title: Superiority of oxaliplatin and fluorouracil-leucovorin compared with either therapy alone in patients with progressive colorectal cancer after irinotecan and fluorouracil-leucovorin: interim results of a phase III trial.
abstract: OBJECTIVE
  In North America, no effective therapy has been available for patients with progressive metastatic colorectal cancer after front-line treatment with irinotecan, bolus fluorouracil (FU), and leucovorin (IFL).
  
  
  METHODS
  Patients with metastatic colorectal cancer who progressed after IFL therapy were randomly assigned to bolus and infusional FU and leucovorin (LV5FU2), single-agent oxaliplatin, or the combination (FOLFOX4). This planned interim analysis evaluated objective response rate (RR), time to tumor progression (TTP), and alleviation of tumor-related symptoms (TRS) in an initial cohort of patients.
  
  
  RESULTS
  Between November 2000 and September 2001, 463 patients from 120 sites in North America were randomly assigned to treatment. FOLFOX4 proved superior to LV5FU2 in all measures of clinical efficacy. Objective RRs determined by an independent radiology panel were 9.9% for FOLFOX4 versus 0% for LV5FU2 (Fisher's exact test, P <.0001). Median TTP was 4.6 months for FOLFOX4 versus 2.7 months for LV5FU2 (two-sided, stratified log-rank test, P <.0001). Relief of TRS occurred in 33% of patients treated with FOLFOX4 versus 12% of patients treated with LVFU2 (chi2 test, P <.001). Single-agent oxaliplatin was not superior to LV5FU2 in any measure of efficacy. Patients treated with FOLFOX4 experienced a higher incidence of clinically significant toxicities than patients treated with LV5FU2, but these toxicities were predictable and did not result in a higher rate of treatment discontinuation or 60-day mortality rate.
  
  
  CONCLUSIONS
  For patients with metastatic colorectal cancer, second-line treatment with FOLFOX4 is superior to treatment with LVFU2 in terms of RR, TTP, and relief of TRS.
authors.affiliation: Vanderbilt-Ingram Cancer Center, 777 Preston Research Building, Nashville, TN 37232-6307, USA. mace.rothenberg@vanderbilt.edu
authors.forename: Mace L
authors.initials: ML
authors.lastname: Rothenberg
authors.forename: Amit M
authors.initials: AM
authors.lastname: Oza
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bigelow
authors.forename: Jordan D
authors.initials: JD
authors.lastname: Berlin
authors.forename: John L
authors.initials: JL
authors.lastname: Marshall
authors.forename: Ramesh K
authors.initials: RK
authors.lastname: Ramanathan
authors.forename: Lowell L
authors.initials: LL
authors.lastname: Hart
authors.forename: Sunil
authors.initials: S
authors.lastname: Gupta
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Garay
authors.forename: Brent G
authors.initials: BG
authors.lastname: Burger
authors.forename: Nathalie
authors.initials: N
authors.lastname: Le Bail
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000077150:Oxaliplatin; D015996:Survival Rate; D014481:United States / Q000453:epidemiology
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin