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.

Following the introduction of abiraterone and enzalutamide, further related medications have become available. One such medication is apalutamide. Apalutamide, like enzalutamide, acts to block the action of testosterone by affecting the androgen receptor. It blocks the androgen receptor’s ability to carry out its functions in a variety of ways including blocking its movement within the cell, blocking its ability to interact with DNA, and blocking its ability to create signals within the cell. In this mechanism, apalutamide acts as a more potent version of prior anti-androgens such as bicalutamide.

Who might be prescribed Apalutamide?

Apalutamide is approved, and has demonstrated survival benefits, for men with advanced prostate cancer in two difference scenarios. First, in men with non-metastatic castration resistant prostate cancer (nmCPRC; in which in apalutamide 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), the SPARTAN study showed the using apalutamide reduced the risk of men developing metastases by 72%. Further, even though men who developed metastases received additional treatment at that time, starting apalutamide early before the metastases developed (at nmCRPC) reduced the risk of death by 22%.

Apalutamide may also be used in men with metastatic castration sensitive prostate cancer (mCSPC; where apalutamide will be started concurrently or shortly after ADT). In this setting, the TITAN trial showed that using apalutamide with ADT, as compared to ADT only, reduced a man’s risk of death by 35%.

Patients who should not take Apalutamide

There are limited reasons why patients should not take apalutamide. 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 apalutamide. Additionally, patients with an allergy or hypersensitivity to apalutamide should not receive it.

As always, let your physician know if you have heart or kidney problems.

Instructions for taking Apalutamide

Apalutamide 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.

Apalutamide may have effects on other medications that you are taking. 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 Apalutamide

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), high blood pressure, nausea, diarrhea, and heart disease. A notable risk of apalutamide that is less common for other similar medications is rash. This can often be treated with creams but sometimes requires other oral medications to treat. Patients taking apalutamide may also have issues with thyroid function that require them to take thyroid-replacement pills and may 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 apalutamide. 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 apalutamide 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.

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, treatment intensification has become common. While chemotherapy was the first treatment intensification approach to be adopted, it has been supplanted by so-called novel hormonal therapies (NHTs; also known as androgen receptor-axis-targeted therapies (ARATs)) for most patients. 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.

The first NHT to have proven benefit was abiraterone acetate. Abiraterone is a “androgen biosynthesis inhibitor”. It acts to block one of the key enzymes in the testicles, adrenal glands, and prostate cancer cells necessary to produce testosterone. Because the production pathway of testosterone is shared with other important hormones in the body, patients who receive abiraterone acetate also take a corticosteroid (prednisone, prednisolone, etc) to prevent a deficiency of these other hormones.

Who might be prescribed Abiraterone Acetate?

Abiraterone is approved, and has demonstrated survival benefits, for men with metastatic castration sensitive prostate cancer (mCSPC; where abiraterone will be started concurrently or shortly after ADT) and in metastatic castration resistant prostate cancer (mCRPC; which abiraterone will be started as a result of disease progression while on ADT). Patients receiving abiraterone for metastatic castration resistant prostate cancer may or may not have previously received chemotherapy. In the mCSPC disease space, the LATITUDE and STAMPEDE trial showed that men receiving ADT + abiraterone had a 38% and 37%, respectively, decreased risk of death compared to men receiving ADT alone. Among men with mCRPC that had not previously received chemotherapy in the COU-AA-302 trial, men receiving abiraterone had a 25% decreased risk of death compared to men receiving placebo + prednisone. Among men with mCRPC that had previously received chemotherapy in the COU-AA-301 trial, men receiving abiraterone had a 35% decreased risk of death compared to men receiving placebo + prednisone.

Patients who should not take Abiraterone

There are limited reasons why patients should not take abiraterone. Patients with an allergy or hypersensitivity to abiraterone should not receive it. Similarly, those with severe liver disease, an excess or deficiency of hormones in the pathway that abiraterone affects (mineralocorticoid excess or adrenocorticoid insufficiency), severe heart disease, and those with low blood potassium (hypokalemia) should take abiraterone with caution.

Instructions for taking Abiraterone

Abiraterone acetate is prescribed at four tablets to be taken each day. These should be taken by mouth on an empty stomach, either 1 hour before or two hours after eating food, to maximize absorption. Additionally, as mentioned before, you will be prescribed a corticosteroid to be taken either one or twice daily.

Abiraterone is metabolized by specific enzymes in the liver. As a result, there may be interactions between abiraterone and medications that block these enzymes (including ketoconazole, itraconazole, clarithromycin, atazanavir, nefazodone, saquinavir, telithromycin, ritonavir, indinavir, nelfinavir, voriconazole) or increase their activity (including phenytoin, carbamazepine, rifampin, rifabutin, rifapentine, phenobarbital).

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 medications.

Side effects of Abiraterone

The most common side effects of abiraterone relate to its action stopping the production not just of testosterone but of other related hormones – these include high blood pressure, low blood potassium (hypokalemia), and swelling of the hands or legs (peripheral edema). Other common side effects include urinary tract infections, diarrhea, rash, and increases in liver enzymes. Numerous other side effects are possible and may be related to abiraterone 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.

Latest FDA Approval Update on Darolutamide | 6.3.25

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.

Darolutamide was the last of the approved NHTs to become available. Like enzalutamide and apalutamide, it acts to block the action of testosterone by affecting the androgen receptor. It blocks the androgen receptor’s ability to carry out its functions in a variety of ways including blocking its movement within the cell, blocking its ability to interact with DNA, and blocking its ability to create signals within the cell. In this mechanism, darolutamide acts as a more potent version of prior anti-androgens such as bicalutamide.

In contrast to apalutamide and enzalutamide, darolutamide cannot get access to the brain so it has fewer brain-related side effects.

Who might be prescribed Darolutamide?

Darolutamide is approved, and has demonstrated survival benefits, for men with advanced prostate cancer in two difference scenarios. First, in men with non-metastatic castration resistant prostate cancer (nmCPRC; in which in darolutamide 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), the ARAMIS study showed the using darolutamide reduced the risk of men developing metastases by 59%. Further, even though men who developed metastases received additional treatment at that time, starting darolutamide early before the metastases developed reduced the risk of death by 31%.

Darolutamide has also, very recently, been approved for men with metastatic castration sensitive prostate cancer (mCSPC; where darolutamide will be started concurrently or shortly after ADT) based on the ARASENS study. In this study, the authors compared the combination of darolutamide with docetaxel chemotherapy and ADT to docetaxel chemotherapy and ADT. This study showed that the so-called “triplet” combination with darolutamide, chemotherapy, and ADT reduced the chance of death by more than 32% compared to chemotherapy and ADT. This triplet approach was approved by the FDA on August 5, 2022.

Patients who should not take Darolutamide

There are limited reasons why patients should not take darolutamide. Patients with an allergy or hypersensitivity to darolutamide should not receive it. As always, let your physician know if you have heart, liver, or kidney problems. Your doctor may opt to give you a lower dose of darolutamide in some of these circumstances. Importantly, unlike apalutamide and enzalutamide, men with a history of seizures or a stroke in the past may safely take darolutamide.

Instructions for taking Darolutamide

Darolutamide is prescribed as two tablets to be taken two times each day. These should be taken at the same time each day and may be taken either with or without food.

Darolutamide may have effects on other medications that you are taking. 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 Darolutamide

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), pain in your arms or legs, and rash. Darolutamide may also increase the chance of heart disease and may have effects on blood tests for liver function. Importantly, darolutamide does not increase the risk of seizures, falls, or fractures (broken bones), unlike apalutamide and enzalutamide.

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.

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.