Therapy Update for Metastatic Castration-Resistant Prostate Cancer

To provide an overview of the efficacy, tolerability, drug interactions, dosing, and administration issues associated with enzalutamide, abiraterone, and radium-223 for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC).

MEDLINE and Web of Science were used to search for relevant articles using a key-word search (enzalutamide, abiraterone, radium-223, and phase 3). No restriction was placed on the date of publication.

Located articles were reviewed and selected based on their relevance to the treatment of mCRPC. Articles were selected if they focused on double-blind, randomized controlled, phase 3 studies conducted in humans and published in English. Other resources were used for the information pertaining to the drug's mechanism of action, administration, drug interactions, and adverse effects. Data extraction for the clinical application (e.g., efficacy, adverse reactions, and monitoring) was obtained from the identified clinical trials and the drug's approved labeling by one of the authors and validated by a second author.

Abiraterone, enzalutamide, and radium-223 have been shown to improve radiographic progression-free survival and overall survival before or after treatment with docetaxel. Abiraterone and enzalutamide has been able to delay time to the initiation of docetaxel. Major adverse effects vary with these medications. Enzalutamide-based therapy was associated with increased risk of seizures. Abiraterone-based therapy was associated with increased mineralocorticoid excess. Radium-223-based therapy was associated with increased risk of myelosuppression.

In clinical trials, abiraterone, enzalutamide, and radium-223 improved the radiographic progression-free survival and overall survival in patients with mCRPC compared with placebo. Each drug has unique adverse effects requiring monitoring of routine laboratory tests and for severe associated symptoms. To better define the role of these drugs in the treatment of mCRPC, clinical trials designed to directly compare these drugs' survival rate is necessary.