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Part 1 of a Series
By Adriane Fugh-Berman, MD
Surveys on unconventional therapies consistent- ly find that these therapies are used most often at two ends of the disease spectrum. The most common use is for chronic, bothersome, non-life-threatening conditions (low back pain, anxiety, headaches). At the other end of the spectrum is its use for life-threatening conditions (including cancer and AIDS) for which conventional medicine may be perceived as insufficient.
This article discusses the prevalence of complementary and alternative medicine use among cancer patients and clinical trials on three alternative cancer therapies: hydrazine sulfate, Livingston-Wheeler therapy, and high-dose vitamin C. Additional therapies and the use of complementary therapies as adjuncts to conventional care will be discussed in a future article.
Prevalence of Use
A telephone survey conducted in 19901 found that 24% of patients with "cancer or tumors" used alternative therapies, making cancer one of the top five reasons for using alternative medicine. However, the recent update of this study did not include information on the use of alternative therapies among cancer patients.2 Most cancer patients using alternative therapies are also receiving conventional treatment. (See Table 1 for use of unconventional therapies by cancer patients in different countries.)
An American Cancer Society telephone survey, which queried 5,000 individuals, found that "questionable" cancer methods were used 9% of the time, with a positive correlation between higher income and higher education and questionable therapy use.3 Interestingly, an article published in 1984 found that 60% of those providing alternative therapies were MDs, PhDs, or both.4 The other 40% were health care professionals. In 35% of cases, the patients’ primary physicians had recommended the treatment method; in 15% of cases the physicians had approved the therapy; in 35% of cases the patients did not tell their primary physicians about the use; and in 2% of cases the therapy was used despite the physicians’ opposition.
What do clinical studies of alternative cancer therapies show? There are not many clinical studies; very few of these studies have used survival as an endpoint, and most are problematic.
One study compared 78 cancer patients who received Livingston-Wheeler therapy (immune-enhancing vaccines, a vegetarian diet, coffee enemas, and injections of the antituberculosis vaccine bCG) with a control group that only received conventional care5 (some Livingston-Wheeler patients also received concurrent conventional therapy). There was no difference in survival between the two groups, and quality-of-life measures were better among the conventionally treated patients.
A controlled, double-blind study compared 60 patients who took 10 g of vitamin C daily with 63 patients who took a placebo.6 There was no difference between the two groups in symptoms, weight, or survival. These were terminal patients with an average survival time of seven weeks. A common criticism of this study is that vitamin C treatment was undertaken too late to do these patients any good.
Hydrazine sulfate, an industrial chemical, is used as an unconventional anti-neoplastic agent and an anti-wasting agent; it is not generally perceived as effective therapy in the United States.
Hydrazine sulfate has Investigational New Drug status in the United States. It may be obtained legally in Canada with a medical prescription from distributors approved by the Health Protection Branch (roughly equivalent to the U.S. FDA) of Health Canada. Neither private nor public insurance in the United States or Canada covers the cost of this treatment.
One positive and two negative controlled trials of lung cancer patients have been conducted. In the positive trial, 65 patients with stage IIIB or IV non-small-cell lung cancer received either hydrazine sulfate or placebo in conjunction with conventional chemotherapy.7 Median survival for patients with an initial performance status of 0 (asymptomatic) or 1 (symptomatic but ambulatory) was significantly higher in the hydrazine sulfate treated group but not in those with an initial performance status > 2 (significant time in bed). Subjects on hydrazine sulfate ate more and their levels of albumin improved.
In 243 patients with unresectable, non-small cell lung cancer randomized to hydrazine sulfate or placebo in combination with cisplatin and etoposide, disease progression was worse in the hydrazine sulfate group.8 There was no significant difference in the groups in terms of median survival time, quality-of-life assessment, weight change, albumin levels, or toxicity.
Two hundred ninety-one patients with IIIB or IV non-small cell lung cancer were randomized to either hy-drazine sulfate or placebo for one month in conjunction with conventional chemotherapy.9 There were no differences in survival, tumor regression, weight gain, or nutritional status between evaluable members of the two groups (dropout rates were >80% in each group).
In a placebo-controlled trial of 128 patients with meta-static colorectal cancer resistant to 5FU, no statistically significant difference was seen in survival, tumor regression, or quality of life.10 (Admission to this trial was prematurely halted when interim analysis showed decreased survival in the hydrazine sulfate treated group.)
Side effects of hydrazine sulfate include anorexia, dizziness, drowsiness, excitation, impaired motor function, nausea, vomiting, numbness of the extremities, peripheral neuritis, pruritus, seizures, and, at high doses, liver damage.
Positive effects on tumor regression or survival have occurred only in small or poorly controlled trials. Controlled trials done in Russia, and a number of uncontrolled trials, show positive results.11 Three of four randomized, controlled trials done in the United States have demonstrated no benefit of hydrazine sulfate as a cancer therapy; only one reported increased survival in end-stage lung cancer patients.
Little clinical trial data are available on alternative cancer therapies. Given the popularity of such treatments, it is vital to do more research in this area.
1. Eisenberg DM, et al. Unconventional medicine in the United States. N Engl J Med 1993;328:246-252.
2. Eisenberg DM, et al. Trends in alternative medicine use in the United States, 1990-1997: Results of a follow-up national survey. JAMA 1998;280:1569-1575.
3. Lerner IJ. The physician and cancer quackery. N Y State J Med 1993;93:96-100.
4. Cassileth BR, et al. Contemporary unorthodox treatments in cancer medicine. A study of patients, treatments, and practitioners. Ann Intern Med 1984;101:105-112.
5. Cassileth BR, et al. Survival and quality of life among patients receiving unproven as compared with conventional cancer therapy. N Engl J Med 1991;324: 1180-1185.
6. Creagan ET, et al. Failure of high-dose vitamin C (ascorbic acid) therapy to benefit patients with advanced cancer. A controlled trial. N Engl J Med 1979;301:687-690.
7. Chlebowski RT, et al. Hydrazine sulfate influence on nutritional status and survival in non-small-cell lung cancer. J Clin Oncol 1990;8:9-15.
8. Loprinzi CL, et al. Placebo-controlled trial of hydrazine sulfate in patients with newly diagnosed non-small-cell lung cancer. J Clin Oncol 1994;12:1126-1129.
9. Kosty MP, et al. Cisplatin, vinblastine, and hydrazine sulfate in advanced, non-small-cell lung cancer: A randomized placebo-controlled, double-blind phase III study of the cancer and leukemia group B. J Clin Oncol 1994;12:1113-1120.
10. Loprinzi CL, et al. Randomized placebo-controlled evaluation of hydrazine sulfate in patients with advanced colorectal cancer. J Clin Oncol 1994;12: 1121-1125.
11. CBCRI Canadian Breast Cancer Research Initiative. Hydrazine Sulphate: An information package. Toronto: CBCRI: 1996. Available from Canadian Breast Cancer Research Initiative, Suite 200, 10 Alcorn Avenue, Toronto, Ontario, Canada M4V 3B1.