As expert panels debate the best way to proceed with research into complementary and alternative medicine therapies (see story, p. 646), tests of three herbal treatments presented at this years annual meeting of the American Association for Cancer Research in San Francisco showed that they may not be as promising for cancer patients as was once believed.
Green Tea
Green tea contains polyphenols, the most potent of which is epigalloca-techin gallate. Its antioxidant properties have been shown in laboratory studies to have anticarcinogenic properties, and in vitro studies have suggested that the polyphenols in green tea can impede the growth of androgen-independent prostate tumors.
Aminah Jatoi, M.D., professor of oncology at the Mayo Clinic, Rochester, Minn., and her colleagues enrolled 48 patients with androgen-independent metastatic prostate cancer into a phase II multicenter study conducted by the North Central Cancer Treatment Group. The patients took 6 grams of green tea daily divided into 6 doses. Patients were monitored monthly for disease progression, toxicity, and prostate-specific antigen level.
After 1 month, only one patient had a greater than 50% decline in PSA level, and the decline was not sustained. There was a median increase in PSA level of 41% in the entire cohort. Several patients dropped out of the study because of disease progression or because of side effects of the green tea preparation, which may have been related to the caffeine content of the green tea preparation, Jatoi said.
St. Johns Wort
St. Johns wort is a widely available over-the-counter herbal product that has gained popularity as a treatment for mild to moderate depression, which can be common among cancer patients.
The herbal product also stimulates the enzyme cytochrome P450 3A4 (CYP3A4), which is involved in drug metabolism. This enzyme mediates the principal elimination route of irinotecan (CPT-11, marketed in the United States as Camptosar), a chemotherapy drug for advanced colorectal cancer.
To test if St. Johns wort could interfere with the metabolism of irinotecan, Ron A. H. J. Mathijssen, M.D., of the Rotterdam Cancer Institute in The Netherlands, and his colleagues administered an initial course of irinotecan to three cancer patients followed by a second course 3 weeks later that combined irinotecan and St. Johns wort. A separate group of patients received St. Johns wort in combination with their initial course of chemotherapy and 3 weeks later received irinotecan alone.
They found that systemic exposure to SN-38, an active metabolite of irinotecan, decreased by about 40% when St. Johns wort was taken in conjunction with irinotecan. The effect persisted in the group that stopped taking St. Johns wort 3 weeks prior to their second course of chemotherapy.
Mathijssen acknowledged that the study included a very small number of patients, but he added that "I think its unethical to expose more people to such a potentially dangerous drug," Mathijssen said.
PC-SPES
PC-SPES is a combination of eight different herbs that has been available as an over-the-counter supplement for about 5 years. First anecdotal reports and then small uncontrolled studies showed surprising drops in PSA levels in men with advanced prostate cancer who took the supplement.
Curious about the active agents in PC-SPES, a team of scientists took seven different lots of PC-SPES and isolated each chemical constituent and identified the chemical components. They found something they did not expectdiethylstilbestrol, a potent synthetic estrogenic drug.
"There appears to be an adulterant [in PC-SPES]," said Robert A. Nagourney, M.D., medical and laboratory director of Rational Therapeutics, Long Beach, Calif., one of the investigators.
Further analysis also revealed the presence of the blood thinner warfarin and the anti-inflammatory drug indomethacin. Nagourney and his colleagues speculate that it is this combination of ingredients and not the herbs themselves that has been producing impressive clinically relevant results.
A study by the California Department of Health Services discovered the presence of warfarin earlier this year, which prompted the company that manufactures PC-SPES, BotanicLab, Brea, Calif., to issue a voluntary recall of the product. The U.S. Food and Drug Administration also issued a warning to consumers to stop taking it.
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