title: Neurotoxicity from oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: NSABP C-07.
abstract: OBJECTIVE
  The randomized, multicenter, phase III protocol C-07 compared the efficacy of adjuvant bolus fluorouracil and leucovorin (FULV) versus FULV with oxaliplatin (FLOX) in stage II or III colon cancer. Definitive analysis revealed an increase in 4-year disease-free survival from 67.0% to 73.2% in favor of FLOX. This study compares neurotoxicity between the treatments.
  
  
  METHODS
  Neurotoxicity was recorded for all patients using standard adverse event reporting. Patients at select institutions completed a neurotoxicity questionnaire through 18 months of follow-up.
  
  
  RESULTS
  A total of 2,492 patients enrolled onto C-07 and 400 patients enrolled onto the patient-reported substudy. Mean patient-reported neurotoxicity was higher with oxaliplatin throughout the 18 months of study (P < .0001). During therapy, patients receiving oxaliplatin experienced significantly more hand/foot toxicity (eg, "quite a bit" of cold-induced hand/foot pain 26% FLOX v 2.6% FULV) and overall weakness (eg, moderate weakness in 27.4% FLOX v 16.2% FULV). At 18 months, hand neuropathy had diminished, but patients who received oxaliplatin experienced continued foot discomfort (eg, moderate foot numbness and tingling for 22.1% FLOX v 4.6% FULV). Observer-reported neurotoxicity was low grade and primarily neurosensory rather than neuromotor. Sixty-eight percent in the FLOX group v 8% in the FULV group had neurotoxicity at their first on-treatment assessment. Time to resolution was significantly longer for those receiving oxaliplatin, and continued beyond 2 years for more than 10% in the oxaliplatin group.
  
  
  CONCLUSIONS
  Oxaliplatin causes significant neurotoxicity. It is experienced primarily in the hands during therapy and in the feet during follow-up. In a minority of patients the neurotoxicity is long lasting.
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project Operations Office and Biostatistical Center, Pittsburgh, PA 15213, USA. land@pitt.edu
authors.forename: Stephanie R
authors.initials: SR
authors.lastname: Land
authors.forename: Jacek A
authors.initials: JA
authors.lastname: Kopec
authors.forename: Reena S
authors.initials: RS
authors.lastname: Cecchini
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Ganz
authors.forename: H Samuel
authors.initials: HS
authors.lastname: Wieand
authors.forename: Linda H
authors.initials: LH
authors.lastname: Colangelo
authors.forename: Kate
authors.initials: K
authors.lastname: Murphy
authors.forename: J Philip
authors.initials: JP
authors.lastname: Kuebler
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Seay
authors.forename: Burton M
authors.initials: BM
authors.lastname: Needles
authors.forename: James D
authors.initials: JD
authors.lastname: Bearden
authors.forename: Lauren K
authors.initials: LK
authors.lastname: Colman
authors.forename: Keith S
authors.initials: KS
authors.lastname: Lanier
authors.forename: Eduardo R
authors.initials: ER
authors.lastname: Pajon
authors.forename: David
authors.initials: D
authors.lastname: Cella
authors.forename: Roy E
authors.initials: RE
authors.lastname: Smith
authors.forename: Michael J
authors.initials: MJ
authors.lastname: O'Connell
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Costantino
authors.forename: Norman
authors.initials: N
authors.lastname: Wolmark
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects*; D000077150:Oxaliplatin; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced*
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil