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Enzalutamide: Antiandrogen for Castration Resistant Prostate Cancer

Indications for Enzalutamide

Enzalutamide is indicated for the treatment of progressive castration-resistant prostate cancer. Enzalutamide is approved for the treatment of progressive castration-resistant prostate cancer after chemotherapy with docetaxel since 2012: Enzalutamide extended progression-free survival compared with placebo (8.3 vs. 3.0 months) and total survival (18.4 vs. 13.6 months) (Scher et al., 2012). In the PREVAIL trial, a high efficacy of enzalutamide before chemotherapy was also demonstrated in castration-resistant prostate carcinoma: prolonged progression-free survival, thus later necessity of chemotherapy, which was even more successful in the enzalutamide group (Beer et al., 2014). Enzalutamide has also been approved as a treatment option before chemotherapy since 2014.

Mechanism of Action of Enzalutamide

Enzalutamide inhibits the signal transduction of the androgen receptor:

• Competitive inhibition of the androgen binding to the androgen receptor
• Prevents translocation of activated receptors to the cell nucleus
• Inhibits the binding of the activated androgen receptor to the DNA

Pharmacokinetics of Enzalutamide

98% plasma protein binding, hepatic metabolism of enzalutamide mainly via CYP2C8, half-life 3–10 days, renal and fecal excretion of the inactive metabolites.

Side Effects of Enzalutamide

The most common side effects of enzalutamide are hot flushes, diarrhea and headache. Less common are hallucinations, anxiety, cognitive disorders, itching, neutropenia, falls with fractures, hypertension and epilepsy.

Interactions with Enzalutamide

Enzalutamide is a potent enzyme inducer, so caution is recommended with many drug groups such as antiepileptic or oral anticoagulation.

Contraindications for Enzalutamide

• Allergy and intolerance
• Women and children
• Severe hepatic impairment

Dosage of Enzalutamide

160 mg enzalutamide (four 40 mg capsules) p.o. once a day. The addition of prednisolone is possible, but not necessary. Discontinue treatment with progress or intolerance to enzalutamide.

Brand Name of Enzalutamide:

Xtandi

References

Beer, T. M.; Armstrong, A. J.; Rathkopf, D. E.; Loriot, Y.; Sternberg, C. N.; Higano, C. S.; Iversen, P.; Bhattacharya, S.; Carles, J.; Chowdhury, S.; Davis, I. D.; de Bono, J. S.; Evans, C. P.; Fizazi, K.; Joshua, A. M.; Kim, C.-S.; Kimura, G.; Mainwaring, P.; Mansbach, H.; Miller, K.; Noonberg, S. B.; Perabo, F.; Phung, D.; Saad, F.; Scher, H. I.; Taplin, M.-E.; Venner, P. M.; Tombal, B. & Investigators, P. R. E. V. A. I. L.

Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med, 2014, 371, 424-433.

Scher, H. I.; Fizazi, K.; Saad, F.; Taplin, M.-E.; Sternberg, C. N.; Miller, K.; de Wit, R.; Mulders, P.; Chi, K. N.; Shore, N. D.; Armstrong, A. J.; Flaig, T. W.; Fléchon, A.; Mainwaring, P.; Fleming, M.; Hainsworth, J. D.; Hirmand, M.; Selby, B.; Seely, L.; de Bono, J. S. & Investigators, A. F. F. I. R. M.

Increased survival with enzalutamide in prostate cancer after chemotherapy.
2012, 367, 1187-1197.

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