Medicine:Early Prostate Cancer (clinical programme)

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The Early Prostate Cancer (EPC) programme was a large clinical trial programme of monotherapy with the nonsteroidal antiandrogen bicalutamide (Casodex) plus standard care versus standard care alone in men with early prostate cancer.[1][2][3] It was started in August 1995,[1] with the first analysis published in 2002[4] and the final follow-up published in 2010.[5] The programme consisted of three large randomized, double-blind, placebo-controlled trials in which a total of 8,113 men with localized or locally advanced prostate cancer were treated with 150 mg/day bicalutamide plus standard care (watchful waiting, radical prostatectomy, or radiation therapy) (n=4052) or given placebo (standard care alone) (n=4061).[3][2] It constituted the largest clinical trial of prostate cancer treatment to have ever been conducted at the time.[1][3][6] The three trials in the EPC programme were as follows:[2][7]

  • Trial 23 (North America; n=3292)[8]
  • Trial 24 (Europe, Australia, Israel, South Africa, and Mexico; n=3603)[9][10][11]
  • Trial 25 (Scandinavia; n=1218) (also known as the Scandinavian Prostate Cancer Group-6 (SPCG-6) study)[12][13][14][15]

Several combined follow-up papers of the EPC programme results were published, including at median 3.0 years in August 2002,[4] median 5.4 years in November 2004,[16] median 7.4 years in February 2006,[17] and median 9.7 years in April 2010.[5]

The EPC programme found that bicalutamide was effective in treating locally advanced prostate cancer.[2] Conversely, it was not effective for localized prostate cancer, where there was instead a statistically insignificant trend toward reduced overall survival with bicalutamide therapy (at median 7.4 years follow-up: HR = 1.16; 95% CI = 0.99–1.37; P = 0.07).[1][2] The increased mortality 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.[13][15] The preceding findings led to the withdrawal of pre-existing approval of bicalutamide for localized prostate cancer in the United Kingdom and Canada .[2]

Liver safety is an important concern with bicalutamide. In the first analysis of the EPC programme at median 3.0 years of follow-up, abnormal liver function tests had occurred in 3.4% of men treated with bicalutamide and 1.9% of men with placebo.[2][3][4] Clinically relevant increases in aspartate transaminase (AST), alanine transaminase (ALT), and bilirubin occurred in 1.6%, 1.6%, and 0.7% with bicalutamide and in 0.5%, 0.3%, and 0.4% with placebo.[2] However, liver changes with bicalutamide were usually transient and rarely severe.[2] Abnormal liver function tests led to treatment withdrawal in 1.4% with bicalutamide and 0.5% with placebo.[4] No cases of fatal hepatotoxicity occurred with bicalutamide in the SPCG-6 substudy of the EPC programme.[13]

