Bortezomib approved for second line treatment of myeloma

U.S. Food and Drug Administration approved bortezomib for injection (Velcade, Millennium Pharmaceuticals, Inc.) for the treatment of patients with multiple myeloma who have received at least one prior therapy on March 25, 2005.

Bortezomib is already approved for patients with multiple myeloma who had received at least two prior therapies and demonstrated disease progression on last therapy. This new approval is granted because of further evidence to the efficiency of response rates and durability.

The new approval is based on a multi-center, controlled clinical trial of 669 myeloma patients who had received at least one prior therapy. These patients were randomized to receive either bortezomib, 1.3 mg/m2 intravenous bolus on days 1, 4, 8, 11 of each 3 week cycle for 8 weeks or dexamethasone, 40 mg/day by mouth once daily on Days 1 to 4, 9 to 12, and 17 to 20 every 5 weeks for 4 cycles. Each arm also had a reduced-dose schedule for further treatment cycles. The primary endpoint of the study was time-to-progression (TTP). Following a planned interim analysis, the study was terminated early on the advice of a Data Monitoring Committee because of the improved results in bortezomib containing arm. The following were the results of Bortezomib Vs dexamethasone respectively:

• Improved time to progression Hazard ration of 0.55 (0.44 Vs 0.69): p <.0001
• Improved response rate 38% Vs 18%: p <.0001
• Improved overall survival Hazard ration 0.57: p <..05

Adverse events were similar to those previously reported for bortezomib. Among the 331 patients treated with bortezomib, the most commonly reported adverset events were asthenic conditions, diarrhea, nausea, fatigue, constipation,peripheral neuropathy, vomiting, pyrexia, thrombocytopenia, anemia, headache, anorexia, cough, and paresthesia . Other adverse events included dyspnea, neutropenia, rash, insomnia, and bone pain. Myelosuppression was moderate in degree and reversible. Neuropathy was slowly reversible. Heart failure and possible tumor lysis syndrome were added to the label warnings in mid-2004.

Did you know?
The new approval is based on a multi-center, controlled clinical trial of 669 myeloma patients who had received at least one prior therapy. These patients were randomized to receive either bortezomib, 1.3 mg/m2 intravenous bolus on days 1, 4, 8, 11 of each 3 week cycle for 8 weeks or dexamethasone, 40 mg/day by mouth once daily on Days 1 to 4, 9 to 12, and 17 to 20 every 5 weeks for 4 cycles. Each arm also had a reduced-dose schedule for further treatment cycles. The primary endpoint of the study was time-to-progression (TTP).