title: [Retrospective analysis of FOLFOX4 neurotoxicity for recovery from advanced colorectal cancer].
abstract: BACKGROUND
  Oxaliplatin (L-OHP) in combination with infusional 5-fluorouracil/leucovorin (FOLFOX), has been established as a key drug for advanced colorectal cancer. Sensory neurotoxicity is its dose-limiting toxicity. No prior recovery from neurotoxicity data is available for Japanese patients treated by FOLFOX4 for advanced colorectal cancer.
  
  
  OBJECTIVE
  We performed a retrospective study on the recovery from chronic neurotoxicity and period for discontinuing FOLFOX4 therapy due to neurotoxicity.
  
  
  METHODS
  One hundred eighty-seven patients with advanced or recurrent colorectal cancer were treated with FOLFOX4 regimen between April 2005 and March 2006. We evaluated chronic peripheral sensory neuropathy by National Cancer Institute Common Terminology Criteria for Adverse Events (version 3.0), and calculated the period of recovery from grade 3 and grade 2 neurotoxicity by the Kaplan-Meier method.
  
  
  RESULTS
  Seventy-two patients had to discontinue FOLFOX4 due to grade 3 and grade 2 neurotoxicity. grade 2 and grade 3 neurotoxicity was observed in 39 (20.8%) and 33 (17.6%) patients, respectively. Patients with grade 2 and grade 3 neurotoxicity had a median age of 59 years (range, 35-75 years), and 62 years (range, 36-73 years), respectively. The median number of courses until expression of grade 2 neurotoxicity was ten (range, 2-23 courses) and that for grade 3 neurotoxicity was also ten (range, 4-14 courses). The period of reducing grade 2 neurotoxicity to grade 1 was 56 days, while that for reducing grade 3 neurotoxicity to grade 1 was 106 days. FOLFOX4 was reintroduced in 15 patients with grade 2 neurotoxicity and in 14 patients with grade 3 neurotoxicity. The main reason that patients could not have reintroduction FOLFOX4 was early progression before reducing neurotoxicity to grade 1. The period from discontinuation of FOLFOX4 to disease progression was 88.5 days in partial response (PR) cases and 58 days in stable disease (SD) cases. PR cases took longer until disease progression than SD cases.
  
  
  CONCLUSIONS
  The incidences of neurotoxicity were similar in Japanese patients compared with those reported in Western studies. These findings provide useful information for clinicians and patients using oxaliplatin.
authors.affiliation: Division of Medical Oncology, Cancer Chemotherapy Center, Japanese Foundation for Cancer Research, Japan.
authors.forename: Masanori
authors.initials: M
authors.lastname: Matsuda
authors.forename: Satoshi
authors.initials: S
authors.lastname: Matsusaka
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Kuboki
authors.forename: Takashi
authors.initials: T
authors.lastname: Itimura
authors.forename: Mariko
authors.initials: M
authors.lastname: Ogura
authors.forename: Mitsukuni
authors.initials: M
authors.lastname: Suenaga
authors.forename: Daigo
authors.initials: D
authors.lastname: Syouji
authors.forename: Chie
authors.initials: C
authors.lastname: Watanabe
authors.forename: Keisho
authors.initials: K
authors.lastname: Chin
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.forename: Kiyohiko
authors.initials: K
authors.lastname: Hatake
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005472:Fluorouracil / Q000009:adverse effects / Q000627:therapeutic use; D006801:Humans; D002955:Leucovorin / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020258:Neurotoxicity Syndromes / Q000473:pathology*; D009944:Organoplatinum Compounds / Q000009:adverse effects / Q000627:therapeutic use; D000077150:Oxaliplatin; D012189:Retrospective Studies
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil