isotretinoin and Xeroderma-Pigmentosum

Topics: Humans; Immunotherapy; In Vitro Techniques; Isotretinoin; Mutation; Skin Neoplasms; Ultraviolet Rays; Xeroderma Pigmentosum

Topics: Adult; Benzoates; Bowen's Disease; Carcinoma, Basal Cell; Child; Etretinate; Female; Humans; Isotretinoin; Male; Precancerous Conditions; Psoriasis; Retinoids; Skin Diseases; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

To confirm reports that skin cancer can be prevented with retinoids, we conducted a three-year controlled prospective study of oral isotretinoin (also called 13-cis retinoic acid) in five patients with xeroderma pigmentosum who had a history of multiple cutaneous basal-cell or squamous-cell carcinomas. Patients were treated with isotretinoin at a dosage of 2 mg per kilogram of body weight per day for two years and then followed for an additional year, without the drug. Before, during, and after treatment, biopsies of all suspicious lesions were performed, and skin cancers were surgically removed. The patients had a total of 121 tumors (mean, 24; range, 8 to 43) in the two-year interval before treatment. During two years of treatment with isotretinoin, there were 25 tumors (mean, 5; range, 3 to 9), with an average reduction in skin cancers of 63 percent (P = 0.019). After the drug was discontinued, the tumor frequency increased a mean of 8.5-fold (range, 2- to 19-fold) over the frequency during treatment (P = 0.007). Although all patients experienced mucocutaneous toxic effects, and triglyceride, liver-function, or skeletal abnormalities developed in some, high-dose oral isotretinoin was effective in the chemoprophylaxis of skin cancers in patients with xeroderma pigmentosum.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Clinical Trials as Topic; Female; Humans; Isotretinoin; Male; Prospective Studies; Skin Neoplasms; Tretinoin; Xeroderma Pigmentosum

The chemoprevention refers to the use of various types of chemical agents for preventing carcinogenic progression. Systemic retinoids are the most studied chemopreventive agents due to their capacity to regulate cell proliferation and their demonstrated efficacy in several clinical studies.. The aim of the authors was to give precise indications regarding the use of the systemic retinoid in the chemoprevention of non-melanoma skin cancer (NMSC).. The authors reviewed the literature found through a search to MEDLINE (from 2001 to December 2011).. Both acitretin and isotretinoin are effective for the prevention of NMSC. Isotretinoin is preferred in xeroderma pigmentosum and nevoid basal cell carcinoma syndrome, whereas acitretin is more used in transplant recipients, psoriasis and severe sun damage.. Despite numerous studies of the literature concerning retinoids in chemoprevention of NMSC, precise details of the type of retinoid to use, dosage and the duration of this preventive treatment and how to manage side effects in the case of long-lasting treatment are still not uniform and comparable. Moreover, neither guidelines nor approval by Food and Drug Administration exist to regulate the use of retinoids in chemoprevention.

Topics: Acitretin; Basal Cell Nevus Syndrome; Dermatologic Agents; Humans; Isotretinoin; Off-Label Use; Organ Transplantation; Psoriasis; Risk Factors; Skin Neoplasms; Sunlight; Xeroderma Pigmentosum

Topics: Aged; Carcinoma, Basal Cell; Child, Preschool; Colitis; Combined Modality Therapy; Eyelid Neoplasms; Female; Homeopathy; Humans; Isotretinoin; Mistletoe; Patient Compliance; Phytotherapy; Plant Extracts; Recurrence; Xeroderma Pigmentosum

We report the case of a 7-year old boy with xeroderma pigmentosum and a large squamous cell carcinoma of the cheek. He received a combination of isotretinoin (1 mg/kg/day) and chemotherapy for a period of 3 months and showed complete remission of the tumor. Treatment modalities of malignancies in xeroderma pigmentosum are reviewed and discussed in relation to the literature. The advantages of our protocol were emphasized because of the rapid improvement in a short time with minimal side effects.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Child; Cisplatin; Fluorouracil; Humans; Isotretinoin; Keratolytic Agents; Male; Skin Neoplasms; Treatment Outcome; Xeroderma Pigmentosum

Patients with xeroderma pigmentosum (XP) frequently develop sunlight-induced skin cancer. Infrequently, internal neoplasms may also occur. A 21-year-old patient with XP, who had many skin cancers, developed a rare internal tumour - a grade II diffuse fibrillary spinal cord astrocytoma - during a break in a therapeutic trial of isotretinoin for skin cancer prevention. Treatment of neoplasms in XP patients presents special difficulties because of their defect in DNA repair.. The study objective was to raise awareness of the cancer surveillance process in XP patients and the concerns involved in choice of therapy.. Since the spinal cord tumour was inoperable, the patient was treated with x-radiation, continued on isotretinoin treatment and was followed closely for tumour response.. Despite sensitivity to sunlight, the patient had a normal acute response to the x-ray treatment without excessive skin reaction. Serial examinations by magnetic resonance imaging (MRI) starting 8 months after x-ray treatment was initiated, showed a marked gadolinium enhancement followed by regression. This clearing was first seen at 2 years after biopsy and persisted to at least 9 years after treatment.. In contrast to the exaggerated sensitivity to UV radiation, XP patients may tolerate therapeutic doses of x-radiation. Isotretinoin treatment may have contributed to the good response of this spinal cord astrocytoma.

Topics: Adult; Astrocytoma; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Isotretinoin; Keratolytic Agents; Male; Skin Neoplasms; Spinal Cord Neoplasms; Xeroderma Pigmentosum

Xeroderma pigmentosum (XP) is a rare autosomal recessive disorder characterized by sun sensitivity, defective DNA repair, markedly increased susceptibility to skin cancer, and a variety of immunological defects, including defective natural killer (NK) cell activity. Retinoid therapy has been demonstrated to protect effectively against the development of skin cancers in patients with XP, although its mechanism of action is unknown. We describe a series of eight XP patients, six of whom were given oral isotretinoin. The NK cell activity was not affected by low-dose isotretinoin, i.e. 0.5 mg/kg per day. However, higher doses of isotretinoin, e.g. 1.0 mg/kg per day, produced a significant decrease in NK cell function, at the same time as producing a reduction in the frequency of development of skin cancers. Retinoid therapy may have a skin cancer preventing effect by enhancing other immune effector mechanisms or via epithelial cell differentiation.

Topics: Adolescent; Adult; Cells, Cultured; Child; Drug Administration Schedule; Female; Humans; Interleukin-2; Isotretinoin; Keratolytic Agents; Killer Cells, Lymphokine-Activated; Killer Cells, Natural; Male; Middle Aged; Skin Neoplasms; Tumor Necrosis Factor-alpha; Xeroderma Pigmentosum

Topics: Administration, Oral; Basal Cell Nevus Syndrome; Female; Humans; Isotretinoin; Keratolytic Agents; Middle Aged; Organ Transplantation; Postoperative Complications; Practice Guidelines as Topic; Retinoids; Risk Factors; Skin Neoplasms; Xeroderma Pigmentosum

Although sun protection is advocated for skin cancer prevention, sunlight is also important in generation of vitamin D in the skin. There is concern that sun protection may result in an abnormally low level of vitamin D.. To assess the risk of vitamin D deficiency in a sunlight-deprived population, we studied eight ambulatory patients with xeroderma pigmentosum (XP) who practiced intensive sun protection during a chemoprevention study of oral isotretinoin.. We surveyed the patients to determine the extent of sun protection and vitamin D intake and measured the serum levels of two vitamin D metabolites (25-hydroxyvitamin D [25-OHD] and 1,25-dihydroxyvitamin D [1,25-(OH)2D]), calcium, and parathyroid hormone during 6 years.. The patients all wore protective clothing and sunscreens when outdoors. Estimated mean vitamin D intake was normal. The mean values of serum 25-OHD were low normal, but 1,25-(OH)2D, calcium, ionized calcium and parathyroid hormone levels were normal. Lack of seasonal variation in serum 25-OHD indicated rigorous photoprotection.. Despite rigorous sun protection normal vitamin D levels can be maintained in ambulatory patients with XP.

