribavirin increased the rate of sustained virologic responses in patients with chronic hepatitis C infections for whom prior interferon/ribavirin therapy had failed, an investigator reported at the annual Digestive Disease Week.
Among patients with hepatitis C virus (HCV) infections who received only pegylated interferon and ribavirin (peg-IFN/RBV) in the control arms of phase II and III studies of boceprevir (Victrelis), more than 90% of those who had relapsed had a sustained virologic response for at least 24 weeks after therapy (SVR24) with combined boceprevir and peg-IFN/RBV, reported Dr. John Vierling, chief of hepatology at Baylor College of Medicine in Houston.
"Overall, the data from this final analysis lead to the conclusion that boceprevir combined with pegylated interferon/ribavirin therapy is efficacious in subjects with all three categories of nonresponse: relapsers, partial responders, and most importantly, null responders," Dr. Vierling said.
The PROVIDE study Included 168 patients (mean age, 52 years) in an intention-to-treat analysis whose peg-IFN/RBV therapy was considered a failure. The cohort included treatment-experienced patients with detectable HCV RNA after 12 weeks of peg-IFN/RBV and treatment-naive patients after 24 weeks of therapy, as well as those who had experienced virological breakthrough or relapse after having an end-of-treatment response.
Patients who had completed peg-IFN/RBV therapy within the previous 2 weeks were enrolled for 44 weeks. Those patients who had completed peg-IFN/RBV more than 2 weeks earlier were assigned to a 4-week lead-in phase with peg-IFN/RBV prior to starting on the study combination.
All participants were given boceprevir 800 mg orally three times daily with food, pegylated interferon-alpha-2b (Intron A) 1.5 mcg/kg subcutaneously once weekly, and weight-based ribavirin 600-1,400 mg daily divided into two oral doses.
Four patients dropped out of the study during the lead-in phase and thus did not receive any boceprevir, leaving 164 for a prespecified full-analysis set. A total of 60 patients discontinued therapy (including the 4 who dropped out in the lead-in phase). Of these patients, 14 stopped due to adverse events, 33 had treatment failure, and 13 dropped out for nonmedical reasons.
In the full analysis set, 27 of 28 (96%) patients who had had a relapse after prior peg-IFN/RBV had an SVR24, the primary endpoint, as did 57 of 85 (67%) prior partial responders and 20 of 49 (41%) prior null responders. Overall, 65% of patients in the full-analysis population and 63% of those in an intention-to-treat population had an SVR24.
In a breakdown by baseline characteristics of patients who had an SVR24, the authors found that SVR occurred more frequently in men than in women, in nonblack vs. black patients, among those with a viral load of 800,000 copies/mL or fewer, HCV genotype 1a vs. 1b (except among those with prior relapse), and patients with platelet counts of 200,000/mcL.
The most frequently reported adverse events were anemia in 45% of patients, dysgeusia in 35%, and neutropenia in 23%. The safety profile was similar to that reported for the combination in phase II and III studies, Dr. Vierling said.
The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
AT DDW 2013
Major finding: Among patients with hepatitis C infections who did not have a sustained virologic response after prior therapy, 63% had an SVR for at least 24 weeks after treatment with boceprevir, pegylated interferon, and ribavirin (intention-to-treat population).
Data source: Single-arm, open-label, nonrandomized study in 168 patients.
Disclosures: The study was sponsored by Merck. Dr. Vierling disclosed serving in an advisory capacity and receiving grants and research support from the company. Three of his coauthors are employees of Merck, and one is a board member.
Frontline bevacizumab fails to boost glioblastoma survival in key trials
CHICAGO – Adding bevacizumab to frontline radiation and temozolomide therapy for glioblastoma produced disappointing results in a double-blind, placebo-controlled phase III trial.
Bevacizumab (Avastin) extended progression-free survival, but did not improve overall survival in the Radiation Therapy Oncology Group (RTOG) 0825 study, and investigators reported that the angiogenesis inhibitor was associated with worse neurocognitve and quality of life outcomes.
Among 637 patients who were randomized, median overall survival reached 16.1 months in those assigned to radiation, temozolomide (Temodar), and placebo, compared with 15.7 months in patients assigned to radiation, temozolomide, and bevacizumab, Dr. Mark R. Gilbert reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.
Median progression-free survival reached 10.7 months in the bevacizumab arm, vs. 7.3 months in the placebo arm, said Dr. Gilbert, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center in Houston. The P value was .0007, but this difference was not statistically significant because of an unusual trial design that split criteria for statistical significance between the two primary outcome measures of overall and progression-free survival. In addition, patients in the bevacizumab arm had significantly worse neurocognitive and overall symptom scores over time.
"We feel that bevacizumab remains an important therapy for our patients with glioblastoma, but the results of this study do not support its frontline use. Rather, it can be reserved as a later treatment," he said at a press briefing prior to his presentation.
Outcomes contrast with Avaglio study
Some results of the publicly funded RTOG 0825 trial run counter to those from the Avaglio study, an industry-sponsored trial whose results were also presented at the ASCO annual meeting.
The Avaglio investigators found that adding bevacizumab to radiotherapy and temozolomide "achieved a clinically meaningful, statistically significant progression-free survival improvement in patients with glioblastoma," Dr. Warren Mason, a neuro-oncologist at the Princess Margaret Hospital in Toronto, reported at another session.
The Avaglio trial, which ran parallel to RTOG 0825 and was very similar in design, showed a quality of life benefit for patients on bevacizumab, but did not look at neurocognitive outcomes.
Median progression-free survival in Avaglio reached 10.6 months in 458 patients in its radiation, temozolomide, and bevacizumab arm, vs. 6.2 months in 463 patients in its radiation, temozolomide, and placebo arm, and the difference was significant (hazard ratio, 0.64; P less than .0001).
However, as in RTOG 0825, median overall survival was virtually identical in both Avaglio trial arms, at 16.8 and 16.7 months, respectively.
Bevacizumab misses RTOG targets
The RTOG trial enrolled neurologically stable patients with glioblastoma who had a Karnofsky performance score of at least 70 and who had tumor tissue samples available for evaluation. They were randomized to receive standard chemoradiation with temozolomide for 3 weeks followed by chemoradiation with temozolomide and either bevacizumab or placebo for 6-12 maintenance cycles.
The treatment type was unblinded at progression, and patients were allowed to cross over, or continue on, bevacizumab. Progression was defined as a greater than 25% increase in tumor area without recent steroid reduction, or worsening of neurologic symptoms.
In a pooled analysis including both study arms, patients with methylation of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) had better median and overall survival than patients with MGMT unmethylated (methylated MGMT is a marker for favorable prognosis). Median overall survival for the MGMT methylated group was 23.2 months, compared with 14.3 months for the unmethylated group (HR in unmethylated tumors, 2.10; P less than .001). Respective median progression-free survival was 14.1 months vs. 8.2 months (HR, 1.67; P less than .001).
(The results of the GLARIUS trial, also reported at this meeting, showed that bevacizumab combined with irinotecan (Camptosar) in chemoradiation was associated with longer progression-free survival than temozolomide chemoradiation in newly diagnosed patients with MGMT-unmethylated glioblastoma. In a preliminary finding from that study, there was a suggestion of an overall survival benefit for the bevacizumab-irinotecan combination.)
As noted, in RTOG 0825, patients in the bevacizumab arm scored significantly worse on a clinical trial battery composite of cognitive function (P = .038), on overall symptom interference with daily activity (P less than .001), and on quality of life cognitive function (P less than .009).
