title: Adjuvant chemotherapy for stage III colon cancer: relative dose intensity and survival among veterans.
abstract: BACKGROUND
  Given the paucity of information on dose intensity, the objective of this study is to describe the use of adjuvant chemotherapy for stage III colon cancer, focusing on relative dose intensity (RDI), overall survival (OS) and disease-free survival (DFS).
  
  
  METHODS
  Retrospective cohort of 367 patients diagnosed with stage III colon cancer in 2003-2008 and treated at 19 VA medical centers. Kaplan-Meier curves summarize 5-year OS and 3-year DFS by chemotherapy regimen and RDI, and multivariable Cox proportional hazards regression was used to model these associations.
  
  
  RESULTS
  5-fluorouracil/leucovorin (FU/LV) was the most commonly initiated regimen in 2003 (94.4%) and 2004 (62.7%); in 2005-2008, a majority of patients (60%-74%) was started on an oxaliplatin-based regimen. Median RDI was 82.3%. Receipt of >70% RDI was associated with better 5-year OS (p < 0.001) and 3-year DFS (P = 0.009) than was receipt of ≤70% RDI, with 5-year OS rates of 66.3% and 50.5%, respectively and 3-year DFS rates of 66.1% and 52.7%, respectively. In the multivariable analysis of 5-year OS, oxaliplatin + 5-FU/LV (versus 5-FU/LV) (HR = 0.55; 95% CI = 0.34-0.91), >70% RDI at the first year (HR = 0.58; 95% CI = 0.37-0.89) and married status (HR = 0.66; 95% CI = 0.45-0.97) were associated with significantly decreased risk of death, while age ≥75 (versus 55-64) (HR = 2.06; 95% CI = 1.25-3.40), Charlson Comorbidity Index (HR = 1.17; 95% CI = 1.06-1.30), T4 tumor status (versus T1/T2) (HR = 5.88; 95% CI = 2.69-12.9), N2 node status (HR = 1.68; 95% CI = 1.12-2.50) and bowel obstruction (HR = 2.32, 95% CI = 1.36-3.95) were associated with significantly increased risk. Similar associations were observed for DFS.
  
