Phase I study of twice-weekly gemcitabine and concomitant external-beam radiotherapy in patients with adenocarcinoma of the pancreas

Purpose: To determine the maximum tolerated dose and dose-limiting toxicity associated with twice-weekly gemcitabine and concomitant external-beam rad iotherapy in patients with adenocarcinoma of the pancreas. Methods and Materials: Twenty-one patients with biopsy-proven adenocarcinom a of the pancreas were treated mt external-beam radiotherapy to a dose of 5 0.4 Gy in 28 fractions, concurrent with gemcitabine, infused over 30 min be fore irradiation on a Monday and Thursday schedule. The dose of gemcitabine was escalated in 5 cohorts of 3-6 patients each. initial gemcitabine dose was 10 mg/m(2), with dose escalation until dose-limiting toxicity was obser ved. Results: The maximum tolerated dose of gemcitabine was 50 mg/m(2), when giv en in a twice-weekly schedule with radiation. Dose-limiting toxicity was se en in 2 patients at 60 mg/m(2), and consisted of severe upper gastrointesti nal bleeding approximately 1 month after completion of treatment. Six patie nts had radiographic evidence of response to treatment, and 5 of these unde rwent complete surgical resection. Three patients who underwent complete re section had been deemed to have unresectable tumors before enrollment on tr ial. Four patients are alive, including 2 without evidence of disease more than 1 year after resection. Conclusion: The combination of external-beam radiation and twice-weekly gem citabine at a dose of 50 mg/m(2) is well tolerated and shows promising acti vity for the treatment of pancreatic cancer. Our data suggest a higher maxi mum tolerated dose and different dose-limiting toxicity than previously rep orted. Further investigation of this regimen is warranted. (C) 2001 Elsevie r Science Inc.