The addition of bicalutamide 150 mg to radiotherapy significantly improves overall survival in men with locally advanced prostate cancer

  • William A. See
  • Chris J. Tyrrell
  • on behalf of the CASODEX™ Early Prostate Cancer Trialists’ Group
Original Paper

Abstract

Purpose:

Castration therapy adjuvant to radiotherapy can significantly improve overall survival compared with radiotherapy alone in patients with locally advanced prostate cancer. Although many of the adverse effects of castration therapy are manageable, they can have a detrimental effect on quality of life. Here we evaluate the efficacy and tolerability of the non-castration-based therapy bicalutamide (‘Casodex’) 150 mg adjuvant to radiotherapy in patients with T1-4, M0, any n prostate cancer.

Methods:

The subset of patients within the early prostate cancer (EPC) program who received radiotherapy with curative intent (n = 1,370) were included in the analysis. These patients were randomized to receive oral bicalutamide 150 mg once daily (n = 699) or placebo (n = 671).

Results:

The median follow-up for patients included in this analysis was 7.2 years. In patients with locally advanced disease (n = 305), bicalutamide adjuvant to radiotherapy significantly improved: progression-free survival (PFS), reducing the risk of objective progression by 44% compared with radiotherapy alone [hazard ratio (HR) 0.56; 95% confidence interval (CI) 0.40, 0.78; P < 0.001). Prostate-specific antigen (PSA)–PFS, reducing the risk of PSA progression by 59% compared with radiotherapy alone (HR 0.41; 95% CI 0.30, 0.55; P < 0.001). Overall survival, reducing the risk of death by 35% compared with radiotherapy alone (HR 0.65; 95% CI 0.44, 0.95; P = 0.03). This significant overall survival benefit for bicalutamide was driven by a lower risk of prostate cancer-related deaths (16.1 vs 24.3%, respectively). There was no significant difference in PFS or overall survival in patients with localized disease (n = 1,065).

Conclusions:

In patients with locally advanced disease, bicalutamide 150 mg adjuvant to radiotherapy demonstrates significant clinical benefits in terms of overall survival, PFS and PSA–PFS compared with radiotherapy alone. The overall survival benefit in these patients is consistent with prior studies evaluating castration-based therapies adjuvant to radiotherapy (Bolla et al. in Lancet 360:103–108, 2002; Pilepich et al. in Int J Radiat Oncol Biol Phys 61:1285–1290, 2005). In addition, the clinical benefit of bicalutamide 150 mg in locally advanced patients, but not in those with localized disease, is consistent with the overall results from the EPC program (McLeod et al. BJU Int 97:247–254, 2006). Given the quality-of-life advantages of bicalutamide relative to castration, bicalutamide 150 mg adjuvant to radiotherapy is an attractive alternative for men with locally advanced prostate cancer.

Keywords

Radiotherapy Adjuvant therapy Bicalutamide 

Notes

Acknowledgments

The EPC program was funded by AstraZeneca. We thank Dr Sarah Goodger from Complete Medical Group, who provided medical writing support on behalf of AstraZeneca.

