PMH 9907: Long‐term outcomes of a randomized phase 3 study of short‐term bicalutamide hormone therapy and dose‐escalated external‐beam radiation therapy for localized prostate cancer

McPartlin, Andrew; Glicksman, Rachel; Pintilie, Melania; Mok, Gary; Bayley, Andrew; Chung, Peter; Bristow, Robert G.; Gospodarowicz, Mary K.; Catton, Charles; Milosevic, Michael; Warde, Padraig

doi:10.1002/cncr.30093

Cited by 22 publications

(11 citation statements)

References 38 publications

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“…Attempts to clinically evaluate the anti‐androgen Bicalutamide as a potential radiosensitizer in radiation therapy for localized PCa, indicate that the only the inclusion of Bicalutamide to existing ADT regime with radiotherapy can significantly improve overall survival in these men versus men solely on ADT prior to XRT. Therefore, the work by Quero et al suggests that the beneficial clinical outcomes of Bicalutamide and radiation on increased patient survival may be a result of the combination of an ADT environment, rather than the independent action with ENZA.…”

Section: Discussionmentioning

confidence: 99%

Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

et al. 2017

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Background Prostate cancer (PCa) is a progressive disease and the most diagnosed cancer in men. The current standard of care for high‐risk localized PCa is a combination of androgen deprivation therapy (ADT) and radiation (XRT). The majority of these patients however become resistant due to incomplete responses to ADT as a result of selective cells maintaining androgen receptor (AR) activity. Improvement can be made if increasing radiosensitivity is realized. Therefore, the aim of this study is to investigate the efficacy of the next‐generation PCa drug Enzalutamide (ENZA), as a radiosensitizer in XRT therapy. Methods Using a number of androgen‐dependent (LNCaP, PC3‐T877A) and androgen‐independent (C4‐2, 22RV1, PC3, PC3‐AR V7) cell lines, the effect of ENZA as a radiosensitizer was studied alone or in combination with ADT and/or XRT. Cell viability and cell survival were assessed, along with determination of cell cycle arrest, DNA damage response and repair, apoptosis and senescence. Results Our results indicated that either ENZA alone (in AR positive, androgen‐dependent PCa cells) or in combination with ADT (in AR positive, hormone‐insensitive PCa cells) potentiates radiation response [Dose enhancement factor (DEF) of 1.75 in LNCAP and 1.35 in C4‐2] stronger than ADT + XRT conditions. Additionally, ENZA sensitized androgen dependent PCa cells to XRT in a schedule‐dependent manner, where concurrent administration of ENZA and radiation lead to a maximal radiosensitization when compared to either drug administration prior or after XRT. In LNCaP cells, ENZA treatment significantly prolonged the presence of XRT‐induced phospho‐γH2AX up to 24 h after treatment; suggesting enhanced DNA damage. It also significantly increased XRT‐induced apoptosis and senescence. Conclusions Our data indicates that ENZA acts as a much stronger radiosensitizer compared to ADT. We have also observed that its efficacy is schedule dependent and related to increased levels of DNA damage and a delay of DNA repair processes. Finally, the initial abrogation of DNA‐PKcs activity by AR inhibition and its subsequent recovery might represent an important mechanism by which PCa cells acquire resistance to combined anti‐androgen and XRT treatment. This work suggests a new use of ENZA in combination with XRT that could be applicable in clinical trial settings for patients with early and intermediate hormone responsive disease.

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Section: Discussionmentioning

confidence: 99%

Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

et al. 2017

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“…After full-text reviews, non-cohort studies (n=397), studies not associated to T1-T3 PC (n=1650), studies unrelated to therapeutic regimens (n=459) and studies lacking data integrity or lacking data (n=1) were ruled out. Finally, 9 cohort studies were eligible for this NMA [19][20][21][22][23][24][25][26][27] (Supplementary Figure 1). All included cohort studies were published between 2004 and 2016.…”

Section: Resultsmentioning

confidence: 99%

Evaluation of overall survival rate of different therapies in the treatment of T1–T3 prostate cancer: a network meta-analysis

Chen¹,

Du²,

Shao³

et al. 2018

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We performed this network meta-analysis (NMA) in order to compare the overall survival rate of six different therapies of T1-T3 prostate cancer (PC). The therapies include radiotherapy (RT), endocrine therapy (ET), Cryoablation (CRYO), radical prostatectomy (RP), RT+ET and RP+ET. Pubmed, Embase, Cochrane Library, Google Scholar, Web of Science and MEDLINE were searched to collect relevant literature from the inception of the study till February 2017. Cohort studies meeting the inclusion criteria were included in the study. A combination of direct and indirect evidence was performed to evaluate the odds ratio (OR) and draw surface under the cumulative ranking curves (SUCRA). Nine eligible cohort studies were included in this NMA, including 20,644 patients suffering from T1-T3 PC. The pairwise meta-analysis revealed that compared with the ET regimen, the RP and RP+ET regimens exhibited comparatively higher overall survival rates (OR = 2.81, 95%CI = 2.09 ~ 3.78; OR = 3.15，95%CI = 1.80 ~ 5.50, respectively). The results of SUCRA values demonstrated that the RP + ET regimen occupied the first place (89.5%) in terms of overall survival rate, and the RP regimen came second (84.83%). Thus, the RP+ET regimen had better efficacy in the treatment of T1-T3 PC in combined-therapeutic regimens, and the RP regimen presented better efficacy in mono-therapeutic regimen. Our findings indicate that the RP+ET regimen had better efficacy on improving the overall survival rate of T1-T3 PC patients, and the RP regimen ranked second.

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“…However concerns about the efficacy of bicalutamide monotherapy have persisted. One randomised trial did not show the expected improvement in biochemical control with bicalutamide compared with radiotherapy alone 33 and, for earlier disease, overall survival with bicalutamide appeared to be worse than watchful waiting in another study 34 .…”

Section: Discussionmentioning

confidence: 96%

Nonrandomized Comparison of Efficacy and Side Effects of Bicalutamide Compared With Luteinizing Hormone-Releasing Hormone (LHRH) Analogs in Combination With Radiation Therapy in the CHHiP Trial

Tree

Griffin

Syndikus

et al. 2022

International Journal of Radiation Oncology*Biology*Physics

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This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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PMH 9907: Long‐term outcomes of a randomized phase 3 study of short‐term bicalutamide hormone therapy and dose‐escalated external‐beam radiation therapy for localized prostate cancer

Abstract: For patients who predominantly have IRPC, the addition of HT to DE-EBRT did not significantly affect BF, OS, or LC. Bicalutamide appeared to be well tolerated. The conclusions from the study are limited by incomplete recruitment. Cancer 2016;122:2595-603. © 2016 American Cancer Society.

Cited by 22 publications

References 38 publications

Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

Enhanced radiosensitization of enzalutamide via schedule dependent administration to androgen‐sensitive prostate cancer cells

Evaluation of overall survival rate of different therapies in the treatment of T1–T3 prostate cancer: a network meta-analysis

Nonrandomized Comparison of Efficacy and Side Effects of Bicalutamide Compared With Luteinizing Hormone-Releasing Hormone (LHRH) Analogs in Combination With Radiation Therapy in the CHHiP Trial

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