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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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Mechanisms of Therapeutic Resistance in Prostate Cancer
TL;DR: The current understanding of mechanisms of therapeutic resistance in progression to and after the development of castration resistance is outlined, highlighting targetable and reversible mechanisms of resistance.
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Early outcome prediction on 18F-fluorocholine PET/CT in metastatic castration-resistant prostate cancer patients treated with abiraterone
Ugo De Giorgi,Paola Caroli,Salvatore Luca Burgio,Cecilia Menna,Vincenza Conteduca,Emanuela Bianchi,Francesca Fabbri,Elisa Carretta,Dino Amadori,Giovanni Paganelli,Federica Matteucci +10 more
TL;DR: Early FCH-PET/CT can predict clinical outcome in CRPC beyond PSA response as well as predict progression-free survival (PFS) and overall survival (OS) in patients with metastatic castration-resistant prostate cancer.
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Targeting bone metastases in prostate cancer: improving clinical outcome
TL;DR: Radium-223 dichloride is the first bone-targeting agent to show improved survival and reduced pain and symptomatic skeletal events in patients with mCRPC without visceral disease, suggesting that managing both the systemic disease and associated bone events is important.
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Niclosamide enhances abiraterone treatment via inhibition of androgen receptor variants in castration resistant prostate cancer
TL;DR: It is found that enzalutamide-resistant cells are cross-resistant to abiraterone, and that AR-V7 confers resistance to abIRater one, and supports the development of combination of abirATERone with niclosamide as a potential treatment for advanced castration resistant prostate cancer.
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Challenges and Recommendations for Early Identification of Metastatic Disease in Prostate Cancer
E. David Crawford,Nelson N. Stone,Evan Y. Yu,Phillip J. Koo,Stephen J. Freedland,Susan F. Slovin,Leonard G. Gomella,E. Roy Berger,Thomas E. Keane,Paul Sieber,Neal D. Shore,Daniel P. Petrylak +11 more
TL;DR: A multidisciplinary group was convened to review the currently available imaging guidelines for metastatic disease in prostate cancer and found no consensus on eligibility criteria, type of imaging modality, and the frequency of scanning for detecting metastatic diseases as discussed by the authors.
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