References

  1. Aus G, Abbou CC, Bolla M, Heidenreich A, Van Poppel H, Schmid H-P, Wolff JM, Zattoni F (2005) European Association of Urology Guidelines on Prostate Cancer (Cited 19 Dec 2005 http://www.uroweb.nl/files/uploaded_files/2005Prostate%20Cancer.pdf)
  2. Boccardo F, Rubagotti A, Battaglia M, Di Tonno P, Selvaggi FP, Conti G, Comeri G, Bertaccini A, Martorana G, Galassi P, Zattoni F, Macchiarella A, Siragusa A, Muscas G, Durand F, Potenzoni D, Manganelli A, Ferraris V, Montefiore F (2005) Evaluation of tamoxifen and anastrozole in the prevention of gynecomastia and breast pain induced by bicalutamide monotherapy of prostate cancer. J Clin Oncol 23:808–815PubMedCrossRefGoogle Scholar
  3. Bolla M, Collette L, Blank L, Warde P, Dubois JB, Mirimanoff R-O, Storme G, Bernier J, Kuten A, Sternberg C, Mattelaer J, Lopez Torecilla J, Pfeffer JR, Cutajar CL, Zurlo A, Pierart M (2002) Long-term results with immediate androgen suppression and external irradiation in patients with locally advanced prostate cancer (an EORTC study): a phase III randomised trial. Lancet 360:103–108PubMedCrossRefGoogle Scholar
  4. Chuba PJ, Moughan J, Forman JD, Owen J, Hanks G (2001) The 1989 patterns of care study for prostate cancer: five-year outcomes. Int J Radiat Oncol Biol Phys 50:325–334PubMedCrossRefGoogle Scholar
  5. Di Lorenzo G, Perdona S, De Placido S, D’Armiento M, Gallo A, Damiano R, Pingitore D, Gallo L, De Sio M, Autorino R (2005) Gynecomastia and breast pain induced by adjuvant therapy with bicalutamide after radical prostatectomy in patients with prostate cancer: the role of tamoxifen and radiotherapy. J Urol 174:2197–2203PubMedCrossRefGoogle Scholar
  6. Green HJ, Pakenham KI, Headley BC, Yaxley J, Nicol DL, Mactaggart PN, Swanson CE, Watson RB, Gardiner RA (2004) Quality of life compared during pharmacological treatments and clinical monitoring for non-localized prostate cancer: a randomized controlled trial. BJU Int 93:975–979PubMedCrossRefGoogle Scholar
  7. Hanks GE, Hanlon AL, Pinover WH, Horwitz EM, Schultheiss TE (1999) Survival advantage for prostate cancer patients treated with high-dose three-dimensional conformal radiotherapy. Cancer J Sci Am 5:152–158PubMedGoogle Scholar
  8. Iversen P, Tyrrell CJ, Kaisary AV, Anderson JB, Van Poppel H, Tammela TL, Chamberlain M, Carroll K, Melezinek I (2000) Bicalutamide monotherapy compared with castration in patients with nonmetastatic locally advanced prostate cancer: 6.3 years of followup. J Urol 164:1579–1582PubMedCrossRefGoogle Scholar
  9. Iversen P, Melezinek I, Schmidt A (2001) Nonsteroidal antiandrogens: a therapeutic option for patients with advanced prostate cancer who wish to retain sexual interest and function. BJU Int 87:47–56PubMedCrossRefGoogle Scholar
  10. Iversen P, Newling D, Kirby R, Eardley I (2002) Sexual function: quality of life issues in patients with locally advanced non-metastatic prostate cancer. Eur Urol Suppl 1:26–32CrossRefGoogle Scholar
  11. Kirby RS, Watson A, Newling DWW (1998) Prostate cancer and sexual function. Prostate Cancer Prostatic Dis 1:179–184PubMedCrossRefGoogle Scholar
  12. McLeod DG, Iversen P, See WA, Morris T, Armstrong J, Wirth MP, on behalf of the ‘Casodex’ Early Prostate Cancer Trialists’ Group (2006) Bicalutamide 150 mg plus standard care versus standard care alone for early prostate cancer. BJU Int 97:247–254PubMedCrossRefGoogle Scholar
  13. Moul JW, Anderson J, Penson DF, Klotz LH, Soloway MS, Schulman CC (2003) Early prostate cancer: prevention, treatment modalities, and quality of life issues. Eur Urol 44:283–293PubMedCrossRefGoogle Scholar
  14. Perdona S, Autorino R, De Placido S, D’Armiento M, Gallo A, Damiano R, Pingitore D, Gallo L, De Sio M, Bianco AR, Di Lorenzo G (2005) Efficacy of tamoxifen and radiotherapy for prevention and treatment of gynaecomastia and breast pain caused by bicalutamide in prostate cancer: a randomised controlled trial. Lancet Oncol 6:295–300PubMedCrossRefGoogle Scholar
