title: Frequency, characteristics, and reversibility of peripheral neuropathy during treatment of advanced multiple myeloma with bortezomib.
abstract: OBJECTIVE
  To determine the frequency, characteristics, and reversibility of peripheral neuropathy from bortezomib treatment of advanced multiple myeloma.
  
  
  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 > or = 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 > or = grade 3 and/or requiring discontinuation, resolution to baseline or improvement occurred in 71%.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Dana-Farber Cancer Institute, Brigham and Women's Hospital, 44 Binney St, Dana 1B02, Boston, MA 02115, USA. paul_richardson@dfci.harvard.edu
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Hannah
authors.initials: H
authors.lastname: Briemberg
authors.forename: Sundar
authors.initials: S
authors.lastname: Jagannath
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Wen
authors.forename: Bart
authors.initials: B
authors.lastname: Barlogie
authors.forename: James
authors.initials: J
authors.lastname: Berenson
authors.forename: Seema
authors.initials: S
authors.lastname: Singhal
authors.forename: David S
authors.initials: DS
authors.lastname: Siegel
authors.forename: David
authors.initials: D
authors.lastname: Irwin
authors.forename: Michael
authors.initials: M
authors.lastname: Schuster
authors.forename: Gordan
authors.initials: G
authors.lastname: Srkalovic
authors.forename: Raymond
authors.initials: R
authors.lastname: Alexanian
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Steven
authors.initials: S
authors.lastname: Limentani
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Robert Z
authors.initials: RZ
authors.lastname: Orlowski
authors.forename: Kevin
authors.initials: K
authors.lastname: Najarian
authors.forename: Dixie
authors.initials: D
authors.lastname: Esseltine
authors.forename: Kenneth C
authors.initials: KC
authors.lastname: Anderson
authors.forename: Anthony A
authors.initials: AA
authors.lastname: Amato
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001897:Boronic Acids / Q000009:adverse effects* / Q000627:therapeutic use*; D000069286:Bortezomib; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000473:pathology; D011719:Pyrazines / Q000009:adverse effects* / Q000627:therapeutic use*
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D000069286:Bortezomib