title: Changes in neurologic function tests may predict neurotoxicity caused by ixabepilone.
abstract: OBJECTIVE
  To investigate baseline factors and neurologic function tests (NFTs) that may predict the development of grade 2 or higher peripheral neuropathy (PN) after treatment with ixabepilone, an epothilone microtubule-stabilizing agent with antitumor activity.
  
  
  METHODS
  Advanced breast cancer patients were treated with ixabepilone (6 mg/m2) for 5 consecutive days every 3 weeks in a phase II clinical trial. Physical examinations, questionnaires, nerve conduction studies, and NFTs, including the Jebsen Test of Hand Function (JTH) and the Grooved Pegboard Test (GPT), were performed at baseline and during subsequent cycles.
  
  
  RESULTS
  Forty-seven patients assessable for PN received a median of five cycles of therapy (range, one to 22 cycles). Nine of these patients developed grade 2 PN, and two developed grade 3 PN, with a median time to onset of 144 days (range, 6 to 189 days). Among these 11 patients, PN resolved in eight patients, with a median of 15 days (range, 6 to 346 days) after onset, but PN did not resolve in three patients during follow-ups at 76, 361, and 746 days after onset. GPT and changes of JTH scores at onset of PN were significantly different between patients with and without PN at comparable follow-up times (P = .006 and P = .002, respectively). Changes in GPT and JTH scores over the first two cycles were often associated with the development of PN by exploratory actuarial analysis.
  
  
  CONCLUSIONS
  Serious ixabepilone-induced neuropathy was relatively rare on the treatment schedule used. NFTs, such as JTH and GPT, may have utility for predicting PN, but further testing is needed.
authors.affiliation: Cancer Therapeutics Branch, Medical Oncology Clinical Research Unit, and Biostatistics and Data Management Section, Center for Cancer Research, Cancer Therapy Evaluation Program, National Institutes of Health, Bethesda, MD 20889-5015, USA.
authors.forename: James J
authors.initials: JJ
authors.lastname: Lee
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Low
authors.forename: Earllaine
authors.initials: E
authors.lastname: Croarkin
authors.forename: Rebecca
authors.initials: R
authors.lastname: Parks
authors.forename: Arlene W
authors.initials: AW
authors.lastname: Berman
authors.forename: Nitin
authors.initials: N
authors.lastname: Mannan
authors.forename: Seth M
authors.initials: SM
authors.lastname: Steinberg
authors.forename: Sandra M
authors.initials: SM
authors.lastname: Swain
mesh_terms: D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000503:physiopathology; D034261:Epothilones / Q000009:adverse effects*; D005260:Female; D006801:Humans; D008875:Middle Aged; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*; D011446:Prospective Studies
chemical_list: D000970:Antineoplastic Agents; D034261:Epothilones; C430592:ixabepilone