title: Oxaliplatin added to 5-fluorouracil-based therapy (5-FU +/- FA) in the treatment of 5-FU-pretreated patients with advanced colorectal carcinoma (ACRC): results from the European compassionate-use program.
abstract: OBJECTIVE
  To provide evidence for the therapeutic efficacy of oxaliplatin (Eloxatin) when given as a 2-6-hour i.v. infusion, alone or in combination with 5-fluorouracil/folinic acid (5-FU +/- FA) in patients with advanced colorectal carcinoma (ACRC) who have failed 5-FU-based therapy. To confirm the safety of the drug and its combination in an extended-access context.
  
  
  METHODS
  Prescribing physicians were supplied oxaliplatin on a nominative compassionate-use basis, after obtaining informed consent. Europe-wide, 206 ACRC patients in 44 centers received 1168 cycles of chemotherapy with oxaliplatin (80-100 mg/m2 q 2 weeks or 100-135 mg/m2 q 3 weeks) delivered as a short (2-6 hours) i.v. infusion, 177 of them (1026 cycles) receiving oxaliplatin + 5-FU +/- FA.
  
  
  RESULTS
  Oxaliplatin added to the 5-FU +/- FA regimens of 111 verified 5-FU-refractory patients (imaging and/or clinical proof of progression under prior 5-FU-based regimen), elicited objective responses in 25 of 98 evaluable patients, (ORR: 25.5%, 95% confidence interval (95% CI: 17-35). The median time to progression was 4.1 months (95% CI: 3.3-5.0) and the median overall survival was 9.6 months (95% CI: 8.2-10.9). Differences in the toxicity profile of the oxaliplatin + 5-FU +/- FA combination appear related to administration modality, dose and schedule of the 5-FU-based regimen.
  
  
  CONCLUSIONS
  The addition of oxaliplatin (2-6-hour i.v. infusion) to 5-FU +/- FA regimens is active in ACRC patients with clinical resistance to fluoropyrimidines. The therapeutic index of oxaliplatin + 5-FU +/- FA combinations administered as salvage therapy compares favorably with those reported in recent phase II-III trials involving other new agents or combinations active in 5-FU-refractory ACRC patients.
authors.affiliation: Debiopharm, Charenton le Pont, Gentilly, France.
authors.forename: S
authors.initials: S
authors.lastname: Brienza
authors.forename: M A
authors.initials: MA
authors.lastname: Bensmaïne
authors.forename: P
authors.initials: P
authors.lastname: Soulié
authors.forename: C
authors.initials: C
authors.lastname: Louvet
authors.forename: E
authors.initials: E
authors.lastname: Gamelin
authors.forename: E
authors.initials: E
authors.lastname: François
authors.forename: M
authors.initials: M
authors.lastname: Ducreux
authors.forename: M
authors.initials: M
authors.lastname: Marty
authors.forename: T
authors.initials: T
authors.lastname: André
authors.forename: F
authors.initials: F
authors.lastname: de Braud
authors.forename: H
authors.initials: H
authors.lastname: Bleiberg
authors.forename: V
authors.initials: V
authors.lastname: Ségal
authors.forename: M
authors.initials: M
authors.lastname: Itzhaki
authors.forename: E
authors.initials: E
authors.lastname: Cvitkovic
mesh_terms: D000328:Adult; D000368:Aged; D000704:Analysis of Variance; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects* / Q000627:therapeutic use*; 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; D005060:Europe; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D005500:Follow-Up Studies; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016879:Salvage Therapy; D012720:Severity of Illness Index; D016019:Survival Analysis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil