Medicines derived from whole plant extracts, and which therefore contain many different types of molecules, are generally described as herbal medicines. The term botanical is used here to reflect that such agents are obtained from a wide variety of natural products, not just from herbs. Medicinal botanicals are minimally toxic, particularly when compared with plant-derived chemotherapeutic agents, and they are readily available without prescription. Described next are some botanicals commonly used by cancer patients. No botanical product has been proven effective against cancer, despite Internet claims of herbal remedy cures.
A principle of CAM for cancer is therefore that patients should not be advised to pursue anticancer therapy with botanicals.
Essiac. Essiac was popularized by a nurse, Rene Caisse, who claims to have derived the formula from a traditional native healer. This product consists of four herbs: burdock root, Turkey rhubarb, sorrel, and slippery elm. A review in the Canadian Medical Association Journal reported no published research on Essiac.37 Mistletoe. Mistletoe extracts, which are more widely known by the trade names Iscador, Helixor, and Eurixor, are popular cancer treatments in Europe and are available in some mainstream European cancer clinics. Unlike many botanical treatments, mistletoe extracts have been subjected to randomized trials in cancer patients. A systematic review of early trials revealed small sample sizes and serious methodologic shortcomings in most studies.38 In subsequent larger studies, no survival benefit was found in patients with malignant melanoma39 or head and neck cancer.40 A small trial in glioma reported possible benefit in a subgroup, but there were no overall differences between groups.41 Noni. This popular botanical product is typical of many unproven therapies: it is a natural product used for "thousands of years" by "traditional Polynesian healers." The discovery of its use against cancer is colorful, involving the miraculous cure of a pet dog. Claims made for noni are ambiguous and implausible, as it is promoted as a "blood purifier" to "cleanse the body of harmful bacteria." Its value for cancer is based on a mouse study42 that used a polysaccharide fraction of the fruit. There are no published human studies of noni. Pau d'arco tea. Pau d'arco tea is said to be an old Incan remedy for many illnesses, including cancer. Made from the bark of an indigenous South American evergreen tree, its putative active ingredient, lapachol, has been isolated. In a Phase I trial, the blood levels of lapachol that were achieved without toxicity were far below those predicted to be effective on the basis of cell culture studies.43 PC-SPES. PC-SPES (PC for prostate cancer; spes is Latin for hope), a botanical treatment for prostate cancer, consists of eight herbs, all but two from Traditional Chinese Medicine. Laboratory research supports the activity of PC-SPES against prostate cancer, and antiproliferate and proapoptotic effects on tumor lines in vitro44 have been demonstrated.45,46 In rat models, PC-SPES decreased the incidence of spontaneous tumors and reduced tumor weight of implanted tumors.47 PC-SPES also demonstrated estrogenic activity in a yeast assay and in mice.44 Phase II studies with PC-SPES show prostate-specific antigen (PSA) declines and improvements in pain and quality of life.48-50 In a single-arm study of PC-SPES involving 70 patients with prostate cancer, no patient progressed objectively or in terms of PSA at median 64-week follow-up. PC-SPES was associated with a number of endocrine side effects51 and with increased risk of thromboembolic events.52-54 A randomized trial comparing PC-SPES to DES in 90 patients with androgen-independent prostate cancer found that 17 of 38 PC-SPES patients, versus 8 of 39 DES patients, achieved a PSA response (P = 0.023).55
Despite these encouraging results, a survival advantage for PC-SPES has yet to be demonstrated. More importantly, the product is no longer available for clinical use: PC-SPES was found to contain warfarin (and SPES, a more generic version for all cancers, to contain alprazolam) and was withdrawn by the manufacturer in February 2002.
b-Glucans. Many mushrooms used in Oriental botanical medicine contain b-glucans, a class of polysaccharide molecule. These agents have been widely studied for their anticancer effects. Most human Phase III trials of mushroom-derived b-glucans have used the polysaccharide Kureha (PSK), an extract of Coriolus versicolor, or an extract from the culture medium of Schizophyllum commune Fries known as SPG. Trials typically compared chemotherapy or radiotherapy plus b-glucan versus conventional treatment alone, finding superior survival for PSK compared to controls following colectomy,56,57 gastrectomy,58,59 and esophagectomy.60 In a typical trial, 120 patients with Dukes' C colorectal cancer undergoing curative resection were randomized to PSK or placebo and followed for up to 10 years. Significant differences between groups for both disease-free and overall survival emerged, with median survival in the PSK group approximately 5 years compared to just over 4 years in controls.56 SPG was slightly but not significantly superior to control for gastrectomy, although improved survival was seen in patients with curative resection in a subgroup analysis.61,62 Results have been less encouraging in breast cancer63,64 and leukemia.65 The most promising results for SPG are seen in cervical cancer, with trials demonstrating improvements in survival66 and increased rates of tumor response.67
In Phase II trials, an extract of Shiitake mushroom given to 61 patients with prostate cancer found that no patient experienced PSA decline, 4 showed some evidence of disease stabilization, and 23 patients progressed.68 In a "preference" study, 269 consecutive patients undergoing liver resection for hepatocellular carcinoma were offered active hexose correlated compound (AHCC), an extract of several different fungi. Overall survival in the 113 patients who selected AHCC was superior to that of nonusers (hazard ratio, 0.64; P < 0.001).
Green tea. Interest in green tea as an anticancer botanical stemmed originally from epidemiologic research that demonstrated lower rates of various cancers, particularly colorectal cancer, in Chinese and Japanese green tea drinkers.69 Typically, tea consumption was compared in cancer patients and matched local controls. Odds ratios for colon and rectal cancer among the highest consumers were 0.6 to 0.8 compared to those who did not consume tea regularly.70 Green tea prevents induced colorectal tumors in animal models71,72 and appears to have moderate inhibitory effects on cell growth.73,74 Although green tea is under study as a possible chemopreventive agent,75 its viability as a cancer treatment has yet to be documented.
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