New SPES Formula Offers Promise for Liver Cancer

Left to Right: Agrimony (Agrimonia pilosa), reishi mushrooms (Ganoderma), and patrinia (Patrinia heterophylla) are three of the key species comprising the 15-herb SPES formula, an immune system enhancer that was shown to destroy hepatoma cell lines in vitro. © 2001 stevenfoster.com.

NEW YORK—The research team that brought the PC-SPES herbal combination to the attention of urologists and prostate cancer patients world-wide, has developed a new formulation—also based on principles of Chinese herbal medicine—that has potential in the treatment of liver cancers.

The new combination, called simply SPES (from the Latin for "hope") is comprised of 15 different herbs, including agrimony, cervus, broomrape, reishi mushroom, and patrinia. It is available commercially, and sold as a general immune system tonic. But preliminary lab work indicates that this combination of herbs is a strong inducer of necrosis in liver cancer cell lines.

"If you add the mixture to hepatoma cell cultures, the surface proteins of the hepatoma cells just peel off, and the cells start to die. The necrosis is very much concentration dependent," explained Sophie Chen, PhD, at the first International Conference on Asian Therapies for Cancer sponsored by Procultura, a non-profit educational organization.

Studies with nude mice implanted with equally-sized hepatomas showed that after 4 weeks of daily administration, an ethanol extract of SPES reduced tumor volume and tumor weight compared with saline, said Dr. Chen, physical chemist who is director of Novaspes Research Laboratory, a non-commercial herbal development lab.

While there are not yet any human studies demonstrating in vivo anti-tumor activity, there are preliminary data from a World Health Organization-sponsored study at two Shanghai hospitals suggesting this formula may be better than morphine in controlling pain in cancer patients. Sixty patients with a wide range of cancer types were randomized to pain control with morphine, SPES, or a starch solution as a control.

The investigators measured current pain, pain at its worst, and pain at its least using the International Association of Special Pain Clinics assessment scale. Patients on morphine had a mean current pain score of 2.5, compared with 0.8 in the SPES group; the pain at its worst score was 5.3 for the morphine group and 1.0 for the SPES patients. On all parameters, scores were consistently highest in the control group (Wang X et al., Anti-Cancer Pain Potency and Mechanism of SPES, 1999, in Management of Pain: A Worldwide Perspective, Raj P et al., eds.).

This study builds on an earlier uncontrolled trial, reported by Sherman Shu Seng Lai, DrAC, at the 1995 World Association of Chinese Medicine conference, showing that among 40 patients with a wide range of cancers, 74% had measurable pain relief and 88% had significant improvement on one or more symptom scores while taking SPES, two 300 mg capsules, twice daily.

So far, there have been no major side-effects recorded in patients taking SPES, but this requires far more study. "This is only preliminary. I don't think any final conclusions can be drawn from these studies. But it does suggest that SPES has potential effects in pain reduction," said Dr. Chen, who is also an associate professor of medicine at New York Medical College, Hawthorne, NY.

Dr. Chen brings a unique perspective to botanical medicine. She spent several decades in research and development for major pharmaceutical companies, including Merck, Sharp and Dohme. It was while working for the drug giants that she "realized the limitations of treating chronic diseases by using an approach based on a single chemical," she told Holistic Primary Care.

This prompted her to turn her attention to traditional Chinese medicine, which had interested her as a girl in Taiwan. "I wanted to study the scientific basis of Chinese (herbal) medicine. I believe there must be a scientific rationale behind these 3,000 year-old herbal formulas."

In 1993, Dr. Chen teamed up with Allan X. Wang, MD, a Chinese physician with thorough training in both allopathic medicine and Chinese herbal medicine. They began to study the biochemical nature of herbs, with an eye toward developing novel formulas that both conform to modern scientific standards but honor the synergistic principles of traditional herbal practice.

"We do need to look at biochemical mechanisms. We need to do assays with cancer cells, and also with immune cells like macrophages and T-cells. And all of this should be done before human clinical trials," said Dr. Chen. "At the same time, it is essential to respect the holistic nature and centuries of practical experience inherent in traditional Asian herbal medicine."

In the mid-1990s, Dr. Chen rocked the urology world with PC-SPES, an 8-herb combination of Chinese botanicals she developed out of a desire to help a friend with prostate cancer. PC-SPES, which includes saw palmetto, skullcap, isatis, and panax ginseng, quickly magnetized both prostate cancer patients and clinical researchers. To date, it has been studied at three major medical centers (University of Kentucky, Columbia Presbyterian, New York, and University of California San Francisco).

