Trimetrexate: experience with solid tumors.

Abstract

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.

• Authors: D G Haller
• Journal: Seminars in oncology (Semin Oncol) Vol. 24 Issue 5 Suppl 18 Pg. S18-71-S18-76 (Oct 1997) ISSN: 0093-7754 [Print] United States
• PMID: 9420024 (Publication Type: Journal Article, Review)

Chemical References

• Antimetabolites, Antineoplastic
• Folic Acid Antagonists
• Trimetrexate

Topics

• Antimetabolites, Antineoplastic (therapeutic use)
• Breast Neoplasms (drug therapy)
• Carcinoma, Non-Small-Cell Lung (drug therapy)
• Clinical Trials as Topic
• Esophageal Neoplasms (drug therapy)
• Folic Acid Antagonists (therapeutic use)
• Head and Neck Neoplasms (drug therapy)
• Humans
• Lung Neoplasms (drug therapy)
• Pancreatic Neoplasms (drug therapy)
• Stomach Neoplasms (drug therapy)
• Trimetrexate (therapeutic use)