Open Access
Commentary on: Abiraterone in Metastatic Prostate Cancer Without Previous Chemotherapy
Reads0
Chats0
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
More filters
Journal ArticleDOI
Endostatin inhibits androgen-independent prostate cancer growth by suppressing nuclear receptor-mediated oxidative stress.
Joo Hyoung Lee,Minsung Kang,Hong Wang,Gurudatta Naik,James A. Mobley,Guru Sonpavde,W. Timothy Garvey,W. Timothy Garvey,Victor M. Darley-Usmar,Selvarangan Ponnazhagan +9 more
TL;DR: It is reported for the first time that human endostatin prevents androgen‐independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro‐oxidant signaling and that the dual targeting action of ES on AR and GR can be further translated to PCa therapy.
Journal ArticleDOI
Phenylbutyl isoselenocyanate induces reactive oxygen species to inhibit androgen receptor and to initiate p53‐mediated apoptosis in LNCaP prostate cancer cells
Wei Wu,Deepkamal N. Karelia,Kartick C. Pramanik,Shantu Amin,Shantu Amin,Arun Sharma,Arun Sharma,Cheng Jiang,Junxuan Lu,Junxuan Lu +9 more
TL;DR: Results show that ISC‐4 was more potent at inducing apoptosis than its sulfur analog phenylbutyl isothiocyanate (PBITC) without suppressing protein kinase AKT Ser473 phosphorylation, and the apoptosis execution was attenuated by pre‐incubation with a pan caspase inhibitor.
Journal ArticleDOI
A high neutrophil-to-lymphocyte ratio is a poor prognostic factor for castration-resistant prostate cancer patients who undergo abiraterone acetate or enzalutamide treatment.
Takashi Kawahara,Masashi Kato,Ken-ichi Tabata,Ippei Kojima,Hiroshi Yamada,Osamu Kamihira,Hideyasu Tsumura,Masatsugu Iwamura,Hiroji Uemura,Yasuhide Miyoshi +9 more
TL;DR: A higher NLR was associated with a poorer OS for CRPC patients who received ABI or ENZ and was positively correlated with prostate cancer progression.
Journal ArticleDOI
Clinical significance of D4A in prostate cancer therapy with abiraterone.
TL;DR: The recently published research demonstrates that Δ4, 3-keto-abi (D4A) is a metabolite of Abi that is formed in patients with prostate cancer and has CYP17A1 inhibition activity that is comparable to Abi, suggesting that it might play an important role in the clinical activity ofAbi in CRPC patients.
Journal Article
Practical guide to the use of abiraterone in castration resistant prostate cancer.
Elahe A. Mostaghel,Daniel W. Lin +1 more
TL;DR: Accumulating data suggest that "androgen independent" or "hormone refractory" tumors remain sensitive to hormonal activation and suggest that despite suppression of circulating testosterone (T), residual tumor androgens play a prominent role in mediating CRPC progression.
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.