@article{3130039,
    title = "Risk factors for, and reversibility of, peripheral neuropathy associated with bortezomib-melphalan-prednisone in newly diagnosed patients with multiple myeloma: Subanalysis of the phase 3 VISTA study",
    author = "Dimopoulos, M.A. and Mateos, M.-V. and Richardson, P.G. and Schlag, R. and Khuageva, N.K. and Shpilberg, O. and Kropff, M. and Spicka, I. and Palumbo, A. and Wu, K.L. and Esseltine, D.-L. and Liu, K. and Deraedt, W. and Cakana, A. and Van De Velde, H. and San Miguel, J.F.",
    journal = "European Journal of Haematology",
    year = "2011",
    volume = "86",
    number = "1",
    pages = "23-31",
    issn = "0902-4441, 1600-0609",
    doi = "10.1111/j.1600-0609.2010.01533.x",
    keywords = "bortezomib;  melphalan;  prednisone, adult;  aged;  article;  cancer patient;  clinical trial;  creatinine clearance;  diabetes mellitus;  disease severity;  drug megadose;  female;  human;  major clinical study;  male;  multiple cycle treatment;  multiple myeloma;  neuropathy;  obesity;  peripheral neuropathy;  priority journal;  prognosis;  risk factor, Aged;  Aged, 80 and over;  Antineoplastic Combined Chemotherapy Protocols;  Boronic Acids;  Female;  Humans;  Male;  Melphalan;  Middle Aged;  Multiple Myeloma;  Multivariate Analysis;  Peripheral Nervous System Diseases;  Prednisone;  Pyrazines;  Risk Factors",
    abstract = "Objectives: This subanalysis of the phase 3 VISTA trial aimed to assess the frequency, characteristics and reversibility of, and prognostic factors for, bortezomib-associated peripheral neuropathy (PN) in newly diagnosed patients with multiple myeloma ineligible for high-dose therapy who received bortezomib plus melphalan-prednisone.Methods: Patients received nine 6-wk cycles of VMP (bortezomib 1.3 mg/m2, days 1, 4, 8, 11, 22, 25, 29, 32, cycles 1-4, and days 1, 8, 22, 29, cycles 5-9; melphalan 9 mg/m2, days 1-4, cycles 1-9; and prednisone 60 mg/m2, days 1-4, cycles 1-9).Results: Overall, 47% of patients receiving VMP developed PN, including 19% grade 2 and 13% grade ≥3 (<1% grade 4). The PN incidence was dose-related and reached a plateau at a cumulative bortezomib dose of approximately 45 mg/m2. Median time to PN onset was 2.3 months. Bortezomib-associated PN was reversible; 79% of events improved by at least one NCI CTCAE grade within a median of 1.9 months and 60% completely resolved within a median of 5.7 months, with reversibility similar in responding and non-responding patients. By multivariate analysis, baseline neuropathy was the only consistent risk factor for any PN [hazard ratio (HR) 1.785, P = 0.0065], grade ≥2 PN (HR 2.205, P = 0.0032), and grade ≥3 PN (HR 2.438, P = 0.023); age, pre-existing diabetes, International Staging System stage, obesity, and creatinine clearance did not affect the overall rate of PN.Conclusions: Rates of bortezomib-induced PN in the frontline setting were similar to those in relapsed patients and resolved in most cases. (Clinicaltrials.gov identifier: NCT00111319). © 2010 John Wiley & Sons A/S."
}