scholarly journals Abiraterone acetate – 10 clinically relevant facts

Oncoreview ◽  
2021 ◽  
Vol 11 (3(43)) ◽  
pp. 80-84
Author(s):  
Jakub Żołnierek
Keyword(s):  
Prostate Cancer ◽  
Systemic Treatment ◽  
Diagnostic Procedures ◽  
Abiraterone Acetate ◽  
Newly Diagnosed ◽  
Castration Resistance ◽  
Specific Mechanism ◽  
Therapeutic Class ◽  
Novel Drugs ◽  
Molecular Signal

Prostate cancer is one of the most frequently diagnosed cancers in men. Number of newly diagnosed cases is increasing due to several factors and the most important ones seem to be: population ageing and more sensitive diagnostic procedures. Secondary – the higher efficacy of treatment with its influence on improving patients’ overall survival and the specific mechanism of action of drugs used in systemic therapy lead to growing population of men suffering from prostate cancer in general and, specifically – patients with castration resistance. It is hormone therapy to play the key role in systemic treatment of prostate cancer with increasing significance of novel drugs focused on inhibition of molecular signal transduction mediated by androgen receptor. Abiraterone acetate is the representative of this therapeutic class. The paper describes the most clinically relevant data regarding the drug.

scholarly journals Selective degradation of AR-V7 to overcome castration resistance of prostate cancer

2021 ◽  
Vol 12 (10) ◽  
Author(s):  
Yuan Liu ◽  
Cuifu Yu ◽  
Zhenlong Shao ◽  
Xiaohong Xia ◽  
Tumei Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Androgen Receptor ◽  
Selective Inhibition ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Selective Degradation ◽  
Castration Resistant ◽  
Novel Drugs ◽  
The Stability ◽  
Androgen Receptor Splice Variant

AbstractAndrogen receptor splice variant 7 (AR-V7), a form of ligand-independent and constitutively activating variant of androgen receptor (AR), is considered as the key driver to initiate castration-resistant prostate cancer (CRPC). Because AR-V7 lacks ligand-binding domain, the AR-targeted therapies that aim to inactivate AR signaling through disrupting the interaction between AR and androgen are limited in CRPC. Thus, the emergence of AR-V7 has become the greatest challenge for treating CRPC. Targeting protein degradation is a recently proposed novel avenue for cancer treatment. Our previous studies have been shown that the oncoprotein AR-V7 is a substrate of the proteasome. Identifying novel drugs that can trigger the degradation of AR-V7 is therefore critical to cure CRPC. Here we show that nobiletin, a polymethoxylated flavonoid derived from the peel of Citrus fruits, exerts a potent anticancer activity via inducing G0/G1 phase arrest and enhancing the sensitivity of cells to enzalutamide in AR-V7 positive PC cells. Mechanically, we unravel that nobiletin selectively induces proteasomal degradation of AR-V7 (but not AR). This effect relies on its selective inhibition of the interactions between AR-V7 and two deubiquitinases USP14 and USP22. These findings not only enrich our understanding on the mechanism of AR-V7 degradation, but also provide an efficient and druggable target for overcoming CRPC through interfering the stability of AR-V7 mediated by the interaction between AR-V7 and deubiquitinase.

Management of Metastatic Castrate-sensitive Prostate Cancer

2018 ◽  
Author(s):  
Derya Tilki ◽  
Marc A Dall’era ◽  
Christopher P Evans
Keyword(s):  
Prostate Cancer ◽  
Androgen Deprivation Therapy ◽  
Survival Benefit ◽  
Metastatic Prostate Cancer ◽  
Oncologic Outcome ◽  
Standard Of Care ◽  
Abiraterone Acetate ◽  
Androgen Deprivation ◽  
Newly Diagnosed ◽  
Treatment Paradigm

