5 Best Enzalutamide Alternatives For Prostate Cancer

Prostate cancer is still one of the most prevalent forms of cancer among men globally. While there are several different treatment pathways available to manage the condition, enzalutamide (brand name Xtandi) has become a cornerstone of therapy, especially for patients with metastatic, castration-resistant prostate cancer (mCRPC). However, some patients do not inherently respond to enzalutamide or suffer adverse effects from it, requiring different therapies. The following article covers all of the enzalutamide alternatives that are available to patients and discusses how they work, their benefits, risks, etc.

 

Define Enzalutamide 

Enzalutamide is an androgen receptor inhibitor used to treat advanced prostate cancer. It functions by inhibiting the actions of androgens (male hormones such as testosterone), which cause the growth of prostate cancer cells. Enzalutamide is usually prescribed for patients with metastatic castration-resistant prostate cancer (mCRPC), which is a form of prostate cancer that no longer responds to standard treatments of hormone treatment; because it is effective, it may not be appropriate for every patient because of potential side effects, cancer resistance, or drug-drug interactions. Thus, physicians may investigate other options for prostate cancer management.

 

Why Consider Alternatives to Enzalutamide?

Despite the benefits of enzalutamide for advanced prostate cancer, some patients will want to pursue alternatives for a variety of reasons, including:

• Drug Resistance: Prostate cancer cells can develop resistance over time, making enzalutamide less effective for some patients.

• Side Effects: Unfortunately, some patients discontinue enzalutamide due to side effects, such as fatigue, hot flashes, and seizures.

• Comorbidities: Many patients with cancer have pre-existing health diagnoses (i.e., cardiovascular, neurological) or current medications (i.e., corticosteroids, proton-pump inhibitors) that may limit other PO options.

Given the above factors, it is essential to understand what viable enzalutamide alternatives can be directed to patients based on their individual preferences and clinical situations.

 

Best Enzalutamide Alternatives

Abiraterone Acetate (Zytiga)

Abiraterone acetate is an androgen receptor pathway inhibitor like enzalutamide, routinely used for metastatic castration-resistant prostate cancer (mCRPC).  This drug works by blocking androgens as well, but it does this by inhibiting an enzyme called CYP17A1, which is important in the synthesis of androgens in the testes, adrenal glands, and prostate tumors. 

 Key Benefits:

• Has been demonstrated that abiraterone can reduce the size of capso by tumor and prolong the progression of capso.

• Often prescribed alongside prednisone, which helps patients adjust to the treatment load, possibly causing side effects such as fluid retention and/or hypertension. 

 Potential Risks:

• Fatigue, joint pain, and elevated liver enzymes.

• Potential cardiovascular issues, including hypertension and hypokalemia.

 

Darolutamide (Nubeqa)

Darolutamide is a new androgen receptor inhibitor akin to enzalutamide, but it has a unique molecular structure that can allow for different pharmacological properties. Research has shown that darolutamide provides similar benefits in regards to survival, and may have a lower incidence of CNS side effects such as seizures.  

Key Benefits:  

• Lower incidence of CNS side effects than enzalutamide, suitable for patients with a seizure history or neurologic disorders.  

• Efficacy was demonstrated with both hormone-sensitive and castration-resistant prostate cancer.

Potential Risks: 

• Fatigue, joint pain, and hypertension can occur in some patients.  

• Some patients can experience a drop in white blood cell count.

 

Apalutamide (Erleada)

Apalutamide is an androgen receptor inhibitor that is similar to enzalutamide as it inhibits the binding of androgen to the androgen receptor. Apalutamide has been shown to delay the progression of metastatic prostate cancer and demonstrate a survival benefit in both non-metastatic and metastatic castration-resistant prostate cancer patients.

Key Benefits:

• Showed a survival benefit in clinical trials.

• Allows the use in non-metastatic castration-resistant prostate cancer (nmCRPC), allowing for earlier treatment.

Potential Risks:

• Generalized fatigue, rash, and, similar to other endocrine therapies, hot flashes.

• Patients may experience seizures or cardiovascular events.

 

Chemotherapy options: Docetaxel and Cabazitaxel

For those patients who have not responded to other hormone therapies such as enzalutamide, there are chemotherapy options such as docetaxel and cabazitaxel. Chemotherapy works by targeting fast-growing cancer cells. Proper studies have shown efficacy in treating advanced prostate cancer, especially after failure of any form of hormone therapy.

Benefits:

• A good option for patients who have failed treatment with prior hormone therapies.

• It can help shrink tumors and improve quality of life.

Potential Side Effects: 

• It is well-known that chemotherapy can come with side effects. There are extreme side effects with chemotherapy, and they may include nausea, tiredness, and suppression of the immune system.

• Docetaxel and cabazitaxel can result in hair loss, anemia, and neuropathy.

 

Radium-223 (Xofigo) 

Radium-223 is a radiopharmaceutical targeted therapy used for prostate cancer with bone metastases. Being a radioactive substance, it imitates calcium and gets taken up into bone. The radiation is produced as it releases radiation and therefore targets cancer cells (within the bones). 

Key Advantages: 

• Very effective for prostate cancer that goes to the bones. 

• Has been shown to increase survival (and decrease bone pain), thereby helping the quality of life of many patients. 

Possible Disadvantages: 

• There is a risk of low blood-cell counts, which may lead to fatigue or an increased risk of infection. 

• It can produce nausea and diarrhea in some patients.

 

Choosing the Right Alternatives

In considering alternatives to enzalutamide, one must consider:

• The patient’s overall health and comorbidity.

• Progression characteristics of their cancer, for example, if it is hormone-sensitive or castration-resistant.

• Side effect profiles of the alternative therapies and the patient's reaction to them.

• Cost and availability of the alternative treatment options.

Patients must work closely with their healthcare providers to select the most appropriate treatment strategy based on their case and needs.

 

Final Words

Enzalutamide has certainly transformed the care of patients with metastatic castration-resistant prostate cancer. For those who cannot tolerate enzalutamide, develop resistance to enzalutamide, or seek alternative treatment options, there are several other promising options available. Abiraterone acetate, darolutamide, apalutamide, some chemotherapy agents, and radium-223 are all acceptable options that can be tailored to each respective patient. Considering additional treatment options can assist healthcare professionals in optimizing treatment and potentially spur a more favorable prognosis for prostate cancer patients.

Although prostate cancer treatment is changing continuously, it is also important for patients to work with and be proactive in their treatments with their oncologists, wherever possible.

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