title: Neurotoxicity of bortezomib therapy in multiple myeloma: a single-center experience and review of the literature.
abstract: BACKGROUND
  Bortezomib is active in heavily pretreated multiple myeloma patients; the dose-limiting toxicity is peripheral neuropathy (PN).
  
  
  METHODS
  The authors retrospectively reviewed the incidence, severity, and risk factors for PN in 78 patients who received bortezomib. The median age was 57 years (range, 33-80 years), 62% of patients were men, and 37% of patients were African Americans. Seventeen patients (22%) had diabetes mellitus (DM), and 66 patients (85%) had received thalidomide. Before bortezomib treatment, 37% of the patients reported subjective, grade 1 or 2 PN. Patients received bortezomib alone (n = 10 patients) plus dexamethasone (n = 36 patients) and thalidomide (n = 20 patients) or chemotherapy (n = 12 patients). PN affected 52% of patients, including grade 3 and 4 PN in 15% and 7%, respectively.
  
  
  RESULTS
  Twelve patients stopped bortezomib because of side effects that included PN (n = 9 patients), diarrhea (n = 2 patients) and cytomegalovirus pneumonia (n = 1 patient); 11 patients had dose reductions because of PN. Grade 4 PN affected 6 patients (sensory, n = 4 patients; motor/sensory, n = 2 patients). The onset of grade 4 PN was sudden rather than cumulative. Factors that were predictive of PN grade were baseline PN (P = .002), prior thalidomide use (P = .03), and the presence of DM (P = .03). Multiple myeloma responses included complete, near complete, and partial responses in 5% of patients, 10% of patients, and 27% of patients, respectively. Responses were independent of PN and of whether bortezomib was combined with chemotherapy or thalidomide. Patients remained on therapy longer for a median of 5 cycles (range, 2-36 cycles) when they received bortezomib plus thalidomide versus 3 cycles (range, 1-19 cycles) for the other combinations. PN therapy was mostly supportive. It was noteworthy that 6 of 9 patients with PN who received lenalidomide as salvage therapy after bortezomib had significant improvement in their symptoms.
  
  
  CONCLUSIONS
  The risk of bortezomib-related PN was greater in patients who had PN and DM at baseline. The authors concluded that an unexpected, symptomatic improvement of PN on lenalidomide is worth further investigation.
authors.affiliation: Greenebaum Cancer Center, University of Maryland, Baltimore, MD 21201, USA. abadros@umm.edu
authors.forename: Ashraf
authors.initials: A
authors.lastname: Badros
authors.forename: Olga
authors.initials: O
authors.lastname: Goloubeva
authors.forename: Jay S
authors.initials: JS
authors.lastname: Dalal
authors.forename: Ilyas
authors.initials: I
authors.lastname: Can
authors.forename: Jennifer
authors.initials: J
authors.lastname: Thompson
authors.forename: Aaron P
authors.initials: AP
authors.lastname: Rapoport
authors.forename: Meyer
authors.initials: M
authors.lastname: Heyman
authors.forename: Gorgon
authors.initials: G
authors.lastname: Akpek
authors.forename: Robert G
authors.initials: RG
authors.lastname: Fenton
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols; D001897:Boronic Acids / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D000069286:Bortezomib; D003907:Dexamethasone / Q000008:administration & dosage; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000473:pathology; D009364:Neoplasm Recurrence, Local; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D011719:Pyrazines / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D012189:Retrospective Studies; D013792:Thalidomide / Q000008:administration & dosage; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D001897:Boronic Acids; D011719:Pyrazines; D013792:Thalidomide; D000069286:Bortezomib; D003907:Dexamethasone