title: Impact of age and medical comorbidity on adjuvant treatment outcomes for stage III colon cancer: a pooled analysis of individual patient data from four randomized, controlled trials.
abstract: BACKGROUND
  Adjuvant oxaliplatin plus capecitabine or leucovorin/5-fluorouracil (LV/5-FU) (XELOX/FOLFOX) is the standard of care for stage III colon cancer (CC); however, there is disagreement regarding oxaliplatin benefit in patients aged >70. In most analyses, the impact of medical comorbidity (MC) has not been assessed. Efficacy and safety of adjuvant XELOX/FOLFOX versus LV/5-FU were compared with respect to age and MC using pooled data from four randomized, controlled trials, selected for access to patient-level MC data and including commonly endorsed and utilized regimens.
  
  
  METHODS
  Individual data from patients with stage III CC in NSABP C-08, XELOXA, X-ACT, and AVANT were pooled, excluding bevacizumab-treated patients. Patients were grouped by treatment, MC (low versus high), or age (<70 versus ≥70), and compared for disease-free survival (DFS), overall survival (OS), and adverse events (AEs). Multivariable Cox proportional hazards regression controlled for gender, T stage, and N stage.
  
  
  RESULTS
  DFS benefits were shown for XELOX/FOLFOX versus LV/5-FU regardless of age or MC, although benefits were modestly attenuated for patients aged ≥70. Hazard ratios were 0.68 (P < 0.0001) and 0.77 (P < 0.014) for <70 and ≥70 age groups; 0.69 (P < 0.0001) and 0.59 (P < 0.0001) for Charlson Comorbidity Index ≤1 and >1 groups; and 0.70 (P < 0.0001) and 0.58 (P < 0.0001) for National Cancer Institute Combined Index ≤1 and >1 groups. OS was also significantly improved in all groups. Grade 3/4 serious AE rates were comparable across cohorts and MC scores and higher in patients aged ≥70. Oxaliplatin-relevant grade 3/4 AEs, including neuropathy, were comparable across ages and MC scores.
  
  
  CONCLUSIONS
  Results further support consideration of XELOX or FOLFOX as standard treatment options for the adjuvant management of stage III CC in all age groups and in patients with comorbidities, consistent with those who were eligible for these clinical trials.
authors.affiliation: Abramson Cancer Center at the University of Pennsylvania, Philadelphia. Electronic address: daniel.haller@uphs.upenn.edu.
authors.forename: D G
authors.initials: DG
authors.lastname: Haller
authors.affiliation: National Surgical Adjuvant Breast and Bowel Project (NSABP), Pittsburgh.
authors.forename: M J
authors.initials: MJ
authors.lastname: O'Connell
authors.affiliation: Department of Oncology, Florida Cancer Affiliates, Ocala, USA.
authors.forename: T H
authors.initials: TH
authors.lastname: Cartwright
authors.affiliation: Leeds Institute of Cancer and Pathology and St James's University Hospital, Leeds, UK.
authors.forename: C J
authors.initials: CJ
authors.lastname: Twelves
authors.affiliation: US Medical Affairs, Genentech, Inc., South San Francisco.
authors.forename: E F
authors.initials: EF
authors.lastname: McKenna
authors.affiliation: University of Pittsburgh Cancer Institute, Pittsburgh.
authors.forename: W
authors.initials: W
authors.lastname: Sun
authors.affiliation: Tufts University School of Medicine, Boston.
authors.forename: M W
authors.initials: MW
authors.lastname: Saif
authors.affiliation: US Medical Affairs, Genentech, Inc., South San Francisco.
authors.forename: S
authors.initials: S
authors.lastname: Lee
authors.affiliation: Biostatistical Center and University of Pittsburgh Graduate School of Public Health Department of Biostatistics, Pittsburgh, USA.
authors.forename: G
authors.initials: G
authors.lastname: Yothers
authors.affiliation: University Clinic, Martin Luther University, Halle, Germany.
authors.forename: H-J
authors.initials: HJ
authors.lastname: Schmoll
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D002986:Clinical Trials as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000401:mortality* / Q000473:pathology; D015897:Comorbidity; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
keywords: adjuvant chemotherapy; age groups; capecitabine; colon cancer; comorbidity; oxaliplatin