SURAMIN IN HORMONE-REFRACTORY METASTATIC PROSTATE-CANCER - A DRUG WITH LIMITED EFFICACY

Purpose: To confirm the previously reported high response rates and pr olonged survival in hormone-refractory prostate cancer treated with su ramin. Patients and Methods: Thirty-six eligible patients with hormone -refractory prostate cancer with either measurable disease or bone dis ease only and a prostate-specific antigen (PSA) level greater than 50 ng/mL were enrolled, Treatment consisted of two 8-week courses of outp atient-based therapy with an interposed rest period. A bayesian adapti ve control strategy and a three-compartment pharmacokinetic model that accommodates clearance changes was used to guide individual dosing. A rapid infusion of 1,000 mg/m(2) suramin was followed by five daily in fusions that targeted 285 mu g/mL peak plasma levels during the first week. All patients received concomitant hydrocortisone, for the next 7 weeks, patients received one to two doses per week that targeted leve ls in the 150 to 285 mu g/mL range and integrated weekly averages of 2 00 mu g/mL. Results: Nine patients (28%) had a partial response to sur amin based on a greater than or equal to 50% decrease in PSA levels co upled with either relief of bone pain or by a 50% decrease in measurab le disease, The median overall survival time for all patients is 31 we eks (95% confidence interval [CI], 23 to 51). Treatment was generally well tolerated, with fatigue being the most common significant toxicit y, but fatal idiosyncratic myelosuppression (grade V) was observed in one patient Conclusion: Using this dosing schedule, suramin has limite d activity against hormone-refractory metastatic prostate cancer, Rece nt data suggest that hydrocortisone administered with suramin may be p artly responsible for the benefit attributed to the drug, Although a s mall cohort of patients appeared to benefit, we were unable to confirm the previously reported high rate of activity and durability of remis sion using this agent. (C) 1996 by American Society of Clinical Oncolo gy.