The Day the FDA Took a Cancer Cure Away
by Bill Sardi by Bill Sardi
Excerpt from the book: You Don’t Have To Be Afraid Of Cancer Any More, by Bill Sardi © 2007
The most significant event in the recent history of prostate cancer care has been the introduction, for a time, of a combination herbal remedy that caught cancer doctors by surprise. This herbal dietary supplement captured the attention of prostate cancer patients and doctors alike. The herbal combo began extending the lives of otherwise helpless prostate cancer patients facing the advanced life-threatening form of their disease. How the cancer industry responded to this development, and the events surrounding the decision to withdraw this herbal formula from the marketplace, despite its unprecedented effectiveness, reveals much about the dismal state of cancer care in America. One cannot read this account without becoming outraged at the final outcome.
An herbal remedy captivates
About 230,000 men learn of their prostate cancer each year in the United States. Among them is a group of about 40,000 men who face the aggressive form of the disease where the cancer has begun to spread to bone and other organs, threatening their lives.
In the mid-1990s, men with this progressive form of prostate cancer found a multi-herbal remedy to be quite effective in subduing the pain, inflammation and spread of prostate cancer. Sadly, the product was suddenly recalled for mislabeling problems, never to be re-introduced.
The whole unfortunate tale is indicative of what is going on in the cancer care industry today and worthy of re-analysis here. This is a story that every male with prostate cancer needs to read and understand. If you are familiar with this story, new data places a different ending to the story.
The saga begins
Long about 1996, a research scientist by the name of Sophie Chen, PhD, a graduate of Columbia University and post-doctoral fellow at Cornell University, who spent 14 years working for pharmaceutical companies (Merck Sharp & Dohme and Bayer USA), developed a multi-herbal product for males with advanced prostate cancer. It was named PC-SPES. The PC stood for prostate cancer, and "spes" is the Latin word for hope.
In 1988, Dr. Chen began her research into the role that natural herbs can play in healing and curing cancer, and obtained a dozen U.S. patents. In 1993, Dr. Chen co-founded the International Medical Research Corporation with "Allan" Xuhui Wang, MD, and John Chen (her brother), which did business under the name BotanicLab, the maker of PC-SPES.
Chen and Wang, who is also an herbalist, collaborated to modify an existing herbal formula used in China to treat urologic problems, which became the PC-SPES product. The first patient to use it was Chen’s brother-in-law, a physician in Taiwan with advanced prostate cancer who was alive and well 10 years later. [Journal National Cancer Institute 94: 1266-68, 2002]
Over time Dr. Chen had secured research grants from the National Cancer Institute and prostate cancer survivor/investor Michael Milken’s CaP CURE organization. Eventually an $8 million study grant from the National Institutes of Health was obtained, but the study never took place due to product quality problems. [PSA Rising, Dec. 19, 2003]
Many urologists and oncologists believed the herbal mix was prolonging their patients’ lives. Over 100 studies were published, validating its beneficial effects.
PC-SPES got spiked
A report published in the Journal of the National Cancer Institute in 2002 said: "PC-SPES was poised to become the first cancer treatment to emerge from the realm of alternative medicine, pass rigorous clinical testing, and add a powerful natural weapon to the oncologist’s arsenal."
As positive as the reports were for PC-SPES, there were nagging reports of side effects. Doctors began to suspect that the side effects caused by PC-SPES were similar to those produced by diethylstilbestrol (DES), a testosterone inhibitor that has been used to treat prostate cancer for decades.
The spiking of PC-SPES with drug molecules wasn’t apparent at first. A study published in 1998 found estrogen-like effects, but couldn’t identify the molecule involved. The study didn’t find any DES in PC-SPES at that time. [New England Journal Medicine 339: 785-91, Sept. 17, 1998] Chen denied the presence of any ingredients not on the label. Three times the California FDA tested PC-SPES and found no contamination, but utilized testing methods that could not detect minute amounts.
Then, as reports of side effects began to accumulate in 2001, some men suddenly noticed PC-SPES stopped working for them. PSA levels started to rise. Also a few cases of hemorrhaging were reported. Trace amounts of a blood thinner (warfarin) had been added to subsequent batches of PC-SPES in an apparent effort to counter reported blood clots.
It was later found that some batches of PC-SPES given to men in a comparative study contained from 0.01 to 3.1 % of DES. [Canadian Journal Urology 9: 1684-88, 2002] However, this wasn’t considered to be sufficient to cause the side effects being reported, in particular, the reports of blood clots.
Patients take charge
Cancer patients were communicating with each other via the internet, learning of the rising PSA levels among PC-SPES users.
Susan Domizi, wife of a Connecticut man taking PC-SPES, sent samples of the product to a laboratory and found it contained small amounts of DES. A second study also found DES. [International Journal Oncology 20: 583-88, 2002] By October of 2001, doctors had published a case of severe hemorrhaging associated with PC-SPES that was aired in the New England Journal of Medicine. [New England Journal Medicine 345: 1213-14, 2001]
Then the State of California FDA returned to BotanicLab to conduct more sensitive tests and surprisingly found DES in the same lots they had tested before, as well as the presence of another drug, warfarin (coumadin), a blood thinner. Retrospective tests now showed the product had been spiked with DES since 1996, and when side effects were reported, subsequent batches of PC-SPES displayed lower doses of DES, and then eventually the blood thinner, as if someone was attempting to limit the side effects. Sophie Chen responded by saying that none of the drugs was present in therapeutic doses and that "lots without DES worked equally well."
The eight herbs in PC-SPES
The Added Drug Ingredients
Licorice root Reishi mushroom Chrysanthemum Dyers woad Rabdosia Saw palmetto Baikal skullcap Ginseng
Diethylstibestrol (DES) (testosterone interruptor) Indomethacin (anti-inflammatory) Warfarin (blood thinner)
Breakthrough in process
Whatever ingredients were in PC-SPES, they were producing a breakthrough in prostate cancer treatment all the while the product was being slammed for adulteration.
Michael Cook is an example. A 49-year-old who was diagnosed with prostate cancer at age 44, his tumors had spread to his ribs and pelvis. PC-SPES dropped his PSA from 80 to 0.2. "I’ve been on PC-SPES for three years now, and I seem to be in complete remission," said the patient. [LA Times Oct. 21, 2000]
A group of men with prostate cancer, called UsToo, reported that their members maintained a low PSA concentration with PC-SPES in two successive surveys (88% and 93%). "Even though there were some side effects, a great majority of men are realizing good PSA control while taking the capsules, with some users now into their fourth year of PC-SPES use," said their report. [Molecular Urology 4: 289-91, 2000]
Moreover, a study conducted by Eric Small, MD and William Oh, MD at the University of California at San Francisco, showed that PC-SPES produced a 47% response rate compared to just 28% for diethylstiberstrol alone, and reduced PSA levels by more than 80% in all of their prostate cancer patients, with one patient experiencing complete disappearance of a bladder mass. In Dr. Small and Oh’s study involving 37 patients, three experienced blood clots. Side effects, however, were deemed to be "acceptable." [Journal Clinical Oncology 18: 3595-3603, 2000; Urology 57: 122-26, 2001]
A report in the Journal of Urology stated the side effect profile of PC-SPES was "comparable to estrogen treatment," with 42% experiencing nipple tenderness, 8% breast enlargement and 7% hot flashes. [Journal Urology 164: 1229-34, 2000]
Dr. Charles Myers of the American Institute for Diseases of the Prostate, in Charlottesville, Virginia, reported the case of a man whose PSA was nearly 3,000, an alarming level, but after taking PC-SPES it fell rapidly to below 1. Dr. Myers called PC-SPES "probably the most active agent" for treating prostate cancer in patients who no longer get results from conventional, hormone-blocking drugs. [Wall Street Journal May 26, 2002]
Still a mystery
Since no proof existed to show that BotanicLab had purchased any of these drug molecules, the blame for adulteration was cast upon sources of the herbs in China. Chen stated that she was not personally involved in mixing the company’s products, saying she was in New York conducting research most of the time, not in their Brea, California headquarters.
But Chen also contradicted herself when she said she had tested the herbal products herself and they were pure prior to encapsulation. She claimed the alcohol extraction of the herbs was conducted by companies in China, not in the United States. One of those suppliers in China also processed pharmaceuticals and could have been to blame. But they would have had to know what was going on in the United States to alter the product as they did.
Strangely, the Washington Post report stated that BotanicLab had conducted tests on its own in 2002 and determined bulk herbs coming into the country were free of pharmaceuticals, while packaged products leaving the Brea facility were adulterated. The Washington Post report said: "Tests conducted after BotanicLab shut down showed changes in pharmaceutical ingredients over time that the people suing BotanicLab regard as evidence of a conscious effort to manage troublesome side effects."
Blood clots are common in cancer patients, so this problem may not be attributed to PC-SPES. [Medicine 56: 1-37, 1977] But the addition of the anti-clotting drug warfarin, and the cases of hemorrhage, were certainly a concern.
