Late-stage prostate cancer: Newly approved treatments examined

This review evaluated newly approved treatments for metastatic castration-resistant prostate cancer.

Researchers concluded that a number of recently developed treatments provide a clinical benefit for men with metastatic castration-resistant prostate cancer.

Treatment for metastatic (cancer that has spread to distant organs) prostate cancer usually involves hormone therapy, such as androgen deprivation therapy (ADT). By reducing the levels of androgens (male sex hormones such as testosterone), cancer progression can be delayed and survival time increased. When cancer continues to spread despite hormone therapy (known as metastatic castration-resistant prostate cancer, or mCRPC), secondary hormone therapy or chemotherapy is often considered. 

The focus of this review was to evaluate newer treatments for mCRPC. Seven randomized trials evaluating new treatments were reviewed.

Enzalutamide (Xtandi) and abiraterone (Zytiga) are secondary hormone therapies. Two large trials explored the use of these treatments in men already treated with the chemotherapy docetaxel (Taxotere). These trials reported increased overall survival (time from treatment until death from any cause) for enzalutamide (average 18.4 months) and abiraterone (average 15.8 months) compared to placebo (a control substance with no active effect; average 12 months). Two other trials examined the use of these treatments in men not previously treated with chemotherapy. Overall survival was increased for enzalutamide (more than 32 months) and for abiraterone (average 34.7 months) compared to placebo (average 30 months). Time to cancer progression, quality of life, and time to the development of drug resistance were all improved by both treatments. Common side effects included fatigue, diarrhea, constipation, hot flashes, high blood pressure, joint pain, and headache.

Immuotherapies stimulate the immune system to fight cancer as it would a bacteria or virus. Sipuleucel-T (Provenge) is an immunotherapy found to significantly increase overall survival (average of 25.8 months) compared to placebo (average of 21.7 months). There was no effect, however, on disease progression. Common side effects with sipuleucel-T included chills, fever, headache, and muscle pain.

Chemotherapies other than docetaxel have also been shown to improve overall survival in mCRPC. In another trial comparing two chemotherapies, cabazitaxel (Jevtana) was noted to be more effective than mitoxantrone (Novantrone) in delaying disease progression and increasing overall survival (by about 3 months). The rate of side effects associated with cabazitaxel, however, was relatively high. These included low white blood cell count, diarrhea, nausea, vomiting, and fatigue.

Radium-233 is a type of radiation therapy used to treat mCRPC spread to the bone. One trial reported that overall survival was significantly longer with radium-233 (average 14.9 months) than placebo (average 11.3 months). Time to bone damage, time to cancer progression, and quality of life were also improved. Pain severity and the need for pain medication were reduced. Radium-233 was associated with a low rate of side effects. Diarrhea, vomiting, and water retention were among the most commonly reported.

Overall, evidence suggests that hormone therapy and chemotherapy can be combined effectively and safely. Careful monitoring of treatment response or resistance can help identify which treatment is most appropriate. Symptom severity, site of metastases, treatment history, and additional medical conditions should also be taken into account when selecting among treatments.

The researchers concluded that a number of recently developed treatments can improve survival in men with metastatic castration-resistant prostate cancer. The researchers also advise that more randomized trials are needed to optimize treatment selection and sequencing for individual patients.