CASODEX(TM) 10-200 MG DAILY, USED AS MONOTHERAPY FOR THE TREATMENT OFPATIENTS WITH ADVANCED PROSTATE-CANCER - AN OVERVIEW OF THE EFFICACY,TOLERABILITY AND PHARMACOKINETICS FROM 3-PHASE-II DOSE-RANGING STUDIES

Objectives: To evaluate the efficacy, tolerability, endocrinological e ffects and the pharmacokinetics of Casodex(TM), when given as monother apy during daily dosing of 10-200 mg to patients with advanced prostat e cancer. Methods: A total of 390 patients with advanced prostate canc er were treated for a minimum of 12 weeks with a daily monotherapy dos e of Casodex. The doses ranged from 10 to 200 mg. Objective assessment s of efficacy included: review of measurable metastases, prostate dime nsion, prostatic acid phosphatase and prostate-specific antigen (PSA) levels. Subjective assessments of efficacy included review of urologic al symptoms, performance status, bone scan and analgesic requirement. Pharmacokinetic samples were taken at various time points up to 3 mont hs, and assayed using an achiral HPLC method. Results: Clear objective responses were observed, particularly at doses of 50 mg and above. Sp ecifically, the median percentage decrease in PSA at 50 mg was 90.0%, and at 100 and 200 mg it was 93.4 and 94.8%, respectively. UP to 53% o f symptomatic patients demonstrated a subjective response at 3 months. Casodex was well tolerated at all doses with no effect on haematologi cal or cardiovascular parameters and no effect on renal function. The expected pharmacological effects of potent antiandrogen therapy, such as breast tenderness (58%), gynaecomastia (48%), and hot flushes (17%) , were reported, but these incidences reflected the direct eliciting o f these events. The intrinsic efficacy of Casodex was demonstrated des pite increases of 60% in testosterone levels. However, this increase r eached a plateau after 4-12 weeks of therapy, but the majority of valu es remained within the normal range. Casodex has a half-life of approx imately 1 week, enabling once-daily dosing with no effect of age or re nal impairment on its pharmacokinetics. Conclusion: Casodex has a favo urable side effect profile compared with the known safety profiles of other antiandrogens and has demonstrated intrinsic efficacy. Casodex w arrants further investigation as a monotherapy for the management of a dvanced prostate cancer.