Treatment and prevention of basal cell carcinoma with oral isotretinoin

doi:10.1016/S0190-9622(88)70162-0

Journal of the American Academy of Dermatology

Volume 19, Issue 1, Part 2, July 1988, Pages 176-185

https://doi.org/10.1016/S0190-9622(88)70162-0 Get rights and content

Twelve patients with multiple basal cell carcinomas resulting from varying causes were treated with high-dose oral isotretinoin (mean daily dosage:3.1 mg/kg/day) for a mean of 8 months. Of the 270 tumors monitored in these patients, only 8% underwent complete clinical and histologic regression. All patients developed moderate to severe acute toxicities, leading five patients to withdraw from the study. Retinoid skeletal toxicity was identified in two patients who were examined after long-term therapy. Lower doses of isotretinoin (0.25 to 1.5 mg/kg/day) were ineffective for chemotherapy but demonstrated a chemopreventive effect in a subset of three patients who received these lower doses for 3 to 8 years. Two of these three patients have been observed after discontinuation of therapy. In one patient with a history of arsenic exposure, only one new tumor has appeared in a 27-month posttreatment observation period;in the other patient with the nevoid basal cell carcinoma syndrome, 29 new tumors have appeared within a 13-month period. This suggests that the need for long-term maintenance therapy with isotretinoin for chemoprevention of basal cell carcinoma may depend on the underlying cause of the skin cancers.

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Cited by (101)

Guidelines for the diagnosis and treatment of basal cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology
2023, ESMO Open
Basal cell carcinoma (BCC) is the most common form of cancer, with a high impact on the public health burden and social costs. Despite the overall prognosis for patients with BCC being excellent, if lesions are allowed to progress, or in a small subset of cases harboring an intrinsically aggressive biological behavior, it can result in local spread and significant morbidity, and conventional treatments (surgery and radiotherapy) may be challenging. When a BCC is not amenable to either surgery or radiotherapy with a reasonable curative intent, or when metastatic spread occurs, systemic treatments with Hedgehog inhibitors are available. These guidelines were developed, applying the GRADE approach, on behalf of the Italian Association of Medical Oncologists (AIOM) to assist clinicians in treating patients with BCC. They contain recommendations with regard to the diagnosis, treatment and follow-up, from primitive tumors to those locally advanced or metastatic, addressing the aspects of BCC management considered as priorities by a panel of experts selected by AIOM and other national scientific societies. The use of these guidelines in everyday clinical practice should improve patient care.
Consensus on the use of oral isotretinoin in dermatology - Brazilian Society of Dermatology
2020, Anais Brasileiros de Dermatologia
Citation Excerpt :
Details of the studies that used it for treatment are presented in Table 5.172–175 The reported indications for prevention include: multiple non-melanoma skin cancers (> 5 per year); multiple actinic keratoses (AKs); eruptive keratoacanthomas or occurring in transplanted and/or immunosuppressed patients, xeroderma pigmentosum, exposure to chronic phototherapy, and verruciform epidermodysplasia.171,176–183 Little is known about the use of retinoids in multiple AKs and field cancerization in immunocompetent or immunodepressed patients, at risk of developing non-melanoma skin cancer.
Isotretinoin is a synthetic retinoid, derived from vitamin A, with multiple mechanisms of action and highly effective in the treatment of acne, despite common adverse events, manageable and dose-dependent. Dose-independent teratogenicity is the most serious. Therefore, off-label prescriptions require strict criteria.
To communicate the experience and recommendation of Brazilian dermatologists on oral use of the drug in dermatology.
Eight experts from five universities were appointed by the Brazilian Society of Dermatology to develop a consensus on indications for this drug. Through the adapted DELPHI methodology, relevant elements were listed and an extensive analysis of the literature was carried out. The consensus was defined with the approval of at least 70% of the experts.
With 100% approval from the authors, there was no doubt about the efficacy of oral isotretinoin in the treatment of acne, including as an adjunct in the correction of scars. Common and manageable common adverse events are mucocutaneous in nature. Others, such as growth retardation, abnormal healing, depression, and inflammatory bowel disease have been thoroughly investigated, and there is no evidence of a causal association; they are rare, individual, and should not contraindicate the use of the drug. Regarding unapproved indications, it may represent an option in cases of refractory rosacea, severe seborrheic dermatitis, stabilization of field cancerization with advanced photoaging and, although incipient, frontal fibrosing alopecia. For keratinization disorders, acitretin performs better. In the opinion of the authors, indications for purely esthetic purposes or oil control are not recommended, particularly for women of childbearing age.
Approved and non-approved indications, efficacy and adverse effects of oral isotretinoin in dermatology were presented and critically evaluated.
Familial skin cancer syndromes Increased risk of nonmelanotic skin cancers and extracutaneous tumors
2016, Journal of the American Academy of Dermatology
Citation Excerpt :
As in cases of sporadic BCC, excision as well as electrodessication and curettage are often used; however, because of concerns of disfigurement and discomfort from multiple surgical procedures, CO2 laser therapy in combination with Mohs micrographic surgery can be an option in select patients.23 In addition, superficial BCCs can be managed by topical 5% 5-fluorouracil (5-FU), topical imiquimod, or photodynamic therapy.24-27 A placebo controlled phase III randomized trial has also found that vismodegib, a smoothened (SMO) antagonist and SHH pathway inhibitor, can reduce the tumor burden in patients with BCNS.28
Nonmelanoma skin cancers (NMSCs) represent the most common malignancies worldwide, with reported incidence rising each year. Both cutaneous squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), as well as other NMSCs, represent complex diseases with a combination of environmental and genetic risk factors. In general, hereditary cancer syndromes that increase the risk of NMSC fall under several broad categories: those associated with immunodeficiencies, those that affect skin pigmentation, and those that perturb key molecular pathways involved in the pathogenesis of NMSCs. Many of the syndromes are also associated with extracutaneous manifestations, including internal malignancies; therefore, most require a multidisciplinary management approach with a medical geneticist. Finally, dermatologists play a critical role in the diagnosis and management of these conditions, because cutaneous findings are often the presenting manifestations of disease.
Retinoic acid and the ocular surface
2015, Survey of Ophthalmology
Citation Excerpt :
These applications indicate that retinoic acid has the potential to contain, but not cure, neoplastic lesions.153 Since then, many authors have demonstrated the ability of retinoic acid, in synergistic combination with other agents such as interferon, to treat and sometimes even reverse squamous metaplasia in the eye50,152,171,172,185 and other areas of the body, including the skin, cervix, and breast cancer cell lines.3,59,78,113,123 Currently, interferon alpha-2b has been combined with retinoic acid 0.01% twice daily to treat ocular surface dysplasias.143
Retinoic acid is known to improve cutaneous wound healing and, in recent years, its application in ophthalmology has been investigated. This review looks at the role of retinoic acid on the ocular surface. Retinoic acid can be produced synthetically, and its mechanism of action includes both nuclear and non-nuclear receptor mediated pathways. It has been shown to improve full and partial thickness corneal lacerations as well as corneal epithelial defects. Retinoic acid plays a critical role in cell differentiation at the cornea, conjunctiva, and limbus, and may have an anti-tumor role. Its positive effect is only achieved at the correct concentration, however; excess concentrations of retinoic acid have a deleterious effect. The main limiting factor of retinoic acid use is its detrimental effect on meibomian glands, resulting in cell death, atrophy of acini, hyposecretion of oils, and altered gene expression, eventually resulting in dry eye symptoms. This effect is reversible on discontinuation of the drug.
Basal cell nevus syndrome: From DNA to therapeutics
2020, Clinics in Dermatology
Citation Excerpt :
Although no controlled trials have definitively established the validity of this measure in this population, its efficacy can be inferred by the reduced prevalence of BCCs in African Americans with this syndrome.4 Several studies suggest that chemoprevention with systemic retinoids (isotretinoin >4 mg/kg and etretinate 0.7 to 1 mg/kg) may reduce the rate of development of new BCCS47,48; however, the clinical benefits are less than those seen in patients with multiple cutaneous SCCs and must be balanced against the potential adverse effects associated with chronic systemic retinoid exposure. Secondary prevention involves close surveillance of BCNS patients in an effort to promote earlier detection and treatment of new lesions.
Basal cell nevus syndrome, also known as Gorlin syndrome, is a hereditary cancer syndrome associated with multiple basal cell carcinomas, congenital defects, and nondermatologic tumors. This disease is autosomal dominant with variable expressivity and is caused by abnormalities in the sonic hedgehog signaling pathway. Management requires a multidisciplinary approach and should include the biopsychosocial needs of patients and their families. Genetic testing is necessary to confirm an unclear diagnosis, evaluate at-risk relatives, and assist with family planning.
The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review
2022, International Journal of Molecular Sciences