In contrast, patients on bevacizumab in Avaglio had improved quality of life, prolonged preservation of performance scores, and reduced steroid doses compared with controls.
Why the differences?
Dr. Howard A. Fine, director of the brain tumor center at New York University, the invited discussant for RTOG 0825, said that the differences in patient-reported outcomes between the trials may reflect differences in statistical analysis, possibly different analytical methodologies used to query the data, or the lack of neurocognitive data in Avaglio.
Another possibility to account for the worsening neurocognitive function with bevacizumab is the drug’s documented ability to stabilize the blood-brain barrier and decrease MRI gadolinium enhancement, he said. This could mean that patients experience radiographic occult disease progression that does not show up well on brain scans.
Dr. Gilbert and Dr. Fine commented that theoretically at least, glioblastoma should be an ideal target for angiogenesis inhibitors such as bevacizumab, because they display a high degree of vascularity, and endothelial proliferation is part of the pathologic definition of the disease.
But although bevacizumab has been demonstrated to improve response rates and delay progression in recurrent glioblastoma, its relative lack of efficacy in the first line is puzzling, Dr. Fine said.
Potential explanations include the crossover designs of both the RTOG and Avaglio studies, suboptimal delivery of bevacizumab to the tumor, or the possibility that the vascular endothelial growth factor receptor may not be the best target in glioblastoma.
"Despite these new data demonstrating its limitation, I feel very strongly that bevacizumab represents the single most important agent in glioblastoma since temozolomide, and maybe even more so. Ongoing and future trials will better define how and when it should be optimally used in these patients that have such limited therapeutic options," Dr. Fine concluded.
The RTOG 0285 study was supported by the National Cancer Institute, with additional support from Genentech. Avaglio was supported by Roche. Dr. Gilbert disclosed consulting for, and receiving honoraria and research support from, Genentech. Dr. Mason disclosed being a consultant/adviser to Hoffman-La Roche. Dr. Fine reported having no relevant financial disclosures.
CHICAGO – Adding bevacizumab to frontline radiation and temozolomide therapy for glioblastoma produced disappointing results in a double-blind, placebo-controlled phase III trial.
Bevacizumab (Avastin) extended progression-free survival, but did not improve overall survival in the Radiation Therapy Oncology Group (RTOG) 0825 study, and investigators reported that the angiogenesis inhibitor was associated with worse neurocognitve and quality of life outcomes.
Among 637 patients who were randomized, median overall survival reached 16.1 months in those assigned to radiation, temozolomide (Temodar), and placebo, compared with 15.7 months in patients assigned to radiation, temozolomide, and bevacizumab, Dr. Mark R. Gilbert reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.
Median progression-free survival reached 10.7 months in the bevacizumab arm, vs. 7.3 months in the placebo arm, said Dr. Gilbert, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center in Houston. The P value was .0007, but this difference was not statistically significant because of an unusual trial design that split criteria for statistical significance between the two primary outcome measures of overall and progression-free survival. In addition, patients in the bevacizumab arm had significantly worse neurocognitive and overall symptom scores over time.
"We feel that bevacizumab remains an important therapy for our patients with glioblastoma, but the results of this study do not support its frontline use. Rather, it can be reserved as a later treatment," he said at a press briefing prior to his presentation.
Outcomes contrast with Avaglio study
Some results of the publicly funded RTOG 0825 trial run counter to those from the Avaglio study, an industry-sponsored trial whose results were also presented at the ASCO annual meeting.
The Avaglio investigators found that adding bevacizumab to radiotherapy and temozolomide "achieved a clinically meaningful, statistically significant progression-free survival improvement in patients with glioblastoma," Dr. Warren Mason, a neuro-oncologist at the Princess Margaret Hospital in Toronto, reported at another session.
The Avaglio trial, which ran parallel to RTOG 0825 and was very similar in design, showed a quality of life benefit for patients on bevacizumab, but did not look at neurocognitive outcomes.
Median progression-free survival in Avaglio reached 10.6 months in 458 patients in its radiation, temozolomide, and bevacizumab arm, vs. 6.2 months in 463 patients in its radiation, temozolomide, and placebo arm, and the difference was significant (hazard ratio, 0.64; P less than .0001).
However, as in RTOG 0825, median overall survival was virtually identical in both Avaglio trial arms, at 16.8 and 16.7 months, respectively.
Bevacizumab misses RTOG targets
The RTOG trial enrolled neurologically stable patients with glioblastoma who had a Karnofsky performance score of at least 70 and who had tumor tissue samples available for evaluation. They were randomized to receive standard chemoradiation with temozolomide for 3 weeks followed by chemoradiation with temozolomide and either bevacizumab or placebo for 6-12 maintenance cycles.
The treatment type was unblinded at progression, and patients were allowed to cross over, or continue on, bevacizumab. Progression was defined as a greater than 25% increase in tumor area without recent steroid reduction, or worsening of neurologic symptoms.
In a pooled analysis including both study arms, patients with methylation of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) had better median and overall survival than patients with MGMT unmethylated (methylated MGMT is a marker for favorable prognosis). Median overall survival for the MGMT methylated group was 23.2 months, compared with 14.3 months for the unmethylated group (HR in unmethylated tumors, 2.10; P less than .001). Respective median progression-free survival was 14.1 months vs. 8.2 months (HR, 1.67; P less than .001).
(The results of the GLARIUS trial, also reported at this meeting, showed that bevacizumab combined with irinotecan (Camptosar) in chemoradiation was associated with longer progression-free survival than temozolomide chemoradiation in newly diagnosed patients with MGMT-unmethylated glioblastoma. In a preliminary finding from that study, there was a suggestion of an overall survival benefit for the bevacizumab-irinotecan combination.)
As noted, in RTOG 0825, patients in the bevacizumab arm scored significantly worse on a clinical trial battery composite of cognitive function (P = .038), on overall symptom interference with daily activity (P less than .001), and on quality of life cognitive function (P less than .009).
In contrast, patients on bevacizumab in Avaglio had improved quality of life, prolonged preservation of performance scores, and reduced steroid doses compared with controls.
Why the differences?
Dr. Howard A. Fine, director of the brain tumor center at New York University, the invited discussant for RTOG 0825, said that the differences in patient-reported outcomes between the trials may reflect differences in statistical analysis, possibly different analytical methodologies used to query the data, or the lack of neurocognitive data in Avaglio.
Another possibility to account for the worsening neurocognitive function with bevacizumab is the drug’s documented ability to stabilize the blood-brain barrier and decrease MRI gadolinium enhancement, he said. This could mean that patients experience radiographic occult disease progression that does not show up well on brain scans.
Dr. Gilbert and Dr. Fine commented that theoretically at least, glioblastoma should be an ideal target for angiogenesis inhibitors such as bevacizumab, because they display a high degree of vascularity, and endothelial proliferation is part of the pathologic definition of the disease.
But although bevacizumab has been demonstrated to improve response rates and delay progression in recurrent glioblastoma, its relative lack of efficacy in the first line is puzzling, Dr. Fine said.
Potential explanations include the crossover designs of both the RTOG and Avaglio studies, suboptimal delivery of bevacizumab to the tumor, or the possibility that the vascular endothelial growth factor receptor may not be the best target in glioblastoma.
"Despite these new data demonstrating its limitation, I feel very strongly that bevacizumab represents the single most important agent in glioblastoma since temozolomide, and maybe even more so. Ongoing and future trials will better define how and when it should be optimally used in these patients that have such limited therapeutic options," Dr. Fine concluded.
