title: Safety analysis of FOLFOX4 treatment in colorectal cancer patients: a comparison between two Asian studies and four Western studies.
abstract: OBJECTIVE
  Oxaliplatin-based therapy, notably FOLFOX4 (5-fluorouracil, leucovorin, and oxaliplatin), is a standard regimen approved globally for the treatment of metastatic colorectal cancer, and as adjuvant treatment of colon cancer. As part of the Japanese submission for the adjuvant indication, the safety profile of FOLFOX4 regimen was compared in Asian and Western patients.
  
  
  METHODS
  A total of 3359 patients with colorectal cancer treated with the FOLFOX4 regimen were included in the analyses: 1515 from 2 Asian studies (Japanese Post Marketing Surveillance and Multicenter Asia Study in Adjuvant Treatment of Colon Cancer with Oxaliplatin/5-FU/LV), and 1844 from 4 Western studies (EFC2962, N9741, EFC4584, and Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer). Doses administered and safety parameters were analyzed by using common definitions and programs.
  
  
  RESULTS
  Demographic and baseline characteristics were comparable between Asian and Western patients. Patients received FOLFOX4 for a median of 6-12 cycles, which ranged from 16 to 28 weeks. Median dose intensities of oxaliplatin and of 5-fluorouracil, bolus and infusion, were within the ranges of 33 to 36 mg/m(2)/week, 297 to 338 mg/m(2)/week, and 467 to 510 mg/m(2)/week, respectively. Most frequently reported adverse events (AE) included hematologic, gastrointestinal, and neurosensory adverse events (NSAE). The incidence of grade ≥3 neutropenia ranged from 37% (422 of 1134) to 52% (83 of 159) in Asian and 41% (455 of 1108) to 56% (144 of 259) in Western studies; of diarrhea, ranged from 1.4% (3 of 222) to 6.3% (10 of 159) and 11% (30 of 268 or 120 of 1108) to 14% (36 of 259); of NSAEs, from 1.9% (21 of 1134) to 4.4% (7 of 159) and 9.3% (25 of 268) to 19% (39 of 209); and of allergic reactions, from 0.6% (7 of 1134) to 3.1% (5 of 159) and 1.1% (3 of 268) to 3.0% (33 of 1108), respectively. The probability of grade ≥3 NSAEs and diarrhea was statistically significantly lower in Asian than in Western studies by using a log-rank test.
  
  
  CONCLUSIONS
  There was no evidence that Asian patients experienced worse toxicity than did Western patients when treated with FOLFOX4, and trends toward reduced neurotoxicity and diarrhea among Asian patients were observed.
authors.affiliation: Department of Surgical Oncology, Tokyo Medical and Dental University, Tokyo, Japan. k-sugi.srg2@tmd.ac.jp
authors.forename: Kenichi
authors.initials: K
authors.lastname: Sugihara
authors.forename: Atsushi
authors.initials: A
authors.lastname: Ohtsu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Shimada
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Mizunuma
authors.forename: Po-Huang
authors.initials: PH
authors.lastname: Lee
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
authors.forename: Richard M
authors.initials: RM
authors.lastname: Goldberg
authors.forename: Mace L
authors.initials: ML
authors.lastname: Rothenberg
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.forename: Silvano
authors.initials: S
authors.lastname: Brienza
authors.forename: Katsushige
authors.initials: K
authors.lastname: Gomi
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001208:Asia; D001315:Australia; D002170:Canada; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000208:ethnology*; D005060:Europe; D005472:Fluorouracil / Q000009:adverse effects; D006801:Humans; D007557:Israel; D002955:Leucovorin / Q000009:adverse effects; D020258:Neurotoxicity Syndromes / Q000208:ethnology*; D009944:Organoplatinum Compounds / Q000009:adverse effects; D014481:United States
chemical_list: D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil
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