Turmoil Over Prostate Cancer Supplement - Estrogen Added or Missing?
UPDATE September 3: Second PC SPES Lab Report Released: "No Question Diethylstilbestrol (DES) Is Present"
BY JACQUELINE STRAX
July 9, 2001 -- David Domizi, aged 64, is seven years out from a failed radical prostatectomy. His recurrent prostate cancer at present appears still to be hormone naive. He has never taken Lupron, Zoladex, Casodex or similar drugs, although he has taken a supplement that doctors believe to contain plant estrogen.
When David's PSA first began to rise, he went to Columbia University Hospital for a clinical trial of the NSAID drug Aptosyn (Exisulind). It didn't work for him. One day Aptosyn might turn out useful for slowing prostate cancer recurrence in men who have aggressive disease. In some trials it has been reported to do that already. But it did not help David Domizi one bit. "It turned out that he was on the drug (the trial was double-blinded)," his wife Susan Domizi told the PC-SPES list last week, "but was one of their 'failures.' His PSA rose to the highest level it had been since the RP."
Susan Domizi has subscribed to various online prostate cancer lists "for years," she said in her late-evening post July 6 to the PC-SPES list. First she explained how David, after the failed RP and failed Aptosyn/Exisulind, turned to the herbal supplement PC-SPES. No surprises there to people on this list. Then Susan dropped her bombshell.
Or was it, as some list members and one eminent doctor asserted in instant outcry, a stale, cracked egg? Either totally imaginary or something known about for years, which no sensible patient's wife would bring up. After this site reported part of Susan's background, some people figured that she wrote her post so as to get publicity for her business (which she had said not a word about).
PC-SPES is a patented compound manufactured by the California company Botaniclab. The label says it is made up of 8 Chinese herbs. In animal studies and early clinical trials for hormone naive and for advanced, hormone-refractory prostate cancer, PC-SPES has proven quite effective. All the studies have been reputable; some were done at leading cancer research hospitals like Memorial Sloan-Kettering Cancer Center and University of California San Francisco.
According to Susan Domizi, David had "good success" on PC-SPES for the last couple of years, even though he has not been strictly careful about dosage and timing of doses. But lately, she indicated. something seemed to be going wrong. She and David believed there may have been a change in the herbal supplement, not just in David.
Any man coping with recurrent prostate cancer must know that the disease can become refractory to a therapy at any time, between one PSA test and the next. But men besides David were reporting that they weren't feeling the usual side effects of PC SPES, notably nipple tenderness.
Susan Domizi has an open mind based, she says, "on the rigors of science." She's disposed to trust, not scoff at herbal supplements -- if evidence shows that they work. For over twenty years, Domizi has run her own company, SOURCE, Inc., which makes seaweed-based supplements "specifically formulated for horses, dogs and people."
In their separate work lives both of these people deal with quality control and product integrity. David, who makes laser equipment, is literally on the cutting edge. This goes quite a long way to explain their "early adapter" style when it comes to David's fight against recurrent cancer.
Susan didn't say much about their background in her post. Rumors abound that some members of this list are not using PC-SPES or don't have prostate cancer and may be "shills" for Botaniclab's competitors. Incipient paranoia is a fact of life on e-lists. And on a cancer list, if anyone announces a treatment is no longer working for them or their partner, almost everyone feels the chill.
We felt that other patients might need to know more about this couple. Susan and David are competitive -- they play competitive bridge and Susan, as we saw when Yahoo pulled up her company's website, trained as an Olympic-standard horsewoman, used her bachelor's degree in science to improve her horse's conditioning and that way founded her own business. She belongs to the National Association of Equine Supplement Manufacturers. She has been an industry liaison to the Association of American Feed Control Officials' Novel Ingredients Regulatory Framework Task Force. Well before this crisis over David's health, Susan pushed to speed up the drug approval process.
She is not, though, as far as we can see, in any competition with her husband's doctors nor with his supplements supplier. We asked her about this in a phone interview July 8. "I have no plans whatsoever of developing any forms of cancer supplements," she said.
On PC-SPES, David's PSA stabilized. But in early June his PSA "showed a startling (to us) rise from 2.7 to 5.2 (It is now 5.6). It had stayed for a very long time in the high 2's, low 3's." Susan wrote to the list Friday night:
I began reading the PC-SPES list much more carefully and eventually saw several posts about concern for hormone naïve men with rising PSAÂs. I needed to find out whether or not David, individually, had become "refractory" to PC-SPES (which would mean it was now time to "move on" to another therapy) or whether some change in the product was making it no longer as effective for David. That's when I became involved on the list, soliciting information about rising PSAÂs , Lot #Âs and then Expiration dates.