The RTOG 0285 study was supported by the National Cancer Institute, with additional support from Genentech. Avaglio was supported by Roche. Dr. Gilbert disclosed consulting for, and receiving honoraria and research support from, Genentech. Dr. Mason disclosed being a consultant/adviser to Hoffman-La Roche. Dr. Fine reported having no relevant financial disclosures.
CHICAGO – Adding bevacizumab to frontline radiation and temozolomide therapy for glioblastoma produced disappointing results in a double-blind, placebo-controlled phase III trial.
Bevacizumab (Avastin) extended progression-free survival, but did not improve overall survival in the Radiation Therapy Oncology Group (RTOG) 0825 study, and investigators reported that the angiogenesis inhibitor was associated with worse neurocognitve and quality of life outcomes.
Among 637 patients who were randomized, median overall survival reached 16.1 months in those assigned to radiation, temozolomide (Temodar), and placebo, compared with 15.7 months in patients assigned to radiation, temozolomide, and bevacizumab, Dr. Mark R. Gilbert reported in the plenary session at the annual meeting of the American Society of Clinical Oncology.
Median progression-free survival reached 10.7 months in the bevacizumab arm, vs. 7.3 months in the placebo arm, said Dr. Gilbert, professor of neuro-oncology at the University of Texas M.D. Anderson Cancer Center in Houston. The P value was .0007, but this difference was not statistically significant because of an unusual trial design that split criteria for statistical significance between the two primary outcome measures of overall and progression-free survival. In addition, patients in the bevacizumab arm had significantly worse neurocognitive and overall symptom scores over time.
"We feel that bevacizumab remains an important therapy for our patients with glioblastoma, but the results of this study do not support its frontline use. Rather, it can be reserved as a later treatment," he said at a press briefing prior to his presentation.
Outcomes contrast with Avaglio study
Some results of the publicly funded RTOG 0825 trial run counter to those from the Avaglio study, an industry-sponsored trial whose results were also presented at the ASCO annual meeting.
The Avaglio investigators found that adding bevacizumab to radiotherapy and temozolomide "achieved a clinically meaningful, statistically significant progression-free survival improvement in patients with glioblastoma," Dr. Warren Mason, a neuro-oncologist at the Princess Margaret Hospital in Toronto, reported at another session.
The Avaglio trial, which ran parallel to RTOG 0825 and was very similar in design, showed a quality of life benefit for patients on bevacizumab, but did not look at neurocognitive outcomes.
Median progression-free survival in Avaglio reached 10.6 months in 458 patients in its radiation, temozolomide, and bevacizumab arm, vs. 6.2 months in 463 patients in its radiation, temozolomide, and placebo arm, and the difference was significant (hazard ratio, 0.64; P less than .0001).
However, as in RTOG 0825, median overall survival was virtually identical in both Avaglio trial arms, at 16.8 and 16.7 months, respectively.
Bevacizumab misses RTOG targets
The RTOG trial enrolled neurologically stable patients with glioblastoma who had a Karnofsky performance score of at least 70 and who had tumor tissue samples available for evaluation. They were randomized to receive standard chemoradiation with temozolomide for 3 weeks followed by chemoradiation with temozolomide and either bevacizumab or placebo for 6-12 maintenance cycles.
The treatment type was unblinded at progression, and patients were allowed to cross over, or continue on, bevacizumab. Progression was defined as a greater than 25% increase in tumor area without recent steroid reduction, or worsening of neurologic symptoms.
In a pooled analysis including both study arms, patients with methylation of the DNA repair enzyme O6-methylguanine-DNA methyltransferase (MGMT) had better median and overall survival than patients with MGMT unmethylated (methylated MGMT is a marker for favorable prognosis). Median overall survival for the MGMT methylated group was 23.2 months, compared with 14.3 months for the unmethylated group (HR in unmethylated tumors, 2.10; P less than .001). Respective median progression-free survival was 14.1 months vs. 8.2 months (HR, 1.67; P less than .001).
(The results of the GLARIUS trial, also reported at this meeting, showed that bevacizumab combined with irinotecan (Camptosar) in chemoradiation was associated with longer progression-free survival than temozolomide chemoradiation in newly diagnosed patients with MGMT-unmethylated glioblastoma. In a preliminary finding from that study, there was a suggestion of an overall survival benefit for the bevacizumab-irinotecan combination.)
As noted, in RTOG 0825, patients in the bevacizumab arm scored significantly worse on a clinical trial battery composite of cognitive function (P = .038), on overall symptom interference with daily activity (P less than .001), and on quality of life cognitive function (P less than .009).
In contrast, patients on bevacizumab in Avaglio had improved quality of life, prolonged preservation of performance scores, and reduced steroid doses compared with controls.
Why the differences?
Dr. Howard A. Fine, director of the brain tumor center at New York University, the invited discussant for RTOG 0825, said that the differences in patient-reported outcomes between the trials may reflect differences in statistical analysis, possibly different analytical methodologies used to query the data, or the lack of neurocognitive data in Avaglio.
Another possibility to account for the worsening neurocognitive function with bevacizumab is the drug’s documented ability to stabilize the blood-brain barrier and decrease MRI gadolinium enhancement, he said. This could mean that patients experience radiographic occult disease progression that does not show up well on brain scans.
Dr. Gilbert and Dr. Fine commented that theoretically at least, glioblastoma should be an ideal target for angiogenesis inhibitors such as bevacizumab, because they display a high degree of vascularity, and endothelial proliferation is part of the pathologic definition of the disease.
But although bevacizumab has been demonstrated to improve response rates and delay progression in recurrent glioblastoma, its relative lack of efficacy in the first line is puzzling, Dr. Fine said.
Potential explanations include the crossover designs of both the RTOG and Avaglio studies, suboptimal delivery of bevacizumab to the tumor, or the possibility that the vascular endothelial growth factor receptor may not be the best target in glioblastoma.
"Despite these new data demonstrating its limitation, I feel very strongly that bevacizumab represents the single most important agent in glioblastoma since temozolomide, and maybe even more so. Ongoing and future trials will better define how and when it should be optimally used in these patients that have such limited therapeutic options," Dr. Fine concluded.
The RTOG 0285 study was supported by the National Cancer Institute, with additional support from Genentech. Avaglio was supported by Roche. Dr. Gilbert disclosed consulting for, and receiving honoraria and research support from, Genentech. Dr. Mason disclosed being a consultant/adviser to Hoffman-La Roche. Dr. Fine reported having no relevant financial disclosures.
AT THE ASCO ANNUAL MEETING 2013
Major finding: Median overall survival for those assigned to radiation, temozolomide, and placebo was 16.1 months, vs. 15.7 months for patients assigned to radiation, temozolomide, and bevacizumab in one study.
Data source: A randomized, double-blind placebo controlled trial in 637 patients with newly diagnosed glioblastoma.
Disclosures: The RTOG 0285 study was supported by the National Cancer Institute, with additional support from Genentech. Avaglio was supported by Roche. Dr. Gilbert disclosed consulting for, and receiving honoraria and research support from, Genentech. Dr. Mason disclosed that he was a consultant/adviser to Hoffman-La Roche. Dr. Fine reported having no relevant financial disclosures.
Bevacizumab plus irinotecan beats temozolomide in stalling glioblastoma
CHICAGO – The combination of bevacizumab and irinotecan far outshone tenozolomide in delaying disease progression among patients with MGMT-unmethylated glioblastoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
In the phase II GLARIUS trial, 79.6% of patients treated with bevacizumab (Avastin) and irinotecan (Camptosar) were free of progression at 6 months, compared with 41.3% of patients randomized to receive temozolmide (Temodar) (P less than .0001), reported Dr. Ulrich Herrlinger from the department of neurology at University Clinic of Bonn, Germany.
