An Oncological and Pharmacological Monograph on Fotemustine (DB04106)

Executive Summary

Fotemustine is a third-generation chloroethylating nitrosourea, a cytotoxic small molecule with established antineoplastic activity.[1] As an alkylating agent, its primary role in oncology is the treatment of disseminated malignant melanoma and primary malignant cerebral tumors.[2] The defining characteristic of Fotemustine, which distinguishes it from earlier-generation nitrosoureas, is the grafting of a phosphonoalanine group onto its core structure. This chemical modification confers high lipophilicity, enabling the molecule to effectively penetrate the blood-brain barrier.[1] This property underpins its specific clinical utility in treating malignancies with central nervous system (CNS) involvement, such as cerebral metastases from melanoma and recurrent high-grade gliomas.[2]

Clinical evidence has demonstrated Fotemustine's efficacy, most notably in a pivotal Phase III trial where it achieved a superior objective response rate compared to the former standard-of-care, dacarbazine (DTIC), in patients with metastatic melanoma.[6] However, this therapeutic benefit is critically counterbalanced by a significant and dose-limiting toxicity profile. The most prominent adverse effect is severe, delayed, and cumulative myelosuppression, manifesting as profound thrombocytopenia and neutropenia.[3] This hematological toxicity dictates the drug's complex administration schedule, which requires intensive patient monitoring and extended therapeutic rest periods.