Abstract

The pharmacology, pharmacokinetics, clinical trials, adverse effects, dosage recommendations, and economic considerations of carfilzomib are reviewed. Multiple myeloma accounts for approximately 10-15% of all hematologic malignancies and 20% of blood-related cancer deaths. Despite recent advances in the treatment of multiple myeloma, most patients will eventually relapse, requiring further treatment. Carfilzomib is a new proteasome inhibitor that primarily targets the chymotrypsin-like activity of the 20S proteasome. The safety and efficacy of carfilzomib was demonstrated in the PX-171-003-A1 trial, a prospective phase II trial in patients with relapsed or refractory multiple myeloma who had received at least 2 prior therapies including a proteasome inhibitor and an immunomodulatory agent. Common adverse effects included fatigue (55.5%), anemia (46.8%), nausea (44.9%), and thrombocytopenia (36.3%). The recommended dose of carfilzomib for the first cycle is 20 mg/m(2) on 2 consecutive days each week for 3 weeks in a 4-week cycle escalating to 27 mg/m(2) for subsequent cycles. It is recommended that patients receive premedication with dexamethasone during cycle 1 and cycle 2 to minimize risk of infusion reactions. Carfilzomib provides a clinical benefit to patients with relapsed or refractory multiple myeloma who have been previously treated with a proteasome inhibitor and an immunomodulatory agent.

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