Association of Androgen Deprivation Therapy and Thromboembolic Events: A Systematic Review and Meta-analysis

Nead, Kevin T.; Boldbaatar, Ninjin; Yang, David D.; Sinha, Sumi; Nguyen, Paul L.

doi:10.1016/j.urology.2017.11.055

Cited by 17 publications

(22 citation statements)

References 29 publications

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“…Estrogens inhibit testosterone production [21] . In clinical practice it lost popularity decades ago, mainly due to cardiovascular side-effects such as thromboembolic events [25] . In lower doses these events may occur less frequently and treatment costs are low compared to other forms of ADT, however in the currently increasing complexity of the therapeutic mCRPC landscape, it might be too late for a “comeback” into routine clinical practice [15] , [26] , [27] , [28] .…”

Section: Current Treatment Patterns For Crpcmentioning

confidence: 99%

Metastatic prostate cancer remains incurable, why?

Dong

Zieren

Xue

et al. 2019

Asian Journal of Urology

129

107

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Metastatic prostate cancer patients present in two ways—with already disseminated disease at the time of presentation or with disease recurrence after definitive local therapy. Androgen deprivation therapy is given as the most effective initial treatment to patients. However, after the initial response, almost all patients will eventually progress despite the low levels of testosterone. Disease at this stage is termed castration resistant prostate cancer (CRPC). Before 2010, the taxane docetaxel was the first and only life prolonging agent for metastatic CRPC (mCRPC). The last decade has witnessed robust progress in CRPC therapeutics development. Abiraterone, enzalutamide, apalutamide and sipuleucel-T have been evaluated as first- and second-line agents in mCRPC patients, while cabazitaxel was approved as a second-line treatment. Radium-223 dichloride was approved in symptomatic patients with bone metastases and no known visceral metastases pre- and post-docetaxel. However, despite significant advances, mCRPC remains a lethal disease. Both primary and acquired resistance have been observed in CRPC patients treated by these new agents. It could be solely cell intrinsic or it is possible that the clonal heterogeneity in treated tumors may result from the adaptive responses to the selective pressures within the tumor microenvironment. The aim of this review is to list current treatment agents of CRPC and summarize recent findings in therapeutic resistance mechanisms.

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Section: Current Treatment Patterns For Crpcmentioning

confidence: 99%

Metastatic prostate cancer remains incurable, why?

Dong

Zieren

Xue

et al. 2019

Asian Journal of Urology

129

107

View full text Add to dashboard Cite

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“…There was also a significant association between ADT and hypertension, particularly for second generation therapies, abiraterone and enzalutamide. Other vascular disorders like thromboembolic events also showed a significant association with GnRHa alone, CAB, anti-androgen alone, oestrogen and orchiectomy (10,18). For vasomotor flashing, enzalutamide had a significant increased risk and anti-androgens a significantly lower risk than other types of ADT (14,15,25,29,57).…”

Section: Discussionmentioning

confidence: 93%

“…Sub analyses examining impact of ADT duration showed a significantly increased risk of thromboembolic events for duration >12months. Significant heterogeneity was resolved in ADT without oestrogen analysis for localized disease (0%) but not for the metastatic disease analysis (84%) or the oestrogen only analysis (71%) (18).…”

Section: B Thromboembolic Eventsmentioning

confidence: 99%

“…Population-based studies of men receiving ADT for PC have revealed an association between ADT and increased risk of thromboembolic events such as deep vein thrombosis (DVT) and pulmonary embolus (PE). Two meta-analyses examined the evidence for ADT associated thromboembolic events (10,18).…”

Section: B Thromboembolic Eventsmentioning

confidence: 99%

“…One restricted the analysis to five cohort studies which compared GnRH agonists alone, GnRH agonists + anti-androgens, anti-androgens alone and orchiectomy with no ADT (10 (10). The other systematic review included oestrogens in addition to the above-mentioned forms of ADT and drew evidence from 20 studies comparing ADT with no ADT, short term ADT and IADT (18). In this meta-analysis, ADT without oestrogen in 10 studies caused a significant increase in risk of thromboembolic events (RR 1.43; 95% CI 1.15, 1.77, p<0.001) as did oestrogen alone in 9 nine studies (RR 3.72; 95% CI 1.78, 7.80, p<0.001).…”

Section: B Thromboembolic Eventsmentioning

confidence: 99%

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Incidence of the adverse effects of androgen deprivation therapy for prostate cancer: a systematic literature review

Edmunds

Tuffaha

Galvão

et al. 2020

Support Care Cancer

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PurposeAndrogen deprivation therapy (ADT) has broad application in the treatment of prostate cancer (PC) and is associated with numerous, debilitating adverse effects. Increasing use of ADT for PC, longer timeframe for treatment (increased uptake of PSA testing and earlier diagnosis), as well as improved survival and an ageing population, means patients can live for a considerable period of time on or after ADT, experiencing these adverse effects. A number of systematic reviews of adverse effects of ADT for PC exist, however, no single systematic review has previously examined the evidence for all adverse effects, including newer forms of ADT. MethodsA systematic review of existing systematic reviews of ADT for PC was conducted (2010 -February 2019), as per Cochrane guidelines, to identify the highest level of risk/incidence evidence available, supplemented by evidence drawn from individual studies where no systematic review existed. ResultsIncidence data was generated for 19 adverse effect sub groups, classified according to the common terminology criteria for adverse events (CTCAE). ConclusionIncidence of adverse effects provides valuable information for future burden of disease studies. This information can better guide clinical management to reduce symptoms for patients and assist patients to make more informed decisions about their treatment, potentially improving disease outcomes. It also highlights the importance of supportive care for PC patients receiving ADT and their carers. For analysts conducting economic evaluations, the inclusion of adverse effects in PC decision analytic models can provide more comprehensive and accurate information for decision makers.

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