title: OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study.
abstract: OBJECTIVE
  In metastatic colorectal cancer, a combination of leucovorin (LV) and fluorouracil (FU) with oxaliplatin (FOLFOX) 4 is a standard first-line regimen. The cumulative neurotoxicity of oxaliplatin often requires therapy to be stopped in patients who are still responding. This study evaluates a new strategy of intermittent oxaliplatin treatment that is based on FOLFOX7, a simplified leucovorin and fluorouracil regimen with high-dose oxaliplatin.
  
  
  METHODS
  Previously untreated patients were randomly assigned to either FOLFOX4 administered every 2 weeks until progression (arm A) or FOLFOX7 for six cycles, maintenance without oxaliplatin for 12 cycles, and reintroduction of FOLFOX7 (arm B).
  
  
  RESULTS
  Six hundred twenty patients were enrolled, including an exploratory cohort of 95 elderly or poor prognosis patients. Median progression-free survival and survival times were 9.0 and 19.3 months, respectively, in patients allocated to arm A compared with 8.7 and 21.2 months, respectively, in patients allocated to arm B (P = not significant). Response rates were 58.5% with arm A and 59.2% with arm B. National Cancer Institute Common Toxicity Criteria grade 3 or 4 toxicity was observed in 54.4% of the patients in arm A v 48.7% of patients in arm B. From cycle 7, fewer patients experienced grade 3 or 4 toxicity in arm B. Grade 3 sensory neuropathy was observed in 17.9% of the patients in arm A v 13.3% of patients in arm B (P = .12). In arm B, oxaliplatin was reintroduced in only 40.1% of the patients but achieved responses or stabilizations in 69.4% of these patients.
  
  
  CONCLUSIONS
  Oxaliplatin can be safely stopped after six cycles in a FOLFOX regimen. Further study is needed to fully evaluate oxaliplatin reintroduction.
authors.affiliation: Hôpital Saint-Antoine, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournigand
authors.forename: Andres
authors.initials: A
authors.lastname: Cervantes
authors.forename: Arie
authors.initials: A
authors.lastname: Figer
authors.forename: Gérard
authors.initials: G
authors.lastname: Lledo
authors.forename: Michel
authors.initials: M
authors.lastname: Flesch
authors.forename: Marc
authors.initials: M
authors.lastname: Buyse
authors.forename: Laurent
authors.initials: L
authors.lastname: Mineur
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Carola
authors.forename: Pierre-Luc
authors.initials: PL
authors.lastname: Etienne
authors.forename: Fernando
authors.initials: F
authors.lastname: Rivera
authors.forename: Isabel
authors.initials: I
authors.lastname: Chirivella
authors.forename: Nathalie
authors.initials: N
authors.lastname: Perez-Staub
authors.forename: Christophe
authors.initials: C
authors.lastname: Louvet
authors.forename: Thierry
authors.initials: T
authors.lastname: André
authors.forename: Isabelle
authors.initials: I
authors.lastname: Tabah-Fisch
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage* / Q000009:adverse effects; D000077150:Oxaliplatin; D020551:Pulse Therapy, Drug; D016019:Survival Analysis; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil