The Early Prostate Cancer (EPC) programme was a large

clinical trial Clinical trials are prospective biomedical or behavioral research studies on human subject research, human participants designed to answer specific questions about biomedical or behavioral interventions, including new treatments (such as novel v ...

programme of monotherapy with the

nonsteroidal antiandrogen A nonsteroidal antiandrogen (NSAA) is an antiandrogen with a nonsteroidal chemical structure. They are typically selective and full or silent antagonists of the androgen receptor (AR) and act by directly blocking the effects of androgens lik ...

bicalutamide Bicalutamide, sold under the brand name Casodex among others, is an antiandrogen medication that is primarily used to treat prostate cancer. It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical remo ...

(Casodex) plus standard care versus standard care alone in men with early prostate cancer. It was started in August 1995, with the first analysis published in 2002 and the final follow-up published in 2010. The programme consisted of three large

randomized In common usage, randomness is the apparent or actual lack of pattern or predictability in events. A random sequence of events, symbols or steps often has no order and does not follow an intelligible pattern or combination. Individual rand ...

double-blind In a blind or blinded experiment, information which may influence the participants of the experiment is withheld until after the experiment is complete. Good blinding can reduce or eliminate experimental biases that arise from a participants' expec ...

placebo-controlled Placebo-controlled studies are a way of testing a medical therapy in which, in addition to a group of subjects that receives the treatment to be evaluated, a separate control group receives a sham "placebo" treatment which is specifically designe ...

trials in which a total of 8,113men with localized or

locally advanced prostate cancer Prostate cancer is cancer of the prostate. Prostate cancer is the second most common cancerous tumor worldwide and is the fifth leading cause of cancer-related mortality among men. The prostate is a gland in the male reproductive system that surr ...

were treated with 150mg/day bicalutamide plus standard care (

watchful waiting Watchful waiting (also watch and wait or WAW) is an approach to a medical problem in which time is allowed to pass before medical intervention or therapy is used. During this time, repeated testing may be performed. Related terms include ''expe ...

radical prostatectomy Prostatectomy (from the Greek , "prostate" and , "excision") as a medical term refers to the surgical removal of all or part of the prostate gland. This operation is done for benign conditions that cause urinary retention, as well as for prosta ...

, or

radiation therapy Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...

) (n=4052) or given

placebo A placebo ( ) is a substance or treatment which is designed to have no therapeutic value. Common placebos include inert tablets (like sugar pills), inert injections (like Saline (medicine), saline), sham surgery, and other procedures. In general ...

(standard care alone) (n=4061). It constituted the largest clinical trial of prostate cancer treatment to have ever been conducted at the time. The three trials in the EPC programme were as follows: * Trial 23 (North America; n=3292) * Trial 24 (Europe, Australia, Israel, South Africa, and Mexico; n=3603) * Trial 25 (Scandinavia; n=1218) (also known as the Scandinavian Prostate Cancer Group-6 (SPCG-6) study) Several combined follow-up papers of the EPC programme results were published, including at median 3.0years in August 2002, median 5.4years in November 2004, median 7.4years in February 2006, and median 9.7years in April 2010. The EPC programme found that bicalutamide was effective in treating locally advanced prostate cancer. Conversely, it was not effective for localized prostate cancer, where there was instead a

statistically insignificant In statistical hypothesis testing, a result has statistical significance when it is very unlikely to have occurred given the null hypothesis (simply by chance alone). More precisely, a study's defined significance level, denoted by \alpha, is the p ...

trend toward reduced

overall survival Survival rate is a part of survival analysis. It is the proportion of people in a study or treatment group still alive at a given period of time after diagnosis. It is a method of describing prognosis in certain disease conditions, and can be us ...

with bicalutamide therapy (at median 7.4years follow-up: = 1.16; 95% = 0.99–1.37; ' = 0.07). The increased

mortality Mortality is the state of being mortal, or susceptible to death; the opposite of immortality. Mortality may also refer to: * Fish mortality, a parameter used in fisheries population dynamics to account for the loss of fish in a fish stock throug ...

with bicalutamide in men with localized prostate cancer was however statistically significant at certain follow-ups in the Trial 25/SPCG-6 substudy of the EPC programme. The preceding findings led to the withdrawal of pre-existing approval of bicalutamide for localized prostate cancer in the

United Kingdom The United Kingdom of Great Britain and Northern Ireland, commonly known as the United Kingdom (UK) or Britain, is a country in Europe, off the north-western coast of the European mainland, continental mainland. It comprises England, Scotlan ...

and

Canada Canada is a country in North America. Its ten provinces and three territories extend from the Atlantic Ocean to the Pacific Ocean and northward into the Arctic Ocean, covering over , making it the world's second-largest country by tota ...

. Liver safety is an important concern with bicalutamide. In the first analysis of the EPC programme at median 3.0years of follow-up, abnormal

liver function test Liver function tests (LFTs or LFs), also referred to as a hepatic panel, are groups of blood tests that provide information about the state of a patient's liver. These tests include prothrombin time (PT/INR), activated partial thromboplastin t ...

s had occurred in 3.4% of men treated with bicalutamide and 1.9% of men with placebo. Clinically relevant increases in

aspartate transaminase Aspartate transaminase (AST) or aspartate aminotransferase, also known as AspAT/ASAT/AAT or (serum) glutamic oxaloacetic transaminase (GOT, SGOT), is a pyridoxal phosphate (PLP)-dependent transaminase enzyme () that was first described by Arthu ...

(AST),

alanine transaminase Alanine transaminase (ALT) is a transaminase enzyme (). It is also called alanine aminotransferase (ALT or ALAT) and was formerly called serum glutamate-pyruvate transaminase or serum glutamic-pyruvic transaminase (SGPT) and was first characte ...

(ALT), and

bilirubin Bilirubin (BR) (Latin for "red bile") is a red-orange compound that occurs in the normal catabolic pathway that breaks down heme in vertebrates. This catabolism is a necessary process in the body's clearance of waste products that arise from the ...

occurred in 1.6%, 1.6%, and 0.7% with bicalutamide and in 0.5%, 0.3%, and 0.4% with placebo. However, liver changes with bicalutamide were usually transient and rarely severe. Abnormal liver function tests led to treatment withdrawal in 1.4% with bicalutamide and 0.5% with placebo. No cases of fatal hepatotoxicity occurred with bicalutamide in the SPCG-6 substudy of the EPC programme.

References

{{Reflist Clinical trials related to cancer Evidence-based medicine Prostate cancer