Mitoxantrone (DB01204): A Comprehensive Monograph on its Pharmacology, Clinical Utility, and Safety Profile

Executive Summary

Mitoxantrone is a synthetic small molecule belonging to the anthracenedione class of antineoplastic agents, structurally related to the anthracyclines.[1] It possesses a dual pharmacological identity, functioning as both a potent cytotoxic drug for cancer therapy and a significant immunomodulatory agent for treating autoimmune disease.[3] Its primary mechanism of action involves the inhibition of DNA topoisomerase II and intercalation into DNA, which disrupts DNA replication and repair, leading to cell death in both proliferating and non-proliferating cells.[1] Concurrently, it exerts profound immunosuppressive effects by inhibiting the proliferation and function of T-cells, B-cells, and macrophages, and by reducing the secretion of pro-inflammatory cytokines.[5]

This dual activity underpins its three main indications approved by the U.S. Food and Drug Administration (FDA): initial therapy for acute nonlymphocytic leukemia (ANLL) in combination with other agents; treatment of pain related to advanced hormone-refractory prostate cancer in combination with corticosteroids; and reduction of neurologic disability and relapse frequency in specific forms of multiple sclerosis (MS), namely secondary progressive, progressive relapsing, and worsening relapsing-remitting MS.[7]