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 c ancer received LY231514 600 mg/m(2) as a 10-minute infusion every three wee ks. Results: Forty-two patients were enrolled in this phase II trial. The media n age was 60.3 (range 37-77) years; 79% had metastatic disease. Neutropenia was common (40% of patients greater than or equal to grade 3) but infectio us complications were rare. Significant anemia or thrombocytopenia occurred in < 20% of patients. Non-hematologic toxicities included grade 2 or 3 ski n reaction which was ameliorated by dexamethasone. Elevations of bilirubin or transaminases were infrequent (< 25% of patients) and did not require do se reductions or treatment delays. Thirty-five patients received two cycles of therapy and were evaluable for response. One complete (duration 16.2 mo nths) and one partial (duration 6.9 months) were observed resulting in an o bjective response rate of 5.7% for evaluable patients. In addition, 17 pati ents (40%) had stable disease that lasted greater than or equal to 6 months in 5 patients. The median survival was 6.5 months, with 28% of patients al ive at one year. Conclusions: LY231514 is a well-tolerated agent with minimal objective anti tumor activity in pancreatic cancer. The median and one year survival times , which may be important indicators in phase II trials of new agents, are o f interest. Combination trials of LY231514 in pancreatic cancer are planned .