It took five years to shut down BotanicLab. PC-SPES was voluntarily recalled in 2002. Under agreements, John Chen, sister Sophie Chen, and Allan Xuhui Wang admitted to single misdemeanors involving the marketing of misbranded and adulterated food. Their defunct company pleaded no contest to the felony count of producing a product that presents a danger to the public. The corporation agreed to pay $350,000, the Chen’s agreed to pay $46,500 each, and Wang agreed to pay $56,500. Cancer survivors who had used PC SPES filed a class-action lawsuit against BotanicLab.
Later patients even sued the Milken Prostate Cancer Foundation. "Giving people prescription drugs without their knowledge is insane. It is total fraud," a woman was quoted as saying in a Washington Post article. [Washington Post, Sept. 5, 2004]
What caused the beneficial effects?
In 2000, researchers at Columbia University reported that "estrogen-like activity is not its [PC-SPES’] sole mechanism of action." [Journal Urology 164: 1229-34, 2000]
Investigators at New York Medical College obtained samples of single herb extracts used in the PC-SPES product and determined that no single herb could exert the reductions in PSA and testosterone reported in other studies. The authors of that study said "PC-SPES should be considered a single function unit since the combination of its biological properties appears to be more effective than its individual components." [International Journal Oncology 20: 583-88, 2002]
Dr. Oh stated there was something else in PC-SPES causing the beneficial results. Another study found that men taking nine PC-SPES capsules a day could get as much as 0.5 mg of DES per day, compared to the 3.0 mg used in the comparative study of the two drugs. So it appeared a small amount of DES was being added intentionally without being identified on the product label.
About 10,000 men in advanced stages of prostate cancer were estimated to be taking 6-9 capsules of PC-SPES per day at a retail cost ranging from $400 to $500 per month. An attorney estimated BotanicLab may have taken in $50 million before it was shut down.
For comparison, Canadian pharmacies are selling Lupron kits for $325-486. Lupron stops production of testosterone by the testes. Side effects with Lupron include breast enlargement and decreased libido, similar to those produced by PC-SPES. Over $876 million of Lupron was sold in 2004. Yet one physician, Glenn Bubley, MD, of Harvard Medical School was quoted as saying the manufacturer of PC-SPES "is making more money than God." [WebMD August 31, 2000] Another comparison: a 10-milliliter dose of Honvol (diethylstilbestrol) costs about $90 from a Canadian pharmacy.
DES, Lupron and side effects
Jacqueline Strax, whose husband succumbed to prostate cancer in 2001, recalls how PC-SPES had initially helped her husband. In 1984, her 44-year-old husband was told he had a month to live. He subsequently underwent orchiectomy (surgical removal of the testes) and the subsequent hormonal suppression was effective for many years. When the tumor later returned with a vengeance, he found PC-SPES on the internet, paid $10,000 to Sophie Chen after speaking with her on the telephone, and soon felt better. In 1998, he died of a hemorrhage. [PSA Rising, December 2003]
Was PC-SPES a killer or a life saver?
On September 5, 2004, the Washington Post ran a report with the headline: "Herbal remedies turn deadly for patients." How so? PC-SPES by all reports was prolonging life and saving men who were clinging to life. The Washington Post asserted the regulatory system of herbal product companies was flawed, claiming BotanicLab spiked its product with rat poison, the blood thinner that was eventually found in PC-SPES. The article called PC-SPES a "disaster," and reported 35 cases where users or their families claimed harm. These were men who were otherwise dying without hope.
The Washington Post article said: "Published studies showed that some of the men who took it (PC-SPES) got enlarged breasts, their nipples grew tender, their penises shrank, and they developed other problems." Yes, but they failed to report that these are the same side effects as are often experienced by those taking Lupron or other estrogen therapy drugs.
The Washington Post article said DES was tested for prostate cancer long ago, "but produced so many side effects, including blood clots, that most doctors concluded it would do more harm than good. It was largely discarded, but interest in it has cropped up from time to time because of scattered research showing it might work at low doses." Over 30 years ago doctors used 5 mg of DES. Today, lower doses are used.
PC-SPES was not intended to be used on men with early-stage prostate cancer. When hormone therapy doesn’t work any longer and the cancer continues to grow, the herbal treatment (PC-SPES) is "effective in those patients" said Dr. Aaron E. Katz. [LA Times, Oct. 21, 2000]
One outcome of the PC-SPES debacle is that physicians began to realize they had overlooked DES in favor of more expensive, but maybe not superior drugs, like Lupron. Thirty years ago 5 milligrams of DES was the standard dose prescribed, with considerable side effects noted. Today it is known that low-dose DES, 1 mg, is effective and produces fewer side effects.
