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Commentary on: Abiraterone in Metastatic Prostate Cancer Without Previous Chemotherapy
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TLDR
Abiraterone inhibits CYP-17, a crucial enzyme in androgen biosynthesis in the testes, adrenal glands, and in prostate cancer cells as discussed by the authors, and showed a strong trend toward improved survival.Abstract:
n this prospective, multicenter, phase 3 trial, 1088 patients with asymptomatic or mildly symptomatic Imetastatic castrate-resistant prostate cancer (mCRPC) were randomized to receive abiraterone (1000 mg) plus prednisone (5 mg twice daily) or placebo plus prednisone. Abiraterone inhibits CYP-17, a crucial enzyme in androgen biosynthesis in the testes, adrenal glands, and in prostate cancer cells. The trial was designed with 2 coprimary end points: radiographic progression-free survival and overall survival. This report was based on a planned interim analysis after 43% (333 of 773) of expected deaths had occurred. The findings were significant enough to warrant unblinding so that patients in the placebo arm could be offered abiraterone. The progression-free survival improved from 8.3 months to 16.5 months with abiraterone (hazard ratio, 0.53; 95% confidence interval, 0.45-0.62; P <.001). The median overall survival was not reached in the abiraterone group but was 27.2 months in the control arm (hazard ratio, 0.75; 95% confidence interval, 0.61-0.93; P 1⁄4 .0097). This did not reach the prespecified P value of .0008 to achieve statistical significance, so that at the time of this interim analysis, it can only be concluded that abiraterone showed a strong trend toward improved survival. Further benefits were observed in secondary end points, including time to initiation of cytotoxic chemotherapy (25.2 vs 16.8 months), to opiate use for cancer-related pain (not reached vs 23.7 months), to prostate-specific antigen progression (11.1 vs 5.6 months), and to a 1-point decline in Eastern Cooperative Oncology Group performance status (12.3 vs 10.9 months). These important milestones in the course of mCRPC were all delayed. Toxicity related to abiraterone was observed, but because prednisone was administered in both treatment groups, rates of toxicity in the control arm were not much different. Grade 3 or 4 adverse events were reported by 48% of patients in the abiraterone arm and by 42% of patients in the control arm. Fatigue, arthralgia, and peripheral edema were important adverse effects observed more frequently in the abiraterone arm. Other signs ofread more
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Impact of prednisone on toxicities and survival in metastatic castration-resistant prostate cancer: A systematic review and meta-analysis of randomized clinical trials
TL;DR: A meta-analysis of randomized trials comparing regimens that included daily oral prednisone (P) in only one arm to investigate its impact on toxicities and outcomes in metastatic castration-resistant prostate cancer (mCRPC) found no difference between the non-P and P groups for severe toxicities.
Journal ArticleDOI
Phase‐1 study of abiraterone acetate in chemotherapy‐naïve Japanese patients with castration‐resistant prostate cancer
Nobuaki Matsubara,Hiroji Uemura,Iwao Fukui,Masashi Niwakawa,Akito Yamaguchi,Koho Iizuka,Hideyuki Akaza +6 more
TL;DR: ABiraterone acetate was generally well‐tolerated, and the recommended AA dosage regimen in Japanese CRPC patients is 1000 mg oral dose under modified fasting conditions (at least 1 h premeal or 2 h postmeal).
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Real-world practice patterns in veterans with metastatic castration-resistant prostate cancer
Ahmad Halwani,Kelli M Rasmussen,Kelli M Rasmussen,Vikas Patil,Catherine Li,Christina Yong,Zachary Burningham,Sumati Gupta,Sujata Narayanan,Shih-Wen Lin,Susheela Carroll,Shivani K. Mhatre,Julie N. Graff,Robert Dreicer,Brian C. Sauer +14 more
TL;DR: The introduction of new therapies has resulted in increased use of the noncytotoxic agents abiraterone and enzalutamide as first-line treatment in lieu of docetaxel.
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Discovery and biological evaluation of novel androgen receptor antagonist for castration-resistant prostate cancer.
TL;DR: A new series of nonsteroidal compounds deriving from the hybridization of Abiraterone (Abi) and Enzalutamide, among which compound 4a featuring the diphenylamine scaffold was identified as a potent and cell selective androgen receptor (AR) antagonist, are designed and synthesized to treat Enza-resistant CRPC.
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Metabolic Alterations, Aggressive Hormone-Naïve Prostate Cancer and Cardiovascular Disease: A Complex Relationship
Simona Di Francesco,Iole Robuffo,Marika Caruso,Giulia Giambuzzi,Deborah Ferri,Andrea Militello,Elena Toniato +6 more
TL;DR: A careful evaluation of obesity, diabetes mellitus, dyslipidemia, systemic arterial hypertension, together with a careful Evaluation of cardiovascular status, in particular coronary and carotid vascular disease, should be carried out after an initial diagnosis of prostatic carcinoma.
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