A randomised trial comparing 5-FU with 5-FU plus cisplatin in advanced pancreatic carcinoma.

BACKGROUND: Chemotherapy is moderately efficient as a treatment for pancreatic adenocarcinoma, but patient survival and quality of life has improved with this modality in some trials. In a previous phase II trial, 5-fluorouracil (5-FU) plus cisplatin (FUP) yielded a 26.5% response rate and a 29% survival rate at 1 year. The present study aimed to compare FUP with 5-FU alone, which was the control arm in former Mayo Clinic trials. PATIENTS AND METHODS: Patients with untreated cytologically or histologically proven metastatic or locally advanced adenocarcinoma of the pancreas were deemed measurable or evaluable. Chemotherapy regimens consisted of a control FU arm (5-FU 500 mg/m(2)/day for 5 days) and the investigational FUP arm (continuous 5-FU 1000 mg/m(2)/day for 5 days plus cisplatin 100 mg/m(2) on day 1 or day 2). In both arms, chemotherapy was repeated at day 29. RESULTS: Two-hundred and seven patients from 18 centres were randomised: 103 in the FU arm and 104 in FUP arm. Treatment arms were balanced with respect to performance status grade 0-1 (83% versus 86%, respectively) and the presence of metastases (92% versus 89%, respectively). The median number of cycles administered was two in both arms (range 0-14). Five patients did not receive any chemotherapy and 45 received only one cycle. Toxicity (WHO grade 3-4) was lower with FU than with FUP (20% versus 48%, P <0.001), as was neutropenia (6% versus 23%), vomiting (4% versus 17%) and toxicity-related deaths (one versus four early in the trial). The response rate was low in both arms, but superior in the FUP arm: 12% versus 0% (intention-to-treat analysis, P <0.01). The survival rates at 6 months were 28% and 38% for the FU and FUP arms, respectively, and 1-year survival rates were 9% and 17% (log-rank test, P = 0.10). One-year progression-free survival was 0% with FU versus 10% with FUP (log-rank test, P = 0.0001). CONCLUSIONS: In advanced pancreatic carcinomas with a poor prognosis, FUP was superior to FU in terms of response and progression-free survival, but not in terms of overall survival. The low response rate is partly related to the number of patients who received only one cycle of chemotherapy. A more effective, better tolerated version of this FUP combination is needed.