A randomized phase II trial of pemetrexed plus irinotecan (ALIRI) versus leucovorin-modulated 5-FU plus irinotecan (FOLFIRI) in first-line treatment of locally advanced or metastatic colorectal cancer.

This multicenter, randomized trial compared overall response rate between pemetrexed plus irinotecan (ALIRI) and leucovorin-modulated 5-fluorouracil plus irinotecan (FOLFIRI) in patients with advanced colorectal cancer. Secondary objectives included overall and progression-free survival, duration of response, toxicities, and biomarkers.ALIRI patients received pemetrexed 500 mg/m(2) and irinotecan 350 mg/m(2) with vitamin supplementation on day 1 of each 21-day cycle. FOLFIRI patients received irinotecan 180 mg/m(2) on days 1, 15, 29; on days 1, 2, 15, 16, 29, 30, patients received leucovorin 200 mg/m(2), bolus 5-fluorouracil 400 mg/m(2), and 5-fluorouracil 600 mg/m(2) as 22-hour infusion.Of 132 patients randomly assigned, 130 patients (64 = ALIRI, 66 = FOLFIRI) received > or =1 dose of treatment. Response rates (ALIRI = 20.0%, FOLFIRI = 33.3%) were not significantly different between arms (p = 0.095). Progression-free survival was 5.7 months for ALIRI and 7.7 months for FOLFIRI (p < 0.001). Neutropenia, fatigue, diarrhea, nausea, and vomiting were the major toxicities. There were 5 drug-related deaths (ALIRI = 4, FOLFIRI = 1). Biomarker analysis failed to reveal that any of the 18 preselected genes were clearly associated with tumor response.Neither efficacy nor safety improved on the ALIRI arm compared to the FOLFIRI arm. Progression-free survival on FOLFIRI was significantly longer compared to ALIRI. Potential biomarkers capable of predicting response to either regimen in advanced or metastatic colorectal carcinoma need further characterization.