Commonly used herbal product lowers PSA level in men with advanced prostate cancer, UCSF study finds

A popular herbal supplement used by prostate cancer patients has been found to significantly reduce prostate specific antigen (PSA) levels—a protein in the blood that often indicates prostate cancer—in men with advanced disease, according to a University of California, San Francisco study.

The study, one of the first of its kind to subject the herb PC-SPES to rigorous scientific scrutiny, will be published November 1 in the Journal of Clinical Oncology. PC-SPES (“PC” stands for prostate cancer, “SPES” is Latin for hope) consists of extracts from eight different Chinese herbs.  It is sold commercially at some health food stores.

“My belief is people approach complementary medicine in two ways. They either accept it without critical thought simply because it’s alternative, or they reject it without critical thought because it’s alternative,” said Eric Small, MD, study lead author and UCSF associate clinical professor of medicine.  “Either way, it’s all opinion. We wanted to study PC-SPES and hold it to the same standard as we would any other new drug. This is the first attempt to study this herb in a scientifically methodical way.”

The phase II study evaluated 70 men divided into two groups: those with hormone dependent disease (33 patients) and those with hormone independent disease (37 patients). Hormone dependent disease is defined by its responsiveness to withdrawal of the male hormone testosterone.  This can be accomplished by the use of several hormonal medications, including the female hormone, estrogen.  Testosterone fuels prostate cancer growth. Lowering testosterone levels can cause tumors to shrink or slow their growth. As a result, PSA levels fall. However, tumors can become resistant to hormonal therapy. Hormone independent disease is defined by cancer progression despite low testosterone levels.

All of the men in the hormone dependent arm of the study had a PSA decline of greater than 80 percent, with a median duration of that decline lasting 57 or more weeks. Only one patient had disease progression while taking the herb. About 97 percent of these patients had steep declines in their testosterone also, causing researchers to theorize PC-SPES may work like standard hormonal therapy, Small said. “We think PC-SPES is estrogen-like,” he said.

In the men with hormone independent disease, 19 men, or about 50 percent, had PSA declines of greater than 50 percent. Median time before PSA increased was 16 weeks. But several men in this group have not had any disease progression in more than a year of taking the herb.

The finding that PC-SPES can lower PSA levels in men with hormone independent disease is significant, Small said, because it represents another line of defense for patients when standard hormonal therapy fails to slow the disease.

“In this group of patients we can use another hormone, but beyond that, short of chemotherapy, there is not much more we can do,”” Small said. “PC-SPES can be used as a second or third line hormone. We don’t know what kind of impact it will have on survival, but it clearly offers a clinical benefit. It provides us with another treatment we can use before chemotherapy.”

In addition, some men in both groups saw shrinkage of their tumors. Side effects included impotency, lowered sex drive and breast tenderness. Overall, PC-SPES was well tolerated. The men were enrolled in the trial for two years and were given a dose of nine capsules daily.

While PC-SPES appears to be mimicking estrogen in men with hormone dependent disease, Small and colleagues believe there may be other active anti-cancer ingredients in the supplement because it lowered PSA levels in men with hormone independent disease whose testosterone was already low.

“We have proven that this has some activity,” Small said. “The next step is to sort out if this is any different from estrogen,” he said.

To that end, Small and colleagues at Dana Farber Cancer Institute in Boston, MA are enrolling 100 men with hormone independent disease for a trial to test which agent, estrogen or PC-SPES, works better to slow the disease. Once one therapy stops producing PSA declines, the patient will be switched to the other agent. Patients will be enrolled for a year.

“The importance of that study is it will help us get to the mechanism of PC-SPES,” Small said.

Prostate cancer is the most common cancer, excluding nonmelanoma skin cancers, in American men, according to the American Cancer Society. The organization estimates that 180,400 new cases of prostate cancer will be diagnosed in the U.S. this year. Prostate cancer is the second leading cause of cancer death in men, exceeded only by lung cancer. About 31,900 men in the United States will die of this disease during 2000, according to the American Cancer Society.

Other authors on the paper include Mark Frohlich, MD, UCSF assistant professor of medicine; Robert Bok, MD, PhD, UCSF assistant clinical professor of medicine; Katsuto Shinohara, MD, UCSF assistant professor of urology; Gary Grossfeld, MD, UCSF assistant professor of urology; Zinovi Rozenblat, UCSF clinical research associate; William Kevin Kelly, DO, Memorial Sloan-Kettering Cancer Center; Michele Corry, NP, UCSF; David Reese, MD, UCSF assistant clinical professor of medicine.

The study was supported by the Association for the Cure of Cancer of the Prostate (CaP CURE).