The American Society of Clinical Oncology (ASCO) released a new guideline this month, recommending that the androgen blocker Zytiga (abiraterone acetate) or the chemotherapy medication docetaxel be added to androgen deprivation therapy (ADT) for men with advanced prostate cancer who have not yet received hormone therapy.
About 4 percent of men diagnosed with prostate cancer in the United States already have metastatic disease that has spread beyond the prostate at the time of diagnosis, according to ASCO. ADT alone has been the standard of care for this group.
“These two additional therapies can substantially change the outcome of men who have newly diagnosed metastatic disease,” Michael J. Morris, MD, cochair of the expert panel that developed the guideline, said in an ASCO statement. “Having two standards of care allows flexibility and options—these choices and decisions can be negotiated between the patient and the doctor.”
Prostate cancer is usually treated with surgery or radiation therapy, typically followed by androgen deprivation therapy. Testosterone and other androgens (commonly known as male hormones, though women produce small amounts too) promote prostate cancer growth; depriving tumors of these hormones can slow disease progression.
Initial ADT usually involves drugs that reduce testosterone production by the testicles, a process known as medical castration. But other organs, including the adrenal glands and the prostate itself, also make small amounts of androgens. Zytiga stops production of androgens throughout the body by blocking an enzyme (CYP17) needed for their biosynthesis.
The new guideline, published in the Journal of Oncology, is based on results from Phase III randomized, controlled clinical trials showing that the addition of Zytiga or docetaxel to ADT improved outcomes for men with advanced prostate cancer who have not yet been treated with testosterone-lowering drugs.
As reported at last year’s ASCO annual meeting, the LATITUDE and STAMPEDE trials showed that starting Zytiga early, along with ADT and prednisone, reduced the risk of death by nearly 40 percent in men who were newly diagnosed with advanced prostate cancer or who experienced disease progression after surgery or radiation but had not yet used hormone therapy.
Another trial known as CHAARTED showed that men with hormone-sensitive metastatic prostate cancer who used docetaxel (Taxotere or generics), a cytotoxic chemotherapy drug that kills fast-growing cells, along with ADT had longer overall survival than men treated with ADT alone. Docetaxel was administered every three weeks for six cycles. The benefit was most pronounced for men with high-volume cancer.
Zytiga and docetaxel have not yet been compared against each other as add-ons to ADT in head-to-head clinical trials, so it is not yet known whether some men might benefit from one regimen more than the other. As such, Zytiga and docetaxel should be considered as two separate standards of care for this population, according to the expert panel.
When considering whether to use Zytiga or docetaxel, a patient’s ability to tolerate chemotherapy, toxicity profiles, coexisting conditions, drug availability, cost and quality-of-life concerns should guide treatment decisions for each individual, the guideline recommends.
“When deciding whether to administer a hormonal agent or chemotherapy, it should be acknowledged that chemotherapy can have greater adverse effects that negatively affect patient quality of life compared with the lesser adverse effects associated with hormonal treatment. However, with the recommended chemotherapy regimen, the time on treatment is relatively short, and the evidence demonstrates that quality of life is restored afterward,” the experts wrote.
“Also, although treatment with abiraterone is well tolerated, in some health care systems it is expensive or not available to all, and treatment must be administered for the full duration of castration sensitivity,” they continued. “Finally, which of the two options is preferable may depend on patient preference based on the balance of priorities in terms of the pros and cons listed above, the local health care system and finances. Because prostate cancer treatment is a rapidly evolving field of study, patients should consider, and clinicians should encourage, enrollment in suitable and appropriate trials.”
Click here to read the new ASCO guideline in the Journal of Oncology.
Click here for the LATITUDE results in the New England Journal of Medicine.
Click here for the STAMPEDE results in the New England Journal of Medicine.
Click here for the CHAARTED results in the New England Journal of Medicine.
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