The evaluation of drug efficacy in patients with advanced prostatic cancer who have progressed to hormonal therapy is difficult, although palliation of the pain related to bone involvement still represents an important endpoint. In this study, epirubicin (EpiADM) plus medroxyprogesterone acetate (MPA) were given to advanced prostatic cancer patients with symptomatic bone involvement who had progressed to hormonal therapy. EpiADM was administered at a dose of 30 mg/m2 i.v. weekly and MPA at a daily dose of 1,000 mg p.o. for the first month and 500 mg thereafter. Fifty-four patients entered the trial, all of whom were evaluable. Amelioration of pain and a > or = 50% reduction in analgesic intake were observed in 52% of cases, with a mean duration of 4 months. Of the 28 responsive patients, 26 had already received two lines of hormonal therapy or were resistant to first-line therapy. Of the 23 patients with measurable lesions, 6 obtained a > or = 50% tumor shrinkage at these sites. The treatment was well tolerated, and no cardiac toxicity was observed up to a total cumulative EpiADM dose of 660 mg/m2. In conclusion, this regimen seems to have a palliative effect in patients with advanced prostatic cancer who have progressed to hormonal therapy, and it is feasible in an outpatient setting.