Cyproterone acetate in the treatment of advanced prostatic cancer: retrospective analysis of liver toxicity in the long-term follow-up of 89 patients.

Cyproterone acetate (CPA) was the first steroidal antiandrogen used for the treatment of prostatic cancer. In recent studies CPA has been linked with DNA adduct formation and increased DNA repair synthesis in vitro, suggesting an increased risk for the development of hepatic malignancies. To assess liver-toxic and carcinogenic effects, 89 patients who received CPA 50 mg/day p.o. over 4 (range 2-152 months) years for prostatic cancer treatment were retrospectively evaluated. 22 patients (28.2%) showed elevated liver enzyme concentrations. In none of the 89 patients alpha-fetoprotein serum levels were elevated. In no case hepatocellular carcinoma has been observed, and in no case CPA administration was discontinued due to side effects. Considering the life expectancy of patients with advanced prostatic cancer and the long-term and high-dose exposure to CPA necessary to possibly induce liver tumors, it appears highly unlikely that CPA treatment may account for a substantial number of liver carcinomas in such patients.