title: Comparative effectiveness of oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy for stage III colon cancer.
abstract: BACKGROUND
  The addition of oxaliplatin to adjuvant 5-fluorouracil (5-FU) improves survival of patients with stage III colon cancer in randomized clinical trials (RCTs). However, RCT participants are younger, healthier, and less racially diverse than the general cancer population. Thus, the benefit of oxaliplatin outside RCTs is uncertain.
  
  
  METHODS
  Patients younger than 75 years with stage III colon cancer who received chemotherapy within 120 days of surgical resection were identified from five observational data sources-the Surveillance, Epidemiology, and End Results registry linked to Medicare claims (SEER-Medicare), the New York State Cancer Registry (NYSCR) linked to Medicaid and Medicare claims, the National Comprehensive Cancer Network (NCCN) Outcomes Database, and the Cancer Care Outcomes Research & Surveillance Consortium (CanCORS). Overall survival (OS) was compared among patients treated with oxaliplatin vs non-oxaliplatin-containing adjuvant chemotherapy. Overall survival for 4060 patients diagnosed during 2004-2009 was compared with pooled data from five RCTs (the Adjuvant Colon Cancer ENdpoinTs [ACCENT] group, n = 8292). Datasets were juxtaposed but not combined using Kaplan-Meier curves. Covariate and propensity score adjusted proportional hazards models were used to calculate adjusted survival hazard ratios (HR). Stratified analyses examined effect modifiers. All statistical tests were two-sided.
  
  
  RESULTS
  The survival advantage associated with the addition of oxaliplatin to adjuvant 5-FU was evident across diverse practice settings (3-year OS: RCTs, 86% [n = 1273]; SEER-Medicare, 80% [n = 1152]; CanCORS, 88% [n = 129]; NYSCR-Medicaid, 82% [n = 54]; NYSCR-Medicare, 79% [n = 180]; and NCCN, 86% [n = 438]). A statistically significant improvement in 3-year overall survival was seen in the largest cohort, SEER-Medicare, and in the NYSCR-Medicare cohort (non-oxaliplatin-containing vs oxaliplatin-containing adjuvant therapy, adjusted HR of death: pooled RCTs: HR = 0.80, 95% CI = 0.70 to 0.92, P = .002; SEER-Medicare: HR = 0.70, 95% CI = 0.60 to 0.82, P < .001; NYSCR-Medicare patients aged ≥65 years: HR = 0.58, 95% CI = 0.38 to 0.90, P = .02). The association between oxaliplatin treatment and better survival was maintained in older and minority group patients, as well as those with higher comorbidity.
  
  
  CONCLUSIONS
  The addition of oxaliplatin to 5-FU appears to be associated with better survival among patients receiving adjuvant colon cancer treatment in the community.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, University of Virginia, Charlottesville, VA, USA. deb_schrag@dfci.harvard.edu
authors.forename: Hanna K
authors.initials: HK
authors.lastname: Sanoff
authors.forename: William R
authors.initials: WR
authors.lastname: Carpenter
authors.forename: Christopher F
authors.initials: CF
authors.lastname: Martin
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Sargent
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Meyerhardt
authors.forename: Til
authors.initials: T
authors.lastname: Stürmer
authors.forename: Jason P
authors.initials: JP
authors.lastname: Fine
authors.forename: Jane
authors.initials: J
authors.lastname: Weeks
authors.forename: Joyce
authors.initials: J
authors.lastname: Niland
authors.forename: Katherine L
authors.initials: KL
authors.lastname: Kahn
authors.forename: Maria J
authors.initials: MJ
authors.lastname: Schymura
authors.forename: Deborah
authors.initials: D
authors.lastname: Schrag
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D017024:Chemotherapy, Adjuvant; D017326:Clinical Trials, Phase III as Topic; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D057186:Comparative Effectiveness Research; D015986:Confounding Factors, Epidemiologic; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008498:Medical Record Linkage; D006278:Medicare; D015201:Meta-Analysis as Topic; D008875:Middle Aged; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage*; D000077150:Oxaliplatin; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D012042:Registries; D018426:SEER Program; D016896:Treatment Outcome; D014481:United States
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D005472:Fluorouracil