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 the safety profile of multitargeted antifolate (MTA) for patients with metastatic colorectal adenocarcinoma. METHODS: Forty-six patients were enrolled in the study, 35 with colon and 11 with rectal carcinoma. Adjuvant therapy was allowed if completed 1 year previously. Patients received MTA 600 mg/m(2) as a 10-minute intravenous infusion once every 21 days. Blood samples were taken every cycle for pharmacokinetic and vitamin metabolite assays. RESULTS: Among 39 patients eligible for efficacy analysis, 1 complete response and 5 partial responses were identified, for an overall response rate of 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 at 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 criteria (CTC) Grades 3 or 4 noted as follows: thrombocytopenia (18%), neutropenia (55%), and anemia (18%). Nonhematologic toxicities included Grade 2 or 3 skin reaction (53%), ameliorated by dexamethasone, and Grade 3 transaminases (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. MTA was well tolerated in this patient group, but myelosuppression was frequent. Toxicity may be increased with folate deficiency.