Bicalutamide Early Prostate Cancer Program Research Articles

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 9.7years

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 9.7years

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

To evaluate the efficacy and tolerability of bicalutamide 150 mg once-daily as immediate hormonal therapy in patients with prostate cancer or as adjuvant to radical prostatectomy or radiotherapy. In all, 8113 patients with localized (T1-2, N0/Nx) or locally advanced (T3-4, any N; or any T, N+) prostate cancer (all M0) were enrolled in three complementary, double-blind, placebo-controlled trials. Patients were randomized to receive standard care plus either oral bicalutamide 150 mg once-daily or oral placebo. Primary endpoints were progression-free survival (PFS) and overall survival (OS). Data were collated from individual trials and evaluated in a combined analysis. Overall, at a median follow-up of 9.7 years, bicalutamide significantly improved PFS (hazard ratio 0.85, 95% confidence interval 0.79-0.91; P= 0.001). Compared with placebo there was no difference in OS (hazard ratio 1.01, P= 0.77). Patients who derived benefit from bicalutamide in terms of PFS were those with locally advanced disease, with OS significantly favouring bicalutamide in patients with locally advanced disease undergoing radiotherapy (P= 0.031). Patients with localized disease showed no clinically or statistically significant improvements in PFS; there was a survival trend in favour of placebo in patients with localized disease undergoing watchful waiting (P= 0.054). The overall tolerability of bicalutamide was consistent with previous analyses, with breast pain (73.7%) and gynaecomastia (68.8%) the most frequently reported adverse events in patients randomized to bicalutamide. Bicalutamide 150 mg, either as monotherapy or adjuvant to standard care, improved PFS in patients with locally advanced prostate cancer, but not in patients with localized disease. A pre-planned subset analysis showed a benefit for OS in patients with locally advanced disease undergoing radiotherapy. Bicalutamide 150 mg might represent an alternative for patients with locally advanced prostate cancer considering androgen-deprivation therapy.

Spotlight on Bicalutamide 150mg in the Treatment of Locally Advanced Prostate Cancer1

Bicalutamide (Casodex) is a competitive androgen receptor antagonist that inactivates androgen-regulated prostate cell growth and function, leading to cell apoptosis and inhibition of prostate cancer growth. It is administered orally as a once-daily dose. In the EU and a number of other countries, bicalutamide 150 mg/day is approved in men with locally advanced nonmetastatic prostate cancer as immediate therapy either as an adjuvant to active treatment or as monotherapy as an alternative to surgical or medical castration. Combined analysis of the three trials that comprise the bicalutamide Early Prostate Cancer programme showed that bicalutamide administered in conjunction with standard care in men with locally advanced prostate cancer offers disease-free survival benefits over standard care alone and is generally well tolerated. Overall survival was improved to a greater extent in the subgroup of patients who received bicalutamide plus radiation therapy compared with radiation therapy alone. Men with localised prostate cancer do not benefit from the addition of bicalutamide to standard care. Combined analysis of two other studies in men with locally advanced prostate cancer show that bicalutamide monotherapy offers better tolerability and higher health-related quality-of-life scores for sexual interest and physical capacity compared with surgical or medical castration, while achieving disease-free and overall survival durations that were not significantly different. Thus, when treatment options are being evaluated, bicalutamide as adjuvant therapy or monotherapy should be considered as an alternative to other available hormonal therapies in men with locally advanced prostate cancer, especially in those who wish to maintain an active lifestyle.

1588: The Bicalutamide Early Prostate Cancer Program: Findings of the North American Trial at 7.7 Years' Median Follow-Up

1588: The Bicalutamide Early Prostate Cancer Program: Findings of the North American Trial at 7.7 Years' Median Follow-Up

The third analysis of the bicalutamide Early Prostate Cancer programme

BJU InternationalVolume 97, Issue 3 p. 438-439 The third analysis of the bicalutamide Early Prostate Cancer programme PETER IVERSEN, Corresponding Author PETER IVERSENPeter Iversen, Department of Urology, University of Copenhagen, Copenhagen, Denmark. e-mail: [email protected]Search for more papers by this authoron behalf of the Early Prostate Cancer programme investigators, on behalf of the Early Prostate Cancer programme investigators Department of Urology, Rigshospitalet, Copenhagen, DenmarkSearch for more papers by this author PETER IVERSEN, Corresponding Author PETER IVERSENPeter Iversen, Department of Urology, University of Copenhagen, Copenhagen, Denmark. e-mail: [email protected]Search for more papers by this authoron behalf of the Early Prostate Cancer programme investigators, on behalf of the Early Prostate Cancer programme investigators Department of Urology, Rigshospitalet, Copenhagen, DenmarkSearch for more papers by this author First published: 10 February 2006 https://doi.org/10.1111/j.1464-410X.2006.06118.xCitations: 9Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Citing Literature Volume97, Issue3March 2006Pages 438-439 RelatedInformation

