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

Abstract

; for the Veterans Affairs Keratinocyte Carcinoma Chemoprevention Trial (VAKCC) Group 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. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00847912

Skin cancer precursor immunotherapy for squamous cell carcinoma prevention

“…Our prospective cohort study has revealed that a 4-day course of calcipotriol plus 5-FU immunotherapy, which effectively eliminated AKs in a double-blind randomized controlled trial (19), is associated with a reduced long-term risk of SCC. Prior to our findings, it had been reported that a 4-week course of topical 5-FU monotherapy for AK field treatment reduces SCC risk on the face and ears at 1 year following treatment; this effect, however, completely dissipates by 2 years (18). In contrast, our results suggest that calcipotriol plus 5-FU treatment is effective in preventing SCC development on the face and scalp within 3 years after the treatment.…”

“…Although they are effective in eliminating AKs, the ability of these cytotoxic and innate-immune-activating agents to prevent SCC in the long term is unknown. The only agent that has been shown to reduce the risk of SCC after treatment cessation is 5-FU, and this benefit is no longer apparent 2 years after treatment (18).…”

The clinical course of actinic keratosis correlates with underlying molecular mechanisms

“…AKs are common preneoplastic lesions that are precursors and risk factors for cutaneous SCCs. 1,6,7,[17][18][19][20] Their prevention and treatment reduce the significant likelihood of developing one or more KCs. 1 We found that the appearance and regression of AKs is a dynamic process.…”

Characteristics of Keratinocyte Carcinomas and Patients with Keratinocyte Carcinomas Following a Single 2–4 Week Course of Topical 5-fluorouracil on the Face and Ears

“…It was recently reported that 5-fluorouracil (5-FU) is effective for prevention of squamous cell carcinoma (SCC) for one year, but not for basal cell carcinoma (BCC) (1). Additionally, a history of 5-FU exposure has been associated with more aggressive BCC subtypes, and we wanted to confirm this finding prospectively by determining the influence of 5-FU on the histopathologic characteristics of BCC and SCC (2).…”