Topics: Administration, Oral; Adolescent; Adult; Ambulatory Care; Calcium; Chemoprevention; Dihydroxycholecalciferols; Female; Follow-Up Studies; Humans; Isotretinoin; Keratolytic Agents; Male; Middle Aged; Parathyroid Hormone; Protective Clothing; Risk Factors; Seasons; Skin; Sunlight; Sunscreening Agents; Vitamin D; Vitamin D Deficiency; Xeroderma Pigmentosum

Xeroderma pigmentosum is a rare recessive disease with sun sensitivity, increased freckling and defective DNA repair. Xeroderma pigmentosum patients have more than a 1000-fold increased risk of developing skin cancer including basal cell carcinoma, squamous cell carcinoma and melanoma. We studied chemoprevention of new skin cancers with oral retinoids in xeroderma pigmentosum patients who had multiple skin cancers. Xeroderma pigmentosum patients were cleared of all pre-existing tumors surgically and then treated with high dose (2 mg/kg/day) oral isotretinoin (13-cis retinoic acid, Accutane) for two years and then for one year off treatment. Patients were examined at regular intervals for new tumor formation and for side effects. Five xeroderma pigmentosum patients had a total of 121 basal or squamous cell carcinomas in 2 years before treatment and only 25 tumors during 2 years of treatment. The tumor frequency increased 8.5-fold after the drug was discontinued (New Engl J Med 318: 1633-1637, 1988). Toxicity (cutaneous, triglyceride, liver-function or skeletal abnormalities) prompted subsequent use of a low dose protocol. Patients were treated initially with 0.5 mg/kg/day oral isotretinoin and the dose was increased sequentially to 1.0 or 1.5 mg/kg/day. We found that toxicity was less with the lower doses. The lowest effective, least toxic dose varied among the xeroderma pigmentosum patients.

Topics: Administration, Oral; Adolescent; Adult; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Child; Female; Humans; Isotretinoin; Male; Middle Aged; Skin Neoplasms; Xeroderma Pigmentosum

Oral administration of isotretinoin (13-cis retinoic acid) was shown previously (Kraemer, K. H., J. J. DiGiovanna, A. N. Moshell, R. E. Tarone, and G. L. Peck. 1988. N. Engl. J. Med. 318:1633-1637) to reduce the frequency of skin cancers in xeroderma pigmentosum (XP) patients. The mechanism of protection was unclear. In the present study, x-ray-induced chromatid damage in PHA-stimulated blood lymphocytes from five XP patients receiving isotretinoin was approximately half that in blood samples from the same patients before or subsequent to treatment. The x-ray-induced chromatid damage in blood lymphocytes from a normal control was reduced significantly by cocultivation with blood or plasma from an XP patient receiving isotretinoin or by addition of 10(-6) M isotretinoin to cultures 1 h before x-irradiation. A similar reduction in x-ray-induced chromatid damage was reported previously by adding to the culture medium, mannitol, a scavenger of the free hydroxyl radical, or catalase, which decomposes hydrogen peroxide; both of these products are generated during ionizing radiation. The present observations suggest that isotretinoin acts as a scavenger of such radiation products, thereby providing protection against x-ray-induced chromatid damage.

Topics: Adult; Aged; Cells, Cultured; Chromatids; DNA Damage; Female; Humans; Isotretinoin; Lymphocytes; Male; Middle Aged; Skin Neoplasms; X-Rays; Xeroderma Pigmentosum