scholarly journals Second-generation androgen receptor inhibitors in therapy of non-metastatic castration resistant prostate cancer: role of safety profile and effect on quality of life

2021 ◽  
Vol 67 (2) ◽  
pp. 217-226
Author(s):  
Elena Ushkalova ◽  
Sergey Zyryanov ◽  
Irina Gopienko
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Safety Profile ◽  
Second Generation ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Clinically Significant

The article discusses the role of second-generation androgen receptor inhibitors (ARi) in therapy of non-metastatic castration resistant prostate cancer (nmCRPC). The phase 3 trials PROSPER (enzalutamide), SPARTAN (apalutamide) and ARAMIS (darolutamide) showed that these medicines if used in combination with androgen deprivation therapy (ADT) make possible to significantly improve, as compared with placebo, metastasis-free survival and overall survival of patients with nmCRPC. An important role in choosing a certain medicine of the group is played by its safety profile, including its drug-drug interaction potential and effect on patient’s quality of life. In this respect, darolutamide has a number of advantages over apalutamide or enzlutamide. The frequency of CNS (cognitive, psychiatric, convulsive) and other adverse drug reactions that significantly worsen the patients’ quality of life (falls, fractures, hypertension, etc.) in therapy with darolutamide does not differ from that with placebo. Moreover, this medicine retains its antagonistic effects to all clinically significant androgen receptor mutations that develop resistance to enzalutamide and apalutamide.

scholarly journals Novel Treatment Strategy Using Second-Generation Androgen Receptor Inhibitors for Non-Metastatic Castration-Resistant Prostate Cancer

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 661
Author(s):  
Doo Yong Chung ◽  
Jee Soo Ha ◽  
Kang Su Cho
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Randomized Clinical Trials ◽  
Specific Antigen ◽  
Significant Proportion ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant

Non-metastatic castration-resistant prostate cancer (nmCRPC) is defined by a progressively rising prostate-specific antigen level, despite a castrate level of testosterone, in the absence of obvious radiologic evidence of metastatic disease on conventional imaging modalities. As a significant proportion of patients with nmCRPC develop metastatic diseases, the therapeutic goals of physicians for these patients are to delay metastasis development, preserve quality of life, and increase overall survival (OS). Since 2018, the treatment of nmCRPC has changed dramatically with the introduction of second-generation androgen receptor inhibitors, such as enzalutamide (ENZA), apalutamide (APA), and darolutamide (DARO). These drugs demonstrated substantial improvements in metastasis-free survival (MFS) and OS in phase Ⅲ randomized clinical trials. In addition, these drugs have an excellent safety profile, preserve quality of life, and can delay disease-related symptoms. A recently published indirect meta-analysis reported that APA and ENZA showed better findings in MFS and that DARO had relatively fewer adverse effects. However, in the absence of a direct comparison, careful interpretation is required. Thus, APA, ENZA, and DARO should be considered the new standard drugs for treating nmCRPC.

scholarly journals Interplay Between SOX9, Wnt/β-Catenin and Androgen Receptor Signaling in Castration-Resistant Prostate Cancer

2019 ◽  
Vol 20 (9) ◽  
pp. 2066 ◽  
Author(s):  
Namrata Khurana ◽  
Suresh C. Sikka
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Signaling Pathways ◽  
Critical Role ◽  
Castration Resistant Prostate Cancer ◽  
Form Complex ◽  
Androgen Receptor Signaling ◽  
Castration Resistant ◽  
Signaling Axis

