Drugs for the treatment of prostate cancer have been in the news because of recent approvals by the FDA, the costs connected with their use, and associated improvements in survival.1 More recently reported was the decision to allow Medicare coverage of sipuleucel-T treatment for men who met the FDA approval criteria. The following information may be helpful for physicians fielding questions from patients who have read or heard about these new drugs and want to know if the drugs are right for them.
What is the FDA-approved use for sipuleucel-T?
Sipuleucel-T (Provenge) was approved in April 2010 for the treatment of v or minimally symptomatic metastatic, castrate-resistant (hormone-refractory) prostate cancer. A cellular immunotherapy, sipuleucel-T consists of autologous peripheral blood mononuclear cells activated with a recombinant human protein consisting of prostatic acid phosphatase linked to granulocyte-macrophage colony-stimulating factor (PAP–GM-CSF). Common adverse reactions reported in safety evaluations were chills, fatigue, fever, back pain, nausea, joint ache, and headache.
What is the FDA-approved use for cabazitaxel?
Cabazitaxel (Jevtana), a taxane, was approved in June 2010 for use in combination with prednisone to treat metastatic, hormone-refractory prostate cancer previously treated with a docetaxel-containing regimen. In clinical trials, the most common grade 3/4 adverse reactions were neutropenia, leukopenia, anemia, diarrhea, fatigue, and asthenia.
What is the FDA-approved use for abiraterone?
Abiraterone (Zytiga) was approved in May 2011 for the treatment of men with metastatic, castrate-resistant prostate cancer who are no longer responding to docetaxel. According to the NCI, “abiraterone is the first in an approaching wave of new agents for prostate cancer that, directly or indirectly, target testosterone.”2
Abiraterone “can also be considered in patients who have symptomatic disease who are not good candidates for chemotherapy” and might be used before chemotherapy, noted Christopher J. Logothetis, MD, of The University of Texas MD Anderson Cancer Center. “The study of abiraterone in patients who have not yet received docetaxel-based chemotherapy has completed accrual, and the results will hopefully be available this year. The results from that study will provide insights into optimizing the sequence of abiraterone and chemotherapy.”
What other new drugs are being used for patients with prostate cancer?
Denosumab (Xgeva) is a monoclonal antibody that was approved in June 2010 for the prevention of skeletal-related events in patients with metastases from solid tumors, including prostate cancer. Denosumab can be used for “the relief and delay of bone symptoms” and “should be considered a supportive agent,” Dr. Logothetis said, but “does not impact survival.”
Cabozantinib (XL184) has not received FDA approval but has been shown in a phase I clinical trial to shrink prostate tumors or stop their growth and shrink bone metastases in most patients with prostate cancer. The FDA granted orphan drug designation to the agent in January 2011. Dr. Logothetis called cabozantinib a “very exciting drug” and said that this targeted therapy “may be particularly relevant because it blocks c-Met and VEGF, two pathways that are known to integrate with androgen signaling.” Cabozantinib has potential toxicities, however, as evidenced by the deaths of six participants in the randomized discontinuation trial of cabozantinib, reported at the 2011 ASCO Annual Meeting. Studies are presently underway to identify the safest, most effective dose of this drug in patients with advanced prostate cancer. ■
References
1. Pollack A: New drugs fight prostate cancer, but a high cost. New York Times, June 27, 2011.
2. FDA approves abiraterone for advanced prostate cancer. NCI Cancer Bulletin 8:9, May 3, 2011.