The combination comes in 320 mg capsules, and the typical treatment dose is 2 capsules, thrice daily, on an empty stomach. Preclinical studies have shown it can induce apoptosis and suppress cell growth in both prostate and breast cancer cell lines. It has hormone receptor modulatory effects, and can down-regulate receptors for androgens, estrogens,and interleukin 6. On a systemic level, it reduces prostate-specific antigen (PSA).

In the Columbia Presbyterian clinical trial, which involved 22 patients with hormone refractory prostate cancer, PSA expression was reduced in 90% after two months, and remained reduced in 74% by 6 months. In the entire cohort of 69 men, which included both hormone responsive and hormone refractory cancers, 88% had reduced PSAs after a full year on PC-SPES (Katz A et al., J Urol 2000; 164: 1229–1234).

A joint study by UCSF and the Memorial Sloan Kettering Cancer Center, NY, also showed massive decline in PSA in all 33 patients, with 21 of the 33 (64%) reaching undetectable levels within the year. In a poster presentation at the 2000 American Society of Clinical Oncologists conference, Eric Small, MD, noted that 14 of the 19 patients with tumors that could be assessed via trans-rectal ultrasound, showed greater than 50% decreases in tumor volume.

Opinions within orthodox medicine vary—sometimes vociferously—over the role of this herbal combo in treatment of prostate cancer: some view it as a sorely needed adjunct or possibly even a monotherapy; others, including New England Journal of Medicine editors Marcia Angell, MD, and Jerome Kassirer, MD, see it as confounding and possibly compromising the effects of orthodox approaches. All agree, though, that PC-SPES does something.

Though it definitely does not contain hormones, PC-SPES has estrogenic effects (DiPaola R et al., 1998, N Engl J Med 339; 12: 785–791). Human trials have shown dramatic reductions of prostate-specific antigen (PSA) in patients taking the compound. Unfortunately, it also has estrogenic side-effects: in all the clinical studies, gynecomastia, reduced libido, and leg cramps were fairly common among patients on PC-SPES.

But judging from prostate cancer patient surveys done by Us Too International, a world-wide patient support group, most men rate the overall PC-SPES experience as very positive, with the negatives balanced out by increases in energy level and appetite and pain palliation (To see what patients have to say, go to www.rootsandsprouts.com/ustoo_survey.htm.)

PC-SPES likely has multiple mechanisms against prostate cancer, evidenced by the fact that it can markedly lower PSA in men with estrogen-refractory forms of prostate cancer. "The anti-tumor mechanism of PC-SPES is complex. It involves multiple targets and metabolic pathways simultaneously, thereby avoiding the redundant mechanisms that otherwise will promote cell survival when using single-target agents," Dr. Chen said.

She stressed that, "Cancer is a whole body disease. It is not just the cancer cells. It involves immunologic responses, organ to organ interactions, problems with levels of Qi. Cancer is a state involving the whole organism." Herbal combinations make it possible to approach multiple processes and mechanisms simultaneously. "Asian herbal medicine has a wealth of experience in terms of whole person effects."

Dr. Chen believes it is essential to study and develop combinations that respect the traditional principles of Asian herbal medicine, rather than seeking to isolate single "active" ingredients. She stressed that neither SPES nor PC-SPES are "classical" Chinese formulas; they are novel combinations of herbs with long histories of use against cancer in China.

And neither SPES nor PC-SPES are inexpensive; purchasing directly from BotanicLab (www.botaniclab.com), the company that licenses and markets the formulas, a 60-capsule bottle of the prostate formula sells for $108.00; a 30-capsule supply of SPES costs $89.40. Like nearly all herbal supplements, these formulas are not covered by third-party payors.

To Learn More:

UCSF's Department of Urologic Oncology maintains a comprehensive site about PC-SPES, including PC-SPES research summaries, with links to ongoing clinical studies (http://cc.ucsf.edu/clinical/uro_pc-spes.html).

The PC-SPES Online Support Group, founded and independently operated by three men with prostate cancer also has a site (www.pcspes.com) containing a wealth of high-quality information on this treatment, disease management strategies, and patient perspectives on PC-SPES and a host of other treatment alternatives.

THE REDUX: A 15-herb formula based on the synergistic principles of Chinese herbal medicine, had marked in vitro activity against liver cancer cell lines, and was shown in a WHO sponsored clinical trial to reduce pain associated with various types of cancer. The combination was developed by the same researchers who formulated PC-SPES, an 8-herb combo that can reduce prostate-specific antigen and lower prostate tumor volume.