title: Oxaliplatin plus high-dose folinic acid and 5-fluorouracil i.v. bolus (OXAFAFU) versus irinotecan plus high-dose folinic acid and 5-fluorouracil i.v. bolus (IRIFAFU) in patients with metastatic colorectal carcinoma: a Southern Italy Cooperative Oncology Group phase III trial.
abstract: OBJECTIVE
  The primary end point of this phase III trial was to compare the response rate (RR) of oxaliplatin (OXA) plus levo-folinic acid (l-FA) and 5-fluorouracil (5-FU) bolus with that of irinotecan (IRI) plus l-FA and 5-FU bolus in advanced colorectal carcinoma.
  
  
  METHODS
  Patients with measurable metastatic colorectal carcinoma were randomly allocated to receive: IRI 200 mg/m(2) on day 1, l-FA 250 mg/m(2) intravenously plus 5-FU 850 mg/m(2) on day 2 (IRIFAFU); or OXA 100 mg/m(2) on day 1, l-FA 250 mg/m(2) plus 5-FU 1050 mg/m(2) on day 2 [OXAFAFU high dose (hd)]. Cycles were given every 2 weeks. After a planned interim analysis, OXA was reduced to 85 mg/m(2) and 5-FU to 850 mg/m(2) [OXAFAFU low dose (ld)].
  
  
  RESULTS
  Two hundred and seventy-four patients (IRIFAFU, 135; OXAFAFUhd, 71; OXAFAFUld, 68) were treated. Forty-two confirmed responses were achieved with IRIFAFU, 29 with OXAFAFUhd and 32 with OXAFAFUld. The response rate with OXAFAFU [44%; 95% confidence interval (CI) 35% to 52%] was significantly higher (P=0.029) than that of IRIFAFU (31%; 95% CI 23% to 40%). Occurrence of grade > or =3 neutropenia with OXAFAFUld was similar to that for IRIFAFU (29% versus 31%), while severe diarrhoea was significantly lower (12% versus 24%). Median failure-free survival (7 versus 5.8 months; P=0.046) and overall survival of patients (18.9 versus 15.6 months; P=0.032) were significantly prolonged with OXAFAFU.
  
  
  CONCLUSIONS
  OXAFAFU was more active and less toxic than IRIFAFU, and it should be preferred in the first-line treatment of advanced colorectal cancer patients.
authors.affiliation: Department of Medical Oncology, National Tumour Institute, Naples, Italy. pasqualecomella@libero.it
authors.forename: P
authors.initials: P
authors.lastname: Comella
authors.forename: B
authors.initials: B
authors.lastname: Massidda
authors.forename: G
authors.initials: G
authors.lastname: Filippelli
authors.forename: S
authors.initials: S
authors.lastname: Palmeri
authors.forename: D
authors.initials: D
authors.lastname: Natale
authors.forename: A
authors.initials: A
authors.lastname: Farris
authors.forename: F
authors.initials: F
authors.lastname: De Vita
authors.forename: F
authors.initials: F
authors.lastname: Buzzi
authors.forename: S
authors.initials: S
authors.lastname: Tafuto
authors.forename: L
authors.initials: L
authors.lastname: Maiorino
authors.forename: S
authors.initials: S
authors.lastname: Mancarella
authors.forename: S
authors.initials: S
authors.lastname: Leo
authors.forename: V
authors.initials: V
authors.lastname: Lorusso
authors.forename: L
authors.initials: L
authors.lastname: De Lucia
authors.forename: M
authors.initials: M
authors.lastname: Roselli
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil