Long-Term Therapy With Low-Dose Isotretinoin for Prevention of Basal Cell Carcinoma: A Multicenter Clinical Trial

Tangrea, Joseph A.; Edwards, Brenda K.; Taylor, Philip R.; Hartman, Anne M.; Peck, Gary L.; Salasche, Stuart J.; Menon, Padman; Benson, Paul M.; Mellette, J. Ramsey; Guill, Marshall A.; Robinson, June K.; Guin, Jere D.; Stoll, Howard L.; Grabski, William J.; Winton, George B.

doi:10.1093/jnci/84.5.328

Cited by 150 publications

(74 citation statements)

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“…125 Oral retinoids (acitretin, oral retinol, and isotretinoin) also do not appear to reduce the incidence of BCC in those with a history of a keratinocyte cancer. [126][127][128][129] Limited evidence is available to support the utility of other agents, including oral nicotinamide, a-difluoromethylornithine, and celecoxib, in reducing the risk for keratinocyte cancer in patients with history of BCC. There is early evidence from a small trial that oral nicotinamide may reduce the risk for subsequent keratinocyte carcinoma in nonimmunosuppressed individuals with a history of such Table XIII.…”

Section: Follow-up and Reducing Risk For Future Skin Cancersmentioning

confidence: 99%

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Guidelines of care for the management of basal cell carcinoma

Baum¹,

Bordeaux²,

Brown³

et al. 2018

Journal of the American Academy of Dermatology

315

219

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Basal cell carcinoma (BCC) is the most common form of human cancer, with a continually increasing annual incidence in the United States. When diagnosed early, the majority of BCCs are readily treated with office-based therapy, which is highly curative. In these evidence-based guidelines of care, we provide recommendations for the management of patients with BCC, as well as an in-depth review of the best available literature in support of these recommendations. We discuss biopsy techniques for a clinically suspicious lesion and offer recommendations for the histopathologic interpretation of BCC. In the absence of a formal staging system, the best available stratification based on risk for recurrence is reviewed. With regard to treatment, we provide recommendations on treatment modalities along a broad therapeutic spectrum, ranging from topical agents and superficially destructive modalities to surgical techniques and systemic therapy. Finally, we review the available literature and provide recommendations on prevention and the most appropriate follow-up for patients in whom BCC has been diagnosed. ( J Am Acad Dermatol

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Section: Follow-up and Reducing Risk For Future Skin Cancersmentioning

confidence: 99%

“…[116][117][118][119]123,[125][126][127][128][129][130][131][132][133][134][135][136][137][138][139][140][141] …”

Section: Follow-up and Reducing Risk For Future Skin Cancersunclassified

Guidelines of care for the management of basal cell carcinoma

Baum¹,

Bordeaux²,

Brown³

et al. 2018

Journal of the American Academy of Dermatology

315

219

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“…Retinoids other than retinol have been most commonly used in human chemoprevention trials (2,3,5,6). A disadvantage of one of the most commonly tested synthetic retinoids, isotretinoin, is that it causes adverse effects such as increases in triacylglycerol concentrations and skeletal changes even at relatively low doses (5,7).…”

Section: Introductionmentioning

confidence: 99%

Effects of long-term intake of retinol on selected clinical and laboratory indexes

Cartmel

Moon

Levine

1999

The American Journal of Clinical Nutrition

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Background:Chemopreventive agents developed to be used in a moderate-risk but otherwise healthy population need to be both efficacious and to have minimal adverse effects. Objective: The objective of this study was to evaluate the adverse effects of long-term retinol intake in a skin cancer chemoprevention trial in a large population at moderate risk for skin cancer. Design: Participants (n = 2297) were randomly assigned to receive retinol [7576 retinol equivalents (RE), or 25 000 IU] or a placebo daily. The adverse effects of retinol intake were studied by monitoring 14 clinical symptoms and laboratory indexes. The median follow-up time was 3.8 y.Results: No adverse effects concerning the 14 symptoms were observed. Significant differences in alkaline phosphatase (P < 0.0001), triacylglycerol (P < 0.0001), cholesterol (P = 0.04), and HDL (P = 0.01) were observed over time between the 2 groups. After 49 mo of follow-up, alkaline phosphatase was 7% higher, triacylglycerol was 11% higher, cholesterol was 3% higher, and HDL was 1% lower in the retinol group than in the placebo group. Conclusions: Because a 1% increase in cholesterol concentrations has been reported to be associated with a 2% increase in coronary artery disease risk, long-term ingestion of 7576 RE vitamin A/d should be considered with caution. However, further studies are needed to confirm this finding.Am J Clin Nutr 1999;69:937-43.