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¹: From the Dermatology Branch, National Cancer Institute

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Journal of the American Academy of Dermatology

References (26)

The effect of vitamin A acid on hyperkeratin-ization and the keratoacanthoma

J Invest Dermatol

Topical vitamin A acid therapy for cutaneous metastatic melanoma

Lancet

Effects of vitamin A and its analogs (retinoids) on normal and neoplastic cells

Biochim Biophys Acta

Chemoprevention of basal cell carcinoma with isotretinoin

J Am Acad Dermatol

Vertebral abnormalities associated with synthetic retinoid use

J Am Acad Dermatol

Retinoids and the immune system: immunostimulation of vitamin A

Retinoids and cancer

Retinoids, a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology

Experientia

Treatment of keratoacanthomas with oral 13-cis-retinoic acid

New Engl J Med

Phase II trial of 13-cis-retinoic acid in metastatic breast cancer and other malignancies

Proc Am Soc Clin Oncol

Retinoids in clinical dermatology

Topical aromatic retinoid in the treatment of ichthyosis vulgaris

Metastatic basal cell carcinoma

J Dermatol Surg Oncol

Cited by (101)

Guidelines for the diagnosis and treatment of basal cell carcinoma: a GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology

Consensus on the use of oral isotretinoin in dermatology - Brazilian Society of Dermatology

Familial skin cancer syndromes Increased risk of nonmelanotic skin cancers and extracutaneous tumors

Retinoic acid and the ocular surface

Basal cell nevus syndrome: From DNA to therapeutics

The Use of Retinoids for the Prevention and Treatment of Skin Cancers: An Updated Review