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.
Dr. Somnath Mukherjee
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.
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