Abstract
The pharmacology, pharmacokinetics, clinical efficacy, safety, dosage and administration, place in therapy, and cost of bortezomib in the treatment of multiple myeloma and mantle cell lymphoma are reviewed. Bortezomib is a modified dipeptidyl boronic acid that disrupts essential intracellular pathways by inhibiting proteasomes. The drug is metabolized by cytochrome P-450 isoenzymes 3A4, 2C19, and 1A2 to four inactive metabolites. Bortezomib was initially developed for the treatment of multiple myeloma based on the findings of early in vitro studies of patients with multiple myeloma who received at least one prior course of treatment; the drug received approval for the treatment of mantle cell lymphoma based on a single, noncomparative, Phase II study of previously treated patients. Significant toxicities have been reported with the use of bortezomib, including peripheral neuropathy, neutropenia, and thrombocytopenia. The dosage of bortezomib recommended by the manufacturer is 1.3 mg/m(2) per dose administered as an i.v. bolus injection twice weekly on days 1, 4, 8, and 11 of a three-week cycle. It is not necessary to adjust the dosage of bortezomib in patients with renal impairment. Bortezomib is being investigated as a treatment for several other malignant conditions. The current wholesale price of bortezomib is $1,322.40 for a single-use vial containing 3.5 mg of bortezomib lyophilized powder, with one course of treatment costing approximately $27,500 in drug cost alone. Bortezomib, an antineoplastic agent that reversibly inhibits the 26S proteasome, offers an important treatment option for patients with multiple myeloma or mantle cell lymphoma.
Published Version
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