Pemetrexed and oxaliplatin for metastatic colorectal cancer: results of a phase I Mayo Cancer Center Research Consortium trial, MC0248
Clinical Colorectal Cancer
Chemotherapy; Thymidylate synthase; Time to progression
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 (> 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.
Alberts, S., Kim, G., Mahoney, M., Gornet, M., Rubin, J., Ames, M., Goetz, M., Weinshilboum, R., Nicol, S., & Goldberg, R. (2007). Pemetrexed and oxaliplatin for metastatic colorectal cancer: results of a phase I Mayo Cancer Center Research Consortium trial, MC0248. Clinical Colorectal Cancer, 6 (8). http://dx.doi.org/10.3816/CCC.2007.n.024