Originally published as JCO Early Release 10.1200/JCO.2005.04.7779 on June 5 2006

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Frequency, Characteristics, and Reversibility of Peripheral Neuropathy During Treatment of Advanced Multiple Myeloma With Bortezomib

Paul G. Richardson, Hannah Briemberg, Sundar Jagannath, Patrick Y. Wen, Bart Barlogie, James Berenson, Seema Singhal, David S. Siegel, David Irwin, Michael Schuster, Gordan Srkalovic, Raymond Alexanian, S. Vincent Rajkumar, Steven Limentani, Melissa Alsina, Robert Z. Orlowski, Kevin Najarian, Dixie Esseltine, Kenneth C. Anderson, Anthony A. Amato

From the Dana-Farber Cancer Institute, Brigham and Women’s Hospital, Boston; Millennium Pharmaceuticals Inc, Cambridge, MA; St Vincent’s Cancer Center; York Presbyterian Hospital, New York, NY; University of Arkansas, Little Rock, AR; Institute for Myeloma and Bone Cancer Research, West Hollywood; Alta Bates Cancer Center, Berkley, CA; Robert H. Lurie Cancer Center, Chicago, IL; Hackensack University Medical Center, Hackensack, NJ; New Sparrow Regional Cancer Center, Lansing, MI; M.D. Anderson Cancer Center, Houston, TX; Mayo Clinic, Rochester, MN; Carolinas Hematology-Oncology Association, Charlotte, NC; H. Lee Moffitt Cancer Center Research Institute, Tampa, FL; and University of North Carolina at Chapel Hill, Chapel Hill, NC

Address reprint requests to Paul G. Richardson, MD, Dana-Farber Cancer Institute, 44 Binney St, Dana 1B02, Boston, MA 02115; e-mail: paul_richardson{at}dfci.harvard.edu

PURPOSE: To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma.

PATIENTS AND METHODS: Peripheral neuropathy was assessed in two phase II studies in 256 patients with relapsed and/or refractory myeloma treated with bortezomib 1.0 or 1.3 mg/m² intravenous bolus on days 1, 4, 8, and 11, every 21 days, for up to eight cycles. Peripheral neuropathy was evaluated at baseline, during the study, and after the study by patient-reported symptoms using the Functional Assessment of Cancer Therapy Scale/Gynecologic Oncology Group–Neurotoxicity (FACT/GOG-Ntx) questionnaire and neurologic examination. During the study, peripheral neuropathy was also evaluated by investigator assessment. A subset of patients underwent nerve conduction studies (n = 13).

RESULTS: Before treatment, 194 (81%) of 239 patients had peripheral neuropathy by FACT/GOG-Ntx questionnaire, and 203 (83%) of 244 patients had peripheral neuropathy by neurologic examination. Treatment-emergent neuropathy was reported in 35% of patients, including 37% (84 of 228 patients) receiving bortezomib 1.3 mg/m² and 21% (six of 28 patients) receiving bortezomib 1.0 mg/m². Grade 1 or 2, 3, and 4 neuropathy occurred in 22%, 13%, and 0.4% of patients, respectively. The incidence of grade 3 neuropathy was higher among patients with baseline neuropathy by FACT/GOG-Ntx questionnaire compared with patients without baseline neuropathy (14% v 4%, respectively). In all 256 patients, neuropathy led to dose reduction in 12% and discontinuation in 5%. Of 35 patients with neuropathy grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%.

CONCLUSION: Bortezomib-associated peripheral neuropathy seemed reversible in the majority of patients after dose reduction or discontinuation. Although severe neuropathy was more frequent in the presence of baseline neuropathy, the overall occurrence was independent of baseline neuropathy or type of prior therapy.

Supported in part by Millennium Pharmaceuticals Inc and Johnson & Johnson Pharmaceutical Research & Development LLC.

P.G.R. and H.B. are both first authors.

Authors’ disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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