In advanced prostate cancer, androgen deprivation therapy (ADT) has been a mainstay of treatment for more than fifty years. The details of ADT are discussed here if you'd like to learn more. In the past decade or so, physicians who treat advanced prostate cancer have come to understand that, in a variety of clinical scenarios, ADT alone is not enough. As a result, other treatments are now being added to ADT in so called “treatment intensification”. While chemotherapy was the first to be added to ADT, so-called novel hormonal therapies (NHTs; also known as androgen receptor-axis-targeted therapies (ARATs)) are more commonly used for most patients today. While ADT effectively decreases the testosterone within the body that drives prostate cancer growth, the success of these treatments clearly shows that targeting of testosterone-driven pathways has benefit in advanced prostate cancer.
Enzalutamide emerged shortly after data for abiraterone acetate as the first NHT became available. Unlike abiraterone which acts to block the production of testosterone and its related hormones, enzalutamide blocks the action of testosterone. Enzalutamide does this through a number of mechanisms:
1) By blocking binding of testosterone to the androgen receptor (the interaction necessary to turn on the receptor)
2) By blocking the activation of the androgen receptor that comes following its binding with testosterone (the “on switch” for testosterone’s function)
3) By blocking the movement of the androgen receptor into the nucleus of the cell (the inside of the cell) where it exerts its effects on DNA (stopping the movement of testosterone and the receptor to the part of the cell where they carry out their function)
In this mechanism, enzalutamide acts as a more potent version of prior anti-androgens such as bicalutamide.
Who might be prescribed Enzalutamide?
Enzalutamide is approved, and has demonstrated survival benefits, for men with metastatic castration sensitive prostate cancer (mCSPC; where enzalutamide will be started concurrently or shortly after ADT), non-metastatic castration resistant prostate cancer (nmCPRC; in which in enzalutamide will be started after the PSA is going up even though the testosterone is low while on ADT and there are no sites of metastasis on imaging), and metastatic castration resistant prostate cancer (mCRPC; which enzalutamide will be started as a result of disease progression while on ADT). Patients receiving enzalutamide for mCRPC may or may not have previously received chemotherapy.
In the mCSPC disease space, both ENZAMET and ARCHES have provided randomized controlled data demonstrating the benefit of enzalutamide, even among patients receiving docetaxel, with a 33% and 34% reduction in the risk of death, respectively, compared to men receiving ADT alone. For patients with nmCRPC, the PROSPER trial was designed to show a decreased chance of developing metastatic disease. Not only did enzalutamide do this (with an impressive 72% decreased risk of metastasis), use of enzalutamide for nmCRPC also decreased the risk of death by 31%, despite the fact that patients who originally received placebo were offered enzalutamide when they developed metastases. Finally, in the mCRPC context, enzalutamide reduced the risk of death (compared to placebo) for patients who had both received docetaxel before (37% decreased risk in the AFFIRM study) and those who had not received chemotherapy before (29% decreased risk in the PREVAIL study).
Patients who should not take Enzalutamide
There are limited reasons why patients should not take enzalutamide. Men with a history of seizures, who have had a stroke, those with prior brain injuries, and those whose cancer has spread to the brain may not be well suited to taking enzalutamide. Additionally, patients with an allergy or hypersensitivity to enzalutamide should not receive it.
As always, let your physician know if you have heart or kidney problems.
Instructions for taking Enzalutamide
Enzalutamide is prescribed at four tablets to be taken each day. These should be taken at the same time each day and may be taken either with or without food.
Because enzalutamide can affect the liver, it may affect other medications that you are taking. This is particularly notable if you are taking medications for high cholesterol, pain, epilepsy, severe anxiety or schizophrenia, sleep problems, heart problems or high blood pressure, thyroid problems, or gout.
As your physician discusses treatment options for advanced prostate cancer, ensure that they are aware of all of the other medications that you are taking. Further, a cancer pharmacist can be very helpful in ensuring that there are not harmful interactions between taking multiple medications.
Side effects of Enzalutamide
There are both common (and often relatively mild) and uncommon (and sometimes severe) side effects. Among the more common side effects are significant fatigue (tiredness), hot flushes, and breast tenderness and swelling. Men taking enzalutamide also have an increased risk of falling and breaking bones (fractures). Other side effects include muscle pains, diarrhea, and constipation. There is a small increased chance of having a seizure for men taking enzalutamide. This risk is higher if you have had seizures before, drink a lot of alcohol, have other health problems that affect the brain (a stroke before, head injuries, or cancer spread to the brain), or are taking medications that make seizures more common. Numerous other side effects are possible and may be related to enzalutamide treatment.
As always, the articles on this site should not constitute specific medical advice. Discuss the specifics of your clinical situation and your treatment options with your physician.