Zytiga Lowers PSA in men with high-risk prostate cancer, at a cost in side-effects

Prostate cancer survivors during the era 2005-2013, as you'll see from our tag cloud (sidebar), were bombarded by Dendreon's controversial campaign to speed FDA approval of its immunotherapy vaccine Provenge. Since then, Provenge hype has calmed down, while the push for Abiraterone acetate (Zytiga) has heated up.

Abiraterone (generic name) aka  Zytiga (brand name) is a high-powered castration drug FDA approved for use with 10-mg prednisone as a treatment for men with metastatic CRPC. Compared to Provenge, which costs around $90,000 for a course of treatment, Zyiga costs about $5,000 a month with expected follow-up doses for around eight months.

Janssen, Zytiga's manufacturer, is pushing to extend the drug for men with high-risk nonmetastatic (M0) castration-resistant prostate cancer (CRPC). According to a study by Dr. David Crawford and colleagues,, abiraterone (Xytiga) "significantly lowered PSA levels with a consistent toxicity profile in men with high-risk nonmetastatic (M0) castration-resistant prostate cancer (CRPC)."

Earlier this month, Scottish prostate cancer advocates protested that under their healthcare system "men with an incurable form of the disease are to be denied access to the life-prolonging and life-enhancing drug abiraterone before chemotherapy" (Abiraterone rejection in Scotland must be overturned, Prostate Cancer advocate says).

Abiraterone (Zytiga) may indeed be "life-enhancing" so far as it relieves the often severely painful symptoms of advancing metastatic prostate cancer. But for men with symptomless advancing PCa in the stage labeled "nonmetastatic castration-resistant prostate cancer (CRPC)," the burden of side effects may have less palpable benefits. A true benefit, of course, may accrue if early use of the drug substantially delays onset of already lurking metastatic HRPC.

Zytiga has serious side effects. According to study coauthor E. David Crawford, MD, professor of surgery, urology, radiation oncology, University of Colorado, Denver, "The drug was fairly well tolerated." Curiously, Crawford assessed this by pointing out that side effects of the lower dose used for these patients were the same as those of the higher dose of prednisone used for patients with more advanced, metastasic prostate cancer. I had to read this twice to make sure it's what he said. Quote:

What was important about the safety profile using 1000 mg [abiraterone] with 5 mg of prednisone was that it was similar to what had been reported with 1000 mg [abiraterone] and 10 mg of prednisone.

The adverse effects to be taken on board by men who do NOT (yet) have metastatic disease are relatively severe. As reported:

Adverse events (AEs) occurred in 92.4% of patients (43.6% had a grade 3 or higher AE), and 29.0% of patients experienced a serious AE (27.5% grade 3 or higher). 10.7% of patients discontinued treatment as a result of AEs. Four patients had AEs resulting in death; these AEs included coronary artery disease, myocardial infarction, acute respiratory failure, and pneumonia.

An unexpected sidelight to the study found, however, that some 40% of the men who wished to enter the trial on the assumption that they were still at the non-metastatic stage had to be excluded when tests and scans showed they were further along.

This story draws on Sandra Kear's article May 20 1015 in Targeted Oncology: Abiraterone Plus Low-Dose Prednisone Lowers PSA in High-Risk M0 CRPC

ASCO poster session presenting findings on Abiraterone for non-metastic HRPC men:Effect of abiraterone acetate and low-dose prednisone on PSA in patients with nonmetastatic castration-resistant prostate cancer: The results from IMAAGEN core study.

Study authors: Charles J. Ryan, E. David Crawford, Neal D. Shore, Willie Underwood, Jim Wang, Jannell DePalantino, Anil Londhe, Zandong Yang, Tracy McGowan, Philip W. Kantoff; University of California San Francisco, San Francisco, CA; University of Colorado Health Science Center, Aurora, CO; Carolina Urologic Research Center, Atlantic Urology Clinics, Myrtle Beach, SC; Roswell Park Cancer Institute, Buffalo, NY; Janssen Scientific Affairs, Spring House, PA; Dana-Farber Cancer Institute, Boston, MA

Study authors' disclosure of financial links to drug companies including Janssen