title: Topical tretinoin therapy and all-cause mortality.
abstract: OBJECTIVE
  To evaluate the relation of topical tretinoin, a commonly used retinoid cream, with all-cause mortality in the Veterans Affairs Topical Tretinoin Chemoprevention Trial (VATTC). The planned outcome of this trial was risk of keratinocyte carcinoma, and systemic administration of certain retinoid compounds has been shown to reduce risk of this cancer but has also been associated with increased mortality risk among smokers.
  
  
  METHODS
  The VATTC Trial was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up. Oversight was provided by multiple independent committees.
  
  
  METHODS
  US Department of Veterans Affairs medical centers. Patients A total of 1131 veterans were randomized. Their mean age was 71 years. Patients with a very high estimated short-term risk of death were excluded. Interventions Application of tretinoin, 0.1%, or vehicle control cream twice daily to the face and ears.
  
  
  METHODS
  Death, which was not contemplated as an end point in the original study design.
  
  
  RESULTS
  The intervention was terminated 6 months early because of an excessive number of deaths in the tretinoin-treated group. Post hoc analysis of this difference revealed minor imbalances in age, comorbidity, and smoking status, all of which were important predictors of death. After adjusting for these imbalances, the difference in mortality between the randomized groups remained statistically significant.
  
  
  CONCLUSIONS
  We observed an association of topical tretinoin therapy with death, but we do not infer a causal association that current evidence suggests is unlikely.
authors.affiliation: Dermatoepidemiology Unit, VA Medical Center, 111D, 830 Chalkstone Ave, Providence, RI 02908, USA. maw@brown.edu
authors.forename: Martin A
authors.initials: MA
authors.lastname: Weinstock
authors.forename: Stephen F
authors.initials: SF
authors.lastname: Bingham
authors.forename: Robert A
authors.initials: RA
authors.lastname: Lew
authors.forename: Russell
authors.initials: R
authors.lastname: Hall
authors.forename: David
authors.initials: D
authors.lastname: Eilers
authors.forename: Robert
authors.initials: R
authors.lastname: Kirsner
authors.forename: Mark
authors.initials: M
authors.lastname: Naylor
authors.forename: James
authors.initials: J
authors.lastname: Kalivas
authors.forename: Gary
authors.initials: G
authors.lastname: Cole
authors.forename: Kimberly
authors.initials: K
authors.lastname: Marcolivio
authors.forename: Joseph
authors.initials: J
authors.lastname: Collins
authors.forename: John J
authors.initials: JJ
authors.lastname: Digiovanna
authors.forename: Julia E
authors.initials: JE
authors.lastname: Vertrees
mesh_terms: D000287:Administration, Topical; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects*; D002280:Basal Cell Carcinoma / Q000517:prevention & control; D002294:Carcinoma, Squamous Cell / Q000517:prevention & control; D002423:Cause of Death; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D012878:Skin Neoplasms / Q000517:prevention & control*; D014212:Tretinoin / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D000970:Antineoplastic Agents; D014212:Tretinoin