Isotretinoin in Preventing Skin Cancer

OBJECTIVES: I. Determine the lowest effective dose of oral isotretinoin for long-term therapy that is capable of reducing the rate of formation of new skin cancers in patients with xeroderma pigmentosum or nevoid basal cell carcinoma syndrome. II. Determine the possible side effects associated with long-term use of isotretinoin in this patient population.

OUTLINE: Patients are stratified according to disease type (xeroderma pigmentosum vs nevoid basal cell carcinoma syndrome). Patients not previously treated with isotretinoin receive oral isotretinoin daily for 2 years and then are followed without receiving isotretinoin for 1 year. After the follow-up period, treatment may be resumed if the rate of new skin tumor formation reaches 2 per year provided original eligibility criteria are met. Treatment may be resumed during the follow-up period if the rate of new skin tumor formation increases to the rate observed before study. Patients previously treated with oral isotretinoin continue treatment and are followed to evaluate any long-term effects of treatment.

PROJECTED ACCRUAL: Approximately 30 patients will be accrued for this study.

DISEASE CHARACTERISTICS: Diagnosis of autosomal recessive disorder xeroderma pigmentosum Diagnosis must be documented by the clinical signs and symptoms listed in standard text books, e.g.: Sun sensitivity Increased number of freckles and other pigmentary lesions Cutaneous atrophy and telangiectasia Actinic keratoses Skin cancers Ocular abnormalities (e.g., photophobia, conjunctivitis, keratitis, or premalignant or malignant tumors of the eye or lid) allowed Neurologic abnormalities (e.g., progressive hearing loss, diminished reflexes, or progressive mental deterioration) allowed OR Diagnosis of autosomal dominant nevoid basal cell carcinoma syndrome Diagnosis must be documented by the clinical signs and symptoms listed in standard text books, e.g.: Basal cell carcinomas Palmar pits Skeletal abnormalities Falx calcification History of at least 2 documented skin cancers a year during the 2 years before study, but currently clear of all skin cancer Patients not previously treated with isotretinoin must agree to undergo a 1 year follow-up period without isotretinoin (to facilitate observation of any chronic toxicity and observe for new tumors) Must undergo appropriate treatment for any skin cancers that arise during study No evidence of metastatic cancer

PATIENT CHARACTERISTICS: Age: Over 2 Hematopoietic: Complete blood cell counts normal Hepatic: SGOT or SGPT less than 3 times upper limit of normal (ULN) Triglycerides less than 200 mg/dL Renal: Creatinine less than 3 times ULN Cardiovascular: No New York Heart Association class III or IV heart disease Other: No hypersensitivity to parabens (used in drug formulation) No proven active malignancy except skin cancer Not pregnant Negative pregnancy test Fertile patients must use effective contraception during and for 1 month after study therapy

PRIOR CONCURRENT THERAPY: See Disease Characteristics No recent, chronic, high-dose vitamin A use (greater than 30,000 IU/day) No concurrent supplemental vitamin A No other concurrent therapy for the skin (except sunscreens) unless approved by the investigators