cyclophosphamide + methotrexate + lomustine

CMC is a combination chemotherapy regimen consisting of cyclophosphamide, methotrexate, and lomustine (also known as CCNU). This regimen has been historically utilized in the treatment of small cell lung cancer (SCLC), often administered as an adjuvant to surgery or in alternating cycles with other regimens like VAP (vincristine, doxorubicin, and procarbazine). The mechanism of action is multi-modal: cyclophosphamide and lomustine are alkylating agents that form covalent bonds with DNA, leading to cross-linking and strand breaks that inhibit DNA replication and transcription. Lomustine also affects RNA and protein function through carbamoylation. Methotrexate is an antimetabolite that competitively inhibits dihydrofolate reductase (DHFR), an enzyme essential for the synthesis of tetrahydrofolate. This inhibition depletes the pool of folate cofactors required for the de novo synthesis of purines and thymidylate, thereby halting DNA synthesis and cell division.

Other names

CMC regimenCCNU-methotrexate-cyclophosphamideCyclophosphamide-Methotrexate-Lomustine