674: The Bicalutamide Early Prostate Cancer Program: Findings of the North American Trial at Median 5.7 Years' Follow-Up

You have accessJournal of UrologyDiscussed Poster, Monday, May 23, 2005, 8:00am - 12:00 pm1 Apr 2005674: The Bicalutamide Early Prostate Cancer Program: Findings of the North American Trial at Median 5.7 Years' Follow-Up David G. McLeod, William A. See, Ira Klimberg, Donald Gleason, Gerald W. Chodak, Tom Morris, and Jon Armstrong David G. McLeodDavid G. McLeod More articles by this author , William A. SeeWilliam A. See More articles by this author , Ira KlimbergIra Klimberg More articles by this author , Donald GleasonDonald Gleason More articles by this author , Gerald W. ChodakGerald W. Chodak More articles by this author , Tom MorrisTom Morris More articles by this author , and Jon ArmstrongJon Armstrong More articles by this author View All Author Informationhttps://doi.org/10.1016/S0022-5347(18)34914-0AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail "674: The Bicalutamide Early Prostate Cancer Program: Findings of the North American Trial at Median 5.7 Years' Follow-Up." The Journal of Urology, 173(4S), p. 184 © 2016 by American Urological AssociationFiguresReferencesRelatedDetailsCited ByMcLeod D, See W, Klimberg I, Gleason D, Chodak G, Montie J, Bernstein G, Morris C and Armstrong J (2018) The Bicalutamide 150 Mg Early Prostate Cancer Program: Findings of the North American Trial at 7.7-Year Median FollowupJournal of Urology, VOL. 176, NO. 1, (75-80), Online publication date: 1-Jul-2006. Volume 173Issue 4SApril 2005Page: 184 Advertisement Copyright & Permissions© 2016 by American Urological AssociationMetricsAuthor Information David G. McLeod More articles by this author William A. See More articles by this author Ira Klimberg More articles by this author Donald Gleason More articles by this author Gerald W. Chodak More articles by this author Tom Morris More articles by this author Jon Armstrong More articles by this author Expand All Advertisement Loading ...

1013: Prostate-Specific Antigen Levels as a Predictor of Positive Bone Scans During Follow-Up After Standard Care for Prostate Cancer: Data from the Bicalutamide Early Prostate Cancer Program

1013: Prostate-Specific Antigen Levels as a Predictor of Positive Bone Scans During Follow-Up After Standard Care for Prostate Cancer: Data from the Bicalutamide Early Prostate Cancer Program

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

We evaluated the efficacy and tolerability of 150 mg bicalutamide daily given in addition to standard care, in patients with localized or locally advanced prostate cancer. The bicalutamide Early Prostate Cancer program consists of 3 randomized, double blind, placebo controlled trials prospectively designed for combined analysis. A total of 8,113 men with T1b-T4, M0, any N (N0 in 1 trial) prostate cancer were randomized to bicalutamide 150 mg/day (4,052) or placebo (4,061) in addition to standard care (radical prostatectomy, radiotherapy or watchful waiting). Primary end points were objective progression-free survival (PFS) and overall survival. At median 5.4 years of followup (21.6% progression events) bicalutamide significantly improved PFS in the overall population. This result was driven by positive results in trials 24 and 25, with the North American trial (trial 23) showing no difference. Patients with locally advanced disease gained most benefit from bicalutamide in terms of PFS, irrespective of underlying therapy. Overall survival was similar in the bicalutamide and placebo groups, across the program and in each trial. Among watchful waiting patients survival appeared to be improved with bicalutamide in those with locally advanced disease, whereas survival appeared to be reduced with bicalutamide in those with localized disease. The most common adverse events with bicalutamide were gynecomastia and breast pain. Other adverse events occurred with a similarly low incidence in the 2 treatment groups. This analysis confirms that bicalutamide provides benefit in patients with locally advanced disease. The current data suggest that early or adjuvant hormonal therapy for patients at low risk of disease progression, such as those with localized disease, is not appropriate.

