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Combination regimen of the small-molecule antimetabolite gemcitabine, the anthracenedione topoisomerase II inhibitor mitoxantrone, and the anti-CD20 monoclonal antibody rituximab, investigated primarily as salvage therapy for relapsed or refractory mantle cell lymphoma. In a phase II trial in relapsed/refractory mantle cell lymphoma, patients received gemcitabine 900 mg/m2 IV on days 1 and 8, mitoxantrone 10 mg/m2 IV day 1, and rituximab 375 mg/m2 IV day 1 of 21-day cycles, showing manageable hematologic toxicity and activity warranting further study.[1] Gemcitabine inhibits DNA synthesis via incorporation of its triphosphate metabolite and ribonucleotide reductase inhibition; mitoxantrone intercalates DNA and inhibits topoisomerase II, causing DNA breaks; rituximab binds CD20 on B cells, mediating B-cell depletion through complement-dependent cytotoxicity, antibody-dependent cellular cytotoxicity, and apoptosis.[1][3][6]
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