Androgen receptor (AR) signaling plays a key role not only in the initiation of prostate cancer (PCa) but also in its transition to aggressive and invasive castration-resistant prostate cancer (CRPC). However, the crosstalk of AR with other signaling pathways contributes significantly to the emergence and growth of CRPC. Wnt/β-catenin signaling facilitates ductal morphogenesis in fetal prostate and its anomalous expression has been linked with PCa. β-catenin has also been reported to form complex with AR and thus augment AR signaling in PCa. The transcription factor SOX9 has been shown to be the driving force of aggressive and invasive PCa cells and regulate AR expression in PCa cells. Furthermore, SOX9 has also been shown to propel PCa by the reactivation of Wnt/β-catenin signaling. In this review, we discuss the critical role of SOX9/AR/Wnt/β-catenin signaling axis in the development and progression of CRPC. The phytochemicals like sulforaphane and curcumin that can concurrently target SOX9, AR and Wnt/β-catenin signaling pathways in PCa may thus be beneficial in the chemoprevention of PCa.

scholarly journals Treatment of nonmetastatic castration-resistant prostate cancer: focus on second-generation androgen receptor inhibitors

2021 ◽  
Author(s):  
Fred Saad ◽  
Martin Bögemann ◽  
Kazuhiro Suzuki ◽  
Neal Shore
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Second Generation ◽  
Imaging Techniques ◽  
Specific Antigen ◽  
Conventional Imaging ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Therapeutic Decisions ◽  
Consensus Statements

Abstract Background Nonmetastatic castration-resistant prostate cancer (nmCRPC) is defined as a rising prostate-specific antigen concentration, despite castrate levels of testosterone with ongoing androgen-deprivation therapy or orchiectomy, and no detectable metastases by conventional imaging. Patients with nmCRPC progress to metastatic disease and are at risk of developing cancer-related symptoms and morbidity, eventually dying of their disease. While patients with nmCRPC are generally asymptomatic from their disease, they are often older and have chronic comorbidities that require long-term concomitant medication. Therefore, careful consideration of the benefit–risk profile of potential treatments is required. Methods In this review, we will discuss the rationale for early treatment of patients with nmCRPC to delay metastatic progression and prolong survival, as well as the factors influencing this treatment decision. We will focus on oral pharmacotherapy with the second-generation androgen receptor inhibitors, apalutamide, enzalutamide, and darolutamide, and the importance of balancing the clinical benefit they offer with potential adverse events and the consequential impact on quality of life, physical capacity, and cognitive function. Results and conclusions While the definition of nmCRPC is well established, the advent of next-generation imaging techniques capable of detecting hitherto undetectable oligometastatic disease in patients with nmCRPC has fostered debate on the criteria that inform the management of these patients. However, despite these developments, published consensus statements have maintained that the absence of metastases on conventional imaging suffices to guide such therapeutic decisions. In addition, the prolonged metastasis-free survival and recently reported positive overall survival outcomes of the three second-generation androgen receptor inhibitors have provided further evidence for the early use of these agents in patients with nmCRPC in order to delay metastases and prolong survival. Here, we discuss the benefit–risk profiles of apalutamide, enzalutamide, and darolutamide based on the data available from their pivotal clinical trials in patients with nmCRPC.

Treatment Given Near the End of Life in Castration-Resistant Prostate Cancer

2012 ◽  
Vol 29 (7) ◽  
pp. 536-540 ◽  
Author(s):  
Hanna A. Zaghloul ◽  
Jose R. Murillo
Keyword(s):  
Quality Of Life ◽  
Prostate Cancer ◽  
End Of Life ◽  
Treatment Options ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistant ◽  
Related Quality ◽  
Impact On Survival ◽  
New Treatments

Chemotherapy treatment options are limited for patients with castration-resistant prostate cancer (CRPC). The purpose of this study is to report treatment use and adverse effects (AEs) within the last three months of life in patients with CRPC. Of the 88 patients identified, 32% received treatment within 3 months of death, and documented AEs occurred in 25% of patients. Of those, neutropenia (18.3%), nausea/vomiting (18.3%), and febrile neutropenia (13.6%) were the most frequent. Results of this study show high treatment utility towards the end-of-life in patients with CRPC, with one fourth of patients experiencing AEs. Attention to health-related quality of life becomes increasingly important as new treatments appear to have small impact on survival, and AEs of those treatments may significantly impact patient quality of life.

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