cyclophosphamide + trimetrexate

Cyclophosphamide + trimetrexate is an investigational combination chemotherapy regimen composed of two small molecule antineoplastic agents. Cyclophosphamide is an alkylating agent of the nitrogen mustard type that interferes with DNA replication and transcription, leading to cell death, particularly in rapidly dividing cells. Trimetrexate is a non-classical antifolate that inhibits dihydrofolate reductase (DHFR), thereby blocking folate metabolism and DNA synthesis. This combination has been studied primarily for the treatment of metastatic or inoperable non-small cell lung cancer (NSCLC). In clinical studies, this regimen demonstrated activity against previously untreated NSCLC, with dose-limiting toxicities including mucositis and myelosuppression[1]. The mechanism involves dual targeting of DNA synthesis pathways through both direct alkylation (cyclophosphamide) and inhibition of folate-dependent enzymes (trimetrexate).