Proteasome inhibition for treatment of multiple myeloma: clinical update.

Multiple myeloma is an incurable hematologic cancer affecting over 50,000 Americans. Current treatment approaches employ various chemotherapeutic regimens; however, relapse is inevitable. A novel treatment for multiple myeloma is bortezomib, a proteasome inhibitor that has shown significant in vitro and in vivo activity. Bortezomib, recently approved by the FDA, has activity in patients with relapsed and refractory multiple myeloma. A clinical update from the SUMMIT and CREST phase II trials is presented; overall response rates were 35% and 38%, respectively, for the 1.3 mg/m2 dose of bortezomib. Side effects, including thrombocytopenia and peripheral neuropathy, are generally manageable APEX, a phase III trial of bortezomib compared to high-dose dexamethasone in multiple myeloma patients who had received 1-3 prior therapies, was stopped early due to superior efficacy on the bortezomib arm.