Abiraterone acetate is a CYP17A1 inhibitor used in the treatment of advanced prostate cancer. It acts by blocking androgen biosynthesis in three locations: the testes, the adrenal glands, and the prostate tumor cells themselves. By inhibiting the CYP17A1 enzyme, it prevents the conversion of cholesterol into androgen precursors, which are often found at much higher levels in metastatic prostate cancer cells.
Clinical Applications
- Metastatic Castrate-Sensitive Prostate Cancer (m1CSPC): Abiraterone combined with ADT is a preferred, Category 1 treatment option for newly diagnosed metastatic disease, as demonstrated by the LATITUDE and STAMPEDE trials. It can also be used as part of a triplet therapy (ADT + docetaxel + abiraterone) for patients with high-volume disease.
- Metastatic Castrate-Resistant Prostate Cancer (m1CRPC): It is a standard first-line option for metastatic disease that has progressed despite castrate levels of testosterone.
- Regional Disease: It is sometimes used in combination with EBRT and ADT for patients with regional (N1, M0) prostate cancer.
Administration and Dosing
- Empty Stomach: Abiraterone must be taken on an empty stomach (1 hour before or 2 hours after a meal) because food significantly increases the drug’s absorption.
- Corticosteroid Requirement: It must always be administered with a corticosteroid (typically prednisone or methylprednisolone). In the castrate-sensitive setting, prednisone is usually dosed at 5mg once daily, while in the castrate-resistant setting, it is dosed at 5mg twice daily.
Side Effects and Monitoring
The inhibition of CYP17A1 causes a reduction in serum cortisol and a compensatory increase in adrenocorticotropic hormone (ACTH), which can lead to mineralocorticoid-related adverse events. The required glucocorticoid replacement (prednisone) helps mitigate these effects. Common adverse events include:
- Hypertension.
- Hypokalemia (low potassium levels).
- Edema (fluid retention).
- Hepatotoxicity (LFT elevations).
- Fatigue and hot flashes.