Chemoprevention of Basal and Squamous Cell Carcinoma With a Single Course of Fluorouracil, 5%, Cream A Randomized Clinical Trial

被引:86
作者
Weinstock, Martin A. [1 ,2 ]
Thwin, Soe Soe [3 ]
Siegel, Julia A. [1 ]
Marcolivio, Kimberly [1 ,2 ]
Means, Alexander D. [1 ,2 ]
Leader, Nicholas F. [1 ,2 ]
Shaw, Fiona M. [1 ]
Hogan, Daniel [4 ]
Eilers, David [5 ]
Swetter, Susan M. [6 ]
Chen, Suephy C. [7 ]
Jacob, Sharon E. [8 ]
Warshaw, Erin M. [9 ]
Stricklin, George P. [10 ]
Dellavalle, Robert P. [11 ]
Sidhu-Malik, Navjeet [12 ]
Konnikov, Nellie [13 ]
Werth, Victoria P. [14 ]
Keri, Jonette E. [15 ]
Robinson-Bostom, Leslie [2 ]
Ringer, Robert J. [16 ]
Lew, Robert A. [3 ]
Ferguson, Ryan [13 ]
DiGiovanna, John J. [17 ]
Huang, Grant D. [18 ]
机构
[1] Vet Affairs VA Med Ctr, Ctr Dermatoepidemiol, Providence, RI USA
[2] Brown Univ, Dept Dermatol, Warren Alpert Med Sch, Providence, RI 02912 USA
[3] Massachusetts Vet Epidemiol & Res Informat Ctr MA, Boston Cooperat Studies Program Coordinating Ctr, Boston, MA USA
[4] Bay Pines VA Healthcare Syst, Bay Pines, FL USA
[5] Edward Hines Jr VA Hosp, Hines, IL USA
[6] VA Palo Alto Hlth Care Syst, Palo Alto, CA USA
[7] Atlanta VA Med Ctr, Atlanta, GA USA
[8] VA Loma Linda Healthcare Syst, Loma Linda, CA USA
[9] Minneapolis VA Hlth Care Syst, Minneapolis, MN USA
[10] VA Tennessee Valley Healthcare Syst, Nashville, TN USA
[11] Denver VA Med Ctr, Denver, CO USA
[12] Durham VA Med Ctr, Durham, NC USA
[13] Boston VA Hlth Care Syst, Boston, MA USA
[14] Philadelphia VA Med Ctr, Philadelphia, PA USA
[15] Miami VA Healthcare Syst, Miami, FL USA
[16] VA Clin Res Pharm Coordinating Ctr, Albuquerque, NM USA
[17] NCI, Ctr Canc Res, Bethesda, MD 20892 USA
[18] Cooperat Studies Program Cent Off, Washington, DC USA
关键词
NONMELANOMA SKIN-CANCER; MULTIPLE KERATINOCYTE CARCINOMAS; ACTINIC KERATOSIS TREATMENT; 5-FLUOROURACIL; NICOTINAMIDE; PREVENTION; VALIDATION; PREDICTORS; TOXICITY; EFFICACY;
D O I
10.1001/jamadermatol.2017.3631
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
IMPORTANCE Keratinocyte carcinoma (ie, cutaneous basal and squamous cell carcinoma) is the most common cancer in the United States. OBJECTIVE To determine whether topical fluorouracil could prevent surgically treated keratinocyte carcinoma. DESIGN, SETTING, AND PARTICIPANTS The Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial was a randomized, double-blind, placebo-controlled trial of topical fluorouracil for chemoprevention of keratinocyte carcinoma. Participants were recruited from May 2009 to September 2011 from 12 Veterans Affairs medical centers and followed until June 30, 2013. Participants were veterans (n = 932) with a history of at least 2 keratinocyte carcinomas in the past 5 years; almost all were white males and the median age was 70 years. INTERVENTIONS Application of fluorouracil, 5%, (n = 468) or vehicle control cream (n = 464) to the face and ears twice daily for 2 to 4 weeks upon randomization. MAIN OUTCOMES AND MEASURES Surgically treated keratinocyte, basal cell, and squamous cell carcinoma risk on the face and ears in the first year after enrollment; and time to first surgically treated keratinocyte, basal cell, and squamous cell carcinoma. The a priori hypothesis was that fluorouracil would be effective in preventing these cancers. RESULTS Of 932 participants (916 men [98%]; 926 white [99%]; median age, 70 years), 299 developed a basal cell carcinoma end point (95 in year 1) and 108 developed a squamous cell carcinoma end point (25 in year 1) over 4 years (median follow-up, 2.8 years). Over the entire study, there was no difference between treatment groups in time to first keratinocyte, basal cell, or squamous cell carcinoma. During the first year, however, 5 participants (1%) in the fluorouracil group developed a squamous cell carcinoma vs 20 (4%) in the control group, a 75%(95% CI, 35%-91%) risk reduction (P = .002). The 11% reduction in basal cell carcinoma risk during year 1 (45 [10%] in the fluorouracil group vs 50 [11%] in the control group) was not statistically significant (95% CI, 39% reduction to 31% increase), nor was there a significant effect on keratinocyte carcinoma risk. However, a reduction in keratinocyte carcinomas treated with Mohs surgery was observed. CONCLUSIONS AND RELEVANCE A conventional course of fluorouracil to the face and ears substantially reduces surgery for squamous cell carcinoma for 1 year without significantly affecting the corresponding risk for basal cell carcinoma.
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页码:167 / 174
页数:8
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