Orchiectomy and Nilutamide or Placebo as Treatment of Metastatic Prostatic Cancer in a Multinational Double-Blind Randomized Trial

Abstract

The efficacy and tolerance of the nonsteroidal antiandrogen nilutamide in the treatment of prostatic cancer were studied in a large double-blind clinical trial initiated in 1986. Patients with metastatic prostatic cancer without prior endocrine manipulation underwent orchiectomy and were randomized to 1 of 2 groups receiving nilutamide (225 patients) or placebo (232). Nilutamide and placebo were evaluated for efficacy in 207 and 216 patients, respectively. Progression-free survival was significantly longer in the nilutamide group (median time to progression 20.8 months on nilutamide and 14.9 months on placebo, p = 0.005). Median time to death from prostatic cancer was 30.0 months in the placebo group and 37 months in the nilutamide group. Objective regressions were higher in the nilutamide group (41%) than in the placebo group (24%). Significant differences in favor of the nilutamide group were found at several intervals for bone pain, prostatic acid phosphatase, prostate specific antigen, alkaline phosphatase and bone scan isotope uptake. Nilutamide and orchiectomy constitute a more effective treatment for metastatic prostatic cancer than orchiectomy alone, and the adverse effects of nilutamide, usually minor, are outweighed by the significant improvements in most disease measures and progression-free survival.

Primary hormonal therapy for prostate cancer: experience with 135 consecutive PSA-ERA patients from a tertiary care military medical center

“…11 There is a continuing debate regarding the clinical value of this combined hormonal therapy. The National Cancer Institute (NCI) study 0036, 11 European Organization for Research and Treatment of Cancer (EORTC) study 30853, 12 Canadian Anandron study, 13 and Multinational Nilutamide Study 14 all showed a survival benefit of 7-15 months with combined hormonal therapy. Other studies, however, have not supported this finding.…”

Stimulation of erythropoiesis by the non-steroidal anti-androgen nilutamide in men with prostate cancer: evidence for an agonistic effect?

“…In keeping with the above, the definition of pure antagonists is further challenged by the observation that these compounds can induce de novo nuclear AR synthesis (Steinsapir et al, 1991) and a sustained decline in prostatespecific antigen levels after their discontinuation (Kelly & Scher, 1993). The anti-tumour efficacy of nilutamide at a lower dose (300mg daily for 1 month followed by 150mg thereafter) was recently evaluated in combination with orchiectomy in a randomised double-blind trial (Janknegt et al, 1993). Among the reported adverse effects, anaemia was observed in 4% of nilutamide-treated patients compared with 7% of placebo patients.…”

Safety and efficacy of a non-steroidal anti-androgen, based on results of a post marketing surveillance of nilutamide

“…11 The most frequently reported adverse events were nausea and vomiting in 83 patients (11%) followed by hot¯ushes in 74 patients (10%) and eye disorders (total of light/dark adaptation and visual disturbances; 57 patients (8%)). Liver function disturbances and respiratory complaints have been reported as well but less than in other clinical studies.…”