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

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dc.contributor.authorMcKay, R.R.
dc.contributor.authorWerner, L.
dc.contributor.authorJacobus, S.J.
dc.contributor.authorJones, A.
dc.contributor.authorMostaghel, E.A.
dc.contributor.authorMarck, B.T.
dc.contributor.authorChoudhury, A.D.
dc.contributor.authorPomerantz, M.M.
dc.contributor.authorSweeney, C.J.
dc.contributor.authorSlovin, S.F.
dc.contributor.authorMorris, M.J.
dc.contributor.authorKantoff, P.W.
dc.contributor.authorTaplin, M.E.
dc.date.issued2019
dc.description.abstractBACKGROUND: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.
dc.description.statementofresponsibilityRana R. McKay, Lillian Werner, Susanna J. Jacobus, Alexandra Jones, Elahe A. Mostaghel, Brett T. Marck ... et al.
dc.identifier.citationCancer, 2019; 125(4):524-532
dc.identifier.doi10.1002/cncr.31836
dc.identifier.issn0008-543X
dc.identifier.issn1097-0142
dc.identifier.orcidSweeney, C.J. [0000-0002-0398-6018]
dc.identifier.urihttp://hdl.handle.net/2440/126764
dc.language.isoen
dc.publisherWiley
dc.rights© 2018 American Cancer Society
dc.source.urihttps://doi.org/10.1002/cncr.31836
dc.subjectabiraterone
dc.subjecthypertension
dc.subjecthypokalemia
dc.subjectmineralocorticoids
dc.subjectprostate cancer
dc.subjectsteroids
dc.titleA phase 2 trial of abiraterone acetate without glucocorticoids for men with metastatic castration-resistant prostate cancer
dc.typeJournal article
pubs.publication-statusPublished

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