Casodex 10-200 mg daily, used as monotherapy for the treatment of patients with advanced prostate cancer. An overview of the efficacy, tolerability and pharmacokinetics from three phase II dose-ranging studies. Casodex Study Group

Abstract

Objectives: To evaluate the efficacy, tolerability, endocrinological effects and the pharmacokinetics of Casodex, when given as monotherapy during daily dosing of 10-200 mg to patients with advanced prostate cancer.

Methods: A total of 390 patients with advanced prostate cancer were treated for a minimum of 12 weeks with a daily monotherapy dose of Casodex. The doses ranged from 10 to 200 mg. Objective assessments of efficacy included: review of measurable metastases, prostate dimension, prostatic acid phosphatase and prostate-specific antigen (PSA) levels. Subjective assessments of efficacy included review of urological symptoms, performance status, bone scan and analgesic requirement. Pharmacokinetic samples were taken at various time points up to 3 months, and assayed using an achiral HPLC method.

Results: Clear objective responses were observed, particularly at doses of 50 mg and above. Specifically, 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% of symptomatic patients demonstrated a subjective response at 3 months. Casodex was well tolerated at all doses with no effect on haematological 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 of these events. The intrinsic efficacy of Casodex was demonstrated despite increases of 60% in testosterone levels. However, this increase reached a plateau after 4-12 weeks of therapy, but the majority of values remained within the normal range. Casodex has a half-life of approximately 1 week, enabling once-daily dosing with no effect of age or renal impairment on its pharmacokinetics.

Conclusion: Casodex has a favourable side effect profile compared with the known safety profiles of other antiandrogens and has demonstrated intrinsic efficacy. Casodex warrants further investigation as a monotherapy for the management of advanced prostate cancer.