Progression-free survival at 6 months (PFS-6) was the study's primary endpoint.
A preliminary analysis also hinted at a potential overall survival advantage for the bevacizumab-irinotecan (BEV/IRI) combination. After nearly 50% of patients in each arm had died, median overall survival was 16.6 months for the BEV/IRI group, compared with 14.8 months for the temozolomide group (hazard ratio, 0.60; P = .031).
"Obviously we did not harm our patients by omitting temozolomide and choosing something different, BEV/IRI, for treating these patients," Dr. Herrlinger said.
The combination is a promising alternative to temozolomide therapy in patients with with MGMT (O6-methylguanine-DNA methyltransferase)-unmethylated glioblastoma, he said. About 55%-65% of newly diagnosed glioblastomas are not methylated by MGMT, a DNA repair enzyme, and these have a worse prognosis than those in which MGMT promotes methylation, according to Dr. Herrlinger.
Investigators at 22 centers in Germany tested patients with glioblastoma for MGMT status, and randomized a total of 182 patients with newly diagnosed, histologically confirmed MGMT-unmethylated glioblastoma. Of these, 170 received at least one course of drug therapy and were evaluable for response; these patients were included in the analysis.
All patients received 60 Gy localized radiation in 30 fragments of 2 Gy each. They were randomized 2:1 to BEV-IRI (116 patients) or temozolomide (54 patients).
The experimental arm received bevacizumab 10 mg/kg every 2 weeks during radiotherapy followed by maintenance bevacizumab at the same dose and irinotecan 125 mg/m2 every 2 weeks without or with enzyme-inducing antiepileptic drugs at a dose of 340 mg/m2. The standard therapy arm was given temozolomide 75 mg/m2 daily during radiotherapy, followed by 6 courses of temozolomide 150-200 mg/m2 for 5 days every 4 weeks.
In addition to the advantage in progression-free survival at 6 months, median progression-free survival also was longer with BEV/IRI: 9.74 months vs. 6 months in patients treated with temozolomide (HR 0.30, P less than .0001).
In addition patients on the combination used fewer mean daily steroids than patients on temozolomide.
The safety analysis showed that grade 3 or 4 vascular disorders – including deep vein thrombosis, pulmonary embolism, and hypertension – occurred in 10.9% of patients on BEV/IRI, compared with 3.6% of those on temozolomide. The combination was also associated with more grade 3 or 4 diarrhea and nausea, wound infections, and proteinuria. However, hematotoxicity was higher among patients on temozolomide, occurring in 14.8%, compared with 1.7% of patients on BEV/IRI.
"I think it’s important to recognize that there is a [bevacizumab] toxicity signal," said Dr Albert Lai, a neuro-oncologist at the University of California, Los Angeles, who was the invited discussant.
Dr. Lai commented that the overall survival signal seen by the GLARIUS investigators may have been affected by an optional crossover to BEV/IRI after disease progression on temozolomide. Of the 54 patients in the temozolomide arm, 29 crossed over to BEV/IRI.
The GLARIUS trial was sponsored by Hoffman-La Roche. Dr. Herrlinger disclosed being a consultant and speaker and receiving research support from the company. Dr. Lai disclosed serving as a consultant and receiving research funding from Genentech/Roche.
CHICAGO – The combination of bevacizumab and irinotecan far outshone tenozolomide in delaying disease progression among patients with MGMT-unmethylated glioblastoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
In the phase II GLARIUS trial, 79.6% of patients treated with bevacizumab (Avastin) and irinotecan (Camptosar) were free of progression at 6 months, compared with 41.3% of patients randomized to receive temozolmide (Temodar) (P less than .0001), reported Dr. Ulrich Herrlinger from the department of neurology at University Clinic of Bonn, Germany.
Progression-free survival at 6 months (PFS-6) was the study's primary endpoint.
A preliminary analysis also hinted at a potential overall survival advantage for the bevacizumab-irinotecan (BEV/IRI) combination. After nearly 50% of patients in each arm had died, median overall survival was 16.6 months for the BEV/IRI group, compared with 14.8 months for the temozolomide group (hazard ratio, 0.60; P = .031).
"Obviously we did not harm our patients by omitting temozolomide and choosing something different, BEV/IRI, for treating these patients," Dr. Herrlinger said.
The combination is a promising alternative to temozolomide therapy in patients with with MGMT (O6-methylguanine-DNA methyltransferase)-unmethylated glioblastoma, he said. About 55%-65% of newly diagnosed glioblastomas are not methylated by MGMT, a DNA repair enzyme, and these have a worse prognosis than those in which MGMT promotes methylation, according to Dr. Herrlinger.
Investigators at 22 centers in Germany tested patients with glioblastoma for MGMT status, and randomized a total of 182 patients with newly diagnosed, histologically confirmed MGMT-unmethylated glioblastoma. Of these, 170 received at least one course of drug therapy and were evaluable for response; these patients were included in the analysis.
All patients received 60 Gy localized radiation in 30 fragments of 2 Gy each. They were randomized 2:1 to BEV-IRI (116 patients) or temozolomide (54 patients).
The experimental arm received bevacizumab 10 mg/kg every 2 weeks during radiotherapy followed by maintenance bevacizumab at the same dose and irinotecan 125 mg/m2 every 2 weeks without or with enzyme-inducing antiepileptic drugs at a dose of 340 mg/m2. The standard therapy arm was given temozolomide 75 mg/m2 daily during radiotherapy, followed by 6 courses of temozolomide 150-200 mg/m2 for 5 days every 4 weeks.
In addition to the advantage in progression-free survival at 6 months, median progression-free survival also was longer with BEV/IRI: 9.74 months vs. 6 months in patients treated with temozolomide (HR 0.30, P less than .0001).
In addition patients on the combination used fewer mean daily steroids than patients on temozolomide.
The safety analysis showed that grade 3 or 4 vascular disorders – including deep vein thrombosis, pulmonary embolism, and hypertension – occurred in 10.9% of patients on BEV/IRI, compared with 3.6% of those on temozolomide. The combination was also associated with more grade 3 or 4 diarrhea and nausea, wound infections, and proteinuria. However, hematotoxicity was higher among patients on temozolomide, occurring in 14.8%, compared with 1.7% of patients on BEV/IRI.
"I think it’s important to recognize that there is a [bevacizumab] toxicity signal," said Dr Albert Lai, a neuro-oncologist at the University of California, Los Angeles, who was the invited discussant.
Dr. Lai commented that the overall survival signal seen by the GLARIUS investigators may have been affected by an optional crossover to BEV/IRI after disease progression on temozolomide. Of the 54 patients in the temozolomide arm, 29 crossed over to BEV/IRI.
The GLARIUS trial was sponsored by Hoffman-La Roche. Dr. Herrlinger disclosed being a consultant and speaker and receiving research support from the company. Dr. Lai disclosed serving as a consultant and receiving research funding from Genentech/Roche.
CHICAGO – The combination of bevacizumab and irinotecan far outshone tenozolomide in delaying disease progression among patients with MGMT-unmethylated glioblastoma, an investigator reported at the annual meeting of the American Society of Clinical Oncology.
In the phase II GLARIUS trial, 79.6% of patients treated with bevacizumab (Avastin) and irinotecan (Camptosar) were free of progression at 6 months, compared with 41.3% of patients randomized to receive temozolmide (Temodar) (P less than .0001), reported Dr. Ulrich Herrlinger from the department of neurology at University Clinic of Bonn, Germany.
