Pemetrexed/Oxaliplatin for First-Line Treatment of Patients with Advanced Colorectal Cancer: A Phase II Trial of the National Surgical Adjuvant Breast and Bowel Project Foundation Research Program

Background Pemetrexed and oxaliplatin have clinical activity as single agents in colorectal cancer (response rates, 10%-17%). In this study, these drugs were used in combination as first-line therapy in a group of patients with metastatic colorectal cancer. Patients and Methods Fifty-four evaluable patients were to receive pemetrexed (500 mg/m2) with folic acid and vitamin B12 supplementation and oxaliplatin (120 mg/m2) every 21 days for 6 cycles or until disease progression occurred. Patients with stable or responding disease could continue therapy beyond 6 cycles at the discretion of the investigator. Eligibility criteria included a diagnosis of untreated metastatic adenocarcinoma of the colon or rectum, measurable disease, Zubrod performance status ≤2, no adjuvant chemotherapy within 6 months, and ≥12 weeks life expectancy. Results The confirmed clinical response rate (primary endpoint) was 29.6% (95% confidence interval [CI], 18%-48.6%), with 1 complete response and 15 partial responses. Median time to progression was 5.3 months (95% CI, 3.9–6.3 months), and median survival was 12.3 months (95% CI, 8.6–17 months). Grade 3/4 nadir neutropenia occurred in 33.3% of patients, and 3 patients experienced grade 3 febrile neutropenia or infection associated with grade 3/4 neutropenia. Grade 3/4 nadir thrombocytopenia was seen in 11.1% of patients. Only 4% of the patients developed grade 3/4 neurotoxicity. Conclusion This regimen of pemetrexed and oxaliplatin has activity in advanced colorectal cancer, and the toxicity profile suggests that escalation of the dose of pemetrexed in this combination may be possible.