Noninflammatory Destruction of Actinic Keratoses by Fluorouracil

Breza, Thomas S.; Taylor, J. Richard; Eaglstein, William H.

doi:10.1001/archderm.1976.01630330026006

Cited by 44 publications

(12 citation statements)

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“…Several studies suggest that it is not necessary for the resolution of the lesion (Breza et al, 1976;Pearlman et al, 1986). Therefore, there could be value in combining 5-FU with an anti-inflammatory drug such as celecoxib.…”

mentioning

confidence: 99%

Treatment with 5-Fluorouracil and Celecoxib Displays Synergistic Regression of Ultraviolet Light B-Induced Skin Tumors

Wilgus

Breza

Tober

et al. 2004

Journal of Investigative Dermatology

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Standard chemotherapeutic agents used for the treatment of pre-cancerous skin lesions and non-melanoma skin cancers are not completely effective. Several studies have suggested that repeated inflammatory sunburn reactions, which include the induction of cyclooxygenase-2 (COX-2) and the subsequent production of prostaglandins, play a role in skin cancer development. COX-2 inhibition has been demonstrated to be a potent means of preventing skin cancer development in mice; however, COX-2 inhibitors alone are not effective as chemotherapeutic agents. Data in a variety of cancer types suggest greater efficacy in treating tumors with combination chemotherapies. Therefore, we hypothesized that a combination of the chemotherapeutic agent 5-fluorouracil (5-FU) and the COX-2 inhibitor and anti-inflammatory drug celecoxib would act synergistically to regress tumors in a murine model of ultraviolet light B- (UVB-) induced carcinogenesis. We found that topical treatment with 5-FU and celecoxib together was up to 70% more effective in reducing the number of UVB-induced skin tumors than 5-FU treatment alone. Our data suggest that more effective chemotherapy regimens can be developed to treat the millions of pre-cancerous and cancerous skin lesions that arise every year, which could ultimately lead to a significant reduction in costs and cosmetic defects (scarring) associated with surgical interventions.

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confidence: 99%

Treatment with 5-Fluorouracil and Celecoxib Displays Synergistic Regression of Ultraviolet Light B-Induced Skin Tumors

Wilgus

Breza

Tober

et al. 2004

Journal of Investigative Dermatology

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“…9,13,15,[23][24][25][26][27][28][29] Seventeen studies were excluded since they did not meet the inclusion criteria for various reasons (Table I). [30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] Meta-analysis of 5-Fluorouracil The efficacy rates found for treating actinic keratoses of the face and/or anterior bald scalp with topical fluorouracil are summarized in Table II.…”

Section: Resultsmentioning

confidence: 99%

“…[30][31][32][33][34][35][36][37][38][39][40][41][42][43][44][45][46] Meta-analysis of 5-Fluorouracil The efficacy rates found for treating actinic keratoses of the face and/or anterior bald scalp with topical fluorouracil are summarized in Table II. 9,13,15,[23][24][25]27 The primary efficacy variable was the complete (100%) clearance rate. Complete clearance was defined as the proportion of patients with no clinically visible AK lesions in the treatment are at the post-treatment followup visit.…”

Section: Resultsmentioning

confidence: 99%

“…Patient response was quite variable among these studies. Breza et al 23 performed a split-face trial using 1% 5-FU alone and 1% 5-FU in combination with topical triamcinolone acetonide to determine its effectiveness in suppressing the unpleasant, painful inflammatory reaction caused by topical 5-FU when used as a therapy for AK. At one month post-treatment, 70% of the subjects had complete clearance of lesions.…”

Section: Resultsmentioning

confidence: 99%

“…A number of studies have been conducted to determine the efficacy, safety, and optimal treatment regimens of 5-FU in the management of AK. 9,13,15,23,38,[51][52][53][54] The mode of action of 5-FU is wellunderstood and relates to the depletion of thymidine resulting in a reduction of DNA synthesis in actively proliferating cells. This action leads to chemotoxic death of AK cells and can be associated with a local inflammatory reaction.…”

Section: Discussionmentioning

confidence: 99%

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