Abstract
Trimetrexate was one of a series of “nonclassic” folate antagonists synthesized in the early 1970s [1, 2]. Following investigation of its mechanism of action [3–6] and spectrum of activity [7–11] and toxicity [12, 13] in preclinical trials, phase I clinical trials were begun in 1984 to define the maximally tolerated doses with various drug administration schedules [14–23]. These preliminary studies and more recent phase II trials [24–31] have shown trimetrexate to have antineoplastic activity in breast cancer, head and neck cancer, and non-small-cell cancer of the lung. The drug is also under intensive investigation for efficacy in other solid tumors and in hematologic malignancy. Of great interest also is the report that trimetrexate in combination with leucovorin is active in the treatment of Pneumocystis carinii pneumonia [32]. In vitro studies of trimetrexate against Toxoplasma gondii also show promise [33, 34]. Phase III trials are currently under way to further define the activity of trimetrexate in these diseases. This chapter summarizes the preclinical and clinical data from published and unpublished reports on this new agent.