Suramin/epidoxorubicin association in hormone-refractory prostate cancer: preliminary results of a pilot phase II study.

PURPOSE: Previous studies indicate that suramin may be an active agent for treating hormone-refractory prostate cancer. However, antitumour responses were observed in initial experiments only when plasma suramin concentrations were maintained in excess of 250 micrograms/ml. Dose-limiting toxicity, especially neurological toxicity, is directly related to the duration of exposure and sustained plasma drug concentrations of 300 micrograms/ml or more. Combination with other agents such as epidoxorubicin, a drug with demonstrable activity in metastatic prostatic carcinoma, could be more effective and allow reduced suramin doses, while maintaining the suramin antitumor effect; this could make suramin therapy more feasible. On the basis of preclinical synergistic activity for combined suramin/doxorubicin in prostate cancer cell lines, a pilot study in patients with metastatic hormone refractory prostate cancer was performed. MATERIALS AND METHODS: Ten patients with hormone-refractory prostate cancer received a fixed dosing scheme of suramin infusion in combination with weekly epidoxorubicin at 25 mg/m2. Therapy was discontinued for dose-limiting toxicity or progressive disease. RESULTS: None of the ten patients achieved a prostate-specific antigen reduction of more than 50% and no objective responses were observed in any patient. Dose-limiting toxicity was observed in four patients: grade 3 neurotoxicity was observed in three patients and grade 3 nephrotoxicity in one patient. CONCLUSIONS: Suramin/epidoxorubicin association, despite the encouraging preclinical results, was not able to improve the antitumour activity of suramin and showed significant toxicity. The results achieved in our study, although in a small number of patients, seem to suggest that this regimen cannot be recommended for use in the treatment of metastatic hormone-refractory prostate cancer.