ANTITUMOR-ACTIVITY OF SURAMIN IN HORMONE-REFRACTORY PROSTATE-CANCER CONTROLLING FOR HYDROCORTISONE TREATMENT AND FLUTAMIDE WITHDRAWAL AS POTENTIALLY CONFOUNDING VARIABLES

Background. A prospective Phase II clinical trial was conducted to ass ess the clinical activity of a pharmacokinetically guided suramin regi men in patients who had documented progression of metastatic prostate cancer after hydrocortisone plus antecedent or simultaneous withdrawal of flutamide. Methods. Fifty-four patients whose disease had progress ed after castration and flutamide administration were enrolled on this trial. The study was divided into two parts. Initially, 52 patients r eceived hydrocortisone (30 mg/day) and for those patients receiving fl utamide, at study entry (34 patients) flutamide was simultaneously dis continued. Forty-three patients whose disease progressed on hydrocorti sone received suramin for 6-8 weeks. Six patients who progressed on hy drocortisone became ineligible for suramin due to clinical deteriorati on, four patients are still responding to hydrocortisone at more than 1 year, and one patient elected to postpone initiation of suramin. Sur amin was given as intermittent infusions at fixed doses on days 1-5 an d thereafter dosing was guided by adaptive control with feedback to ma intain plasma suramin concentrations between 300-175 mu g/ml, Antitumo r activity was assessed by prostate specific antigen (PSA) decline and soft-tissue disease response. Results. Ten patients (19%; 95% CI, 9.6 %-32.5%) responded to hydrocortisone therapy with either a 50% or grea ter PSA decline for at least 4 weeks (9 patients) and/or a partial res ponse of measurable soft-tissue disease (2 patients). Five of these pa tients (10%) demonstrated a 80% or greater PSA decline. All responders to hydrocortisone had simultaneous flutamide withdrawal, and had been receiving flutamide as part of initial combined androgen blockade. Se ven of 37 evaluable patients (19%; 95% CI, 8.0%-35.2%) responded to su ramin with a 50% or greater decline in PSA for 4 weeks or longer. One patient (3%) had a 80% or greater decline in PSA, There were no soft-t issue disease responses to suramin, The median time to progression was 1.9 months for hydrocortisone therapy and 2.6 months for suramin ther apy. The median survival for all patients was 14.6 months. Conclusion. Suramin has antitumor activity in metastatic prostate carcinoma indep endent of the therapeutic effect of hydrocortisone administration or f lutamide withdrawal. The role of prior flutamide withdrawal and hydroc ortisone replacement should be taken into account in future studies of suramin.