Progression-free survival at 6 months (PFS-6) was the study's primary endpoint.
A preliminary analysis also hinted at a potential overall survival advantage for the bevacizumab-irinotecan (BEV/IRI) combination. After nearly 50% of patients in each arm had died, median overall survival was 16.6 months for the BEV/IRI group, compared with 14.8 months for the temozolomide group (hazard ratio, 0.60; P = .031).
"Obviously we did not harm our patients by omitting temozolomide and choosing something different, BEV/IRI, for treating these patients," Dr. Herrlinger said.
The combination is a promising alternative to temozolomide therapy in patients with with MGMT (O6-methylguanine-DNA methyltransferase)-unmethylated glioblastoma, he said. About 55%-65% of newly diagnosed glioblastomas are not methylated by MGMT, a DNA repair enzyme, and these have a worse prognosis than those in which MGMT promotes methylation, according to Dr. Herrlinger.
Investigators at 22 centers in Germany tested patients with glioblastoma for MGMT status, and randomized a total of 182 patients with newly diagnosed, histologically confirmed MGMT-unmethylated glioblastoma. Of these, 170 received at least one course of drug therapy and were evaluable for response; these patients were included in the analysis.
All patients received 60 Gy localized radiation in 30 fragments of 2 Gy each. They were randomized 2:1 to BEV-IRI (116 patients) or temozolomide (54 patients).
The experimental arm received bevacizumab 10 mg/kg every 2 weeks during radiotherapy followed by maintenance bevacizumab at the same dose and irinotecan 125 mg/m2 every 2 weeks without or with enzyme-inducing antiepileptic drugs at a dose of 340 mg/m2. The standard therapy arm was given temozolomide 75 mg/m2 daily during radiotherapy, followed by 6 courses of temozolomide 150-200 mg/m2 for 5 days every 4 weeks.
In addition to the advantage in progression-free survival at 6 months, median progression-free survival also was longer with BEV/IRI: 9.74 months vs. 6 months in patients treated with temozolomide (HR 0.30, P less than .0001).
In addition patients on the combination used fewer mean daily steroids than patients on temozolomide.
The safety analysis showed that grade 3 or 4 vascular disorders – including deep vein thrombosis, pulmonary embolism, and hypertension – occurred in 10.9% of patients on BEV/IRI, compared with 3.6% of those on temozolomide. The combination was also associated with more grade 3 or 4 diarrhea and nausea, wound infections, and proteinuria. However, hematotoxicity was higher among patients on temozolomide, occurring in 14.8%, compared with 1.7% of patients on BEV/IRI.
"I think it’s important to recognize that there is a [bevacizumab] toxicity signal," said Dr Albert Lai, a neuro-oncologist at the University of California, Los Angeles, who was the invited discussant.
Dr. Lai commented that the overall survival signal seen by the GLARIUS investigators may have been affected by an optional crossover to BEV/IRI after disease progression on temozolomide. Of the 54 patients in the temozolomide arm, 29 crossed over to BEV/IRI.
The GLARIUS trial was sponsored by Hoffman-La Roche. Dr. Herrlinger disclosed being a consultant and speaker and receiving research support from the company. Dr. Lai disclosed serving as a consultant and receiving research funding from Genentech/Roche.
AT ASCO ANNUAL MEETING 2013
Major finding: The 6-month progression-free survival 6 months after randomization was 79.6% for patients treated with bevacizumab and irinotecan vs. 41.3% with temozolomide.
Data source: Randomized controlled trial in 170 patients with MGMT-unmethylated glioblastoma from 22 centers in Germany.
Disclosures: The GLARIUS trial was sponsored by Hoffman-La Roche. Dr. Herrlinger disclosed being a consultant and speaker and receiving research support from the company. Dr. Lai disclosed serving as a consultant and receiving research funding from Genentech/Roche.
Oral HPV-related cancer risk not transmitted to sex partners
CHICAGO – Partners of patients with human papillomavirus-positive oropharyngeal cancer do not appear to be at an increased risk for HPV-related cancers, investigators reported at the annual meeting of the American Society of Clinical Oncology.
Of 88 female partners of persons with HPV-positive oropharyngeal cancers, 4 were found to be positive for HPV infection, and 2 of the 4 were positive for the oncogenic HPV-16 subtype. The prevalence of HPV infection in this sample was 5%, similar to that of women in the general population (3.6%), reported Gypsyamber D’Souza, Ph.D., an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.
None of the male partners in this small pilot study tested positive for oral HPV 16, but the male sample size was too small to draw significant conclusions about the risks of HPV transmission in men, Dr. D’Souza said.
"This is the first study to examine oral HPV prevalence among spouses of HPV-related oropharyngeal cancer patients, and it’s very reassuring that the oral HPV prevalence was similar to that observed in the general population. This suggests that risk of HPV-related cancer remains low among these spouses," she said in a media briefing prior to her presentation.
The study also supports epidemiologic data showing that although HPV infections are common in the general population, the overwhelming majority of people who are infected will spontaneously clear the virus and not get cancer.
"We certainly will need longer follow-up on how HPV infection and co-infection in the partners will affect patients and the development of cancer, but we recognize this as an important breakthrough in the understanding of the biology of oropharyngeal cancer," commented Dr. Gregory Masters, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Del., who moderated the briefing.
Dr. Marcia S. Brose, a head and neck surgeon at the Hospital of the University of Pennsylvania in Philadelphia, said that despite the handful of male partners, the study sends an important message to patients and their partners.
"As oncologists, we’re not just in the business of the disease itself; we also have to treat the family members and their concerns. If you’re the spouse of someone who has a communicable disease-related cancer, you’re going to have to make decisions that affect your private life, and it means a lot that someone is doing the research that says you don’t have to worry," she said in an interview.
The study was prompted by concerns frequently expressed by patients with oropharyngeal cancer and their spouses/sexual partners about oral transmission of HPV and increased cancer risk, Dr. D’Souza said.
The investigators enrolled 147 men and 19 women (median age 56) with oropharyngeal cancers, and 94 of their spouses or long-term partners.
Oral rinse and gargle samples were collected from all cases and partners in the study at baseline and 1 year later. The samples were tested for the presence of HPV DNA. Imperfect as it is in sensitivity and specificity for HPV, the test is nonetheless the gold standard for detecting HPV in oral cancers, Dr. D’Souza said.
At the time of diagnosis, 65% of patients tested positive for HPV, and 54% of all patients had HPV 16.
At 1 year, however, following completion of therapy, only 5.6% of patients still tested positive for HPV 16.
Overall, the prevalence of oral HPV among partners was 6.5%, comparable to HPV prevalence among the general population in National Health and Nutrition Examination Survery (NHANES) data from 2009-2010. Among male partners, the prevalence of HPV also was similar to that seen among men in the general population (10.1%), but the small number made it difficult if not impossible to draw meaningful conclusions.
No oral or oropharyngeal cancers were detected in partners in an oral cancer screen, but three patients reported having previous partners with oropharyngeal cancer. In addition, five male patients reported having a partner who developed cervical cancer or a precancerous condition (one current partner and two previous partners had cervical cancers, and two current partners had cervical dysplasia).
The study was supported by the Johns Hopkins Innovation Fund. Dr. D’Souza reported receiving research support from Merck, maker of Gardasil.
CHICAGO – Partners of patients with human papillomavirus-positive oropharyngeal cancer do not appear to be at an increased risk for HPV-related cancers, investigators reported at the annual meeting of the American Society of Clinical Oncology.
