Pemetrexed and oxaliplatin for metastatic colorectal cancer: results of a phase I Mayo Cancer Center Research Consortium trial, MC0248

Purpose: Pemetrexed, an antifolate involved in purine and pyrimidine formation, is a potential alternative to fluoropyrimidines in the treatment of colorectal cancer. A phase I trial was performed to establish the maximum tolerated dose (MTD) of pemetrexed and oxaliplatin when B12 and folate supplementation is used. Patients and Methods: Patients with metastatic colorectal cancer received folate (\u3e 350 μg) daily and vitamin B 12 (1000 pg) every 9 weeks starting 7 days before chemotherapy. Pemetrexed over 10 minutes and oxaliplatin over 2 hours were given every 3 weeks in escalating dose cohorts. Results: Twenty-two patients were entered on 6 dose levels. The MTD was established at the highest dose level, pemetrexed 900 mg/m2 and oxaliplatin 130 mg/m2. Toxicities related to treatment at the MTD included grade 3 neutropenia and thrombocytopenia. For all dose levels combined, grade 3/4 toxicities included hematologic, neurologic, and gastrointestinal. Nine of 21 evaluable patients responded overall (response rate, 43%). The time to tumor progression was 11.9 months. Conclusion: The MTD was determined to be pemetrexed 900 mg/m2 and oxaliplatin 130 mg/m2 every 21 days when folate and B12 supplementation are used. Because of the observed tolerability and activity of this regimen, further evaluation is warranted