Phase II study of biweekly pemetrexed plus irinotecan as second-line therapy for metastatic colorectal cancer

Background. this open-label,single-arm,two-stage,phase ii study investigated the efficacy and safety of bi-weekly pemetrexed combined with irinotecan,in patients with metastatic colorectal cancer (mcrc),after first-line chemotherapy using folfox regimen. patients and methods. patients received pemetrexed 400 mg/m2 as a 10-minute intravenous infusion (with vitamin supplementation) followed by irinotecan 180 mg/m as a 90-minute infusion on day 1 of a 14-day cycle,for a maximum of 12 cycles. the primary endpoint was response rate (rr; h0 ≤ 5%,ha ≥ 20%,α = 0.05,power = 90%). secondary endpoints were duration of response,progression-free survival (pfs),overall survival (os),and toxicities. results. partial response was observed in six out of 44 patients enrolled in the study (rr = 13.6%). the median pfs and os were 4.0 and 13.9 months,respectively. the most common grade 3-4 toxicities were fatigue: 20.5% of patients,neutropenia: 18.6%,diarrhea: 13.6%,elevated transaminases: 9.5%,anemia: 9.3%,and vomiting: 6.8%. conclusion. pemetrexed plus irinotecan administered every two weeks is an active and well-tolerated regimen in mcrc patients pretreated with folfox regimen. however,this regimen does not seem to provide clinically relevant advantage over historical data of a classical folfiri regimen. © 2010 c. louvet et al.