Why phase III trials of maximal androgen blockade versus castration in M<sub>1</sub> prostate cancer rarely show statistically significant differences*

Collette, Laurence; Studer, Urs E.; Schröder, Fritz H.; Denis, L.; Sylvester, Richard

doi:10.1002/pros.1078

Cited by 22 publications

(3 citation statements)

References 25 publications

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“…Moreover, the meta-analysis included trials in which a short-term antiandrogen was not used for disease-flare prevention. Exclusion of those trials from the meta-analysis, however, resulted in no difference in survival between CAB and castration [61]. In fact, when LHRH agonists are administered alone, the increase in circulating testosterone during the first week may cause a painful disease flare in patients with high-volume, symptomatic, bony disease (4–10% of M1 patients) [62].…”

Section: Evidence Synthesismentioning

confidence: 99%

Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

et al. 2012

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Context Androgen deprivation therapy (ADT) for prostate cancer (PCa) represents one of the most effective systemic palliative treatments known for solid tumors. Although clinical trials have assessed the role of ADT in patients with metastatic and advanced locoregional disease, the risk–benefit ratio, especially in earlier stages, remains poorly defined. Given the mounting evidence for potentially life-threatening adverse effects with short- and long-term ADT, it is important to redefine the role of ADT for this disease. Objective Review the published experience with currently available ADT approaches in various contemporary clinical settings of PCa and reported serious treatment-related adverse events. This review addresses the level of evidence associated with the use of ADT in PCa, focusing upon survival outcome measures. Furthermore, this paper discusses evolving approaches targeting androgen receptor signaling pathways and emerging evidence from clinical trials with newer compounds. Evidence acquisition A comprehensive review of the literature was performed, focusing on data from the last 10 yr (January 2000 to July 2011) and using the terms androgen deprivation, hormone treatment, prostate cancer and adverse effects. Abstracts from trials reported at international conferences held in 2010 and 2011 were also evaluated. Evidence synthesis Data from randomized controlled trials and population-based studies were analyzed in different clinical paradigms. Specifically, the role of ADT was evaluated in patients with nonmetastatic disease as the primary and sole treatment, in combination with radiation therapy (RT) or after surgery, and in patients with metastatic disease. The data suggest that in men with nonmetastatic disease, the use of primary ADT as monotherapy has not shown a benefit and is not recommended, while ADT combined with conventional-dose RT (<72 Gy) for patients with high-risk disease may delay progression and prolong survival. The postoperative use of ADT remains poorly evaluated in prospective studies. Likewise, there are no trials evaluating the role of ADT in patients with biochemical relapses after surgery or RT. In patients with metastatic disease, there is a clear benefit in terms of quality of life, reduction of disease-associated morbidity, and possibly survival. Treatment with bilateral orchiectomy, luteinizing hormone–releasing hormone agonist therapy, with and without antiandrogens has been associated with various serious adverse events, including cardiovascular disease, diabetes, and skeletal complications that may also affect mortality. Conclusions Although ADT is an effective treatment of PCa, consistent long-term benefits in terms of quality and quantity of life are predominantly evident in patients with advanced/metastatic disease or when ADT is used in combination with RT (<72 Gy) in patients with high-risk tumors. Implementation of ADT should be evidence based, with special consideration to adverse events and the risk–benefit ratio.

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Section: Evidence Synthesismentioning

confidence: 99%

Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

et al. 2012

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“…High-risk patients with short PSADT, high initial PSA and symptomatic patients should preferably receive combined androgen blockade[69707172737475] (EL-2).…”

Section: Manuscriptmentioning

confidence: 99%

Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer

et al. 2014

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“…An overview of the RCTs involving 8,275 patients conducted by the Prostate Cancer Trialists' Collaborative Group (PCTCG) [26] demonstrated that CAB (orchidectomy or LHRH agonists plus an NSAA) resulted in marginally better OS (27.6 vs. 24.7%; p = 0.005) beyond 5 years, while CAB with an SAA (cyproterone acetate) resulted in worse OS (15.4 vs. 18.1%; p = 0.04). Exclusion of trials in which a short-term AA was not used for disease flare prevention resulted in no difference in survival between CAB and castration even if the AA used was an NSAA [27]. Therefore, CAB is no longer considered as a standard of care [1].…”

Section: Combined Therapy or Monotherapy?mentioning

confidence: 99%

Androgen Deprivation Therapy in Prostate Cancer - Current Status in M1 Patients

Habchi¹,

Mottet²

2015

Oncol Res Treat

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Androgen deprivation therapy is the cornerstone treatment for metastatic prostate cancer. It can be done either surgically or medically. Luteinizing hormone-releasing hormone agonists and antagonist are the most effective drugs, with different side effects and modes of action, but no clear efficacy differences. Adding a non-steroidal antiandrogen adds a marginal benefit but also significant side effects and costs. Non-steroidal antiandrogens should not be used as monotherapy. In most patients with metastases, immediate castration is the standard of care. The intermittent modality is apparently non-inferior to the continuous one, with some other benefits. Upfront chemotherapy added to castration should be considered as the new standard of care in many metastatic patients. Castration leads to many adverse effects, some potentially life-threatening such as cardiovascular side effects.

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Why phase III trials of maximal androgen blockade versus castration in M₁ prostate cancer rarely show statistically significant differences*

Cited by 22 publications

References 25 publications

Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer

Androgen Deprivation Therapy in Prostate Cancer - Current Status in M1 Patients

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Why phase III trials of maximal androgen blockade versus castration in M1 prostate cancer rarely show statistically significant differences*

Cited by 22 publications

References 25 publications

Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

Contemporary Role of Androgen Deprivation Therapy for Prostate Cancer

Saudi oncology society and Saudi urology association combined clinical management guidelines for prostate cancer

Androgen Deprivation Therapy in Prostate Cancer - Current Status in M1 Patients

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Why phase III trials of maximal androgen blockade versus castration in M₁ prostate cancer rarely show statistically significant differences*