Authors: Diane Check, Jerome H. Check, Carrie Wilson.
Alpelisib is a new targeted anticancer drug approved for the treatment of certain types of cancers, including advanced breast cancer. Mifepristone is a progesterone receptor antagonist that has generated renewed interest in its use as an anticancer agent. Some studies find the risk of hypokalemia to be 18% when treating with alpelisib. In higher dosages, mifepristone also blocks the glucocorticoid receptor but not the mineralocorticoid receptor. Thus, it has been approved for treatment of hyperglycemia related to Cushing’s syndrome. However, the higher dosages needed for Cushing’s syndrome can cause hypokalemia related to excessive mineralocorticoid effect. This case of advanced breast cancer did not exhibit hypokalemia when treated with single agent alpelisib. When mifepristone was added, hypokalemia ensued along with very high serum cortisol levels. Discontinuing the mifepristone and treating with single agent alpelisib, resulted in normal potassium levels. Furthermore, the elevated cortisol levels returned to normal. Stopping alpelisib and switching to single agent mifepristone also resulted in normokalaemia and normal cortisol levels. These data suggest that alpelisib interferes with metabolism or clearance of mifepristone. A treating physician must be cautious about using these two drugs together. If treatment with both is intended, a dose reduction should be considered.
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