Part of the PC-SPES reputation and mystique is built on anecdotes and testimonials. More than thirty anecdotes men sent to Domizi and/or the list were negative. "Many men were experiencing an uncharacteristic rise in their PSAÂs. I could think of only one possible explanation; i.e., that there was a difference in the effectiveness in the product that David took earlier, and the product that he has taken this spring."
From what she says, Domizi agonized over this, but not for too long. "I decided to have PC-SPES analyzed by a qualified independent testing laboratory." And she did so. On Friday night at 20:00:43 -0400 Susan Domizi wrote to the members of the PC-SPES mailing list URGENT: NEWS about PC-SPES testing!
I have just received a fax from an independent commercial testing laboratory that I retained to test four different Lot #'s of PC-SPES. The final, complete hard copy report will not be available until next week. However, I felt that the information received thus far was so important that it needed to be shared immediately.
Two of the Lot. #Âs are reported to contain DES (the non-steroidal synthetic estrogen, diethylstilbestrol.) Both of them were Âold Lot #Âs from the Âeffective days (Lot #5430125, Exp. 6/2002 and Lot#5436285, Exp. 3/2000).
This explains to my satisfaction why David has had an unexpected increase in his PSA (and I'm sure it will interest the rest of you who are also experiencing this problem).
The two Lots samples reported to contain no DES are from a recent Lot, #5431106 Exp. 4/2003, and the current new batch Lot# 5431164, Exp. 6/2003, Domizi said.
Two weeks ago, before Domizi went public about the lab report, PSA Rising called Botaniclab for any information from Dr. Sophie Chen, their leading scientist. Unable to reach Chen, we spoke to Debbie Alder, Botaniclab's marketing director, about sheer rumors about DES in the product. Alders said the FDA has already tested PC-SPES for the synthetic female hormone DES.
"Our quality control is spotless," Alder said. There is "no lot to lot variation." Testing "for the footprint" has shown it to be the same, Alder said. Botaniclab is using "the same formula" and "the same herbs," Alder said.
So far, Domizi has declined to name the test laboratory. She says she has promised the lab not to bring down a flood of phone calls from the general public. She is seeking a way to release the information from the hard copy when she receives it later this week. She chose this company to do the tests, Domizi told the list, "because it had the expensive 'standard' for DES and had successfully performed DES testing previously." The laboratory used Gas Chromatography Mass Spectrographic Analysis.
Does Domizi have any commercial motive to undermine confidence in PC-SPES? She says not at all. She says she does not "have any 'axe' to grind with Botaniclab," the manufacturers. "They have made no claims," Domizi said. Quoting from the label in her post to the list she said, "They have marketed 'A synergistic blend of high quality herbal extracts based on ancient Chinese remedy.' 'For Prostate Health'."
The DES that, according to Domizi, was found in the two samples of two different lots could not, in her opinion, be a "natural" DES from herbal sources. In other words, it could not be phytoestrogen, the so-called "weak" estrogen already identified in PC-SPES. "The laboratory informs me," she wrote, "that the test is specific for the synthetic DES molecule. DES was first synthesized in 1938. It is a man-made drug. Eventually, at least 270 companies have manufactured it."
Did the lab test produce two false positives? Some patients are talking about paying for re-tests and second opinions.
In 1998, Dr. Robert DiPaolo and Huayan Zhang of the Cancer Institute of New Jersey published an article in The New England Journal of Medicine to report that PC-SPES contains "plant estrogen" (phytoestrogen). Several of the herbs listed as ingredients in PC SPES are known to contain "weak," phytoestrogen. [PC-SPES Contains Estrogen: Lowers Testosterone and PSA].
"We measured the estrogenic activity of PC-SPES with transcriptional-activation assays in yeast and a biologic assay in mice," Di Paolo and team said. They reported that tests at their lab found organic estrogen but no traces of synthetic estrogen.
"In complementary yeast assays, a 1:200 dilution of an ethanol extract of PC-SPES had estrogenic activity similar to that of 1 nM estradiol," DiPaolo said. "High-performance liquid chromatography, gas chromatography, and mass spectrometry showed that PC-SPES contains estrogenic organic compounds that are distinct from diethylstilbestrol, estrone, and estradiol."
The PC SPES formula, privately held, comes from Taiwan named to appeal to Westerners - "PC" stands for prostate cancer; "SPES" is Latin for hope. PC-SPES is sold at health stores, by phone and mail order and over the Internet. It is recommended by leading oncologists and by US-TOO International support group.
Leading health store distributors, contacted last week, indicate no serious problems. The owner of The Apothecary/Pathway International in Maryland (www.the-apothecary.com) said, "None of our customers have really complained about a change, but quite a few have called because they had seen reports on the Internet or heard about those reports. Botaniclab has assured us they have the highest quality control and all batches were triple assayed."
