Bicalutamide (Casodex®, AstraZeneca), an oral anti-androgen has been approved by some regulatory authorities for the treatment of localized (early) prostate cancer. The Canadian and UK Health Authority have recently withdrawn the approval of Casodex® for this indication as data obtained from the follow-up second analysis of the Casodex® Early Prostate Cancer (EPC) trial programme revealed a trend towards increased risk of death in patients with localised (early) prostate cancer who were put on Casodex® as compared to those on placebo.

The EPC trial is an on-going international programme comprising 3 geographically distinct trials. All trials are prospective, randomised, double blind, placebo-controlled clinical trials (n = 8,113) that compare Casodex® 150 mg/day and placebo, when given in addition to standard care in men with localised or locally advanced prostate cancer. The programme considered standard care to be radical prostatectomy, radiotherapy or watchful waiting (initiation of therapy only if symptoms or signs of progression occurred). Primary endpoints are progression free survival and overall survival. The findings are as follows:

There was a significant reduction in the risk of progression free survival in the combined analysis of the 3 trials after 5.4 years of follow-up [797 (19.7%) events vs 960 (23.6%) events, hazard ratio (HR) = 0.73].

• Benefits in terms of reduced risk of disease progression were largest in those at high risk of disease progression (e.g. locally advanced disease, elevated serum levels of Prostate Specific Antigen (PSA) at baseline or high Gleason grade).
  
  
• For overall survival, as reported in the first analysis, the second analysis showed no difference between treatment groups for either the combined analysis all 3 trials or separate analysis for each of the trial.
  
  
• In the subgroup analysis of patients with localized prostate cancer at low risk of disease progression, otherwise managed by watchful waiting, there were more numbers of accelerated deaths in the Casodex® group vs the placebo group [196 (25.2%) deaths vs 174 (20.5%) deaths, HR = 1.23, 95% CI 1.00-1.50]. In the higher risk subgroup of patients with locally advanced disease showed a trend towards improved survival with Casodex® compared to the placebo arm [113 (33.7%) deaths vs 133 (41.3%) deaths, HR = 0.80, 95% CI 0.62-1.04).
  
  
• No survival differences were apparent in patients receiving adjuvant therapy, although the data in this setting is relatively immature (approximately 10% deaths in adjuvant setting).

• Casodex® is only licensed for the treatment of locally advanced prostate cancer in Singapore.
  
  
• Patients with locally advanced prostate cancer are not affected by this new safety information.
  
  
• In view of these data, and in the absence of factors to suggest high risk of disease progression, AstraZeneca has advised physicians in countries where Casodex® is licensed for early prostate cancer to discontinue Casodex® in patients with localised (early) prostate cancer who would otherwise be undergoing watchful waiting.