SURAMIN AND HYDROCORTISONE - DETERMINING DRUG EFFICACY IN ANDROGEN-INDEPENDENT PROSTATE-CANCER

Purpose: The combination of suramin and hydrocortisone has shown clini cal benefit in patients with androgen-independent prostate cancer. Wid espread use was limited by the complex dose schedules and the need for pharmacologic monitoring. This study reports three sequential pharmac okinetically derived treatment regimens that simplified the administra tion of suramin and hydrocortisone with reduced toxicity. Patients and Mefhods: Three cohorts of patients with advanced prostate cancer that progressed despite castrate levels of testosterone received oral hydr ocortisone plus suramin administered in the following manners: (1) a l oading dose of suramin followed by a continuous infusion using an adap tive control program (cohort A); (2) an intermittent schedule using a simplified adaptive control schedule (cohort B); and (3) an empiric do sing regimen (cohort C). Drug concentrations were monitored along with the toxicities associated with each regimen. Efficacy was assessed us ing measurable-disease criteria, radionuclide scans, and posttherapy c hanges in prostate-specific antigen (PSA) levels. Results: Fifty-six p atients were treated and plasma suramin concentrations were similar fo r each regimen. A partial response was observed in 4%(one of 28; 95% c onfidence interval, 0% to 18.4%) of patients with measurable disease, while 12%(six of 50; 95% confidence interval, 4.5% to 24.3%) had a gre ater than 80% decline in the baseline PSA level. The median duration o f response was 12 months. No responses on radionuclide scans were seen . Anemia and lymphocytopenia were the most common toxicities, while 7% of patients developed a sensory or motor neurotoxicity. In the sequen tial regimens, the frequency of renal insufficiency (P = .04) and coag ulopathy (P < .0001) decreased, while transaminase elevations (P = .05 ) were more common using intermittent infusions (cohorts B and C) vers us continuous infusion schedules (cohort A). Conclusion: The administr ation of suramin was simplified and the drug concentrations were maint ained. In this cohort of patients with advanced prostate cancer, the c linical activity of suramin using these dosing schedules was limited. Pharmacodynamic issues, patient selection, and criteria to assess effi cacy could have effected the clinical outcome. (C) 1995 by American So ciety of Clinical Oncology.