Phase II study of the multitargeted antifolate LY231514 (ALIMTA(TM), MTA, pemetrexed disodium) in patients with advanced pancreatic cancer

Purpose: To determine the safety and activity of LY231514 (ALIMTA(TM), MTA, pemetrexed disodium, Eli Lilly and Co., Indianapolis, IN) in chemotherapy-naive patients with advanced pancreatic cancer. Patients and methods: Patients with unresectable or metastatic pancreatic cancer received LY231514 600 mg/m² as a 10-minute infusion every three weeks. Results: Forty-two patients were enrolled in this phase II trial. The median age was 60.3 (range 37-77) years; 79% had metastatic disease. Neutropenia was common (40% of patients ≥ grade 3) but infectious complications were rare. Significant anemia or thrombocytopenia occurred in < 20% of patients. Non- hematologic toxicities included grade 2 or 3 skin reaction which was ameliorated by dexamethasone. Elevations of bilirubin or transaminases were infrequent (< 25% of patients) and did not require dose reductions or treatment delays. Thirty-five patients received two cycles of therapy and were evaluable for response. One complete (duration 16.2 months) and one partial (duration 6.9 months) were observed resulting in an objective response rate of 5.7% for evaluable patients. In addition, 17 patients (40%) had stable disease that lasted ≥6 months in 5 patients. The median survival was 6.5 months, with 28% of patients alive at one year. Conclusions: LY231514 is a well-tolerated agent with minimal objective antitumor activity in pancreatic cancer. The median and one year survival times, which may be important indicators in phase II trials of new agents, are of interest. Combination trials of LY231514 in pancreatic cancer are planned.