Phase I trial of twice-weekly gemcitabine and concurrent radiation in patients with advanced pancreatic cancer

Purpose: To determine the maximum-tolerated dose, dose-limiting toxicities, and potential antitumor activity of twice-weekly gemcitabine and concurren t radiation in patients with locally advanced pancreatic cancer, Patients and Methods: Nineteen patients with histologically confirmed adeno carcinoma of the pancreas were studied at the Wake Forest University Baptis t Medical Center and the University of North Carolina at Chapel Hill, The i nitial dose of gemcitabine was 20 mg/m(2) by 30-minute intravenous infusion each Monday and Thursday for 5 weeks concurrent with 50.4 Gy of radiation to the pancreas. Gemcitabine doses were escalated in 20-mg/m(2) increments in successive cohorts of three to six additional patients until dose-limiti ng toxicity was observed, Results: The dose-limiting toxicities at 60 mg/m(2) given twice-weekly were nausea/vomiting, neutropenia, and thrombocytopenia. Twice-weekly gemcitabi ne at a 40-mg/m(2) dose was well tolerated, Of the eight patients eligible for a minimum follow-up of 12 months, three remain alive, one of whom has n o evidence of disease progression, Conclusion: A dose of twice-weekly gemcitabine at 40 mg/m(2) produced mild thrombocytopenia, neutropenia, nausea, and vomiting when delivered with con current radiation to the upper abdomen in patients with advanced pancreatic cancer. These data suggest this regimen is well tolerated and may possess significant activity. There data and other observations have resulted in a phase II Cancer and Leukemia Group B study to ascertain the efficacy of thi s treatment regimen in patients with locally advanced pancreatic cancer. (C ) 1999 by American Society of Clinical Oncology.