Trimetrexate: experience with solid tumors.
Trimetrexate (TMTX), a potent inhibitor of the enzyme dihydrofolate reductase, is biochemically and metabolically similar to methotrexate (MTX). Fundamental differences between TMTX and MTX, however, mandate investigation of TMTX in both MTX-sensitive and MTX-resistant tumors. In a number of phase II clinical trials, the antitumor activity of single-agent TMTX has been variable, in part because of the heterogeneity of doses and schedules used and in part because of diverse patient populations. Single-agent activity has been documented in some commonly occurring tumors, including breast, non-small cell lung, and head and neck cancers. Other tumors with sensitivity to single-agent TMTX include transitional cell carcinomas of the urothelium, prostate cancer, and gastric carcinoma. In a small series of children with renal cell carcinoma, significant clinical activity was suggested. The single-agent activity of TMTX, coupled with the finding that TMTX may act as a biochemical modulator of 5-fluorouracil/leucovorin, suggests that the addition of TMTX to 5-fluorouracil/leucovorin should be investigated further. The possibility that TMTX may both exhibit single-agent activity and modulate the effectiveness of other agents makes combination therapy attractive.
Haller
D G
DG
Department of Medicine, University of Pennsylvania Cancer Center, The University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use*; D001943:Breast Neoplasms / Q000188:drug therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy*; D002986:Clinical Trials as Topic; D004938:Esophageal Neoplasms / Q000188:drug therapy; D005493:Folic Acid Antagonists / Q000627:therapeutic use*; D006258:Head and Neck Neoplasms / Q000188:drug therapy; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy*; D010190:Pancreatic Neoplasms / Q000188:drug therapy; D013274:Stomach Neoplasms / Q000188:drug therapy; D016597:Trimetrexate / Q000627:therapeutic use*
D000964:Antimetabolites, Antineoplastic; D005493:Folic Acid Antagonists; D016597:Trimetrexate