Oncologic outcome of patients with newly diagnosed metastatic prostate cancer (mPCa) is poor. The treatment paradigm for newly diagnosed mPCa has changed. The standard of care for men with metastatic hormone-naive prostate cancer has been systemic androgen deprivation therapy (ADT). Previous randomized studies demonstrated an overall survival benefit by the addition of early chemotherapy with six cycles of docetaxel. More recently, results from randomized trials also demonstrated a survival benefit by the addition of abiraterone acetate to the ADT in men with metastatic disease. The aim of this review is to summarize the results from most recent studies, including men with newly diagnosed metastatic hormone-naive prostate cancer, focusing on chemotherapy and ADT. This review contains 1 figure, 2 tables, and 47 references.  Key Words: abiraterone acetate, androgen deprivation therapy, androgen deprivation, castrate sensitive, chemotherapy, continuous androgen deprivation, docetaxel, hormone-naive, intermittent androgen deprivation, metastatic prostate cancer

scholarly journals Efficacy and safety of abiraterone acetate plus prednisone in Japanese patients with newly diagnosed, metastatic hormone-naive prostate cancer: final subgroup analysis of LATITUDE, a randomized, double-blind, placebo-controlled, phase 3 study

2020 ◽  
Vol 50 (7) ◽  
pp. 810-820
Author(s):  
Hiroyoshi Suzuki ◽  
Toshitaka Shin ◽  
Satoshi Fukasawa ◽  
Katsuyoshi Hashine ◽  
Sumiko Kitani ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Overall Survival ◽  
Subgroup Analysis ◽  
Interim Analysis ◽  
Abiraterone Acetate ◽  
Newly Diagnosed ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Double Blind ◽  
Cutoff Date

Abstract Background LATITUDE was a randomized, double-blind, international and phase 3 study of abiraterone acetate plus prednisone in patients with high-risk metastatic hormone-naïve prostate cancer. In the first interim analysis of LATITUDE (clinical cutoff date: 31 October 2016), significant prolongation in overall survival and radiographic progression-free survival (co-primary endpoints) was observed when compared with placebo. The results of the Japanese subgroup analysis of LATITUDE first interim analysis were consistent with those of the overall population. In this study, overall survival and safety results from the final analysis of the Japanese subgroup of the LATITUDE study are presented (clinical cutoff date: 15 August 2018). Methods Abiraterone acetate (1000 mg/day) and prednisone (5 mg/day) were administered orally in the abiraterone acetate plus prednisone group, and matching placebos in the placebo group. Results Of the 1199 patients included in LATITUDE, 70 constituted the Japanese subgroup (abiraterone acetate plus prednisone: n = 35, placebo: n = 35). Following a median (range) follow-up of 56.6 (2.5, 64.2) months, the median overall survival was not reached in both the treatment arms of the Japanese subgroup (hazard ratio: 0.61; 95% confidence interval: 0.27–1.42; nominal P = 0.2502). A total of 23 deaths (abiraterone acetate plus prednisone: 9 [25.7%], placebo group: 14 [40.0%]) were reported in Japanese subgroup. Grade 3/4 adverse events were reported in 24 (68.6%) and 9 (25.7%) patients in the abiraterone acetate plus prednisone and placebo groups, respectively. Conclusions In this Japanese subgroup analysis, addition of abiraterone acetate plus prednisone to androgen-deprivation therapy demonstrated favorable efficacy and safety outcomes in patients with newly diagnosed, high-risk metastatic hormone-naïve prostate cancer. Survival benefits observed in the Japanese subgroup first interim analysis were sustained long-term and were consistent with the overall population.

Randomized double-blind, comparative study of abiraterone acetate (AA) plus low-dose prednisone (P) plus androgen deprivation therapy (ADT) versus ADT alone in newly diagnosed, high-risk, metastatic hormone-naive prostate cancer (mHNPC).

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. TPS5097-TPS5097 ◽  
Author(s):  
Karim Fizazi ◽  
Julie S. Larsen ◽  
Shannon Matheny ◽  
Arturo Molina ◽  
Jinhui Li ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
High Risk ◽  
Gleason Score ◽  
Metastatic Disease ◽  
Localized Prostate Cancer ◽  
Bone Lesions ◽  
Newly Diagnosed ◽  
Castration Resistant Prostate Cancer ◽  
Castration Resistance ◽  
Androgen Synthesis

