Cisplatin, cytarabine, caffeine, and continuously infused 5-fluorouracil (PACE) in the treatment of advanced pancreatic carcinoma - A phase II study

Encouraging results using cisplatin, cytarabine, and caffeine for the treat ment of pancreatic carcinoma prompted a phase II study using these agents a nd adding continuous intravenous infusion (CI) 5-fluorouracil (5-FU) (PACE) . Patients with advanced pancreatic adenocarcinoma who had not received pri or cytotoxic therapy were eligible. Treatment consisted of the following: o n day 1, the administration of cisplatin 100 mg/m(2) IV, cytarabine 2 g/m(2 ) IV every 12 hours X 2 doses, and caffeine 400 mg/m(2) subcutaneously afte r each cytarabine dose; and on days 3 to 21, 5-FU 250 mg/m(2)/day given by CI. Cycles were repeated every 28 days. Thirty eligible patients were enter ed in the study. The median number of cycles received was three. Grade IV n eutropenia and thrombocytopenia occurred in 53% and 27% of patients, respec tively. Among 30 treated patients, complete remission (CR) was seen in 2 pa tients and partial remission (PR) in 3 patients, for an overall response ra te of 16.7% (95% confidence interval 6.8-32.4%). The median survival was 5. 0 months (range: 0.3-32.4 months) and 16.7% and 10% of patients were alive at 1 and 2 years, respectively. Changes in the serum level of CA 19-9 provi ded an early marker of response which translated in differences in survival . Those with increasing or decreasing/stable levels of CA 19-9 after the fi rst cycle of therapy had median survivals of 1.7 and 8.3 months, respective ly (p = 0.0002). Although PACE chemotherapy produced durable responses in p ancreatic cancer, the toxicity was substantial. A modification of this regi men with newer, less toxic drugs may provide better results and reduced tox icity. Also, the monitoring of the serum CA 19-9 level may provide a means to assess response and predict survival.