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Cancer. 2019 Feb 15;125(4):524-532. doi: 10.1002/cncr.31836. Epub 2018 Nov 14.

A phase 2 trial of abiraterone acetate without glucocorticoids for men with metastatic castration-resistant prostate cancer.

Author information

1
Department of Medicine, University of California at San Diego, San Diego, California.
2
Department of Medicine, Dana-Farber Cancer Institute, Boston, Massachusetts.
3
Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, Massachusetts.
4
Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, New York.
5
Department of Medicine, University of Washington at Seattle, Seattle, Washington.
6
Department of Medicine, Veterans Affairs Puget Sound Health Care System, Seattle, Washington.
7
Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, Massachusetts.

Abstract

BACKGROUND:

Abiraterone acetate suppresses adrenal androgens and glucocorticoids through the inhibition of CYP17; however, given the risk of mineralocorticoid excess, it is administered with glucocorticoids. Herein, the authors performed a phase 2, single-arm study that was designed to assess the safety of abiraterone acetate without steroids in patients with castration-resistant prostate cancer.

METHODS:

Eligible patients had castration-resistant prostate cancer with controlled blood pressure and normal potassium. Patients initially received abiraterone acetate at a dose of 1000 mg daily alone. Those with persistent or severe mineralocorticoid toxicity received treatment with prednisone initiated at a dose of 5 mg twice daily. Therapy was continued until radiographic progression, toxicity, or withdrawal. The primary objective of the current study was to determine the percentage of men requiring prednisone to manage mineralocorticoid toxicity. Toxicity was graded according to Common Terminology Criteria for Adverse Events, version 4.0.

RESULTS:

A total of 58 patients received at least 1 dose of abiraterone acetate; the majority had metastases (53 patients; 91.4%). Sixteen patients (27.6%) received prior chemotherapy, 6 patients (10.3%) received prior enzalutamide, and 4 patients (7%) received prior ketoconazole. Grade 3 to 4 adverse events of interest included hypertension (9 patients; 15.5%) and hypokalemia (4 patients; 7%). There was no grade ≥3 edema. Seven patients (12%) initiated prednisone therapy for mineralocorticoid toxicity, 3 patients for hypertension (5%), and 4 patients for hypokalemia (7%). Two patients initiated prednisone therapy for fatigue (3%). Forty patients (68%) experienced a decline in prostate-specific antigen of ≥50% with the use of abiraterone acetate alone. Patients with lower baseline levels of androstenedione (P = .04), androsterone (P = .01), dehydroepiandrosterone (P = .03), and 17-hydroxyprogesterone (P = .03) were found to be more likely to develop mineralocorticoid toxicity.

CONCLUSIONS:

Treatment with abiraterone acetate without steroids is feasible, although clinically significant adverse events can occur in a minority of patients. The use of abiraterone acetate without prednisone should be balanced with the potential for toxicity and requires close monitoring.

KEYWORDS:

abiraterone; hypertension; hypokalemia; mineralocorticoids; prostate cancer; steroids

PMID:
30427533
PMCID:
PMC6353689
[Available on 2020-02-15]
DOI:
10.1002/cncr.31836

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