Enzalutamide: Mechanism of Action, Indications and Important Notes
Enzalutamide is an androgen receptor inhibitor used in oncology for certain forms of prostate cancer. The active substance interferes with the androgen signalling pathway, which can stimulate the growth of prostate cancer cells. Enzalutamide was specifically developed to be effective even against cancer cells that have become resistant to older hormonal therapies. Since its approval, enzalutamide has become one of the important active substances in modern prostate cancer treatment.
Mechanism of Action
Androgens such as testosterone and the more potent dihydrotestosterone bind to the androgen receptor in prostate cancer cells. After binding, this receptor migrates into the cell nucleus and activates genes that promote cell growth and survival. Enzalutamide blocks this process at multiple levels.
First, enzalutamide competes with androgens for the binding site on the androgen receptor and blocks it with high affinity. Compared to the older antiandrogen bicalutamide, enzalutamide binds significantly more strongly to the androgen receptor. Second, enzalutamide inhibits the translocation of the androgen-receptor complex into the cell nucleus. Third, the binding of the receptor complex to DNA and thus the activation of androgen-dependent genes is also blocked. Due to this triple mechanism, enzalutamide is also effective against cells that have developed resistance mechanisms to older antiandrogens.
Because enzalutamide blocks the androgen receptor signalling pathway significantly more strongly than older antiandrogens and shows no partial agonistic effect, it can also be used in so-called castration-resistant prostate cancers where androgen deprivation alone is no longer sufficient.
Indications
Castration-Resistant Prostate Cancer
The primary indication for enzalutamide is castration-resistant prostate cancer (CRPC). This is a phase of the disease in which the tumour continues to grow despite therapy aimed at reducing testosterone levels to castration levels. Enzalutamide is approved both for patients who have not yet received chemotherapy (chemotherapy-naive) and for those in whom chemotherapy with docetaxel has already proven insufficient.
Metastatic Hormone-Sensitive Prostate Cancer
Enzalutamide is also approved for metastatic hormone-sensitive prostate cancer (mHSPC), meaning patients whose tumour still responds to androgen deprivation but has already formed metastases. In this situation, enzalutamide is used in combination with androgen deprivation therapy. Clinical studies have shown that the combination prolongs overall survival and progression-free survival compared to androgen deprivation alone.
Non-Metastatic Castration-Resistant Prostate Cancer
A further approval exists for non-metastatic castration-resistant prostate cancer in men at high risk of developing metastases, identifiable by a rapidly rising PSA value. Here too, enzalutamide is used together with androgen deprivation therapy.
Dosage Form and Dosing
Enzalutamide is available as soft capsules or film-coated tablets for oral administration. The usual daily dose is 160 mg, divided into four capsules of 40 mg each or as corresponding tablets. The medication is taken once daily, with or without food. The treating oncologist or urologist determines the exact dosage and duration of treatment and adjusts it to the individual course of the disease. A dose reduction may be necessary in cases of certain interactions or side effects.
Important Notes
Enzalutamide is a potent inducer of liver enzymes (CYP3A4 and CYP2C9) and can therefore accelerate the breakdown of many other medications in the body. This gives rise to a considerable interaction potential. A thorough medication history is required before starting therapy. Certain active substances must not be taken simultaneously, as their plasma levels could be significantly reduced by enzalutamide. The treating physicians inform patients comprehensively about this aspect.
Enzalutamide can lower the seizure threshold, which is particularly important to consider in patients with pre-existing seizures or corresponding risk factors. If seizures occur, therapy must be stopped immediately and a doctor consulted. Vehicles should be operated with caution, as psychiatric side effects and fatigue may impair reaction time.
Adverse Effects
Enzalutamide has a characteristic side-effect profile about which the treating physicians provide detailed information:
- Fatigue and general weakness are common complaints, especially at the beginning of therapy
- Hot flushes as a result of low androgen levels occur frequently
- Hypertension may develop or worsen during therapy and requires monitoring
- Headaches and dizziness are reported by some patients
- Memory impairment and cognitive changes may occur
- Bone and muscle pain are possible
- Seizures occur in rare cases but represent an important adverse effect
- Falls and bone fractures, also due to osteoporotic changes under androgen deprivation
- Elevated liver enzyme levels have been observed
Drug Interactions
Enzalutamide is a potent inducer of CYP3A4 and CYP2C8. As a result, many other medicines are broken down more quickly, which may reduce their efficacy. This is particularly relevant for active substances that are also metabolised by these enzymes, including certain anticoagulants, immunosuppressants, analgesics and other cancer medications. At the same time, inhibitors of CYP2C8 can increase enzalutamide blood levels. The complete list of potential interactions is extensive and is discussed as part of medical supervision.
Enzalutamide on Sanoliste
On Sanoliste you will find urologists and oncologists who offer competent diagnostics and therapy support for prostate cancer and related conditions. Therapy with enzalutamide requires close medical supervision and regular check-ups, including PSA progression, bone density and comorbidities.
The information on this page is for general information purposes only and does not replace consultation with a physician. Enzalutamide is a prescription-only medicine and may only be taken under medical supervision.
Frequently Asked Questions about Enzalutamide
What does castration-resistant prostate cancer mean?
Castration-resistant prostate cancer refers to a phase of the disease in which prostate cancer continues to progress despite therapy that has reduced testosterone levels to castration level (very low). This is achieved either by surgical removal of the testes or by pharmacological androgen suppression. The designation does not mean that the tumour is completely independent of androgens, but rather that it continues to grow under very low testosterone levels. Enzymes in the tumour can produce androgens from precursors, or the receptor may be hypersensitive to low hormone levels. This is where enzalutamide comes in.
How does enzalutamide differ from bicalutamide?
Both active substances are antiandrogens that target the androgen receptor. The essential difference lies in the strength and completeness of receptor blockade and in the mechanism of action. Bicalutamide is a partial antagonist and can in some situations also act weakly agonistically. This is one of the reasons why tumours can develop resistance under bicalutamide. Enzalutamide binds more strongly to the receptor and additionally inhibits translocation of the receptor into the cell nucleus and binding to DNA. This superior blockade explains why enzalutamide can be effective even in patients whose tumour has become resistant to bicalutamide.
Does enzalutamide need to be taken together with other hormones?
In most indications, enzalutamide is used not alone but in combination with androgen deprivation therapy. This can be done either pharmacologically through GnRH agonists or GnRH antagonists that suppress testosterone production in the body, or by surgical removal of the testes. The combination aims to keep androgen levels as low as possible while simultaneously blocking the androgen receptor signalling pathway directly. In some approval situations, existing androgen deprivation is a prerequisite for the use of enzalutamide.