Eastern Cooperative Oncology Group Phase I Trial of Protracted Venous Infusion Fluorouracil Plus Weekly Gemcitabine With Concurrent Radiation Therapy in Patients With Locally Advanced Pancreas Cancer: A Regimen With Unexpected Early Toxicity

作者：Mark S. Talamonti, Paul J. Catalano, David J. Vaughn, Richard Whittington, Robert Daniel Beauchamp, Jordan D. Berlin, Al B. Benson · 发表于：Journal of Clinical Oncology · 年份：2000 · DOI：10.1200/jco.2000.18.19.3384 · 被引用次数：124 · 研究领域：Pancreatic and Hepatic Oncology Research、Colorectal and Anal Carcinomas、Colorectal Cancer Treatments and Studies

PURPOSE: We performed a phase I trial of protracted venous infusion (PVI) fluorouracil (5-FU) plus weekly gemcitabine with concurrent radiation therapy in patients with locally advanced pancreas cancer to determine the maximum-tolerated dose of gemcitabine that could be safely administered. We also sought to identify the toxicities associated with this treatment protocol. PATIENTS AND METHODS: Seven patients with locally advanced pancreas cancer were treated with planned doses of radiation (59.4 Gy) and PVI of 5-FU (200 mg/m(2)/d) with gemcitabine doses of 50 to 100 mg/m(2)/wk. RESULTS: Two of three patients at the 100-mg/m(2)/wk dose level experienced dose-limiting toxicity (DLT), as did three of four at the 50-mg/m(2)/wk dose level. One patient experienced a mucocutaneous reaction described as a Stevens-Johnson syndrome that was attributed to chemotherapy. Three patients developed gastric or duodenal ulcers with severe bleeding requiring transfusion. One patient developed severe thrombocytopenia lasting longer than 4 weeks. Three of the five episodes of DLT developed at radiation doses < or = 36 Gy. CONCLUSION: Based on this experience, we cannot recommend further investigation of regimens incorporating gemcitabine into regimens of radiation with PVI 5-FU. The mechanism of this synergistic toxicity remains to be determined.