  
  CONCLUSIONS
  Patients with stage III colon cancer who received >70% RDI had improved 5-year OS. The association between RDI and survival needs to be examined in studies of adjuvant chemotherapy for colon cancer outside of the VA.
authors.affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. sherrie.aspinall@va.gov.|Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Building 30, Pittsburgh, PA, 15240, USA. sherrie.aspinall@va.gov.|University of Pittsburgh, School of Pharmacy, Pittsburgh, PA, USA. sherrie.aspinall@va.gov.
authors.forename: Sherrie L
authors.initials: SL
authors.lastname: Aspinall
authors.affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. chester.good@va.gov.|Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Building 30, Pittsburgh, PA, 15240, USA. chester.good@va.gov.|University of Pittsburgh, School of Pharmacy, Pittsburgh, PA, USA. chester.good@va.gov.|University of Pittsburgh, School of Medicine, Pittsburgh, PA, USA. chester.good@va.gov.
authors.forename: Chester B
authors.initials: CB
authors.lastname: Good
authors.affiliation: Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Building 30, Pittsburgh, PA, 15240, USA. xinhua.zhao@va.gov.
authors.forename: Xinhua
authors.initials: X
authors.lastname: Zhao
authors.affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. fran.cunningham@va.gov.
authors.forename: Francesca E
authors.initials: FE
authors.lastname: Cunningham
authors.affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. bernadette.heron@va.gov.
authors.forename: Bernadette B
authors.initials: BB
authors.lastname: Heron
authors.affiliation: VA Pharmacy Benefits Management Services, Hines, IL, USA. mark.geraci@va.gov.
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authors.lastname: Geraci
authors.affiliation: VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. vida.passero@va.gov.
authors.forename: Vida
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authors.lastname: Passero
authors.affiliation: Center for Health Equity Research and Promotion, VA Pittsburgh Healthcare System, University Drive (151C), Building 30, Pittsburgh, PA, 15240, USA. roslyn@pitt.edu.|University of Pittsburgh Graduate School of Public Health, Pittsburgh, PA, USA. roslyn@pitt.edu.
authors.forename: Roslyn A
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authors.lastname: Stone
authors.affiliation: Division of Clinical Modeling and Decision Sciences, University of Pittsburgh, Pittsburgh, PA, USA. smitkj2@upmc.edu.
authors.forename: Kenneth J
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authors.lastname: Smith
authors.affiliation: VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. renee.summerson@gmail.com.
authors.forename: Renee
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authors.affiliation: VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. jenna.shields@va.gov.
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authors.affiliation: VA Pittsburgh Healthcare System, Pittsburgh, PA, USA. megan.sartore@va.gov.
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authors.affiliation: VA Maine Health Care System, Augusta, ME, USA. daniel.boyle@va.gov.
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authors.affiliation: VA Maine Health Care System, Augusta, ME, USA. sherry.giberti@va.gov.
authors.forename: Sherry
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authors.affiliation: VA Connecticut Healthcare System, West Haven, CT, USA. john.szymanski@va.gov.
authors.forename: John
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authors.lastname: Szymanski
authors.affiliation: Martinsburg VA Medical Center, Martinsburg, WV, USA. douglas.smithd6e05@va.gov.
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authors.affiliation: Richmond VA Medical Center, Richmond, VA, USA. allen.ha@va.gov.
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authors.affiliation: Asheville VA Medical Center, Asheville, NC, USA. jolynn.sessions@msj.org.
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authors.affiliation: James A. Haley Veterans Hospital, Tampa, FL, USA. sdep1482@gmail.com.
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authors.affiliation: James A. Haley Veterans Hospital, Tampa, FL, USA. shane.fishco@va.gov.
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authors.lastname: Fishco
authors.affiliation: Miami VA Medical Center, Miami, FL, USA. gus221@gmail.com.
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authors.affiliation: Miami VA Medical Center, Miami, FL, USA. tanja.lepir@va.gov.
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authors.lastname: Lepir
authors.affiliation: Miami VA Medical Center, Miami, FL, USA. carmela.jean@va.gov.
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authors.affiliation: VA Caribbean Healthcare System, San Juan, PR, USA. lymaris.cruz-diaz@va.gov.
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authors.affiliation: VA Caribbean Healthcare System, San Juan, PR, USA. rebeca.calderon@att.net.
authors.forename: Rebeca
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authors.affiliation: Harry S. Truman VA Hospital, Columbia, MO, USA. janelle.maland@va.gov.
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authors.affiliation: Kansas City VA Medical Center, Kansas City, MO, USA. sean.keefe@va.gov.
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authors.affiliation: Iowa City VA Medical Center, Iowa City, IA, USA. marshall.tague@va.gov.
authors.forename: Marshall
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authors.affiliation: Louis Stokes Cleveland VA Medical Center, Cleveland, OH, USA. ackleone@sbcglobal.net.
authors.forename: Alice
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authors.affiliation: Jesse Brown VA Medical Center, Chicago, IL, USA. brian.glovack@va.gov.
authors.forename: Brian
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authors.affiliation: Jesse Brown VA Medical Center, Chicago, IL, USA. blairjkaplan@gmail.com.
authors.forename: Blair
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authors.affiliation: Portland VA Medical Center, Portland, OR, USA. sean.cosgriff@va.gov.
authors.forename: Sean
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authors.affiliation: Boise VA Medical Center, Boise, ID, USA. lindsay.kaster@va.gov.
authors.forename: Lindsay
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authors.affiliation: Long Beach VA Medical Center, Long Beach, CA, USA. ivy.tonnu-mihara@va.gov.
authors.forename: Ivy
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authors.affiliation: Long Beach VA Medical Center, Long Beach, CA, USA. kimmai.nguyen@gmail.com.
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authors.affiliation: Sacramento VA Medical Center, Mather, CA, USA. kan.lu@va.gov.
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authors.affiliation: Virginia Mason Medical Center, Seattle, WA, USA. kamal.chatta@virginiamason.org.
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mesh_terms: D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage* / Q000009:adverse effects*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000009:adverse effects; D006801:Humans; D002955:Leucovorin / Q000008:administration & dosage / Q000009:adverse effects; D008297:Male; D008875:Middle Aged; D009944:Organoplatinum Compounds / Q000008:administration & dosage / Q000009:adverse effects; D000077150:Oxaliplatin; D012189:Retrospective Studies; D012307:Risk Factors; D016019:Survival Analysis; D016896:Treatment Outcome; D014728:Veterans
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D002955:Leucovorin; D005472:Fluorouracil