Patrick Walsh, MD says that DES may be a more cost-effective agent in reducing PSA than other more aggressive regimens. [Journal Urology 173: 1966-68, 2005].
A more recent study showed that DES plus aspirin can produce a significant drop in PSA (23% experienced a more than 50% drop; 65% experienced a decline overall). [Urology International 75: 217-21, 2005]
DES, which reduces testosterone levels in the body by inhibiting luteinizing hormone in the pituitary gland, is still manufactured under the trade names Honvol (Baxter) and Stibestrol (Wellspring). It is also known to cause blood clots, reduced libido, and cause breast tenderness and related feminization in males. It is listed for primary use for the intensive and selective palliative therapy of inoperable prostate cancer. DES slows growth of tumor cells and may cause shrinkage of prostate tumors.
Back in the 1970s when diethylstilbestrol was being utilized with regularity among advanced-stage prostate cancer patients, here is what some of the reports said:
- "High-dose diethylstilbestrol can used effectively in cases of prostate cancer when standard doses of estrogen have failed." [Canadian Medical Association Journal 109: 697-99, 1973]
- "Of the conventional chemotherapy drugs available, only diethylstilbestrol has been safe, effective (at least in relieving bone pain) and available for repeat courses of treatment." [Urology Clinics North America 2: 185-96, 1975]
- In 15 patients with advanced prostate cancer receiving diethylstilbestrol, their disease remained stable without evidence of progression for an average of 25.6 weeks. "There were no complete remissions, and no significant side effects were seen." [Urology 8: 231-33, 1976]
- "Diethylstilbestrol has shown effective symptomatic relief in patients with metastatic carcinoma of the prostate. Diethylstilbestrol is recommended in the treatment of advanced carcinoma of the prostate with soft tissue metastasis. It is safe and effective, and the tumor responses outweigh the side effects of the drug." [Urology 7: 598-601, 1976]
So why was PC-SPES being recalled for containing trivial doses of DES? Moreover, why weren’t oncologists and urologists prescribing low-dose DES more often for their patients with advanced prostate cancer?
Call for greater regulation
Regulatory agencies have been waiting for the opportunity to change public opinion regarding dietary supplements and turn all dietary supplements into high-priced drugs. The calls for greater regulation of the dietary supplement industry during the PC-SPES ordeal were deafening. In one report on PC-SPES, The Wall Street Journal said that "makers of supplements don’t have to adhere to as rigorous manufacturing requirements or submit results of clinical trials to the FDA." [WSJ May 26, 2002] However, current laws require dietary supplements to be pure and contain only the ingredients listed on the label, which PC-SPES failed to do. No new regulations were needed to force BotanicLab to recall PC-SPES.
The journal CA, A Cancer Journal For Clinicians, said "natural products such as PC-SPES should be subject to the same standards and approaches as substances that are classified as pharmaceuticals. And for any anticancer modality to be considered for clinical use, it must compare favorably against a proven therapy in comparable groups of patients." [CA Cancer Journal Clinicians 51: 199-204, 2001] That’s exactly what PC-SPES demonstrated, in both animal and human studies.
The CA Journal report tabulated the results from four published studies and found 83% of males who took PC-SPES with advanced prostate cancer experienced greater than a 50% drop in their PSA levels. The report acknowledged that advanced prostate cancer patients have "limited options," noted that most investigators characterized the side effects associated with PC-SPES "as mild," and added that men on estrogen hormone therapy experienced similar side effects. The blood-clotting problems that arose later were the most serious side effects. Dr. Aaron E. Katz, of Columbia University College of Physicians & Surgeons said 2 to 4 % of PC-SPES users run the risk of blood clots, which is a potentially fatal problem. [Los Angeles Times, Oct. 21, 2000]
The report in CA Journal stated, that since the herbal formula had not undergone as rigorous studies as would pharmaceuticals, "physicians and patients must take the place of the agency that provides oversight for the regulated pharmaceuticals."
The FDA can ban supplements, but to do so it has to show "a significant or unreasonable risk of illness or injury." For men who were at the end of their rope, PC-SPES posed no greater risk than many approved drugs, namely DES or Lupron. The herbal products industry was brought to task for poor-quality products and cries for greater regulation are still being heard.