Of 88 female partners of persons with HPV-positive oropharyngeal cancers, 4 were found to be positive for HPV infection, and 2 of the 4 were positive for the oncogenic HPV-16 subtype. The prevalence of HPV infection in this sample was 5%, similar to that of women in the general population (3.6%), reported Gypsyamber D’Souza, Ph.D., an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.
None of the male partners in this small pilot study tested positive for oral HPV 16, but the male sample size was too small to draw significant conclusions about the risks of HPV transmission in men, Dr. D’Souza said.
"This is the first study to examine oral HPV prevalence among spouses of HPV-related oropharyngeal cancer patients, and it’s very reassuring that the oral HPV prevalence was similar to that observed in the general population. This suggests that risk of HPV-related cancer remains low among these spouses," she said in a media briefing prior to her presentation.
The study also supports epidemiologic data showing that although HPV infections are common in the general population, the overwhelming majority of people who are infected will spontaneously clear the virus and not get cancer.
"We certainly will need longer follow-up on how HPV infection and co-infection in the partners will affect patients and the development of cancer, but we recognize this as an important breakthrough in the understanding of the biology of oropharyngeal cancer," commented Dr. Gregory Masters, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Del., who moderated the briefing.
Dr. Marcia S. Brose, a head and neck surgeon at the Hospital of the University of Pennsylvania in Philadelphia, said that despite the handful of male partners, the study sends an important message to patients and their partners.
"As oncologists, we’re not just in the business of the disease itself; we also have to treat the family members and their concerns. If you’re the spouse of someone who has a communicable disease-related cancer, you’re going to have to make decisions that affect your private life, and it means a lot that someone is doing the research that says you don’t have to worry," she said in an interview.
The study was prompted by concerns frequently expressed by patients with oropharyngeal cancer and their spouses/sexual partners about oral transmission of HPV and increased cancer risk, Dr. D’Souza said.
The investigators enrolled 147 men and 19 women (median age 56) with oropharyngeal cancers, and 94 of their spouses or long-term partners.
Oral rinse and gargle samples were collected from all cases and partners in the study at baseline and 1 year later. The samples were tested for the presence of HPV DNA. Imperfect as it is in sensitivity and specificity for HPV, the test is nonetheless the gold standard for detecting HPV in oral cancers, Dr. D’Souza said.
At the time of diagnosis, 65% of patients tested positive for HPV, and 54% of all patients had HPV 16.
At 1 year, however, following completion of therapy, only 5.6% of patients still tested positive for HPV 16.
Overall, the prevalence of oral HPV among partners was 6.5%, comparable to HPV prevalence among the general population in National Health and Nutrition Examination Survery (NHANES) data from 2009-2010. Among male partners, the prevalence of HPV also was similar to that seen among men in the general population (10.1%), but the small number made it difficult if not impossible to draw meaningful conclusions.
No oral or oropharyngeal cancers were detected in partners in an oral cancer screen, but three patients reported having previous partners with oropharyngeal cancer. In addition, five male patients reported having a partner who developed cervical cancer or a precancerous condition (one current partner and two previous partners had cervical cancers, and two current partners had cervical dysplasia).
The study was supported by the Johns Hopkins Innovation Fund. Dr. D’Souza reported receiving research support from Merck, maker of Gardasil.
CHICAGO – Partners of patients with human papillomavirus-positive oropharyngeal cancer do not appear to be at an increased risk for HPV-related cancers, investigators reported at the annual meeting of the American Society of Clinical Oncology.
Of 88 female partners of persons with HPV-positive oropharyngeal cancers, 4 were found to be positive for HPV infection, and 2 of the 4 were positive for the oncogenic HPV-16 subtype. The prevalence of HPV infection in this sample was 5%, similar to that of women in the general population (3.6%), reported Gypsyamber D’Souza, Ph.D., an epidemiologist at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Md.
None of the male partners in this small pilot study tested positive for oral HPV 16, but the male sample size was too small to draw significant conclusions about the risks of HPV transmission in men, Dr. D’Souza said.
"This is the first study to examine oral HPV prevalence among spouses of HPV-related oropharyngeal cancer patients, and it’s very reassuring that the oral HPV prevalence was similar to that observed in the general population. This suggests that risk of HPV-related cancer remains low among these spouses," she said in a media briefing prior to her presentation.
The study also supports epidemiologic data showing that although HPV infections are common in the general population, the overwhelming majority of people who are infected will spontaneously clear the virus and not get cancer.
"We certainly will need longer follow-up on how HPV infection and co-infection in the partners will affect patients and the development of cancer, but we recognize this as an important breakthrough in the understanding of the biology of oropharyngeal cancer," commented Dr. Gregory Masters, a medical oncologist at the Helen F. Graham Cancer Center in Newark, Del., who moderated the briefing.
Dr. Marcia S. Brose, a head and neck surgeon at the Hospital of the University of Pennsylvania in Philadelphia, said that despite the handful of male partners, the study sends an important message to patients and their partners.
"As oncologists, we’re not just in the business of the disease itself; we also have to treat the family members and their concerns. If you’re the spouse of someone who has a communicable disease-related cancer, you’re going to have to make decisions that affect your private life, and it means a lot that someone is doing the research that says you don’t have to worry," she said in an interview.
The study was prompted by concerns frequently expressed by patients with oropharyngeal cancer and their spouses/sexual partners about oral transmission of HPV and increased cancer risk, Dr. D’Souza said.
The investigators enrolled 147 men and 19 women (median age 56) with oropharyngeal cancers, and 94 of their spouses or long-term partners.
Oral rinse and gargle samples were collected from all cases and partners in the study at baseline and 1 year later. The samples were tested for the presence of HPV DNA. Imperfect as it is in sensitivity and specificity for HPV, the test is nonetheless the gold standard for detecting HPV in oral cancers, Dr. D’Souza said.
At the time of diagnosis, 65% of patients tested positive for HPV, and 54% of all patients had HPV 16.
At 1 year, however, following completion of therapy, only 5.6% of patients still tested positive for HPV 16.
Overall, the prevalence of oral HPV among partners was 6.5%, comparable to HPV prevalence among the general population in National Health and Nutrition Examination Survery (NHANES) data from 2009-2010. Among male partners, the prevalence of HPV also was similar to that seen among men in the general population (10.1%), but the small number made it difficult if not impossible to draw meaningful conclusions.
No oral or oropharyngeal cancers were detected in partners in an oral cancer screen, but three patients reported having previous partners with oropharyngeal cancer. In addition, five male patients reported having a partner who developed cervical cancer or a precancerous condition (one current partner and two previous partners had cervical cancers, and two current partners had cervical dysplasia).
The study was supported by the Johns Hopkins Innovation Fund. Dr. D’Souza reported receiving research support from Merck, maker of Gardasil.
AT THE ASCO ANNUAL MEETING 2013
Major finding: The prevalence of human papillomavirus infections is 5% among female partners of patients with HPV-related oropharyngeal cancers and 3.6% in the general population of women.
Data source: Pilot surveillance study of 166 people with oropharyngeal cancer and 94 of their spouses/long-term partners.
Disclosures: The study was supported by the Johns Hopkins Innovation Fund. Dr. D'Souza reported receiving research support from Merck, maker of Gardasil.
Funding cuts imperil cancer advances
CHICAGO – Publicly funded research in oncology has great potential for reducing the costs of health care. Over the last 10 years, however, funding has dropped off appreciably.
