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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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Relation between plasma trough concentration of abiraterone and prostate-specific antigen response in metastatic castration-resistant prostate cancer patients.
Edith Carton,Gaëlle Noé,Olivier Huillard,Lisa Golmard,Julie Giroux,Anatole Cessot,Nathaniel Edward Bennett Saidu,M. Peyromaure,Marc Zerbib,Céline Narjoz,Jean Guibourdenche,A. Thomas,Michel Vidal,François Goldwasser,Benoit Blanchet,Jérôme Alexandre +15 more
TL;DR: It is shown that ABI trough concentration correlates with PSA response and PFS, and ABI concentration monitoring appears as a new approach to improve clinical outcome in mCPRC patients.
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Biological and clinical effects of abiraterone on anti-resorptive and anabolic activity in bone microenvironment.
Michele Iuliani,Francesco Pantano,Consuelo Buttigliero,Marco Fioramonti,Valentina Bertaglia,Bruno Vincenzi,Alice Zoccoli,Giulia Ribelli,Marcello Tucci,Francesca Vignani,Alfredo Berruti,Giorgio V. Scagliotti,Giuseppe Tonini,Daniele Santini +13 more
TL;DR: It is shown that non-cytotoxic doses of ABI have a statistically significant inhibitory effect on OCL differentiation and activity inducing a down-modulation of OCL marker genes TRAP, cathepsin K and metalloproteinase-9, and a novel biological mechanism of action consisting in a direct bone anabolic and anti-resorptive activity is suggested.
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Aberrant expression of CITED2 promotes prostate cancer metastasis by activating the nucleolin-AKT pathway.
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Co-targeting hexokinase 2-mediated Warburg effect and ULK1-dependent autophagy suppresses tumor growth of PTEN- and TP53-deficiency-driven castration-resistant prostate cancer
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TL;DR: It is reported that co-deletion of Pten and p53 in murine prostate epithelium leads to AR-independent CRPC and thus confers de novo resistance to second generation androgen deprivation therapy (ADT) in multiple independent yet complementary preclinical mouse models.
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Sequencing of Cabazitaxel and Abiraterone Acetate After Docetaxel in Metastatic Castration-Resistant Prostate Cancer: Treatment Patterns and Clinical Outcomes in Multicenter Community-Based US Oncology Practices.
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TL;DR: Administration of 3 agents in the DCA sequence was more optimal for treating mCRPC in this hypothesis-generating study.
References
More filters
Journal ArticleDOI
Global cancer statistics
TL;DR: A substantial proportion of the worldwide burden of cancer could be prevented through the application of existing cancer control knowledge and by implementing programs for tobacco control, vaccination, and early detection and treatment, as well as public health campaigns promoting physical activity and a healthier dietary intake.
Journal ArticleDOI
Docetaxel plus Prednisone or Mitoxantrone plus Prednisone for Advanced Prostate Cancer
Ian F. Tannock,Ronald de Wit,William R. Berry,Jozsef Horti,Anna Pluzanska,Kim N. Chi,Stéphane Oudard,Christine Theodore,Nicholas D. James,Ingela Turesson,Mark Rosenthal,Mario A. Eisenberger +11 more
TL;DR: When given with prednisone, treatment with docetaxel every three weeks led to superior survival and improved rates of response in terms of pain, serum PSA level, and quality of life, as compared with mitoxantrone plusprednisone.
Journal ArticleDOI
Sipuleucel-T immunotherapy for castration-resistant prostate cancer.
Philip W. Kantoff,Celestia S. Higano,N. Shore,E. Roy Berger,Eric J. Small,David F. Penson,Charles H. Redfern,Anna C. Ferrari,Robert Dreicer,Robert B. Sims,Yi Xu,Mark W. Frohlich,Paul F. Schellhammer +12 more
TL;DR: The use of sipuleucel-T prolonged overall survival among men with metastatic castration-resistant prostate cancer and immune responses to the immunizing antigen were observed in patients who received sipuleUcel- T.
Journal ArticleDOI
A sharper Bonferroni procedure for multiple tests of significance
TL;DR: In this article, a simple procedure for multiple tests of significance based on individual p-values is derived, which is sharper than Holm's (1979) sequentially rejective procedure.
Journal ArticleDOI
Abiraterone and Increased Survival in Metastatic Prostate Cancer
Johann S. de Bono,Christopher J. Logothetis,Arturo Molina,Karim Fizazi,Scott North,Luis Chu,Kim N. Chi,Robert Jones,Oscar B. Goodman,Fred Saad,John Staffurth,Paul N. Mainwaring,S. J. Harland,Thomas W. Flaig,Thomas E. Hutson,Tina Cheng,Helen Patterson,John D. Hainsworth,Charles J. Ryan,Cora N. Sternberg,Susan Ellard,Aude Flechon,Mansoor N. Saleh,Mark C. Scholz,Eleni Efstathiou,Andrea Zivi,Diletta Bianchini,Yohann Loriot,Nicole Chieffo,Thian Kheoh,Christopher M. Haqq,Howard I. Scher +31 more
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.