182 Bicalutamide (‘Casodex’) 150 mg as adjuvant to radiotherapy significantly improves progression-free survival in early non-metastatic prostate cancer: Results from the bicalutamide early prostate cancer programme after a median 5.4 years' follow-up

182 Bicalutamide (‘Casodex’) 150 mg as adjuvant to radiotherapy significantly improves progression-free survival in early non-metastatic prostate cancer: Results from the bicalutamide early prostate cancer programme after a median 5.4 years' follow-up

Bicalutamide Monotherapy for Early Stage Prostate Cancer: An Update

The current evidence is considered to support 150 mg of the nonsteroidal antiandrogen bicalutamide for early stage prostate cancer. Data from phase III trials of 150 mg bicalutamide monotherapy for locally advanced disease are discussed. In addition, the first overall results are examined from the bicalutamide early prostate cancer program conducted at a median followup of 3 years, in which patients with localized or locally advanced disease were randomized to receive 150 mg bicalutamide or placebo as well as standard care. Mature data from phase III studies have shown that 150 mg bicalutamide monotherapy provide similar survival outcome to that observed with castration in patients with locally advanced (M0) disease. Moreover, 150 mg bicalutamide have benefits over castration in terms of quality of life, particularly sexual interest and physical capacity, and preservation of bone mineral density. In the bicalutamide early prostate cancer program 150 mg significantly reduced the risk of objective progression in patients with localized or locally advanced disease at 3 years of median followup, with the greatest benefit seen in patients with poorer prognosis. Followup is ongoing to further determine the benefit of 150 mg bicalutamide in early prostate cancer. Bicalutamide is emerging as a useful treatment option for early prostate cancer.

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

We determine the efficacy and tolerability of bicalutamide as immediate therapy, either alone or as adjuvant to treatment of curative intent, in patients with clinically localized or locally advanced prostate cancer. This international program consists of 3 ongoing, randomized, double-blind, placebo controlled clinical trials (trials 23, 24, and 25). Men with localized or locally advanced (T1-T4, Nx/N0, M0) prostate cancer were randomized to receive 150 mg. bicalutamide daily or placebo, in addition to standard care with radical prostatectomy, radiotherapy or watchful waiting. Primary end points are time to objective progression and overall survival. In this first analysis data from the trials were combined in a single overview analysis according to protocol. Data are available for 8,113 patients (4,052 randomized to bicalutamide, 4,061 to standard care alone) at a median followup of 3.0 years. Treatment with bicalutamide provided a highly significant reduction of 42% in the risk of objective progression compared with standard care alone (9.0% versus 13.8%, hazards ratio 0.58; 95% confidence interval 0.51, 0.66; p <<0.0001). The overall result was reflected in 2 of the 3 trials (trials 24 and 25) with trial 3 (trial 23) showing a nonsignificant difference at this time. Reductions in the risk of disease progression were seen across the entire patient population, irrespective of primary treatment or disease stage. Overall survival data are currently immature and longer followup will determine if there is also a survival benefit with bicalutamide. The most frequently reported side effects of bicalutamide were gynecomastia and breast pain. Immediate treatment with 150 mg. bicalutamide daily, either alone or as adjuvant to treatment of curative intent, significantly reduces the risk of disease progression in patients with localized or locally advanced prostate cancer. This benefit must be balanced with the morbidity associated with long-term hormonal therapy. Followup is ongoing to determine potential survival benefits of this treatment approach.

The bicalutamide Early Prostate Cancer Program: Demography

BACKGROUND: The optimal treatment for early prostate cancer has yet to be established. A well-tolerated hormonal therapy such as bicalutamide could be a useful treatment option in this setting, either as adjuvant or immediate therapy. A major collaborative clinical trials program was set up to investigate bicalutamide as a treatment option for local prostate cancer (localized or locally advanced disease). METHODS: The bicalutamide Early Prostate Cancer program comprises three randomized, double-blind, placebo-controlled trials of similar design that are being conducted in distinct geographical areas (North America; Australia, Europe, Israel, South Africa and Mexico; and Scandinavia). Men with T1b-4N0-1M0 (TNM 1997) prostate cancer have been randomized on a 1:1 basis to receive bicalutamide 150 mg daily or placebo. Recruitment to the program closed in July 1998, and follow-up is ongoing. Study endpoints include time to clinical progression, overall survival and tolerability. RESULTS: 8113 men aged 38 to 93 years (mean 66.9) were randomized over a 3-year period. 67.4% of the enrolled patients had localized disease (T1-2) and 66.4% had a Gleason score ⩽6 at study entry, while the majority of patients had node-negative (N0) disease; only 3.1% in two of the studies and none in the third study had confirmed N+ disease. Overall, 71.8% of the patients received therapy of primary curative intent within 16 weeks of randomization; the remainder received watchful waiting as their primary approach. Across the program, the two randomized groups are well balanced. CONCLUSION: This is the largest randomized clinical trial program to date in local prostate cancer and is expected to provide critical information on the role of bicalutamide as an addition to standard care for patients with local prostate cancer who have received a therapy of curative intent or are candidates for watchful waiting.