For management of malignant lymphomas, multiple myeloma,leukemias, mycosis fungoides (advanced disease), neuroblastoma (disseminated disease), adenocarcinoma of the ovary, retinoblastoma and carcinoma of the breast
Alkylating agents work by three different mechanisms: 1) attachment of alkyl groups to DNA bases, resulting in the DNA being fragmented by repair enzymes in their attempts to replace the alkylated bases, preventing DNA synthesis and RNA transcription from the affected DNA, 2) DNA damage via the formation of cross-links (bonds between atoms in the DNA) which prevents DNA from being separated for synthesis or transcription, and 3) the induction of mispairing of the nucleotides leading to mutations.
infection, myelosuppression, and cardiac toxicity
90-100%
3-12 hours
It is eliminated primarily in the form of metabolites, but from 5% to 25% of the dose is excreted in urine as unchanged drug.
For the treatment of secondary (chronic) progressive, progressive relapsing, or worsening relapsing-remitting multiple sclerosis
Mitoxantrone, a DNA-reactive agent that intercalates into deoxyribonucleic acid (DNA) through hydrogen bonding, causes crosslinks and strand breaks. Mitoxantrone also interferes with ribonucleic acid (RNA) and is a potent inhibitor of topoisomerase II, an enzyme responsible for uncoiling and repairing damaged DNA. It has a cytocidal effect on both proliferating and nonproliferating cultured human cells, suggesting lack of cell cycle phase specificity.
Severe leukopenia with infection.
Poorly absorbed following oral administration
75 hours
* 1000 L/m2
* 21.3 L/hr/m2 [Elderly patients with breast cancer receiving IV administration of 15-90 mg/m2] * 28.3 L/hr/m2 [Non-elderly patients with nasopharyngeal carcinoma receiving IV administration of 15-90 mg/m2] * 16.2 L/hr/m2 [Non-elderly patients with malignant lymphoma receiving IV administration of 15-90 mg/m2]