PHASE-II TRIAL OF SURAMIN, LEUPROLIDE, AND FLUTAMIDE IN PREVIOUSLY UNTREATED METASTATIC PROSTATE-CANCER

Purpose: To assess the efficacy and toxicity of suramin, hydrocortison e, leuprolide, and flutamide in previously untreated metastatic prosta te cancer. Patients and Methods: patients with stage D2 and poor-progn osis stage D1 prostate cancer were given suramin on a pharmacokinetica lly derived dosing schedule to maintain suramin concentrations between 175 and 300 mu g/mL. Additionally, all patients received flutamide 25 0 mg orally three times daily, initiated on day 1 and continued until disease progression; depot leuprolide 7.5 mg intramuscularly begun on day 5 and repeated every 4 weeks indefinitely; and replacement doses o f hydrocortisone. Results: Fifty patients were entered onto the study: 48 with stage D2 and two with stage D1 disease, The median age was 59 years (range, 42 to 79) and 31 patienf 5 had a Karnofsky performance status (KPS) of 100%. Forty-five patients had bone metastases and 25 h ad measurable soft tissue disease, Forty-one (82%) had severe disease. The overall response rate in 49 assessable patients was three complet e responses (CRs) and 30 partial responses (PRs) for an overall respon se rate of 67%, Eighteen patients have died, The median survival time has not been reached, with a median potential follow-up duration of 44 months. Grade 3 to 4 toxicity was seen in 38% of patients and was pre dominantly hematologic and reversible. Conclusion: The high response r ate and prolonged survival in a poor-prognosis group of patients with metastatic prostate cancer warrant a phase III randomized comparison o f this regimen versus hormonal therapy alone, Toxicity was moderate an d reversible.