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The use of topoisomerase I inhibitors in multiple myeloma.

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. In addition, phase II studies of new drugs in myeloma have been disappointing, with low response rates and no prolongation in survival. The topoisomerase I (topo I) inhibitors are a new class of anticancer agents with a wide spectrum of activity in human malignancies. 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.