  15. Pickles T, Agranovich A, Berthelet E, Duncan GG, Keyes M, Kwan W, McKenzie MR, Morris WJ (2002) Testosterone recovery following prolonged adjuvant androgen ablation for prostate carcinoma. Cancer 94:362–367PubMedCrossRefGoogle Scholar
  16. Pilepich MV, Winter K, Lawton CA, Krish RE, Wolkov HB, Movsas B, Hug EB, Asbell SO, Grignon D (2005) Androgen suppression adjuvant to definitive radiotherapy in carcinomas of the prostate—long term results of phase III RTOG 85-31. Int J Radiat Oncol Biol Phys 61:1285–1290PubMedGoogle Scholar
  17. Roach III M, Jiandong L, Pilepich MV, Asbell SO, Mohuidden M, Terry R, Grignon D, Lawton C, Shipley W, Cox J (2000) Predicting long-term survival and the need for hormonal therapy: a meta-analysis of RTOG prostate cancer trials. Int J Radiat Oncol Biol Phys 47:617–627CrossRefGoogle Scholar
  18. See WA, Wirth MP, McLeod DG, Iversen P, Klimberg I, Gleason D, Chodak G, Montie J, Tyrrell C, Wallace DMA, Delaere KPJ, Vaage S, Tammela TLJ, Lukkarinen O, Persson B-E, Carroll K, Kolvenbag GJCM, on behalf of the Casodex Early Prostate Cancer Trialist Group (2002) 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 168:429–435PubMedCrossRefGoogle Scholar
  19. Sieber PR, Keiller DL, Kahnoski RJ, Gallo J, McFadden S (2004) Bicalutamide 150 mg maintains bone mineral density during monotherapy for localized or locally advanced prostate cancer. J Urol 171:2272–2276PubMedCrossRefGoogle Scholar
  20. Smith MR (2003) Bisphosphonates to prevent osteoporosis in men receiving androgen deprivation therapy for prostate cancer. Drugs Aging 20:175–183PubMedCrossRefGoogle Scholar
  21. Smith Jr JA, Soloway MS, Young MJ (1999) Complications of advanced prostate cancer. Urology 54(Suppl 6A):8–14PubMedCrossRefGoogle Scholar
  22. Smith MR, McGovern FJ, Zietman AL, Fallon MA, Hayden DL, Schoenfeld DA, Kantoff PW, Finkelstein JS (2001) Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer. N Engl J Med 345:948–955PubMedCrossRefGoogle Scholar
  23. Smith MR, Goode M, Zietman AL, McGovern FJ, Lee H, Finkelstein JS (2004) Bicalutamide monotherapy versus leuprolide monotherapy for prostate cancer: effects on bone mineral density and body composition. J Clin Oncol 22:2546–2553PubMedCrossRefGoogle Scholar
  24. Soloway M, Roach III M (2005) Prostate cancer progression after therapy of primary curative intent. Cancer 104:2310–2322PubMedCrossRefGoogle Scholar
  25. Tyrrell CJ, Payne H, Tammela TL, Bakke A, Lodding P, Goedhals L, Van Erps P, Boon T, Van De Beek BC, Andersson SO, Morris T, Carroll K (2004) Prophylactic breast irradiation with a single dose of electron beam radiotherapy (10 Gy) significantly reduces the incidence of bicalutamide-induced gynecomastia. Int J Radiat Oncol Biol Phys 60:476–483PubMedGoogle Scholar
  26. Ullrich PM, Carson MR, Lutgendorf SK, Williams RD (2003) Cancer fear and mood disturbance after radical prostatectomy: consequences of biochemical evidence of recurrence. J Urol 169:1449–1452PubMedCrossRefGoogle Scholar
  27. Van Poppel H, Tyrrell CJ, Haustermans K, Cangh PV, Keuppens F, Colombeau P, Morris T, Garside L (2005) Efficacy and tolerability of radiotherapy as treatment for bicalutamide-induced gynaecomastia and breast pain in prostate cancer. Eur Urol 47:587–592PubMedCrossRefGoogle Scholar
  28. Vicini FA, Martinez A, Hanks G, Hanlon A, Miles B, Kernan K, Beyers D, Ragde H, Forman J, Fontanesi J, Kestin L, Kovacs G, Denis L, Slawin K, Scardino P (2002) An interinstitutional and interspecialty comparison of treatment outcome data for patients with prostate carcinoma based on predefined prognostic categories and minimum follow-up. Cancer 95:2126–2135PubMedCrossRefGoogle Scholar
  29. Wirth MP, See WA, McLeod D, Iversen P, Morris T, Carroll K, Casodex Early Prostate Cancer Trialists’ Group (2004) 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 172:1865–1870PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • William A. See
    • 1
  • Chris J. Tyrrell
    • 2
  • on behalf of the CASODEX™ Early Prostate Cancer Trialists’ Group
  1. 1.Department of UrologyMedical College of WisconsinMilwaukeeUSA
  2. 2.Derriford HospitalPlymouthUK

Personalised recommendations