carmustine + lomustine + temozolomide

This is a combination chemotherapy regimen consisting of three alkylating agents—carmustine, lomustine, and temozolomide. All three drugs are nitrosourea or imidazotetrazine derivatives that exert their antitumor effects primarily by causing DNA damage through alkylation, leading to cell cycle arrest and apoptosis in rapidly dividing tumor cells. Carmustine (BCNU) and lomustine (CCNU) are both nitrosoureas with the ability to cross the blood-brain barrier, making them effective for brain tumors such as glioblastoma. Temozolomide is an oral imidazotetrazine prodrug that also methylates DNA at the O6 and N7 positions of guanine residues. The rationale for combining these agents is based on their complementary mechanisms of action and potential to overcome resistance mediated by DNA repair pathways such as MGMT (O6-methylguanine-DNA methyltransferase). This combination has been explored in clinical trials for high-grade gliomas, particularly newly diagnosed or recurrent glioblastoma multiforme[5][10]. While combinations like carmustine plus temozolomide or lomustine plus temozolomide have been studied more extensively[1][8][9], triple regimens may be considered investigational.