title: Predicting acute and persistent neuropathy associated with oxaliplatin.
abstract: OBJECTIVE
  We sought to predict oxaliplatin-associated peripheral neuropathy during modified FOLFOX6 (mFOLFOX6) therapy.
  
  
  METHODS
  Equal numbers of male and female patients with previously untreated, primary or recurrent colorectal cancer were followed through a first course of mFOLFOX6 with 85 mg/m² oxaliplatin every 2 weeks. Accounting for correlation among a subject's cycle, logistic regression estimated per cycle risk of acute (under 14 d) and persistent (14 d or more) neuropathy. Proportional hazards regression predicted time to persistent neuropathy.
  
  
  RESULTS
  Among mFOLFOX6 recipients (n = 50, age 58.9 ± 10.1 y), 36% received concomitant bevacizumab. Of the total number of cycles, 94.2% (422/448) were evaluable. Most (84%) subjects reported neuropathy at least once; 74% reported acute and 48% reported persistent symptoms. On multivariate analysis, risk factors shared by acute and persistent neuropathy were body surface area >2.0, acute neuropathy in a past cycle, and lower body weight. In addition, risk of acute neuropathy decreased with age (adjusted for renal function and winter season), whereas risk of persistent neuropathy increased with cumulative dose of oxaliplatin and persistent neuropathy in a past cycle. Concomitant bevacizumab was not a risk factor when administered in stage IV disease but was associated with persistent neuropathy when administered experimentally in stage III. Females had no increased risk of either form of neuropathy. After 3 cycles, weight, body surface area, and prior acute neuropathy predicted time to persistent neuropathy.
  
  
  CONCLUSIONS
  Routinely available clinical factors predict acute and persistent neuropathy associated with oxaliplatin. When validated, the proposed prognostic score for persistent neuropathy can help clinicians counsel patients about chemotherapy.
authors.affiliation: Department of Pharmacy, City of Hope National Medical Center, Duarte, CA, USA. lalejandro@ucsd.edu
authors.forename: Linh M
authors.initials: LM
authors.lastname: Alejandro
authors.forename: Carolyn E
authors.initials: CE
authors.lastname: Behrendt
authors.forename: Kim
authors.initials: K
authors.lastname: Chen
authors.forename: Harry
authors.initials: H
authors.lastname: Openshaw
authors.forename: Stephen
authors.initials: S
authors.lastname: Shibata
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects*; D002908:Chronic Disease; D015331:Cohort Studies; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D016001:Confidence Intervals; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced* / Q000453:epidemiology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects*; D012189:Retrospective Studies; D018570:Risk Assessment; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D002955:Leucovorin; D005472:Fluorouracil