In an exclusive interview at the annual meeting of the American Society of Clinical Oncology, Dr. Monica M. Bertagnolli, group chair of the Alliance for Clinical Trials in Oncology, discusses how cost-saving advances in oncology are being affected by the cut backs.
CHICAGO – Publicly funded research in oncology has great potential for reducing the costs of health care. Over the last 10 years, however, funding has dropped off appreciably.
In an exclusive interview at the annual meeting of the American Society of Clinical Oncology, Dr. Monica M. Bertagnolli, group chair of the Alliance for Clinical Trials in Oncology, discusses how cost-saving advances in oncology are being affected by the cut backs.
CHICAGO – Publicly funded research in oncology has great potential for reducing the costs of health care. Over the last 10 years, however, funding has dropped off appreciably.
In an exclusive interview at the annual meeting of the American Society of Clinical Oncology, Dr. Monica M. Bertagnolli, group chair of the Alliance for Clinical Trials in Oncology, discusses how cost-saving advances in oncology are being affected by the cut backs.
AT THE ASCO ANNUAL MEETING 2013
Amitriptyline eases functional dyspepsia symptoms
ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.
ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.
ORLANDO – Amitriptyline, but not escitalopram, significantly topped a placebo to provide sustained symptom relief in some patients with functional dyspepsia, based on early results of the Functional Dyspepsia Treatment Trial.
Approximately half (53%) of patients with functional dyspepsia who were randomized to the tricyclic antidepressant (TCA) amitriptyline reported at least 5 weeks of symptom relief, compared with 38% of patients randomized to the selective serotonin reuptake inhibitor (SSRI) escitalopram and 40% of patients on placebo, reported Dr. Nicholas J. Talley of the Mayo Clinic in Rochester, Minn.
Patients with normal gastric emptying had significantly better relief with amitriptyline than did patients with delayed gastric emptying (P = .006). This finding supported data from a separate study presented at the annual Digestive Disease Week, which showed that another TCA, nortriptyline, was not effective for symptom relief in patients with gastroparesis.
"Our data with amitriptyline also appears, based on at least the first cut of the data, to be negative in slow gastric emptying, which really overlaps with gastroparesis. I don’t think we should be using this drug class in those sorts of patients unless they are depressed or if there is some other indication," Dr. Talley said in an interview.
In the Functional Dyspepsia Treatment Trial (FDTT), investigators at seven centers in the United States and one in Canada screened 400 patients with functional dyspepsia and enrolled a total of 292 patients with a mean age of 44 years. Of these, 208 had dysmotilitylike dyspepsia, characterized by satiety or fullness, and 88 had ulcerlike dyspepsia, characterized by epigastric pain.
Patients were randomized to a placebo, 10 mg escitalopram, or 25 mg amitriptyline during a 2-week run-in phase, followed by 50 mg amitriptyline for a total of 12 weeks. They were evaluated at baseline with gastric-emptying tests, nutrient drink tests, and blood draws; a subset of patients also underwent evaluation of gastric accommodation by single-photon emission computed tomography.
In an intent-to-treat analysis, amitriptyline met the primary endpoint of patient-rated adequate relief for 5 weeks or more (P = .005, vs. placebo and escitalopram each). A treatment response was defined as a report of adequate relief for at least 50% of the 10-week treatment period.
However, when the primary endpoint was broken down by functional dyspepsia subtype, the treatment effect trended toward significance, but did not reach it. Among patients with dysmotilitylike dyspepsia, 46% of those on amitriptyline, 43% on escitalopram, and 41% on placebo reported sustained relief. In the ulcerlike dyspepsia group, the respective rates of reported relief were 67%, 27%, and 39%.
There were no significant differences in reported response rates between men and women, or between obese and nonobese patients, the researchers noted.
In a partial analysis of the Nepean Dyspepsia Index, patients on amitriptyline scored significantly better in the change from baseline on the quality of life sleep disturbance subscale compared with the other treatment groups (P = .01), but not on other quality of life subscales.
Other secondary endpoints, including ratings scales for bowel disease and dyspepsia symptom severity, mood, sleep, and overall clinical impressions were still under evaluation and would be reported at a later date, Dr, Talley said.
The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he was previously a consultant to the company.
AT DDW 2013
Major finding: In a clinical trial, 53% of patients with functional dyspepsia assigned to amitriptyline reported at least 5 weeks of symptom relief compared with 38% of patients on escitalopram and 40% on placebo.
Data source: A prospective, randomized, double-blind double-dummy study of 292 patients with functional dyspepsia.
Disclosures: The study was sponsored by the National Institutes of Health. Escitalopram was donated by Forest Laboratories. Dr. Talley disclosed that he served as a consultant to the company.
Onsite cytopathology improves pancreatic biopsy quality
ORLANDO – Having a cytopathologist on hand during an ultrasound-guided biopsy of the pancreas can increase the likelihood of getting it right on the first try, according to results from a randomized controlled trial reported at the annual Digestive Disease Week.
Among 131 patients at three clinical centers who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic masses, those randomized to procedures with on-site cytopathology (CyP+) had a significantly higher proportion of biopsies deemed suspicious or malignant than did those randomized to biopsies with no cytopathologist immediately at hand.
Patients with on-site cytopathology also were significantly more likely to have adequate specimens taken, and to require fewer EUS-FNA passes per procedure, reported Dr. Sachin Wani, of the University of Colorado Anschutz Medical Center in Aurora, and his colleagues.
Biopsies performed with cytopathologists present took about 4 minutes longer to perform, however.
Investigators in three tertiary care centers in Missouri and Colorado randomly assigned patients with pancreatic masses to undergo EUS-FNA with cytopathology on-site, with the number of needle passes determined by the judgment of the adequacy of the sample by the pathologist (maximum of 10) or the same procedure with 7 passes, with cytopathology performed later.
At each center, all final pathology slides were reviewed by cytopathologists using standard criteria for both cytologic characteristics and final cytologic diagnosis.
Cytologic criteria include adequacy of the sample, amount of blood, cellularity, and contamination. The final diagnosis categories were benign, atypical, suspicious, malignant, or inadequate.
Although more patients in the CyP+ group were diagnosed with a malignancy (80.3% vs. 67.7%), this difference was not significant. However, when samples deemed to be suspicious were included, on-site cytopathologists identified significantly more samples than pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
In addition, more patients in the CyP+ group had adequate specimens (93.9% vs. 81.5%; P = .03), and these specimens were acquired with significantly fewer median needle passes (three vs. seven; P less than .001).
CyP+ biopsies took an average of 23.4 minutes, compared with 19.1 minutes for biopsies with later pathology review (P = .04). But the time to review slides was significantly shorter when the cytopathologist was present (16.4 vs. 27.7 minutes; P less than .001).
Dr. Wani noted that his presentation was based on an interim analysis of an ongoing study, and that pathology readings were left to the individual treatment centers, with no central pathology performed.
The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
ORLANDO – Having a cytopathologist on hand during an ultrasound-guided biopsy of the pancreas can increase the likelihood of getting it right on the first try, according to results from a randomized controlled trial reported at the annual Digestive Disease Week.
Among 131 patients at three clinical centers who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic masses, those randomized to procedures with on-site cytopathology (CyP+) had a significantly higher proportion of biopsies deemed suspicious or malignant than did those randomized to biopsies with no cytopathologist immediately at hand.
Patients with on-site cytopathology also were significantly more likely to have adequate specimens taken, and to require fewer EUS-FNA passes per procedure, reported Dr. Sachin Wani, of the University of Colorado Anschutz Medical Center in Aurora, and his colleagues.
Biopsies performed with cytopathologists present took about 4 minutes longer to perform, however.
