HIGH-DOSE FOLINIC ACID AND FLUOROURACIL WITH OR WITHOUT IFOSFAMIDE ISAN INACTIVE COMBINATION IN ADVANCED PANCREATIC-CANCER - A RANDOMIZED PHASE-II STUDY OF THE ITALIAN ONCOLOGY GROUP FOR CLINICAL RESEARCH (GOIRC)

The Italian Oncology Group for Clinical Research (GOIRC) randomized 55 naive patients with advanced pancreatic cancer (APC) between intraven ous fluorouracil (5FU) 400 mg/m(2), days 1-5 and folinic acid (FA) 200 mg/m(2), days 1-5 alone, using Machover's schedule, or with FU, FA, a nd ifosfamide (IFO) 5 g/m(2), day 1 and Mesna. In both arms, treatment was repeated every 28 days. Fifty-one patients were evaluable for res ponse. The overall response rate was 6% (3 out of 51), 1 out of 29 (3% ) complete response (CR) in the arm with FU plus FA, and 2 out of 22 ( 9%) partial responses (PR) in the arm with IFO. The duration of respon se rate was 39, 55, and 74 weeks, respectively. Median survival time w as 21 weeks (range, 4-83 weeks) for 5FU/FA and 16 weeks (range, 3-106 weeks) for the FU/FA/IFO arm. Diarrhea, mucositis, and vomiting occurr ed in the majority of patients. One patient died due to toxicity. The combination of 5FU plus FA failed to demonstrate therapeutic activity in patients with APC and was associated with moderate to severe toxici ty that could lower the quality of life of these patients. Ifosfamide did not potentiate the activity of this combination. Neither of these combinations should be considered for treatment of patients with APC.