The role of pemetrexed in the treatment of gastrointestinal malignancy.
Although advanced colorectal cancer (CRC) is a leading cause of morbidity and mortality in the United States and Europe, chemotherapeutic options have only 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 (TS) 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 TS. This agent has theoretical and preclinical advantages over fluoropyrimidines and more specific antifolates. Phase II studies have shown a broad spectrum of activity in solid tumors, including CRC and pancreatic cancer. Combinations of pemetrexed with gemcitabine, irinotecan, and oxaliplatin have also proven feasible. Further studies of higher and biweekly doses with the use of vitamin supplementation are under way. In pancreatic cancer, the phase II studies of pemetrexed and gemcitabine were sufficiently promising to warrant a completed phase III comparison. Based on a recent abstract presentation, it appears that this combination did not improve survival compared with gemcitabine alone. Nonetheless, pemetrexed has important promise for new and improved regimens in the therapy of gastrointestinal cancer.
Hochster
Howard S
HS
New York University School of Medicine, New York 10016, USA. howard.hochster@med.nyu.edu
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D005971:Glutamates / Q000627:therapeutic use*; D006147:Guanine / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D006801:Humans; D010190:Pancreatic Neoplasms / Q000188:drug therapy*; D000068437:Pemetrexed
D000964:Antimetabolites, Antineoplastic; D005971:Glutamates; D000068437:Pemetrexed; D006147:Guanine