ABSTRACT
Keratinocyte carcinoma (KC) is the most common cancer in the United States, with no proven means for prevention other than systemic retinoids, which have significant toxicity, and sunscreen. Topical tretinoin has been used for KC chemoprevention, although this use is unproven. Hence, we conducted the randomized Veterans Affairs Topical Tretinoin Chemoprevention Trial of high-dose topical tretinoin for KC prevention. We randomized 1,131 patients to topical 0.1% tretinoin or a matching vehicle control for 1.5-5.5 years. The primary outcomes were time to development of new basal cell carcinoma (BCC) and new invasive squamous cell carcinoma (SCC) on the face or ears. The effects were not significant (P=0.3 for BCC and P=0.4 for SCC). The proportions of the tretinoin and control groups who developed a BCC at 5 years were 53 and 54% and an invasive SCC at 5 years were 28 and 31%. These differences (95% confidence intervals) were: for BCC, 1.0% (-6.5, 8.6%); for SCC, 3.6% (-3.1, 10.3%). No differences were observed in any cancer-related end points or in actinic keratosis counts. The only quality of life difference was worse symptoms in the tretinoin group at 12 months after randomization. This trial in high-risk patients demonstrates that high-dose topical tretinoin is ineffective at reducing risk of KCs.
Subject(s)
Carcinoma, Basal Cell/prevention & control , Carcinoma, Squamous Cell/prevention & control , Keratinocytes/drug effects , Skin Neoplasms/prevention & control , Tretinoin/administration & dosage , Administration, Topical , Aged , Aged, 80 and over , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Carcinoma, Basal Cell/epidemiology , Carcinoma, Squamous Cell/epidemiology , Female , Humans , Male , Middle Aged , Quality of Health Care , Risk Factors , Skin Neoplasms/epidemiology , Tretinoin/adverse effects , Veterans/statistics & numerical dataSubject(s)
Gangrene/diagnosis , Postoperative Complications/diagnosis , Pyoderma Gangrenosum/diagnosis , Anti-Bacterial Agents/therapeutic use , Gangrene/drug therapy , Humans , Postoperative Complications/drug therapy , Postoperative Complications/microbiology , Prednisolone/therapeutic use , Pyoderma Gangrenosum/drug therapy , Plastic Surgery Procedures/adverse effectsABSTRACT
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. DESIGN: The VATTC Trial was a blinded randomized chemoprevention trial, with 2- to 6-year follow-up. Oversight was provided by multiple independent committees. SETTING: 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. MAIN OUTCOME MEASURES: 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.