Upfront: Opinion

PC SPES PUZZLE

BY JACQUELINE STRAX

New York, July 16, 2001. Herbal mysteries can be fascinating, but not if your life's at stake. Yesterday I asked a man on the PC-SPES list, Bob Davis in Ventura, CA -- can it be that so many men now are taking PC-SPES that the numbers of men at any one time who see their PSA's rise (or who don't respond in the first place) make a crowd, not a blip?

Quite a few men on the PC SPES list believe that the herbal supplement's formula has been changed, making it ineffective. Are they imagining this? Could this arise out of some weird statistical illusion?

Bob Davis replied by e-mail:"The key thing to know here is that the guys that constitute this 'little blip' are 'the' core group and the most knowledgeable experienced users of PC-SPES as a front line treatment for prostate cancer." Most of the other guys reporting serious problems with the last two batches of PC-SPES," Davis said, "are the most well informed and self managing experts of their own disease that I have run across in my 6 years battling PCa. The idea that this large of a group went refractory all in the same timeline is preposterous."

"I think I am safe in saying that all this group of malcontents want," Davis said, "is getting our PC-SPES of a year ago back."

One salient fact is this -- a man goes refractory to Lupron not because the drug no longer holds down his testosterone level but if some cancer cells in his body change and start to thrive without testosterone. But these PC-SPES users say their testosterone is coming back. Plus, these men say, they are hearing about some hormone-naive men who say their PSA's and testosterone are not dropping on PC-SPES and no side effects develop.

If this is true there can be only two explanations -- either some high-estrogen herbal content is reduced or missing or some non-organic estrogenic content is no longer added.

In 1998, Dr. Robert DiPaolo at Cancer Institute of New Jersey treated some patients who were using PC-SPES. These men experienced breast tenderness and enlargement, penis shrinkage and loss of libido, "typical side effects of pharmaceutical doses of estrogen," DiPaolo said. These men were not taking Lupron or Zoladex, nor Casodex (hormonal therapies that cause those side effects plus hot flashes).

With the introduction of Zoladex and Lupron, estrogen became "old fashioned" for prostate cancer, seldom used. At one time it had been a key therapy but it tends to cause blood clots, which can give rise to pulmonary embolisms and heart attacks. DiPaolo and toxicologist Michael Gallo Ph.D. found, PC-SPES acted like potent estrogen. One of their patients developed a deep vein thrombosis in the leg.

Many plants and herbs contain forms of estrogen, known as phyto- or plant estrogen and classified as "weak" estrogen. PC-SPES tested so surprisingly high in estrogen that DiPaolo checked it for synthetic types. In their article in The New England Journal of Medicine reporting plant estrogen in PC SPES, the authors state that they looked for synthetic estrogen but did not find it. They say they found a chemical profile or "footprint" that looked distinct from any known form of synthetic estrogen (click for illustration).

We have calls in to Dr. DiPaolo and Dr. Gallo to ask them if a potent mix of plant estrogens can mask the DES footprint. From their article in the New England Journal of Medicine, it's not clear whether their lab looked for this.

Of note is the PC SPES patent, Patent US 5,665,393 awarded September 9, 1997 for an Herbal composition for treating prostate carcinoma. The patent includes anecdotes and forward-looking claims for:

7. A method of treating prostate cancer in an individual in need thereof which comprises of administering a therapeutically effective amount of the composition of claim 1.

8. The method of claim 7 which further comprises administering a therapeutically effective amount of a compound selected from the group consisting of: luteinizing hormone releasing hormone, estrogen, antiandrogen, gonadotrophin-releasing hormone and synthetic analogs thereof which have hormone activity.

9. The method of claim 7 which further comprises administering a therapeutically effective mount of a compound selected from the group consisting of antibiotics, antimetabolites and cytotoxic agents.

The herbal composition, the patent says, is made up of

"Panax pseudo-ginseng Wall, Isatis Indigotica Fort, Ganoderma lucidum Karst, Dendranthema morifolium Tzvel, Glycyrrhiza glabra L., Scutellaria baicalensis Georgi, Rabdosia rubescens, Serenoa repens."

These eight herbs are listed on most PC SPES bottles, with slight variation. "Preferably" the patent specifies, "the material from each of such herbs is an alcohol extract of dried, cut plants and of the Panax the pseudo-ginseng Wall and each of the other materials are present in a dried, weight-to-weight range of about 1:1-6."

Considering how it was evident to Dr. DiPaolo that his patients must be taking some type of estrogen, it seems odd that the PC-SPES inventors never listed estrogenic activity in their patent. It is well known that Glycyrrhiza glabra (licorice), for one, is high in estrogens (it also contains antiestrogens). The inventors were manifestly familiar with hormonal therapy for prostate cancer. They proposed combining their herbal therapy with "luteinizing hormone releasing hormone, estrogen, antiandrogen, gonadotrophin-releasing hormone and synthetic analogs thereof which have hormone activity." Also, both of the two patients described anecdotally in the patent were hormonally suppressed. Presumably hormonal interactions were a concern.

The first patient took 3.6 mG Zoladex monthly and 250 mG of Eulexin (Flutamide) 3 times per day. His PSA fell from 182 to 149 in 105 days. He then started the herb composition at 1200 mG per day. "This combination treatment continued for two and one-half months. During this period, the patient's appetite improved and his energy and well-being were enhanced. There was no apparent adverse effect reported. On Day 182, a follow-up serum PSA of 0.84 was reported."

This man's PSA was not rising, he was not refractory, and by the time the herbal composition was added he was three months' into hormonal suppression. The second patient was on Lupron, had taken Eulexin and stopped it, taken Ketoconazole and prednisone. At that point (still on Lupron, the usual way) the herbal mix brought this man's PSA down from 89 to about 3 ng/mL.

LINKS & SOURCES

United States Patent 5,665,393 Herbal composition for treating prostate carcinoma, Chen , et al. September 9, 1997

None of the herbs in PC SPES are inert "do-nothings." They have documented activity in herbal medicine. A lot of information is available online and in your local library about herbs and herbal products. To take as one example, licorice:

Herb FAQS at purdue.edu Licorice (Glycycrhiza glabra L.)

Chemicals in: Glycyrrhiza glabra L. (Fabaceae) -- Common Licorice, Licorice, Licorice-Root, Smooth Licorice Dr. Duke's Phytochemical and Ethnobotanical Databases

Licorice (Springboad Nutrition Notebook) contains corticosteroids and plant estrogen. "Licorice extracts produce estrogenic activity due to the phenolic compound clycestrone which is 1/533 of the potency of estrone. Too much licorice can cause cardiac depression and edema." "It exhibits many pharmacological activities, including estrogenic activities in laboratory animals; it is anti-tumoral, anti-trichomonas, anti-inflammatory, anti-allergenic, anti-toxic, anti-tussive (comparable to codeine for severe coughing), anti-convulsive, and anti-bacterial."

Islamset: Science Medicinal Plants Radix Glycyrrhizae

DNA Sequences for Licorice (Plant Gene Register)