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Benefits Outweigh Risks of Bortezomib for Multiple Myeloma

By Martha Kerr

NEW YORK (Reuters Health) Jul 25 - Approximately one third of patients with multiple myeloma will develop bortezomib-induced peripheral neuropathy, oncologists at the Dana Farber Cancer Institute of Harvard University in Boston, report in the July 1st issue of the Journal of Clinical Oncology.

The relatively high efficacy rate is worth the risk, Dr. Paul G. Richardson and colleagues conclude. Bortezomib (Velcade, Millennium Pharmaceuticals, Inc., Cambridge, Massachusetts) has additional neurotoxicity, but it is reversible after drug discontinuation.

Dr. Richardson's team assessed peripheral neuropathy in patients in two phase II studies. The total population of 256 patients had relapsed or refractory myeloma, or both. They were treated with bortezomib 1.0 or 1.3 mg/square meters intravenous bolus, on day 1, 4, 8 and 11 every 21 days for up to eight cycles.

At baseline, 81% of patients had neuropathy, as assessed by Dana Farber's Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group-Neurotoxicity questionnaire and neurologic examination.

Drug-emergent neuropathy developed in 37% of patients on the higher dose of bortezomib and in 21% of patients receiving the lower dose.

The incidence of drug-emergent neuropathy of grade 3 or higher was more prevalent in patients with baseline neuropathy than those without (14% versus 4%). Neuropathy was the cause of dose reduction in 12% and drug discontinuation in 5%.

"Multiple myeloma has a high baseline rate of peripheral neuropathy in the first place," Dr. Richardson commented in correspondence with Reuters Health, "and peripheral neuropathy is an issue with most of the effective therapies in multiple myeloma."

The bortezomib-related "neuropathy is manageable with gabapentin or other therapies, Dr. Richardson added. "Dose reduction is also key."

Compared with other treatment strategies, bortezomib shows a strong durable response with high survival rates in multiple myeloma. As such, "bortezomib-related neuropathy is manageable and reversible. Given the benefit of bortezomib in terms of efficacy," the benefits far outweigh the risks, he concluded.

J Clin Oncol 2006;24:3113-3120.