Long-term therapy with low-dose isotretinoin for prevention of basal cell carcinoma: a multicenter clinical trial. Isotretinoin-Basal Cell Carcinoma Study Group.
BACKGROUND: High-dose isotretinoin has been reported to have a prophylactic effect on nonmelanoma skin cancer, although it is associated with significant toxicity. PURPOSE: To test the effectiveness of the long-term administration of low-dose isotretinoin in reducing the occurrence of basal cell carcinoma at a new site in patients with previously treated basal cell carcinomas and to measure the toxicity associated with this regimen, we conducted a clinical trial at eight cancer centers. METHODS: Nine hundred and eighty-one patients with two or more previously confirmed basal cell carcinomas were randomly assigned to receive either 10 mg of isotretinoin or a placebo daily. Patients were followed for 36 months and monitored at 6-month intervals for skin cancer and toxic effects. RESULTS: After 36 months of treatment, no statistically significant difference in either the cumulative percent of patients with an occurrence of basal cell carcinoma at a new site or the annual rate of basal cell carcinoma formation existed between patients receiving isotretinoin and those receiving the placebo. Elevated serum triglycerides, hyperostotic axial skeletal changes, and mucocutaneous reactions were more frequent in the group receiving isotretinoin than in the control group, and these differences were all statistically significant (P less than .001). CONCLUSION: This low-dose regimen of isotretinoin not only is ineffective in reducing the occurrence of basal cell carcinoma at new sites in patients with two or more previously treated basal cell carcinomas but also is associated with significant adverse systemic effects. IMPLICATION: 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.