William A See1, Chris J Tyrrell. 1. Department of Urology, Medical College of Wisconsin, 9200 W. Wisconsin Avenue, Milwaukee, WI 53226, USA. wsee@mcw.edu
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.
RCT Entities:
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.
Authors: Frank A Vicini; Alvaro Martinez; Gerald Hanks; Alex Hanlon; Brian Miles; Ken Kernan; David Beyers; Haakon Ragde; Jeffrey Forman; James Fontanesi; Larry Kestin; Gyorgy Kovacs; Louis Denis; Kevin Slawin; Peter Scardino Journal: Cancer Date: 2002-11-15 Impact factor: 6.860
Authors: H Van Poppel; C J Tyrrell; K Haustermans; P Van Cangh; F Keuppens; P Colombeau; T Morris; L Garside Journal: Eur Urol Date: 2004-12-30 Impact factor: 20.096
Authors: Michel Bolla; Laurence Collette; Léo Blank; Padraig Warde; Jean Bernard Dubois; René-Olivier Mirimanoff; Guy Storme; Jacques Bernier; Abraham Kuten; Cora Sternberg; Johan Mattelaer; José Lopez Torecilla; J Rafael Pfeffer; Carmel Lino Cutajar; Alfredo Zurlo; Marianne Pierart Journal: Lancet Date: 2002-07-13 Impact factor: 79.321
Authors: H J Green; K I Pakenham; B C Headley; J Yaxley; D L Nicol; P N Mactaggart; C E Swanson; R B Watson; R A Gardiner Journal: BJU Int Date: 2004-05 Impact factor: 5.588
Authors: William A See; Manfred P Wirth; David G McLeod; Peter Iversen; Ira Klimberg; Donald Gleason; Gerald Chodak; James Montie; Chris Tyrrell; D M A Wallace; Karl P J Delaere; Sigmund Vaage; Teuvo L J Tammela; Olavi Lukkarinen; Bo-Eric Persson; Kevin Carroll; Geert J C M Kolvenbag Journal: J Urol Date: 2002-08 Impact factor: 7.450
Authors: Chengfei Liu; Cameron M Armstrong; Wei Lou; Alan P Lombard; Vito Cucchiara; Xinwei Gu; Joy C Yang; Nagalakshmi Nadiminty; Chong-Xian Pan; Christopher P Evans; Allen C Gao Journal: Mol Cancer Ther Date: 2017-05-12 Impact factor: 6.261
Authors: Vincenzo Pagliarulo; Sergio Bracarda; Mario A Eisenberger; Nicolas Mottet; Fritz H Schröder; Cora N Sternberg; Urs E Studer Journal: Eur Urol Date: 2011-08-19 Impact factor: 20.096
Authors: Christian Tovar; Brian Higgins; Kenneth Kolinsky; Mingxuan Xia; Kathryn Packman; David C Heimbrook; Lyubomir T Vassilev Journal: Mol Cancer Date: 2011-05-03 Impact factor: 27.401
Authors: Tao Wang; Lucia R Languino; Jane Lian; Gary Stein; Michael Blute; Thomas J Fitzgerald Journal: Front Oncol Date: 2011-07-13 Impact factor: 6.244