Intense Androgen-Deprivation Therapy With Abiraterone Acetate Plus Leuprolide Acetate in Patients With Localized High-Risk Prostate Cancer: Results of a Randomized Phase II Neoadjuvant Study
| Autor: | Huihui Ye, Mary-Ellen Taplin, Zhenyang Jiang, Alvin M. Matsumoto, Glenn J. Bubley, Arturo Molina, Wanling Xie, John W. Davis, Trevor M. Penning, Elahe A. Mostaghel, Massimo Loda, Philip W. Kantoff, Brett T. Marck, Martin G. Sanda, Christopher J. Logothetis, Bruce Montgomery, Rosina T. Lis, Nam Phuong Tran, Lawrence D. True, Daniel Tamae, Weimin Peng, Peter S. Nelson, Patricia Troncoso, C. M. Haqq, Bruce L. Dalkin, Jerome P. Richie, Steven P. Balk, Thian Kheoh |
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| Rok vydání: | 2014 |
| Předmět: |
Oncology
Male Cancer Research medicine.medical_specialty Urology medicine.medical_treatment Abiraterone Acetate Androgen suppression Androgen deprivation therapy Prostate cancer chemistry.chemical_compound Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Testosterone In patient Neoadjuvant therapy Aged Prostatectomy business.industry Abiraterone acetate Prostatic Neoplasms Androgen Antagonists ORIGINAL REPORTS Middle Aged Prostate-Specific Antigen medicine.disease Neoadjuvant Therapy Neoadjuvant Study Androstadienes Radiation therapy Prostate-specific antigen Endocrinology chemistry Receptors Androgen Leuprolide business |
| Zdroj: | Journal of Clinical Oncology. 32:3705-3715 |
| ISSN: | 1527-7755 0732-183X |
| Popis: | Purpose Cure rates for localized high-risk prostate cancers (PCa) and some intermediate-risk PCa are frequently suboptimal with local therapy. Outcomes are improved by concomitant androgen-deprivation therapy (ADT) with radiation therapy, but not by concomitant ADT with surgery. Luteinizing hormone–releasing hormone agonist (LHRHa; leuprolide acetate) does not reduce serum androgens as effectively as abiraterone acetate (AA), a prodrug of abiraterone, a CYP17 inhibitor that lowers serum testosterone (< 1 ng/dL) and improves survival in metastatic PCa. The possibility that greater androgen suppression in patients with localized high-risk PCa will result in improved clinical outcomes makes paramount the reassessment of neoadjuvant ADT with more robust androgen suppression. Patients and Methods A neoadjuvant randomized phase II trial of LHRHa with AA was conducted in patients with localized high-risk PCa (N = 58). For the first 12 weeks, patients were randomly assigned to LHRHa versus LHRHa plus AA. After a research prostate biopsy, all patients received 12 additional weeks of LHRHa plus AA followed by prostatectomy. Results The levels of intraprostatic androgens from 12-week prostate biopsies, including the primary end point (dihydrotestosterone/testosterone), were significantly lower (dehydroepiandrosterone, Δ4-androstene-3,17-dione, dihydrotestosterone, all P < .001; testosterone, P < .05) with LHRHa plus AA compared with LHRHa alone. Prostatectomy pathologic staging demonstrated a low incidence of complete responses and minimal residual disease, with residual T3- or lymph node–positive disease in the majority. Conclusion LHRHa plus AA treatment suppresses tissue androgens more effectively than LHRHa alone. Intensive intratumoral androgen suppression with LHRHa plus AA before prostatectomy for localized high-risk PCa may reduce tumor burden. |
| Databáze: | OpenAIRE |
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