What can be concluded from the saga of PC-SPES? Who was responsible for spiking the dietary supplement? Why did drug molecules need to be added when PC-SPES appeared to work well without them? Why was the product recalled, actually taken out of the hands of patients with advanced prostate cancer, when it was by all reports working better than existing drugs and had similar side effect profiles?
The National Center for Complementary and Alternative Medicine, which was ready to sponsor a multi-million dollar study of PC-SPES before the accusations were raised, says it is "interested in resuming studies of PC-SPES with patients and funding new laboratory studies, but can only do so when a fully characterized and standardized, contaminant-free product using the original formulation becomes available." [NCCAM Publication No. D149, September 2002]
When BotanicLab conducted studies of its products, certainly any variances in the potency of active ingredients should have been apparent. Herbs can vary in the content of active ingredients, but herbal extracts can be standardized for a certain minimum percentage of the primary active ingredient. Why didn’t BotanicLab do this?
The chances of a product like PC-SPES returning to the marketplace with patients and attorneys ready to sue, and regulatory agencies ready to pounce, is nil.
PC-SPES was being asked to demonstrate absolute safety — no side effects, a standard that drugs with all their testing can’t achieve.
For comparison, regulated pharmaceutical drugs cause over 100,000 needless deaths annually from side effects caused by their proper use drugs and Public Citizen warns there are 181 unsafe or ineffective prescription drugs on the market. The Vioxx scandal only served to reveal that the FDA approves relatively unsafe drugs that increase mortality rates. The flawed regulatory model should not be used for dietary supplements.
Was there magic inside?
Scientific investigation of PC-SPES continues to this day, with batches of the product still under scrutiny. Researchers at the Keck Science Center in Clarement, California, tested PC-SPES from batches produced in 1998 and 2001. [Cancer Letters 220: 171-75, 2005]
PC-SPES and DES were tested in lab dishes with lung cancer cells. PC-SPES was effective even in cells that had developed resistance against chemotherapy drugs. PC-SPES both killed cancer cells and interrupted their normal immortal state to cause them to naturally die off (apoptosis), whereas none of the contaminants in PC-SPES (warfarin, DES or indomethacin) induced apoptosis.
Both batches of PC-SPES, even though they varied in the amount of contaminants, were equally effective against this non-sex hormone type of tumor cell. Even adding more DES, indomethacin and warfarin to the less contaminated PC-SPES samples did not increase its effectiveness.
Researchers conclude that "natural components in the herbal extract were responsible for the cancer cell destructiveness of PC-SPES." PC-SPES also inhibited detoxifying enzymes (cytochrome p450) that are involved in cancer drug resistance. This may have played a part in its unusual effectiveness against drug-resistant strains of tumor cells. [Cancer Letters 220: 171-75, 2005]
Was there some magic synergism in the array of eight botanical herbs in PC-SPES? By examination of the data, this appears to be so.
Dr. Fulton L. Saier, a physician and prostate cancer patient, said the recall of PC-SPES "will potentially cause the death of thousands of men." [Wall Street Journal, May 26, 2002]
Dr. William Oh said "the worst part (of the PC-SPES saga) was that PC-SPES was a very effective treatment with minimal toxicity for advanced cancer patients. These men don’t have many choices for therapy."
Dr. Sophie Chen added: "I feel the patients who had used PC-SPES are the victims of the whole thing."
So, in summary, what we have here is multi-herbal dietary supplement……
…whose individual ingredients are commonly sold without noticeable side effects
…that was “contaminated” with small amounts of FDA-approved drugs (DES, ibuprofen, warfarin)
…whose effectiveness was not attributed to minute quantities of drug molecules
…which worked better than the sum of its parts
…which exceeded the effectiveness of existing drug therapies for men with advanced prostate cancer
…and had similar side effect ratios to hormone treatment (Lupron, DES, estrogen)
…whose manufacturer somehow was implicated in covering up the side effects by spiking the product with drugs
… and whose manufacturer and even agencies that funded research studies, were sued by its users and their families
…because its ingredients were “undeclared” on the label and therefore, “could cause serious health effects if not taken under medical supervision”
…however, in most instances, was being prescribed by doctors
…and was therefore recalled by the FDA
Desperate men, for whom hormone therapy had failed, were then asked to return bottles of PC-SPES, thus condemning themselves to an inevitable fate.
The FDA recalled a valid cure for cancer because it was mislabeled, not because it was ineffective. The FDA enforced a product recall that doomed men to their certain early demise. Instead of allowing PC-SPES to remain on the market for compassionate reasons and working with doctors to minimize side effects, as they do with Lupron, the FDA banned PC-SPES.