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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
Citations
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Journal ArticleDOI
A phase I study of niclosamide in combination with enzalutamide in men with castration-resistant prostate cancer
Michael T. Schweizer,Michael T. Schweizer,Kathleen Haugk,Jožefa S. McKiernan,Roman Gulati,Heather H. Cheng,Heather H. Cheng,Jessica L. Maes,Ruth Dumpit,Peter S. Nelson,Peter S. Nelson,Bruce Montgomery,Bruce Montgomery,Jeannine S. McCune,Stephen R. Plymate,Evan Y. Yu,Evan Y. Yu +16 more
TL;DR: A Phase I dose-escalation study testing oral niclosamide plus standard-dose enzalutamide in men with metastatic CRPC previously treated with abiraterone closed for futility because Niclosamide could not be escalated above 500mg TID, and plasma concentrations were not consistently above the threshold shown to inhibit growth in CRPC models.
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A Randomised Phase 2 Trial of Dexamethasone Versus Prednisolone in Castration-resistant Prostate Cancer
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Review Article Drug resistance in castration resistant prostate cancer: resistance mechanisms and emerging treatment strategies
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TL;DR: Standarts of care of prostate cancer were modified from 2010 to 2013 because of results of prospective studies and new therapeutics, which allowed precise treatments for each specific clinical situation.
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TL;DR: The inhibition of androgen biosynthesis by abiraterone acetate prolonged overall survival among patients with metastatic castration-resistant prostate cancer who previously received chemotherapy.