Topical tretinoin therapy and all-cause mortality.
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.
Weinstock
Martin A
MA
Dermatoepidemiology Unit, VA Medical Center, 111D, 830 Chalkstone Ave, Providence, RI 02908, USA. maw@brown.edu
Bingham
Stephen F
SF
Lew
Robert A
RA
Hall
Russell
R
Eilers
David
D
Kirsner
Robert
R
Naylor
Mark
M
Kalivas
James
J
Cole
Gary
G
Marcolivio
Kimberly
K
Collins
Joseph
J
Digiovanna
John J
JJ
Vertrees
Julia E
JE
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*
D000970:Antineoplastic Agents; D014212:Tretinoin