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SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
The primary endpoint of this study was progression-free survival at 9 months, but keep in mind that all the patients received the same induction chemotherapy for 4 months, and the same radiotherapy dose, but with the sole difference of being either on capecitabine or low-dose gemcitabine during the 6 weeks of radiotherapy. The use of this primary endpoint, therefore, challenges our ability to properly ask a regular standardization question and must make us think about how best to choose endpoints that are more informative in this multimodality treatment setting in a complex disease.
The efficacy and toxicity parameters favored capecitabine. The impact of subject selection is beautifully illustrated by a table that showed almost doubling in survival in patients who made it to randomization versus those who were taken off the study.
What does SCALOP tell us? The major take-home message confirms the feasibility of the common practice of using capecitabine concurrently with radiotherapy in patients with pancreatic cancer. A number of other factors may have contributed to the differences in outcome, such as proportion of males to females. Several important questions remain in this disease, including the role of chemoradiation.
Ultimately we have to find better systemic therapies. However, one of the most important things in my mind is that we have to design trials to include primary endpoints that stick with the question we are asking. There are different questions we can ask in pancreatic cancer, but each question should have a specific design and a specific endpoint.
Dr. Philip A. Philip is leader of the gastrointestinal cancer multidisciplinary team, and a professor of medicine and oncology, at Wayne State University, Detroit. These were among his comments as discussant of Dr. Mukherjee’s study at the meeting. Dr. Philip disclosed having financial relationships with many pharmaceutical companies including Eli Lilly, Roche, and Genentech.
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
SAN FRANCISCO – Following induction chemotherapy with radiotherapy plus capecitabine seemed to be equally effective and less toxic compared with following with radiotherapy plus gemcitabine in a randomized trial of 74 patients with locally advanced pancreatic cancer.
The multicenter phase II clinical trial randomized 36 patients to radiotherapy plus capecitabine (Xeloda, Roche/Genentech) and 38 to radiotherapy plus gemcitabine (Gemzar, Eli Lilly) after induction chemotherapy. Analysis of the primary outcome, progression-free survival after 9 months, included 35 evaluable patients in each group. No disease progression was noted in 62% of patients in the capecitabine-radiotherapy arm and in 51% in the gemcitabine-radiotherapy arm, Dr. Somnath Mukherjee reported.
The median time to disease progression was 12 months in patients given capecitabine-radiotherapy and 10.4 months in those given gemcitabine-radiotherapy. The differences between groups in progression-free survival were not statistically significant, Dr. Mukherjee and his associates said at a meeting on gastrointestinal cancers sponsored by the American Society of Clinical Oncology.
Based on secondary outcomes, however, capecitabine-radiotherapy seemed to show some advantages, including less toxicity and improved overall survival, said Dr. Mukherjee of the University of Oxford, England.
None of the patients in the capecitabine-radiotherapy arm and 18% of those in the gemcitabine-radiotherapy arm had grade 3 or 4 hematologic adverse events. The rates of nonhematologic adverse events were similarly lower with capecitabine-radiotherapy, 12%, than with gemcitabine-radiotherapy, 26%. Median overall survival was 15.2 months in the capecitabine-radiotherapy group and 13.4 months in the gemcitabine-radiotherapy group.
There is no consensus on the optimal treatment for locally advanced pancreatic cancer, Dr. Mukherjee said. Previous trials of chemotherapy alone or chemoradiotherapy suggest a median survival of 10 months. One meta-analysis suggested that gemcitabine-based chemoradiotherapy might be more effective but also more toxic compared with chemoradiotherapy based on 5-fluoruracil. No prior study has compared gemcitabine-radiotherapy with capecitabine-radiotherapy, he added.
The study, known as the SCALOP trial, initially registered 114 patients, but excluded 40 patients from randomization due to disease progression (15 patients), the clinician’s decision (10 patients), the patient’s decision (9), death (5), or because the patient shouldn’t have been eligible for the trial (1). Among randomized patients, median overall survival was 14.6 months, and 78% were alive after 1 year. Among nonrandomized patients, median survival was 8.1 months, and 17% were alive at 1 year.
All 114 registered patients were to receive three cycles of induction chemotherapy with gemcitabine plus capecitabine. The investigators then randomized 74 patients to the two groups, all of whom received another cycle of gemcitabine-capecitabine chemotherapy before starting radiation therapy plus either gemcitabine or capecitabine.
Among 35 patients on capecitabine-radiotherapy and 36 on gemcitabine-radiotherapy who had follow-up data at 26 weeks, the pancreatic cancer showed a complete response, partial response, or stable disease in 86% of each treatment group. The proportions of patients who became eligible for surgical resection after radiotherapy were 6% in the capecitabine group and 10% in the gemcitabine group.
Any kind of grade 3 or 4 toxicities occurred in 12% on capecitabine-radiotherapy and in 37% on gemcitabine-chemotherapy.
Males comprised 47% of the capecitabine-radiotherapy arm and 63% of the gemcitabine-radiotherapy arm. The median patient age was 63 years in the capecitabine group and 66 years in the gemcitabine group.
Meeting cosponsors were the American Gastroenterological Association Institute, the American Society for Radiation Oncology, and the Society of Surgical Oncology.
Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Sanofi, or Roche, which markets capecitabine through its subsidiary, Genentech.
On Twitter @sherryboschert
AT A MEETING ON GASTROINTESTINAL CANCERS SPONSORED BY THE AMERICAN SOCIETY OF CLINICAL ONCOLOGY
Major Finding: Median progression-free survival after 9 months of follow-up was 12 months in 35 patients given capecitabine plus radiotherapy after induction chemotherapy and 10.4 months in patients given gemcitabine plus radiotherapy following induction chemotherapy.
Data Source: A multicenter trial that randomized 74 patients with locally advanced pancreatic cancer.
Disclosures: Dr. Mukherjee has been a consultant or adviser to Celgene. Some of his associates reported financial relationships with Merck/Serono, Roche, or Sanofi.
