Objective: Abiraterone is a relatively noncytotoxic drug approved by the US Food and Drug Administration in 2011 for the treatment of metastatic prostate cancer (MPC). As an inhibitor of 17α-hydroxylase and C17,20-lyase (CYP17), abiraterone blocks androgen synthesis and glucocorticoid production. Decreased cortisol levels result in an increased ACTH release, which can lead to increased mineralocorticoid levels. While coadministration of abiraterone and glucocorticoids has been effective in reducing an apparent mineralocorticoid excess, adequate replacement of physiologic glucocorticoids, especially in times of acute stress, remains less well-defined.
Methods: A literature search was conducted using the PubMed and Google Scholar databases for abiraterone and adrenal insufficiency. Publications were selected based on the quality of the data and clinical relevance. We reviewed the landmark trials leading to FDA approval and establishment of the standard glucocorticoid replacement dosing.
Results: We present 2 patients with MPC on abiraterone therapy. These 2 patients required modification of the glucocorticoid therapy because of adverse effects.
Conclusions: We found that a standard dose of prednisone of 5 mg/day as recommended previously may be inadequate to achieve physiologic glucocorticoid replacement in some patients with prostate cancer while on abiraterone treatment and as a result adrenal insufficiency due to inadequate dosing might be more common than initially thought. Additionally 10 mg of prednisone daily may cause adverse effects in some patients. Thus clinicians should be aware of the potential for development of adrenal insufficiency or symptoms of glucocorticoid excess in these patients receiving prednisone so that appropriate modifications in glucocorticoid dosing can be instituted without any delay. Prednisone dosing may need to be individualized in each patient receiving abiraterone therapy.
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