Seminars in hematology
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The standard treatment of multiple myeloma is systemic chemotherapy. Despite 30 years of drug development in myeloma, there are no new drug regimens significantly superior to melphalan and prednisone. ⋯ Recent evaluation of the topo I inhibitor topotecan demonstrated activity in advanced myeloma, suggesting a possible role for these drugs in the treatment of this disease. Further evaluation of the mechanisms of resistance to topo I inhibitors, study of combination therapy with topotecan, and evaluation of other topo I poisons in multiple myeloma is proposed.
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The camptothecins are a new class of antitumor agents that target topoisomerase I. Irinotecan and topotecan are the most widely used camptothecin analogs in clinical practice, with documented clinical activity in colorectal and ovarian cancer. ⋯ Newer camptothecin analogs in clinical development, such as 9-aminocamptothecin, 9-nitrocamptothecin, GI1147211, and DX-8951f, are also being studied to determine if they have improved toxicity and efficacy profiles compared with existing analogs. The successful development of the camptothecins as antitumor agents demonstrates the importance of topoisomerase 1 as a target for cancer chemotherapy.