CAM Trials Can Be Done in a Traditional Clinical Setting

BOSTON—Although some see complementary and alternative medicine (CAM) therapies as lying outside the mainstream clinical setting, Charles Loprinzi MD, of the Mayo Clinic College of Medicine, reviewed 27 CAM trials done in traditional clinical settings, some complete, some in process. These studies are well-designed, adequately powered, are accruing large numbers of patients, and are being published in peer-reviewed medical journals, Dr. Loprinzi said at the Society for Integrative Oncology Third International Conference.

These trials done by the Mayo Clinic, often in conjunction with the North Central Cancer Treatment Group, began in the late 1970s. Their earliest work involved trying to find ways of alleviating some of the adverse symptoms associated with cancer treatments, including mucositis. A randomized trial of 95 patients showed that patients who put ice chips in their mouth for 30 minutes during chemotherapy had significantly less severe ulcerations and a 50% reduction in the number of days of mucositis, compared with a control group. However, a double-blind placebo-controlled trial involving 164 patients found no difference in mucositis between patients who used chamomile or placebo mouthwash.

Another symptom studied by the Mayo group is skin inflammation, such as pain, infection, and scarring, caused by radiotherapy. Aloe vera, an extract from a cactus plant, has been promoted as an agent for treating burns and other skin irritations. A placebo-controlled, double-blind trial of 194 breast cancer patients scheduled to have radiation therapy to the chest, found no difference in the severity of the dermatitis or its duration between the women who received aloe vera gel vs placebo gel.

Dr. Loprinzi reported that randomized trials have failed to show a benefit for vitamin E, soy, black cohosh, or acupuncture to prevent hot flashes. The jury is still out on one nutritional supplement DHEA (dehydroepiandrosterone), an androgen that is converted to testosterone in the body. A pilot study with 22 patients found a 64% decrease in hot flashes from baseline. A larger placebo-controlled study is being developed.

Capsaicin for Chronic Pain

Chronic pain can be a problem after mastectomy or limb amputations, he said. Capsaicin cream, a substance made from hot chili peppers, was tested in a placebo-controlled, double-blind study of 99 patients. Patients using the cream had significantly more pain relief throughout the entire 8 weeks of the study. The mean pain reduction was 53% in the capsaicin group vs 17% in the placebo group. Capsaicin cream is known to deplete substance P, a peptide involved in transmitting pain along the nerves.

Extract from the root of the valerian plant is an herbal substance commonly available and used for insomnia, restlessness, and anxiety. Dr. Loprinzi said that researchers are actively recruiting up to 200 cancer patients with insomnia for a randomized placebo-controlled trial to test the effectiveness of valerian.

Several products touted in the lay press have been tested and found wanting, he said. Laetrile from apricot pits was promoted as a promising cancer therapy in the 1970s. A controlled clinical trial with 178 cancer patients not only found no benefit but also found that too much laetrile led to blood cyanide levels near a lethal range. Similarly, there was no significant difference in survival between advanced cancer patients taking 10 g/d of vitamin C vs placebo. Likewise, green tea was found ineffective in a phase II trial of men with metastatic prostate cancer.

Finally, shark cartilage, evaluated in patients with advanced breast or colorectal cancer, was not only poorly tolerated (with a dropout rate of 50% within 1 month of entering the study), but produced no survival difference between the treatment group and control group.

Ongoing CAM Trials

Several trials of CAM products are in process, Dr. Loprinzi said. Ginkgo biloba is being evaluated for prevention of cognitive changes associated with chemotherapy for breast cancer. The herb appears to be effective in decreasing progress to dementia in Alzheimer's disease. Accrual is nearly complete. Other ongoing trials with completed accrual include zinc sulfate for radiation-induced taste changes; American ginseng for cancer-related fatigue; and a tomato-based, lycopene-rich product for prostate cancer.

Unique Considerations

Although Dr. Loprinzi sees more similarities than differences between research studies involving CAM products and products from more traditional sources, he reminded the audience that there are unique considerations when using products not regulated by FDA. "When an herbal agent is used, it is important to batch-test the product, using an independent laboratory to verify that the appropriate substances are present in the desired amount, and to look for contaminants, such as heavy metals and pesticides," he said.

He also encouraged CAM researchers to replicate studies that guide clinical practice and to test encouraging results from phase II trials in well-designed phase III studies.

His group is looking down several new avenues for future testing: DHEA for libido complaints; vitamin E for preventing chemotherapy-induced neuropathy; yoga for cancer-related fatigue; and nutritional derivatives for cancer prevention. A complete description of the trials appears in the Journal of the Society for Integrative Oncology (Fall 2006).