Bortezomib for injection

Velcade

Bortezomib for injectionMILLENNIUMProteasome inhibitor approved for treatment of relapsed mantle cell lymphoma

This agent works by inhibiting the chymotrypsin-like activity of the 26S proteasome within cells. Inhibition of this proteasome stops targeted proteolysis, leading to a disruption of homeostasis and eventual cell death. Studies have demonstrated that bortezomib is cytotoxic to a variety of cancer cells. Bortezomib was approved on December 8, 2006, for the treatment of patients with mantle cell lymphoma who have received ≥1 prior therapy. Bortezomib was previously approved for the treatment of multiple myeloma in patients who have received ≥1 prior therapy.

Safety. Cases of severe sensory and motor peripheral neuropathy have been reported in patients treated with bortezomib. Patients with pre-existing symptoms or signs of peripheral neuropathy may experience worsening peripheral neuropathy during treatment. Hypotension, acute development or exacerbation of congestive heart failure, and new onset of decreased left ventricular ejection fraction have also been reported, including in patients with few or no risk factors for decreased left ventricular ejection fraction. There have been rare reports of pneumonitis, interstitial pneumonia, lung infiltration, and acute respiratory distress syndrome; some of these cases have been fatal. Reversible posterior leukoencephalopathy syndrome has been observed in rare cases; if this syndrome develops, bortezomib should be discontinued. Gastrointestinal and intra-cerebral hemorrhages have been reported in patients treated with bortezomib. Because bortezomib is a cytotoxic agent, the complications of tumor lysis syndrome may occur. The most common adverse events associated with bortezomib treatment include fatigue, malaise, weakness, nausea, diarrhea, constipation, peripheral neuropathy, thrombocytopenia, decreased appetite, pyrexia, vomiting, and anemia.

Dosing. The recommended dose of bortezomib is 1.3 mg/m² /dose administered as an intravenous injection twice weekly for 2 weeks (Days 1, 4, 8, and 11), followed by a 10-day rest period (Days 12–21). For extended therapy of >8 cycles, bortezomib can be administered on either the standard schedule or on a maintenance schedule of 1 weekly injection for 4 weeks (Days 1, 8, 15, and 22), followed by a 13-day rest period (Days 23–35).