A Controlled Trial of Castration With and Without Nilutamide in Metastatic Prostatic Carcinoma

Abstract

A randomized double‐blind trial in patients with disseminated, previously untreated prostate cancer (Stage D2) was conducted in eight Canadian centers. All 203 patients enrolled in this study underwent bilateral orchiectomy and were randomized to receive either the nonsteroidal anti‐androgen nilutamide or a placebo. Patient responses were graded according to the criteria of the National Prostatic Cancer Project (NPCP). Patients treated with nilutamide had a significantly greater number of positive objective responses (partial and complete regression) than did the patients treated with castration alone (46% versus 20%, P = 0.001). Progression‐free survival was improved initially in the nilutamide group, but the median time to progression was 12 months for both groups. Despite an increase in the median length of survival from 18.9 to 24.3 months with the nilutamide, the survival time was not significantly longer in the nilutamide group (log = rank test, P = 0.048). Although minor side effects were frequent, adverse effects related to the medication and leading to discontinuation of treatment were observed in 9% of cases. These results suggest some benefit of the combined treatment (orchiectomy + nilutamide) over orchiectomy alone in the treatment of metastatic prostatic carcinoma.

A Prospective, Randomised Study to Compare Goserelin Acetate (Zoladex®) versus Cyproterone Acetate (Cyprostat®) versus a Combination of the Two in the Treatment of Metastatic Prostatic Carcinoma

“…Three large controlled studies [13,18,19] support Labrie's hypothesis with a significant improvement in both time to disease progression and survival in the combination arm in comparison to the monotherapy treatment. However, two other studies comparing goserelin acetate alone and in combination with flutamide [15,20] and also a com bined analysis [21] of one of the studies previously cited [18] showed no difference in survival time.…”

Update of Monotherapy Trials with the New Anti-Androgen, Casodex (IC1176,334)

“…On reviewing the entire safety database for Casodex, only 1 patient (<0.1 %) has been withdrawn because of diarrhoea. The incidence of diarrhoea with flu tamide when used either as monotherapy or in combina tion with castration has, however, been reported as 2-5% Problems of light/dark adaptation and pulmonary fi brosis, both of which have been reported with nilutamide [13][14][15], have not been witnessed with Casodex.…”

“…Nilutamide has, however, a reported rate of alcohol intolerance of 19% [13,15]. for any reason, such as death, progression, adverse events) and 9% had died.…”

Controversies in the management of advanced prostate cancer

“…No statistically significant differences between the groups were found with respect to either time to progression (mean 21 and 18 months respectively) or survival (mean 31 and 30 months). Similarly, studies with nilutamide in combination with either orchidectomy or LH-RH analogue showed no statistically significant difference in time to progression and median survival from the castration alone treatment (medical or surgical; Brisset et al, 1987;Knönagel et al, 1989;Béland et al, 1990;Crawford et al, 1990;Le Duc et al, 1990;Namer et al, 1990). CPA has also been evaluated in combination therapy and there was no significant difference in survival between CPA plus goserelin acetate and the LH-RH analogue alone (Di Silverio et al, 1990;Brewster et al, 1992).…”