title: 5-Fluorouracil and folinic acid with or without CPT-11 in advanced colorectal cancer patients: a multicenter randomised phase II study of the Southern Italy Oncology Group.
abstract: OBJECTIVE
  The combination regimen CPT-11 plus bolus and infusion 5-fluorouracil (5-FU) with high-dose leucovorin (hybrid regimen LV5FU2) has been tested for activity and toxicity against advanced colorectal carcinoma in a randomised, multicenter phase II trial.
  
  
  METHODS
  A total of 102 chemotherapy-naïve patients were randomised in a 1:2 fashion to receive: leucovorin 100 mg/m2 administered as a two-hour infusion before 5-FU 400 mg/m2 as an intravenous bolus, and FU 600 mg/m2 as a 22-hour infusion immediately after 5-FU bolus injection repeated on days 1 and 2 (LV5FU2 regimen, arm A, 34 patients) or CPT-11 at 180 mg/m2 (150 mg/m2 for patients of age > or = 70 and < 75 years) only on day 1 immediately before LV5FU2 therapy (LV5FU2 + CPT-11 regimen, arm B 68 patients). Both treatments were repeated every two weeks. The presence of a calibration arm assured consistency and more realistic evaluation of results achieved with the LV5FU2 + CTP-II regimen.
  
  
  RESULTS
  Thirty-three and sixty-four patients were evaluable in arm A and B, respectively. The overall response rate was 18% in arm A (95% CI: 7%-34%) and 40% in arm B (95% CI: 28%-52%). Median time to progression, median duration of response and survival were similar in both groups. Responders (CR + PR) survived statistically longer than non-responders only in arm B (20 vs. 10 months, P = 0.0016). All patients were evaluable for toxicity which was mild in both groups; gastrointestinal disturbances were the most common. There were no treatment-related deaths. Grade 3-4 toxicity was uncommon in both arms.
  
  
  CONCLUSIONS
  The addition of CPT-11 to the hybrid LV5FU2 regimen provided a significant overall response rate (40%) with relatively mild toxicity. The overall response rate was 18% in patients treated with LV5FU2 alone in the calibration arm. Thus, considering other encouraging data from the literature, the CPT-11 + FU-LV combination therapy can be regarded as a new, very effective treatment option for first-line treatment of advanced colorectal cancer patients.
authors.affiliation: Medical and Experimental Oncology Unit Oncology Institute, Bari, Italy.
authors.forename: E
authors.initials: E
authors.lastname: Maiello
authors.forename: V
authors.initials: V
authors.lastname: Gebbia
authors.forename: F
authors.initials: F
authors.lastname: Giuliani
authors.forename: G
authors.initials: G
authors.lastname: Paoletti
authors.forename: N
authors.initials: N
authors.lastname: Gebbia
authors.forename: S
authors.initials: S
authors.lastname: Cigolari
authors.forename: S
authors.initials: S
authors.lastname: Fortunato
authors.forename: T
authors.initials: T
authors.lastname: Pedicini
authors.forename: N
authors.initials: N
authors.lastname: Borsellino
authors.forename: M
authors.initials: M
authors.lastname: Lopez
authors.forename: G
authors.initials: G
authors.lastname: Colucci
mesh_terms: D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D007275:Injections, Intravenous; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin