Practical guide to the use of enzalutamide.
BACKGROUND
We summarize the development, definitive trials, and practical use of enzalutamide for practicing urologists and medical oncologists. The care paradigm for patients with metastatic castration resistant prostate cancer (mCRPC) is a changing landscape, with the ongoing discovery of drivers of cancer progression yielding actionable targets for drug development. Since 2010, sipuleucel-T, cabazitaxel, abiraterone with prednisone, radium 223 and enzalutamide have been Food and Drug Administration approved based upon improvement in overall survival in men with mCRPC.


METHODS
A MEDLINE search for "enzalutamide or MDV3100" yielded 258 results. Prospective trials were reviewed. Abstracts from ASCO (American Society of Clinical Oncology) meetings and press release information were included where applicable.


RESULTS
Enzalutamide, an oral inhibitor of the androgen receptor pathway, was approved in 2012 based upon improvement in overall survival of 4.8 months in men with mCRPC following docetaxel versus placebo. Measures of prostate-specific antigen (PSA) and radiographic response, and clinically significant endpoints such as quality of life improvement and toxicity parameters favored enzalutamide. Toxicity is modest with asthenia and fatigue being most common, with a 1% incidence of seizure reported, though patients can be selected to decrease this risk.


CONCLUSIONS
Enzalutamide is an effective oral therapy for mCRPC, with an overall survival benefit before and following chemotherapy. Toxicity is mild, and seizure risk can be mitigated by careful patient selection. Ongoing studies will help determine the best sequence of novel agents for prostate cancer, along with safe and effective combinations of therapies. Better understanding of tumor characteristics, particularly reliance on the androgen receptor pathway, will lead to personalized approaches to prostate cancer therapy.
Jefferson Medical College of Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
Jean
J
Hoffman-Censits
Wm Kevin
WK
Kelly
D059002:Androgen Receptor Antagonists / Q000009:adverse effects / Q000627:therapeutic use*; D000736:Androstenes; D000737:Androstenols / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D001549:Benzamides; D004359:Drug Therapy, Combination; D006801:Humans; D008297:Male; D009570:Nitriles; D010669:Phenylthiohydantoin / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D017410:Practice Guidelines as Topic; D011241:Prednisone / Q000627:therapeutic use; D064129:Prostatic Neoplasms, Castration-Resistant / Q000188:drug therapy* / Q000401:mortality; D015996:Survival Rate; D016896:Treatment Outcome
D059002:Androgen Receptor Antagonists; D000736:Androstenes; D000737:Androstenols; D000970:Antineoplastic Agents; D001549:Benzamides; D009570:Nitriles; D010669:Phenylthiohydantoin; C540278:enzalutamide; C089740:abiraterone; D011241:Prednisone