References

  1. ↑ 1.0 1.1 1.2 1.3 "The Early Prostate Cancer program: bicalutamide in nonmetastatic prostate cancer". Expert Rev Anticancer Ther 8 (3): 361–9. March 2008. doi:10.1586/14737140.8.3.361. PMID 18366284. 
  2. ↑ 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 "Bicalutamide 150mg: a review of its use in the treatment of locally advanced prostate cancer". Drugs 66 (6): 837–50. 2006. doi:10.2165/00003495-200666060-00007. PMID 16706554. 
  3. ↑ 3.0 3.1 3.2 3.3 "The role of antiandrogen monotherapy in the treatment of prostate cancer". BJU Int 91 (5): 455–61. March 2003. doi:10.1046/j.1464-410x.2003.04026.x. PMID 12603397. 
  4. ↑ 4.0 4.1 4.2 4.3 "Bicalutamide as immediate therapy either alone or as adjuvant to standard care of patients with localized or locally advanced prostate cancer: first analysis of the early prostate cancer program". J Urol 168 (2): 429–35. August 2002. doi:10.1016/S0022-5347(05)64652-6. PMID 12131282. 
  5. ↑ 5.0 5.1 "Antiandrogen monotherapy in patients with localized or locally advanced prostate cancer: final results from the bicalutamide Early Prostate Cancer programme at a median follow-up of 9.7 years". BJU Int 105 (8): 1074–81. April 2010. doi:10.1111/j.1464-410X.2010.09319.x. PMID 22129214. 
  6. ↑ "Bicalutamide (Casodex) in the treatment of prostate cancer". Expert Rev Anticancer Ther 4 (1): 37–48. February 2004. doi:10.1586/14737140.4.1.37. PMID 14748655. 
  7. ↑ "The bicalutamide Early Prostate Cancer Program. Demography". Urol Oncol 6 (2): 43–47. March 2001. doi:10.1016/s1078-1439(00)00118-6. PMID 11166619. 
  8. ↑ "The bicalutamide 150 mg early prostate cancer program: findings of the North American trial at 7.7-year median followup". J Urol 176 (1): 75–80. July 2006. doi:10.1016/S0022-5347(06)00495-2. PMID 16753373. 
  9. ↑ "Bicalutamide (Casodex) 150 mg as immediate therapy in patients with localized or locally advanced prostate cancer significantly reduces the risk of disease progression". Urology 58 (2): 146–51. August 2001. doi:10.1016/s0090-4295(01)01213-4. PMID 11489683. 
  10. ↑ "Bicalutamide ('Casodex') 150 mg in addition to standard care in patients with nonmetastatic prostate cancer: updated results from a randomised double-blind phase III study (median follow-up 5.1 y) in the early prostate cancer programme". Prostate Cancer Prostatic Dis 8 (2): 194–200. 2005. doi:10.1038/sj.pcan.4500799. PMID 15931272. 
  11. ↑ "Bicalutamide (Casodex) 150 mg plus standard care in early non-metastatic prostate cancer: results from Early Prostate Cancer Trial 24 at a median 7 years' follow-up". Prostate Cancer Prostatic Dis 10 (1): 87–93. 2007. doi:10.1038/sj.pcan.4500916. PMID 17102802. 
  12. ↑ "A randomised comparison of bicalutamide ('Casodex') 150 mg versus placebo as immediate therapy either alone or as adjuvant to standard care for early non-metastatic prostate cancer. First report from the Scandinavian Prostatic Cancer Group Study No. 6". Eur Urol 42 (3): 204–11. September 2002. doi:10.1016/s0302-2838(02)00311-1. PMID 12234503. 
  13. ↑ 13.0 13.1 13.2 "Bicalutamide (150 mg) versus placebo as immediate therapy alone or as adjuvant to therapy with curative intent for early nonmetastatic prostate cancer: 5.3-year median followup from the Scandinavian Prostate Cancer Group Study Number 6". J Urol 172 (5 Pt 1): 1871–6. November 2004. doi:10.1097/01.ju.0000139719.99825.54. PMID 15540741. 
  14. ↑ "Bicalutamide 150 mg in addition to standard care for patients with early non-metastatic prostate cancer: updated results from the Scandinavian Prostate Cancer Period Group-6 Study after a median follow-up period of 7.1 years". Scand J Urol Nephrol 40 (6): 441–52. 2006. doi:10.1080/00365590601017329. PMID 17130095. 
  15. ↑ 15.0 15.1 "Survival benefit of early androgen receptor inhibitor therapy in locally advanced prostate cancer: long-term follow-up of the SPCG-6 study". Eur J Cancer 51 (10): 1283–92. July 2015. doi:10.1016/j.ejca.2015.03.021. PMID 25892647. 
  16. ↑ "Bicalutamide 150 mg in addition to standard care in patients with localized or locally advanced prostate cancer: results from the second analysis of the early prostate cancer program at median followup of 5.4 years". J Urol 172 (5 Pt 1): 1865–70. November 2004. doi:10.1097/01.ju.0000140159.94703.80. PMID 15540740. 
  17. ↑ "Bicalutamide 150 mg plus standard care vs standard care alone for early prostate cancer". BJU Int 97 (2): 247–54. February 2006. doi:10.1111/j.1464-410X.2005.06051.x. PMID 16430622. 



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