title: Irinotecan/fluorouracil combination in first-line therapy of older and younger patients with metastatic colorectal cancer: combined analysis of 2,691 patients in randomized controlled trials.
abstract: OBJECTIVE
  Uncertainty exists about whether elderly patients benefit to the same extent as younger patients from combination therapy with irinotecan in the first-line treatment of metastatic colorectal cancer (CRC).
  
  
  METHODS
  Combined analysis was carried out with source data from the fluorouracil (FU)/folinic acid (FA) and the irinotecan/FU/FA arms of four first-line, phase III trials of CRC to investigate the efficacy and safety of combination and monotherapy in elderly (age > or = 70 years; n = 599) compared with younger (age < 70 years; n = 2,092) patients.
  
  
  RESULTS
  Response rates were improved with irinotecan-based combination therapy compared with FU/FA in patients both younger than 70 years and > or = 70 years (46.6% v 29.0% P < .0001; and 50.5% v 30.3%, P < .0001, respectively). With irinotecan/FU/FA, progression-free survival was better for both younger (hazard ratio [HR], 0.77; 95% CI, 0.70 to 0.85; P < .0001) and elderly patients (HR, 0.75; 95% CI, 0.61 to 0.90; P = .0026). In younger patients, overall survival was improved with combination therapy (HR, 0.83; 95% CI, 0.75 to 0.92; P = .0003). The same trend was observed in elderly patients (HR, 0.87; 95% CI, 0.72 to 1.05; P = .15). There was no significant interaction between treatment arm and age in the regression analysis. The expected differences in toxicity between combination and monotherapy in elderly and younger patients were observed. A significant interaction between treatment and age (cutoff, 70 years) for vomiting and hepatotoxicity was not confirmed by analysis that used age as a continuous variable.
  
  
  CONCLUSIONS
  Patients older than 70 years of age who were selected for inclusion in phase III trials derived similar benefits as younger patients from irinotecan-containing chemotherapy, and the risk of toxicity was similar.
authors: University Hospital Dresden, Fetscherstr 74, Dresden, Germany 01307. gunnar.folprecht@uniklinikum-dresden.de
authors: Gunnar
authors: G
authors: Folprecht
authors: Matthew T
authors: MT
authors: Seymour
authors: Leonard
authors: L
authors: Saltz
authors: Jean-Yves
authors: JY
authors: Douillard
authors: Hartmut
authors: H
authors: Hecker
authors: Richard J
authors: RJ
authors: Stephens
authors: Timothy S
authors: TS
authors: Maughan
authors: Eric
authors: E
authors: Van Cutsem
authors: Philippe
authors: P
authors: Rougier
authors: Emmanuel
authors: E
authors: Mitry
authors: Ute
authors: U
authors: Schubert
authors: Claus-Henning
authors: CH
authors: Köhne
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects / Q000627:therapeutic use*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D017326:Clinical Trials, Phase III as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D000077146:Irinotecan; D053208:Kaplan-Meier Estimate; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D016896:Treatment Outcome
chemical_list: D000077146:Irinotecan; D002955:Leucovorin; D005472:Fluorouracil; D002166:Camptothecin