Paul Anderson at Roots & Sprouts in Chicago area said "All this controversy is ridiculous. We have well over 1000 customers taking PC-SPES with no noticeable change in the results. I personally talk to 30 PC survivors on average each day. Maybe one or two are having problems but that is typical." Anderson cited a patient in Maine who started with a PSA of 5343. "Taking the same stuff some of these complainers are yelling about (same batch), his PSA dropped ... to 3.5 in 120 days. He should be under ground but he's thriving." Anderson said: "This entire controversy is a hoax as far as I'm concerned."
"We send PC-SPES all over Europe," a supplier in Holland, Peter den Boer at Medpro, said. "We have not heard of any change of the results from PC-SPES. None of our customers ... complain of any change in the product."
Eric Small MD at UCSF, in a 1999 study paid for by the Association for the Cure of Cancer of the Prostate (CaP CURE), found that PC-SPES lowers both PSA and testosterone levels. He took this as evidence that PC-SPES may work like standard hormonal therapy. "We think PC-SPES is estrogen-like," Dr. Eric Small said.
Side effects included impotence, lowered sex drive and breast and nipple tenderness. In men with hormone dependent disease, Small said, PC-SPES appeared to "mimic" estrogen. Everyone agrees there may also 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."
Susan and David Domizi, rather than wait years for this to be sorted out, are acting on the basis of the tests they sought and paid for. "Frankly, I am far more optimistic and less worried than I was a few short weeks ago," Susan Domizi said on Friday night. "At that point I feared that David had become 'refractory' to PC-SPES and didnÂt know where to turn next. Now, I believe that by simply adding low-dose DES to the herbs we will have him back on an 'even keel'."
What is David going to do? "We think that we will try to find a knowledgeable MD who will prescribe low levels of DES," she wrote to the PC-SPES list, "to mimic the activity level of the 'effective' PC-SPES, and monitor the results very carefully. He will then continue to take the 'non' effective (no DES) PC-SPES that we already have until it runs out. Then we may switch to one of the far less expensive 'knockoffs.' We still believe the herbs are contributing benefit."
This raises a possibility that a mix-and-match strategy might have gone into the original formula for PC SPES, the one Domizi believes test results show is not currently available. In China, she says, she has heard that traditional and western approaches can mingle "from both ends of the stick."
Dr. Charles "Snuffy" Myers, an oncologist and cancer researcher who is himself a prostate cancer survivor, in response to a query from a member of the PC-SPES list, said: "I do not believe this for a minute. This issue was taken to the FDA, who had PC-SPES analyzed and found no, I repeat, no DES. Additionally, DiPaolo from the New Jersey Cancer Center ... looked for and did not find DES. I suspect that this is someone wanting to hurt BotanicLabs for some reason. Also, among my patients, I have seen no increase in the number of patients failing PC-SPES."
"I know that this information will, at first, be very upsetting," Susan Domizi wrote on Friday to the PC-SPES group. "If youÂre at all like me you will run the gamut of emotions from disbelief and denial to anger and fear and frustration. IÂve had a few more hours to digest this than you have yet. I can tell you that I now am filled with relief and an increasing sense of joy that there is help for David." © PSA Rising, J. Strax.
Updated Index of PC SPES Reports on this site
Background on DES
Estrogen was used often to treat prostate cancer in the 1940s through the mid 1980s. One serious problem is thrombosis and heart attack from estrogen's clotting action on the blood. In some parts of the world estrogen, in cheap generic forms, is still used to treat advanced prostate cancer, or is being retested at lower doses.
Last year, doctors in London, UK tested low-dose DES (stilboestrol, 1 mg/day) combined with hydrocortisone (40 mg/day) for patients with metastatic disease who progressed on hormone therapy with recurrent/worsening symptoms and an increase in prostate-specific antigen (PSA) level. To reduce risk of thrombosis, patients took daily aspirin (75 mg/day). Out of 29 symptomatic patients, 24 had some relief lasting for a median of six months. Abstract of report in BJU Int 2000 Jun;85(9):1069-73
UCSF PC SPES "Medical Care & Info" page for patients on study.
PC-SPES Effects on Patients With Androgen Dependent Prostate Cancer Fox-Chase March 1, 2000.
PC-SPES UPDATE: Early Results of UCSF Phase II Trial: Herbal Therapy Lowers PSA in Men With Advanced Prostate Cancer, Study Shows May 6-July 9, 1999
PC-SPES Contains Plant Estrogen November 26, 1998 Two sets of results from a New Jersey study of the herbal mixture PC-SPES show that it is strongly positive for estrogen.
Riding the Rockies, by Damon Phinney "My response to the PC SPES is not typical by any means. It was very bad stuff for me...." September, 1999.
Bilateral Orchiectomy, by Ric Masten Where were you PC SPES folks when I needed you? Well, at least I have found you now! Live and learn!
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