TPS5097 Background: Patients (pts) who initially present with metastatic prostate cancer (MPC) (up to 30% of men in Europe; 4% in US) typically progress to metastatic castration-resistant prostate cancer (mCRPC) with a poor prognosis. Prognostic factors impacting survival include high PSA concentration, high Gleason score, high volume of metastatic disease, and bone symptoms. AA decreases testosterone via CYP17 inhibition and is approved for treatment of mCRPC before and after docetaxel-based chemotherapy. Two recent reports (J Clin Oncol. 2012: 30 [suppl. abstr 4521 and 4556]) showed that AA + P in addition to ADT (LHRH agonist) in the neoadjuvant setting led to higher rates of undetectable PSA and complete pathologic response (cPR) or near-cPR in pts undergoing prostatectomy for high risk-localized prostate cancer than with ADT alone, suggesting a potential role for inhibiting extragonadal androgen synthesis prior to emergence of castration-resistance. Because of its benefit in mCRPC, as well as early activity in high risk-localized prostate cancer, AA is being evaluated in high risk mHNPC. Methods: Approximately 1,270 men with newly diagnosed (within 3 months of randomization) high risk mHNPC with at least 2 of 3 high risk factors (≥ 3 bone lesions, presence of visceral metastases or Gleason score ≥ 8) are being randomized to AA 1000 mg + P 5 mg daily + ADT or ADT alone. Pts are stratified by presence of visceral disease and ECOG PS (0-1 vs 2). Distant metastatic disease must be documented by positive bone scan or CT/MRI. ADT or orchiectomy within 3 mos of randomization is allowed. Continued use of anti-androgens after randomization is not allowed on study. The primary endpoint is overall survival. Secondary endpoints include radiographic PFS, time to next skeletal-related event, PSA progression, and subsequent therapy. Two interim analyses and a final analysis are planned. 300 sites from 36 countries will participate. As of February 4, 2013, one patient has entered screening. Clinical trial information: NCT01715285.

Optimizing Anticancer Therapy in Metastatic Non-Castrate Prostate Cancer: American Society of Clinical Oncology Clinical Practice Guideline

2018 ◽  
Vol 36 (15) ◽  
pp. 1521-1539 ◽  
Author(s):  
Michael J. Morris ◽  
R. Bryan Rumble ◽  
Ethan Basch ◽  
Sebastien J. Hotte ◽  
Andrew Loblaw ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Clinical Practice ◽  
Clinical Practice Guideline ◽  
Practice Guideline ◽  
Metastatic Prostate Cancer ◽  
De Novo ◽  
High Volume ◽  
Abiraterone Acetate ◽  
Newly Diagnosed ◽  
The Impact

Purpose This clinical practice guideline addresses abiraterone or docetaxel with androgen-deprivation therapy (ADT) for metastatic prostate cancer that has not been treated (or has been minimally treated) with testosterone-lowering agents. Methods Standard therapy for newly diagnosed metastatic prostate cancer has been ADT alone. Three studies have compared ADT alone with ADT and docetaxel, and two studies have compared ADT alone with ADT and abiraterone. Results Three prospective randomized studies (GETUG-AFU 15, STAMPEDE, and CHAARTED) examined overall survival (OS) with adding docetaxel to ADT. STAMPEDE and CHAARTED favored docetaxel (hazard ratio [HR], 0.78; 95% CI, 0.66 to 0.93; n = 2,962 and HR, 0.73; 95% CI, 0.59 to 0.89; n = 790, respectively). GETUG-AFU 15 was negative. LATITUDE and STAMPEDE examined the impact on OS of adding abiraterone (with prednisone or prednisolone) to ADT. LATITUDE and STAMPEDE favored abiraterone (HR, 0.62; 95% CI, 0.51 to 0.76; n = 1,199 and HR, 0.63; 95% CI, 0.52 to 0.76; n = 1,917, respectively). Recommendations ADT plus docetaxel or abiraterone in newly diagnosed metastatic non-castrate prostate cancer offers a survival benefit as compared with ADT alone. The strongest evidence of benefit with docetaxel is in men with de novo high-volume (CHAARTED criteria) metastatic disease. Similar survival benefits are seen using abiraterone acetate in high-risk patients (LATITUDE criteria) and in the metastatic population in STAMPEDE. ADT plus abiraterone and ADT plus docetaxel have not been compared, and it is not known if some men benefit more from one regimen as opposed to the other. Fitness for chemotherapy, patient comorbidities, toxicity profiles, quality of life, drug availability, and cost should be considered in this decision. Additional information is available at www.asco.org/genitourinary-cancer-guidelines .

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