Introduction:
Most early-stage prostate cancers can be successfully treated, with most patients being cured. However, approximately one-third of patients may experience biochemical recurrence, where their prostate-specific antigen (PSA) levels rise again after initial treatment. The progression of the disease can be slow, but develops into metastatic prostate cancer and becomes resistant to castration.
Androgen deprivation therapy (ADT) is the treatment cornerstone for progressive and metastatic prostate cancer despite being accepted universally due to its inhibition and resistance action. FDA (Food and Drug Administration) has approved novel hormonal therapy in the form of vaccines and drugs that act by second-line hormonal manipulation.
What Is Novel Hormone Therapy?
Novel hormone therapy is a second-line treatment used for advanced prostate cancers to target prostate-specific antigen (PSA) and achieve PSA responses by hormone manipulation. The novel hormone therapy drugs include Abiraterone acetate, Darolutamide, Enzalutamide, and Apalutamide.
What Are the Drugs Used in Novel Hormone Therapy?
The drugs used in novel hormone therapy and their functions include:
Abiraterone Acetate: It is a medication used to treat advanced prostate cancer. It belongs to a set of drugs called androgen biosynthesis inhibitors. This drug is specifically used in metastatic castration-resistant prostate cancer (mCRPC) cases, which means cancer has spread to other parts of the body and is no longer responding to standard androgen deprivation therapy (ADT).
Abiraterone acetate is a prodrug that is converted into Abiraterone in the body. Abiraterone is a potent and selective inhibitor of CYP17A1, an enzyme that plays a crucial role in producing androgens (male sex hormones), including testosterone. By inhibiting CYP17A1, Abiraterone remarkably lowers the adrenal glands and the tumor's androgen levels. This reduction in androgens helps slow the growth and development of prostate cancer, especially in metastatic castration-resistant prostate cancer (mCRPC) cases, where cancer no longer responds to standard androgen deprivation therapy (ADT).
Abiraterone acetate has shown a notable promise in extending overall survival and delaying disease development in patients with advanced prostate cancer. Oncologists usually prescribe it for appropriate patients based on their medical history, disease stage, and overall health condition. As with any medication, it may have potential side effects; hence, regular monitoring and follow-up are recommended.
Enzalutamide: This is a drug used to treat advanced prostate cancer, particularly in metastatic castration-resistant prostate cancer (mCRPC). Like Abiraterone acetate, Enzalutamide is also an androgen receptor inhibitor, but it works through a different mechanism of action.
It works by binding to androgen receptors in prostate cancer cells and preventing androgens (such as testosterone) from binding to these receptors. By blocking androgen receptor signaling, Enzalutamide resists the growth-promoting effects of androgens on prostate cancer cells. This results in a slowdown of cancer cell growth and helps manage the disease in metastatic castration-resistant prostate cancer (mCRPC) cases, where cancer continues to metastasize despite standard androgen deprivation therapy (ADT).
Enzalutamide is typically taken orally in capsules and is often prescribed after the failure of standard androgen deprivation therapy (ADT) or in cases where other treatments are ineffective. Common side effects may include fatigue, hot flashes, headaches, and changes in blood pressure.
Apalutamide: This drug is also an androgen receptor inhibitor, similar to Enzalutamide, used in treating prostate cancer, especially in non-metastatic castration-resistant prostate cancer (nmCRPC). Non-metastatic castration-resistant prostate cancer is a stage where the cancer cells continue to grow despite castration (lowering of androgen levels).
It works by blocking the binding of androgens (such as testosterone) to androgen receptors in prostate cancer cells. By doing so, Apalutamide inhibits the androgen signaling pathway, which helps slow the growth and progression of prostate cancer.
The key difference between Apalutamide and Enzalutamide is their specific approval for different stages of prostate cancer. While Enzalutamide is used for metastatic castration-resistant prostate cancer (mCRPC), Apalutamide is indicated explicitly for non-metastatic castration-resistant prostate cancer.
In clinical trials, Apalutamide has been shown to delay the spread of cancer to other parts of the body and increase the time before metastasis occurs in patients with nmCRPC. It is usually prescribed with androgen deprivation therapy (ADT) for appropriate patients to improve treatment outcomes. Common side effects may include fatigue, rash, joint pain, and hot flashes.
Darolutamide: It is another medication used in the treatment of non-metastatic castration-resistant prostate cancer (nmCRPC). Like Apalutamide and Enzalutamide, Darolutamide belongs to the class of androgen receptor inhibitors. Non-metastatic castration-resistant prostate cancer refers to a stage of prostate cancer where the disease continues to progress despite castration (lowering of androgen levels), and there is no detectable spread of cancer to other parts of the body.
Darolutamide works by blocking the binding of androgens (such as testosterone) to androgen receptors in prostate cancer cells, just like Apalutamide and Enzalutamide. This action helps inhibit the androgen signaling pathway and slow the growth and progression of prostate cancer. Darolutamide has been shown in clinical trials to extend metastasis-free survival in patients with nmCRPC, meaning it delays the spread of cancer to other parts of the body and provides a period without metastasis.
As with other androgen receptor inhibitors, Darolutamide may have potential side effects, including fatigue, joint pain, rash, and decreased appetite. Darolutamide is typically prescribed with androgen deprivation therapy (ADT) for appropriate patients to improve treatment outcomes in nmCRPC.
What Is Meant by Castrate-Resistance?
Castrate resistance, also called castration-resistant prostate cancer (CRPC), refers to a stage in the progression of prostate cancer where the disease continues to grow and progress despite medical or surgical treatments to lower the levels of androgens (male sex hormones) in the body. Androgens, particularly testosterone, play a significant role in the growth and function of the prostate gland, as well as the development and progression of prostate cancer.
The most common initial treatment for advanced prostate cancer is androgen deprivation therapy (ADT), which aims to lower androgen levels to "castrate" levels (similar to those seen after surgical removal of the testicles, also known as castration). By reducing the levels of androgens, ADT helps slow the growth of prostate cancer cells and can lead to significant tumor shrinkage or stabilization.
However, in some cases, despite the initial response to ADT, prostate cancer can adapt and become resistant to the treatment. Castrate resistance occurs when the cancer cells find alternative pathways to continue growing and progressing even without high androgen levels. This means that the cancer cells have developed mechanisms to survive and thrive with lower levels of androgens, and they no longer depend solely on the androgen signaling pathway for growth.
Patients with castrate-resistant prostate cancer may experience a rise in prostate-specific antigen (PSA) levels, indicating disease progression, despite having low testosterone levels. At this stage, further treatment options become necessary, such as second-line hormonal therapies (e.g., Abiraterone acetate, Enzalutamide, Apalutamide, and Darolutamide), chemotherapy, immunotherapy, or other targeted therapies, depending on the individual's condition and the specific treatments previously received.
Conclusion:
The treatment landscape for advanced prostate cancer has evolved significantly in recent years, offering a range of therapeutic options to improve patient outcomes. Drugs like Abiraterone acetate, Enzalutamide, Apalutamide, and Darolutamide have emerged as valuable treatments, especially in cases of metastatic castration-resistant prostate cancer (mCRPC) and non-metastatic castration-resistant prostate cancer (nmCRPC). These medications target key pathways involved in prostate cancer growth, such as androgen signaling, which plays a pivotal role in the disease progression.
