NEW YORKA regimen of twice-weekly gemcitabine(Drug information on gemcitabine) (Gemzar) plus radiation therapy in patients with unresectable pancreatic cancer appears promising, according to results of a phase I dose escalation study presented at the Chemotherapy Foundation Symposium XVII. The twice-weekly delivery may be more cytotoxic than standard once-weekly dosing, and gemcitabine may act as a radiation sensitizer, said A. William Blackstock, MD, assistant professor of Radiation Oncology, Wake Forest University, Winston-Salem, NC.
Laboratory studies have confirmed that gemcitabine is a potent radiation sensitizer, and ongoing studies of the gemcitabine-radiation interaction are expected to shed more light on the underlying mechanism, he said.
In this study, Dr. Blackstock and his colleagues escalated gemcitabine from 20 mg/m² to a maximum tolerated dose of 60 mg/m². The agent was given as a 30-minute IV infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation delivered over the course of 5 days. The optimal schedule was to give gemcitabine within 72 hours of delivery of radiation. Dose-limiting toxicities were nausea and vomiting, neutropenia, and thrombocytopenia.
At 40 mg/m², the regimen was well tolerated, although thrombocytopenia frequently necessitated a break in treatment during the third week. Median survival in the 19-patient group was an encouraging 12.3 months, Dr. Blackstock said.
Based on these findings, a phase II trial has been initiated through the Cancer and Leukemia Group B (CALGB) to evaluate the efficacy of twice-weekly gemcitabine plus radiation in locally advanced unresectable pancreatic cancer. A second phase II study is looking at the same approach as adjuvant therapy following surgery in resectable pancreatic cancer.