title: Impact of age on the efficacy of newer adjuvant therapies in patients with stage II/III colon cancer: findings from the ACCENT database.
abstract: OBJECTIVE
  Prior studies have suggested that patients with stage II/III colon cancer receive similar benefit from intravenous (IV) fluoropyrimidine adjuvant therapy regardless of age. Combination regimens and oral fluorouracil (FU) therapy are now standard. We examined the impact of age on colon cancer recurrence and mortality after adjuvant therapy with these newer options.
  
  
  METHODS
  We analyzed 11,953 patients age < 70 and 2,575 age ≥ 70 years from seven adjuvant therapy trials comparing IV FU with oral fluoropyrimidines (capecitabine, uracil, or tegafur) or combinations of fluoropyrimidines with oxaliplatin or irinotecan in stage II/III colon cancer. End points were disease-free survival (DFS), overall survival (OS), and time to recurrence (TTR).
  
  
  RESULTS
  In three studies comparing oxaliplatin-based chemotherapy with IV FU, statistically significant interactions were not observed between treatment arm and age (P interaction = .09 for DFS, .05 for OS, and .36 for TTR), although the stratified point estimates suggested limited benefit from the addition of oxaliplatin in elderly patients (DFS hazard ratio [HR], 0.94; 95% CI, 0.78 to 1.13; OS HR, 1.04; 95% CI, 0.85 to 1.27). No significant interactions by age were detected with oral fluoropyrimidine therapy compared with IV FU; noninferiority was supported in both age populations.
  
  
  CONCLUSIONS
  Patients age ≥ 70 years seemed to experience reduced benefit from adding oxaliplatin to fluoropyrimidines in the adjuvant setting, although statistically, there was not a significant effect modification by age, whereas oral fluoropyrimidines retained their efficacy.
authors.affiliation: Dana-Farber Cancer Institute, 450 Brookline Ave, Boston, MA 02215, USA. nj_mccleary@dfci.harvard.edu
authors.forename: Nadine J
authors.initials: NJ
authors.lastname: McCleary
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: Erin
authors.initials: E
authors.lastname: Green
authors.forename: Greg
authors.initials: G
authors.lastname: Yothers
authors.forename: Aimery
authors.initials: A
authors.lastname: de Gramont
authors.forename: Eric
authors.initials: E
authors.lastname: Van Cutsem
authors.forename: Michael
authors.initials: M
authors.lastname: O'Connell
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Twelves
authors.forename: Leonard B
authors.initials: LB
authors.lastname: Saltz
authors.forename: Daniel G
authors.initials: DG
authors.lastname: Haller
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage*; D002166:Camptothecin / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D000069287:Capecitabine; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D003082:Colectomy / Q000379:methods; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology / Q000601:surgery; D016208:Databases, Factual; D003841:Deoxycytidine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives; D018572:Disease-Free Survival; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage* / Q000009:adverse effects / Q000031:analogs & derivatives; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D011379:Prognosis; D011725:Pyridines / Q000008:administration & dosage / Q000009:adverse effects; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D016019:Survival Analysis; D005641:Tegafur / Q000008:administration & dosage / Q000009:adverse effects; D016896:Treatment Outcome
chemical_list: D009944:Organoplatinum Compounds; D011725:Pyridines; C431073:oxiplatin; D003841:Deoxycytidine; D005641:Tegafur; D000069287:Capecitabine; D000077146:Irinotecan; D005472:Fluorouracil; D002166:Camptothecin