Tretinoin and the prevention of keratinocyte carcinoma (Basal and squamous cell carcinoma of the skin): a veterans affairs randomized chemoprevention trial.
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.
Dermatoepidemiology Unit, VA Medical Center, Providence, Rhode Island 02908, USA. maw@brown.edu
Martin A
MA
Weinstock
Stephen F
SF
Bingham
John J
JJ
Digiovanna
Amilcar E
AE
Rizzo
Kim
K
Marcolivio
Russell
R
Hall
David
D
Eilers
Mark
M
Naylor
Robert
R
Kirsner
James
J
Kalivas
Gary
G
Cole
Julia E
JE
Vertrees
D000287:Administration, Topical; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000009:adverse effects; D002280:Basal Cell Carcinoma / Q000453:epidemiology / Q000517:prevention & control*; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000517:prevention & control*; D005260:Female; D006801:Humans; D015603:Keratinocytes / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D011787:Quality of Health Care; D012307:Risk Factors; D012878:Skin Neoplasms / Q000453:epidemiology / Q000517:prevention & control*; D014212:Tretinoin / Q000008:administration & dosage* / Q000009:adverse effects; D014728:Veterans / Q000706:statistics & numerical data
D000970:Antineoplastic Agents; D014212:Tretinoin