The role of pemetrexed in the treatment of colorectal cancer

Advanced colorectal cancer is a leading cause of cancer-related morbidity and mortality. Chemotherapeutic options, however, have recently expanded with concomitant improvements in survival. Through the 1980s and early 1990s research focused mainly on the major fluoropyrimidine, 5-fluorouracil, a thymidylate synthase inhibitor, and methods to enhance its activity through scheduling changes or by biochemical modulation. Pemetrexed is a novel antifolate that inhibits several folate-dependent enzymes in addition to thymidylate synthase. This agent has theoretical and preclinical advantages over fluoropyrimidines and specifically acting antifolates. Phase II studies have shown a broad spectrum of activity in solid tumors, including colorectal cancer. Further studies at higher doses with the use of vitamin supplementation may be desirable. Combinations of pemetrexed with irinotecan and oxaliplatin have also proven feasible. Pemetrexed is a promising new drug for the treatment of colorectal cancer.