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New indication: Bortezomib (Velcade), an antineoplastic agent, was approved on June 20, 2008, for the initial treatment of multiple myeloma.
Bortezomib is a reversible inhibitor of the chymotrypsin-like activity of the 26S proteasome. By inhibiting this proteasome, bortezomib disrupts normal homeostatic mechanisms, eventually resulting in cell death. This agent was previously approved for the treatment of relapsed multiple myeloma and for the treatment of mantle cell lymphoma in patients who have received ≥1 prior therapy; on June 20, 2008, bortezomib was approved for the initial treatment of multiple myeloma.
Efficacy. The efficacy of bortezomib for the initial treatment of multiple myeloma was evaluated in a prospective, international, randomized, open-label clinical trial. Patients (N=682) were treated with a combination of bortezomib 1.3 mg/m2, melphalan 9 mg/m2, and prednisone 60 mg/m2 or with melphalan 9 mg/m2 plus prednisone 60 mg/m2 for a maximum of 9 cycles, with early discontinuation for disease progression or unacceptable toxicity. The median follow-up was 16.3 months. Patients treated with bortezomib demonstrated significant improvement in the primary end point of time to progression (TTP) (bortezomib, melphalan, and prednisone median TTP, 20.7 mo; melphalan plus prednisone median TTP, 15.0 mo; HR=0.54; P=.000002). Patients treated with bortezomib also demonstrated significant improvements in progression-free survival (P=.00001), overall survival (P=.00782), and response rate (P<10–10) versus those who received melphalan plus prednisone alone.
Safety. Healthcare professionals should frequently monitor the complete blood counts of patients undergoing treatment with bortezomib. Women should avoid becoming pregnant during bortezomib treatment. Bortezomib therapy has been associated with peripheral neuropathy, including cases of severe sensory and motor peripheral neuropathy. This agent has been associated with an increased incidence of hypotension. Patients treated with bortezomib have experienced acute development or exacerbation of congestive heart failure, as well as new onset of decreased left ventricular ejection fraction. Cases of acute diffuse infiltrative pulmonary disease, including some fatal cases, have been reported in patients treated with bortezomib. Patients treated with bortezomib have experienced reversible posterior leukoencephalopathy syndrome. Bortezomib therapy is associated with thrombocytopenia and neutropenia. Tumor lysis syndrome may occur in patients treated with bortezomib. Acute liver failure has been reported in bortezomib-treated patients who were receiving multiple medications concomitantly and who had serious underlying medical conditions. The most common adverse events associated with bortezomib for the initial treatment of multiple myeloma include thrombocytopenia, neutropenia, nausea, peripheral neuropathy, diarrhea, anemia, constipation, neuralgia, leukopenia, and vomiting.