Lomustine (CCNU): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Toxicological Profile

Executive Summary

Lomustine, also known by the abbreviation CCNU, is a potent, small-molecule chemotherapeutic agent belonging to the nitrosourea class of alkylating drugs. First approved in 1976, it has a long and established history in the treatment of specific malignancies. The defining physicochemical characteristic of Lomustine is its high lipophilicity, a property that facilitates its passage across the blood-brain barrier. This unique distribution profile has established Lomustine as a cornerstone therapy for central nervous system (CNS) cancers, particularly primary and metastatic brain tumors such as glioblastoma, and as a second-line agent for refractory Hodgkin's lymphoma.[1]

The therapeutic utility of Lomustine is fundamentally intertwined with its significant and challenging toxicological profile. As a cell-cycle non-specific agent, it exerts its cytotoxic effects by inducing lethal damage to the DNA of cancer cells. However, this same mechanism affects rapidly dividing healthy cells, leading to a predictable and severe pattern of toxicity. The principal and dose-limiting toxicity is a profound, delayed, and cumulative myelosuppression, which manifests as leukopenia and thrombocytopenia. The nadir of this effect occurs 4 to 6 weeks post-administration, a pharmacokinetic reality that dictates the drug's unique and mandatory single-dose, 6-week treatment cycle to allow for bone marrow recovery.[4]