Nilutamide plus orchidectomy for metastatic prostatic cancer

Clinical bottom line : Nilutamide is associated with pain relief in patients who have undergone orchidectomy for prostatic cancer. Although nilutamide has a number-needed-to-treat of 7.5 (5 to 15) for any pain relief at six months compared with placebo, it remains to be established whether this is of clinical relevance.

The most effective treatment for prostatic cancer with metastases is thought to be removal of the testicular and adrenal androgens. Testicular androgens are suppressed by orchidectomy and luteinizing hormone releasing hormone agonists (LHRH agonists) or oestrogens. Anti-androgens such as nilutamide, flutamide or cyproterone acetate are used to suppress the effects of adrenal androgens. Nilutamide (Anandron) is an oral non-steroidal anti-androgen, and like other anti-androgens is associated with a number of adverse effects.

Systematic review

Bertagna C, De Gery A, Hucher M, Francois JP, Zanirato J. Efficacy of the combination of nilutamide plus orchidectomy in patients with metastatic prostatic cancer. A meta-analysis of seven randomized double-blind trials (1056 patients). Br-J-Urol. 1994; 73: 396-402.

• Date review completed: most recent included trial, 1986
• Number of trials included: 6
• Number of patients: 1056 For pain: 839 (439 orchidectomy plus nilutamide / 400 orchidectomy plus placebo)
• Control group: placebo anti-androgen
• Main outcomes: pain, biochemical measures, disease regression, survival

Inclusion criteria were randomised double blind placebo-controlled trials of orchidectomy plus nilutamide for stage D prostate cancer; no previous hormone treatment; hormone treatment started not later than three months after orchidectomy; short- and long-term outcomes.

Data were extracted from original trials. Short-term outcomes were defined as symptoms at six months. Patients were categorised as improved, unchanged or deteriorated compared with baseline. For tumour markers, this was defined as a 25% change. Long-term outcomes were summed progression outcomes (of 6 month measures) and the summed survival outcome (of 12 month measures). For pain, reviewers presented six month data, with patients either percent improved, unchanged or deteriorated in comparison with baseline measures (pain measure not stated). Definition of improved, etc, was not given so we have assumed this was any change, however small.

Reviewers pooled dichotomous data and calculated odds ratios with 95% confidence intervals. We used the same data to calculate relative benefit and numbers-needed-to-treat with 95% confidence intervals.

Findings

Six trials on 839 patients were included in the analysis. Five trials had a dosing regime of 300 mg/day of nilutamide, and one trial gave nilutamide 300 mg/day for one month and then 150 mg/day from then on. Length of follow-up varied within and across trials. The largest trial had a follow-up period ranging from one to 3.5 years. The other trials had follow-up periods ranging from approximately two to four, five or six years.

Four of six trials had significant relative benefits, suggesting significant pain relief with nilutamide compared with placebo. This included the lower dose trial. The overall relative benefit was significant, 1.4 (1.2 to 1.7), and nilutamide had a number-needed-to-treat of 7.5 (5 to 15) for any pain relief over six months compared with placebo.

Data on other outcomes are clearly presented in the paper. However, there is a more recent review (listed below) which, although has no pain outcomes, has more up-to-date survival and regression data.

Adverse effects

Reviewers did not report on adverse effects.

Related topics

• Identifier CP012 - 118 NILUTAMIDE PLUS ORCHIDECTOMY FOR METASTATIC PROSTATIC CANCER: Jul-99