Tretinoin With or Without Fenretinide in Treating Patients With Dysplastic Nevus Syndrome

OBJECTIVES: I. Compare the efficacy (clinical and histologic evidence of regression) of
topical tretinoin with or without systemic fenretinide in patients with dysplastic nevi with
personal or family history of cutaneous melanoma.

OUTLINE: This is a randomized, double-blind study. Patients are stratified according to
personal history of cutaneous melanoma vs family history of cutaneous melanoma in at least 2
blood relatives. Patients are randomized to one of two treatment arms. Arm I: Patients
receive topical tretinoin twice daily and oral fenretinide once a day for 6 months. Tretinoin
is applied to one half of the back with the untreated side of the back serving as a matched
control. Arm II: Patients receive topical tretinoin as in arm I twice daily and oral placebo
once a day for 6 months. Treatment continues in both arms in the absence of disease
progression or unacceptable toxicity. Patients are followed at 6 months.

PROJECTED ACCRUAL: There will be 38 patients accrued for this study.

DISEASE CHARACTERISTICS: Clinically dysplastic nevi with a personal history of cutaneous
melanoma and/or a family history of cutaneous melanoma in two or more blood relatives
(blood relatives include first, second, or third degree relatives from the same blood line)
Clinically dysplastic nevi defined as: At least 4 mm in diameter and flatness (either a
component or throughout) with at least 1 of the following: Variable pigmentation Irregular
or asymmetrical outline Indistinct border Must have at least 10 or more large (diameter at
least 4 mm) clinically dysplastic nevi on the trunk or extremities (excluding head, pubic
area, breasts in women, hands, and/or below the knees) No stage III or IV melanoma Patients
with history of melanoma who received adjuvant therapy must be more than 1 year from
completion of therapy

PATIENT CHARACTERISTICS: Age: 18 and over Performance status: ECOG 0-2 Life expectancy: Not
specified Hematopoietic: WBC greater than 3,500/mm3 Platelet count greater than 100,000/mm3
Hepatic: Bilirubin less than 2.0 mg/dL AST less than 2 times normal Alkaline phosphatase
less than 2 times normal Renal: Creatinine less than 2.0 mg/dL Cardiovascular: No
symptomatic arteriosclerotic coronary artery disease No history of coronary artery disease
Other: Fasting triglyceride level less than 210 mg/dL Fasting cholesterol level less than
350 mg/dL No nonmalignant disease that would preclude administration of retinoids No
psychiatric conditions that would preclude study compliance Not pregnant or nursing
Negative pregnancy test Fertile patients must use effective contraception during and for 6
months after study

PRIOR CONCURRENT THERAPY: See Disease Characteristics Biologic therapy: Not specified
Chemotherapy: Not specified Endocrine therapy: Not specified Radiotherapy: Not specified
Surgery: No prior coronary bypass surgery Other: No prior systemic retinoids No concurrent
vitamin (except a daily multivitamin) or dietary supplement No concurrent systemic therapy
for hyperlipidemia