Treating Castrate-Resistant Prostate Cancer

Orlando—Although the prevalence of prostate cancer is stable, it remains the most common cancer for men. The introduction of new therapies has led to improved survival rates, but most men must take several agents to treat the disease, particularly those with castrate-resistant prostate cancer.

The treatment costs are also “staggering,” according to Pamela Ellsworth, MD, associate professor of urology and surgery at Brown University in Providence, Rhode Island. She discussed the options at the Spring Managed Care Forum in a session titled The Evolving Role of Current and Emerging Therapies in the Management of Castrate-Resistant Prostate Cancer. Allergan, Inc. supported the presentation with an educational grant.

For recurrent or advanced prostate cancer, the initial option is usually hormone therapy, including gonadotropin-releasing hormone agonists and antagonists and androgen receptor blockers. However, there are limitations, according to Dr. Ellsworth. For example, patients with metastatic prostate cancer taking hormonal therapy have a median progression-free survival of 12 to 30 months. When androgen independency occurs, the median progression-free survival decreases to 8 to 16 months.

Dr. Ellsworth defined castrate-resistant prostate cancer as disease where patients experience disease progression despite using androgen deprivation therapy and castrate levels of testosterone. She noted it does not necessarily mean patients were completely resistant to hormonal therapy.

One of the treatment options is Provenge^® (sipuleucel-T), which the FDA approved in April 2010 to treat asymptomatic or minimally symptomatic metastatic castrate-resistant prostate cancer. It is the first immunotherapy approved for prostate cancer and costs $25,000 to $31,000 per infusion, according to Dr. Ellsworth. Patients have 3 infusions administered every 2 weeks. Dr. Ellsworth added that in clinical trials, 71.2% of patients had acute infusion reactions reported within a day of infusion, with common side effects including fever, chills, respiratory events, and fatigue.

If patients fail when taking sipuleucel-T, they typically begin taking docetaxel, which costs $3000 per treatment cycle with patients typically having 6 cycles. Adverse events associated with docetaxel include bone marrow suppression, reversible cutaneous reactions, dyspnea, and interstitial pneumonia.

Dr. Ellsworth also mentioned Jevtana^® (cabazitaxel) injection, which the FDA approved in June 2010 to be used with prednisone to treat prostate cancer after patients failed with other treatments, including docetaxel. In a phase 3 trial, patients taking cabazitaxel plus prednisone had a median overall survival of 15.1 months compared with 12.7 months for patients taking mitoxantrone plus prednisone (hazard ratio, 0.70; 95% confidence interval, 0.59-0.83; P<.0001).

In April 2011, the FDA approved Zytiga^® (abiraterone acetate), an oral drug used in combination with prednisone for patients with metastatic castrate-resistant prostate cancer whose disease progressed after prior docetaxel therapy. In December 2012, the FDA expanded the indication of abiraterone acetate to include men with metastatic castrate-resistant prostate cancer before they received chemotherapy. Patients take four, 250-mg tablets of abiraterone acetate once daily with
5 mg of prednisone; they cannot eat for 2 hours before dosing and for at least 1 hour after taking the drug. Dr. Ellsworth said abiraterone acetate costs approximately $5000 per month.

Another new therapy is Xtandi^® (enzalutamide), which the FDA approved in August 2012 to treat men with recurrent metastatic castrate-resistant prostate cancer who had previously received docetaxel. The oral androgen receptor blocker, administered in four, 40-mg capsules once daily, has a wholesale price of $7450 per month, according to Dr. Ellsworth. She added that adverse events associated with enzalutamide include fatigue, back pain, diarrhea, muscular weakness, dizziness, and insomnia.