Investigators in three tertiary care centers in Missouri and Colorado randomly assigned patients with pancreatic masses to undergo EUS-FNA with cytopathology on-site, with the number of needle passes determined by the judgment of the adequacy of the sample by the pathologist (maximum of 10) or the same procedure with 7 passes, with cytopathology performed later.
At each center, all final pathology slides were reviewed by cytopathologists using standard criteria for both cytologic characteristics and final cytologic diagnosis.
Cytologic criteria include adequacy of the sample, amount of blood, cellularity, and contamination. The final diagnosis categories were benign, atypical, suspicious, malignant, or inadequate.
Although more patients in the CyP+ group were diagnosed with a malignancy (80.3% vs. 67.7%), this difference was not significant. However, when samples deemed to be suspicious were included, on-site cytopathologists identified significantly more samples than pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
In addition, more patients in the CyP+ group had adequate specimens (93.9% vs. 81.5%; P = .03), and these specimens were acquired with significantly fewer median needle passes (three vs. seven; P less than .001).
CyP+ biopsies took an average of 23.4 minutes, compared with 19.1 minutes for biopsies with later pathology review (P = .04). But the time to review slides was significantly shorter when the cytopathologist was present (16.4 vs. 27.7 minutes; P less than .001).
Dr. Wani noted that his presentation was based on an interim analysis of an ongoing study, and that pathology readings were left to the individual treatment centers, with no central pathology performed.
The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
ORLANDO – Having a cytopathologist on hand during an ultrasound-guided biopsy of the pancreas can increase the likelihood of getting it right on the first try, according to results from a randomized controlled trial reported at the annual Digestive Disease Week.
Among 131 patients at three clinical centers who underwent endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) of pancreatic masses, those randomized to procedures with on-site cytopathology (CyP+) had a significantly higher proportion of biopsies deemed suspicious or malignant than did those randomized to biopsies with no cytopathologist immediately at hand.
Patients with on-site cytopathology also were significantly more likely to have adequate specimens taken, and to require fewer EUS-FNA passes per procedure, reported Dr. Sachin Wani, of the University of Colorado Anschutz Medical Center in Aurora, and his colleagues.
Biopsies performed with cytopathologists present took about 4 minutes longer to perform, however.
Investigators in three tertiary care centers in Missouri and Colorado randomly assigned patients with pancreatic masses to undergo EUS-FNA with cytopathology on-site, with the number of needle passes determined by the judgment of the adequacy of the sample by the pathologist (maximum of 10) or the same procedure with 7 passes, with cytopathology performed later.
At each center, all final pathology slides were reviewed by cytopathologists using standard criteria for both cytologic characteristics and final cytologic diagnosis.
Cytologic criteria include adequacy of the sample, amount of blood, cellularity, and contamination. The final diagnosis categories were benign, atypical, suspicious, malignant, or inadequate.
Although more patients in the CyP+ group were diagnosed with a malignancy (80.3% vs. 67.7%), this difference was not significant. However, when samples deemed to be suspicious were included, on-site cytopathologists identified significantly more samples than pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
In addition, more patients in the CyP+ group had adequate specimens (93.9% vs. 81.5%; P = .03), and these specimens were acquired with significantly fewer median needle passes (three vs. seven; P less than .001).
CyP+ biopsies took an average of 23.4 minutes, compared with 19.1 minutes for biopsies with later pathology review (P = .04). But the time to review slides was significantly shorter when the cytopathologist was present (16.4 vs. 27.7 minutes; P less than .001).
Dr. Wani noted that his presentation was based on an interim analysis of an ongoing study, and that pathology readings were left to the individual treatment centers, with no central pathology performed.
The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
AT DDW 2013
Major finding: Onsite cytopathologists identified significantly more samples as suspicious or malignant than did pathologists who examined samples after the fact (87.9% vs. 70.8%; P = .01).
Data source: A randomized controlled trial conducted with 131 patients at three clinical centers.
Disclosures: The study was supported by a clinical research award from the American College of Gastroenterology. Dr. Wani reported having no financial disclosures.
Drug combo curbs organ failures in acute pancreatitis patients
ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
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ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
ORLANDO – Adding celecoxib to octreotide within 48 hours of onset of acute pancreatitis may reduce the risk of progression to severe acute disease and its consequences, based on data from a randomized controlled trial of more than 300 patients.
The findings were presented at the annual Digestive Disease Week.
Overall, 25.6% of patients predicted to progress to severe acute pancreatitis (SAP) who were assigned to octreotide (Sandostatin) alone had organ failure at day 8, compared with 12.9% who received both octreotide and celecoxib (Celebrex), reported Dr. Rui Wang of West China Hospital, Sichuan University, in Chengdu, China.
In addition, 36.7% of patients on octreotide-only had CT severity index (CTSI) scores of 6 or greater at day 8, compared with 15.1% of patients on octreotide and celecoxib combined.
"Celecoxib exerted special effects on reducing incidences of pulmonary failure, acute respiratory distress syndrome, and encephalopathy," Dr. Wang said.
Dr. Wang and colleagues hypothesized that celecoxib may decrease serum levels of the inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor–alpha (TNF-alpha), and increase levels of the anti-inflammatory interleukin-10 (IL-10).
To see whether celecoxib could augment the anti-inflammatory action of octreotide, an analogue of the endogenous anti-inflammatory peptide somatostatin, the investigators conducted a study of high-dose octreotide and somatostatin in patients with predicted or actual SAP.
They enrolled 195 patients with predicted SAP, defined as an Acute Physiology and Chronic Health Evaluation II (APACHE II) score greater than 8, and a multiorgan failure (MOF) score lower than 2; and 159 patients with SAP, defined as an APACHE II score greater than 8 and a MOF score of 2 or greater.
Patients in each disease category were randomized within 48 hours to receive either octreotide alone in an IV infusion at 50 mcg/hour for 3 days, and then 25 mcg/hour for 4 days, or to the same 7-day octreotide regimen plus 200 mg of oral celecoxib twice daily.
Patients with predicted SAP who received the combination had less than half the rate of progression to SAP (P = .001) and half the rate of organ failure (P = .030).
Among patients with frank SAP, there were no significant differences between octreotide alone and octreotide/celecoxib for organ failure, local complications, CTSI or MOF scores, or length of hospital stay, the researchers noted.
Compared with octreotide alone, the addition of celecoxib significantly reduced day 8 rates of acute respiratory distress syndrome (ARDS) (24% vs. 11%, respectively; P = .037), and encephalopathy (16% vs. 5.5%; P = .039).
With regard to the secondary outcome of plasma cytokine levels, the researchers found that octreotide alone or combined with celecoxib similarly restored somatostatin levels to normal by day 8.
The investigators also found that the combination therapy, but not octreotide alone, normalized plasma levels of both IL-6 and TNF-alpha (P less than .05 over baseline), and that IL-10 levels were markedly increased in both groups, although the combination treatment significantly outperformed octreotide-only (P less than .05).
The findings suggest that early treatment with a combination of octreotide and celecoxib may prevent progression to SAP and also ameliorate both ARDS and encephalopathy through simultaneous down-regulation of inflammatory cytokines and promotion of the anti-inflammatory IL-10, the researchers noted.
The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.
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Major finding: The combination of octreotide and celecoxib halved rates of organ failure and disease progression in patients with acute pancreatitis.
Data source: A randomized controlled trial of patients with severe acute pancreatitis and those at risk for it.
Disclosures: The funding source was not disclosed. Dr. Wang and colleagues reported having no financial disclosures.