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“…Also, long-term therapy with low doses of systemic retinoids such as isotretinoin/ATRA and 13-cis retinoic acid, was not effective in reducing the occurrence of BCCs at new sites in patients with previously reported small numbers (1, 2) of BCCs (31). The differences between our observations and those observed for skin cancer patients treated with systemic retinoids may be (a) mode of delivery: topical tazarotene application may result in more retinoid reaching the tumor cells; (b) type of retinoid: the human studies were carried out using other pan-RAR agonists (that is, 13-cis retinoic acid and ATRA); from our observations, the outcome of activating different RARs in the skin may be quite different; (c) there may be a species difference in the response to retinoids; and/or (d) the sustained and curative effects of tazarotene applied topically may be specific to microscopic BCCs; previous observations showed that systemic retinoids prevented the occurrence of new BCCs in BCNS patients during therapy but had no effect against the majority of existing BCCs in these patients (10).…”

Section: Discussionmentioning

confidence: 77%

Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis

So¹,

Fujimoto²,

Epstein³

2008

Molecular Cancer Therapeutics

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Basal cell carcinoma (BCC) is the most common human cancer. Patients with basal cell nevus syndrome (Gorlin syndrome) are highly susceptible to developing many BCCs as a result of a constitutive inactivating mutation in one allele of PATCHED 1, which encodes a tumor suppressor that is a major inhibitor of Hedgehog signaling. Dysregulated Hedgehog signaling is a common feature of both hereditary and sporadic BCCs. Recently, we showed remarkable anti-BCC chemopreventive efficacy of tazarotene, a retinoid with retinoic acid receptor (RAR) B/; specificity, in Ptch1+/-mice when treatment was commenced before carcinogenic insults. In this study, we assessed whether the effect of tazarotene against BCC carcinogenesis is sustained after its withdrawal and whether tazarotene is effective against preexisting microscopic BCC lesions. We found that BCCs did not reappear for at least 5 months after topical drug treatment was stopped and that already developed, microscopic BCCs were susceptible to tazarotene inhibition. In vitro, tazarotene inhibited a murine BCC keratinocyte cell line, ASZ001, suggesting that its effect in vivo is by direct action on the actual tumor cells. Down-regulation of Gli1, a target gene of Hedgehog signaling and up-regulation of CRABPII, a target gene of retinoid signaling, were observed with tazarotene treatment. Finally, we investigated the effects of topical applications of other retinoid-related compounds on BCC tumorigenesis in vivo. Tazarotene was the most effective of the preparations studied, and its effect most likely was mediated by RAR; activation. Furthermore, inhibition of basal RAR signaling in the skin promoted BCC carcinogenesis, suggesting that endogenous RAR signaling restrains

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Long-Term Therapy With Low-Dose Isotretinoin for Prevention of Basal Cell Carcinoma: A Multicenter Clinical Trial

Abstract: The toxicity associated with the long-term administration of isotretinoin, even at the low dose used in this trial, must be weighted in planning future prevention trials.

Cited by 150 publications

References 0 publications

Guidelines of care for the management of basal cell carcinoma

Guidelines of care for the management of basal cell carcinoma

Effects of long-term intake of retinol on selected clinical and laboratory indexes

Pharmacologic retinoid signaling and physiologic retinoic acid receptor signaling inhibit basal cell carcinoma tumorigenesis

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