Androgen Receptor Pathway Inhibitors, or ARPIs, are medications for prostate cancer. These therapies target pathways that fuel cancer growth. ARPIs disrupt signals that allow prostate cancer cells to multiply, controlling tumor progression. Their development has broadened the treatment landscape for men with prostate cancer.
Understanding ARPIs
ARPIs directly interfere with the androgen receptor pathway, a driver of prostate cancer growth. Androgens, such as testosterone, are male hormones that bind to androgen receptors on prostate cancer cells. This binding stimulates cell growth and division. ARPIs work by either blocking androgen production or preventing androgens from binding to their receptors.
One way ARPIs function is by inhibiting enzymes involved in androgen synthesis, effectively reducing the amount of testosterone and other androgens available to cancer cells. Another mechanism involves directly binding to the androgen receptor, thereby physically blocking androgens from attaching and activating the receptor. This interference disrupts the signaling cascade that promotes cancer cell proliferation. These medications are often more potent and specific than older anti-androgen therapies, leading to improved outcomes.
When ARPIs Are Prescribed
ARPIs are prescribed for prostate cancer that has become “castration-resistant.” This means the cancer continues to grow even when testosterone levels are very low, typically achieved through androgen deprivation therapy (ADT). Initially, ADT lowers androgen levels, but cancer cells can adapt and grow despite these low levels.
These medications are used in both metastatic castration-resistant prostate cancer (mCRPC), where the cancer has spread, and non-metastatic castration-resistant prostate cancer (nmCRPC), where the cancer is confined to the prostate but no longer responds to ADT. ARPIs have demonstrated improvements in overall survival and delayed disease progression in these settings. They are also increasingly used earlier in the disease course for metastatic hormone-sensitive prostate cancer (mHSPC), where cancer is responsive to hormone therapy but has spread. This earlier use, often in combination with ADT, can enhance treatment effectiveness.
Navigating Treatment with ARPIs
Several ARPI medications are available, including abiraterone acetate, enzalutamide, apalutamide, and darolutamide. These medications are taken orally, often as daily pills. Abiraterone acetate is often taken with prednisone, a corticosteroid, to manage side effects. Darolutamide may be taken twice daily, with or without food.
Patients undergoing ARPI treatment may experience various side effects. Common side effects include fatigue, hot flashes, high blood pressure (hypertension), fluid retention (edema), joint or muscle pain, and changes in liver function. Some patients may also report gastrointestinal issues, such as upset stomach or diarrhea. Enzalutamide, in particular, has been associated with a higher incidence of fatigue and neurocognitive symptoms.
Healthcare providers monitor patients for these side effects through regular blood tests and doctor visits. Managing side effects often involves adjusting ARPI dosages or prescribing additional medications. For example, high blood pressure or fluid retention might be managed with appropriate medications. Open communication with the healthcare team is encouraged to address any new or worsening symptoms.