Suramin in combination with weekly epirubicin for patients with advanced hormone-refractory prostate carcinoma

BACKGROUND. Suramin and epirubicin are both active agents in the treatment of patients with hormone-refractory advanced prostate carcinoma, with demon strated antitumor synergism in vitro on human prostate carcinoma cells and different dose-limiting toxicities. The authors conducted this Phase II stu dy to determine the feasibility, toxicity, and antitumor activity of surami n in combination with epirubicin. METHODS. Only patients with hormone-independent advanced prostate carcinoma who had progressive disease after the last therapeutic maneuver they had u ndergone, including antiandrogen withdrawal, entered the study. Suramin was administered initially as a B-day continuous infusion for 10 consecutive w eeks and then for 6 days every 28 days for a maximum of 6 months. Doses wer e determined by a computer-assisted dosing system that used Bayesian pharma cokinetics to maintain suramin plasma concentrations of 200-250 mu g/mL. Co rtisone acetate 25 mg, administered at 8 a.m. and 8 p.m. daily, was begun 4 weeks after the initiation of suramin therapy. Epirubicin 25 mg/m(2) was g iven as a weekly intravenous bolus beginning on Day 1 and was continued for a maximum of 6 months. RESULTS. Twenty-six patients entered the study. Toxicities mainly included World Health Organization Grade 1-2 nausea, fatigue, anorexia, neutropenia, peripheral neuropathy, creatinine elevation, proteinuria, and prolonged pr othrombin time, whereas Grade 3 toxicities were uncommon. Among 11 patients with measurable disease, 3 (27%) demonstrated an objective response. Among 24 patients evaluated for prostate specific antigen (PSA) response, 8 (33% ; 95% confidence interval 16-55%) had a greater than or equal to 50% decrea se in PSA levels, which lasted a median of 32 (range, 8-52) weeks. Median p rogression free and overall survival were both. 8 months. CONCLUSIONS. The combination of suramin and epirubicin used in the current study is feasible, is associated with moderate toxicities, and has antitumo r activity in advanced hormone-refractory prostate carcinoma. However, the results obtained with this combination do not represent major improvements in the treatment of patients with this disease; compared with suramin or ep irubicin alone or other available treatments. (C) 1999 American Cancer Soci ety.