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.

Abstract

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, Δ(4)-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.

• Authors: Mary-Ellen Taplin, Bruce Montgomery, Christopher J Logothetis, Glenn J Bubley, Jerome P Richie, Bruce L Dalkin, Martin G Sanda, John W Davis, Massimo Loda, Lawrence D True, Patricia Troncoso, Huihui Ye, Rosina T Lis, Brett T Marck, Alvin M Matsumoto, Steven P Balk, Elahe A Mostaghel, Trevor M Penning, Peter S Nelson, Wanling Xie, Zhenyang Jiang, Christopher M Haqq, Daniel Tamae, NamPhuong Tran, Weimin Peng, Thian Kheoh, Arturo Molina, Philip W Kantoff
• Journal: Journal of clinical oncology : official journal of the American Society of Clinical Oncology (J Clin Oncol) Vol. 32 Issue 33 Pg. 3705-15 (Nov 20 2014) ISSN: 1527-7755 [Electronic] United States
• PMID: 25311217 (Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, N.I.H., Intramural, Research Support, Non-U.S. Gov't)
• Copyright: © 2014 by American Society of Clinical Oncology.

Chemical References

• AR protein, human
• Androgen Antagonists
• Androstadienes
• Receptors, Androgen
• Testosterone
• Prostate-Specific Antigen
• Leuprolide
• Abiraterone Acetate

Topics

• Abiraterone Acetate
• Aged
• Androgen Antagonists (therapeutic use)
• Androstadienes (administration & dosage)
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Humans
• Leuprolide (administration & dosage, adverse effects)
• Male
• Middle Aged
• Neoadjuvant Therapy
• Prostate-Specific Antigen (blood)
• Prostatectomy
• Prostatic Neoplasms (blood, drug therapy, pathology)
• Receptors, Androgen (analysis)
• Testosterone (blood)