Activity of multitargeted antifolate (Pemetrexed disodium, LY231514) in patients with advanced colorectal carcinoma - Results from a phase II study

BACKGROUND. The aim of this study was to confirm the activity and assess th e safety profile of multitargeted antifolate (MTA) for patients with metast atic colorectal adenocarcinoma. METHODS, Forty-six patients were enrolled in the study, 35 with colon and 1 1 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year p reviously. Patients received MTA 600 mg/m(2) as a 10-minute intravenous inf usion once every 21 days. Blood samples were taken every cycle for pharmaco kinetic and vitamin metabolite assays. RESULTS. Among 39 patients eligible for efficacy analysis, 1 complete respo nse and 5 partial responses were identified, for an overall response rate o f 15.4% (95% confidence interval [CI], 4.1-26.7%) for all patients. Fifteen patients had stable disease, with 9 living longer than 1 year. The median survival was 16.2 months (95% CI, 10.5-17.0%); 65% of patients were alive a t 1 year, and the median time to progression was 4.4 months (range, 3.2-5.7 months). The main toxicities were hematologic, with common toxicity criter ia (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropeni a (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminase s (23%). Dose omissions were not required and 21% of doses were reduced. CONCLUSIONS, MTA has clear activity in patients with colorectal carcinoma, and encouraging survival times were noted. MW was well tolerated in this pa tient group, but myelosuppression was frequent. Toxicity may be increased w ith folate deficiency. Cancer 2000;88:1807-13. (C) 2000 American Cancer Soc iety.