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Brief Critical Reviews

Unproven Nutritional Remedies and Cancer

Questionable dietary remedies for cancer decreased quality of life and did nothing to improve cancer outcomes in patients with extensive disease.

April 1992: (1HO6-118

Therapies for general use in cancer treatment must be safe and efficacious. Questionable treatments are those that are not demonstrated to be so. At times, the term unconventional is used to refer to questionable treatments; this is unfortunate, since it implies that the lack of acceptance by conventional medical authorities is related to the treatments being unusual. Similarly, referring to questionable therapies as alternatives is inaccurate, since evidence is lacking that they are adequate substitutes for conventional alternatives. To establish the safety and efficacy of new dietary or other therapies and to determine whether they are likely to benefit patients it is necessary to gather empirical data, using valid, rigorous methods and clinical trials. Patients who are afflicted with diseases that are severe, chronic, have an erratic course, are incurable, and involve considerable morbidity and mortality are especially prone to the use of questionable dietary regimens. The therapists views are influential,2 and the personal characteristics of patients and of the social milieu in which they live also predict the degree of use of such therapies. Recent studies indicate that better-educated patients seek unorthodox cancer cures, perhaps even more frequently than the stereotypical poorly educated lowincome persons that many health professionals assume to be most ~ u l n e r a b l e Patients who suffer .~ from cancers of a type or at a stage for which conventional therapies are ineffective are also especially likely to adopt questionable therapies. Unfortunately, the role of diet in cancer risk reduction and control is poorly understood by health professionals and the public. This confusion has itself led to the proliferation and use of unconvenThis review was prepared by Johanna T. Dwyer, D.Sc, R.D., at the Tufts University Schools of Medicine and Nutrition, USDA Human Nutrition Research Center on Aging at Tufts University, and the Frances Stern Nutrition Center, New England Medical Center, Boston, MA 02111.

tional and questionable nutritional recommendations. Questionable dietary regimens involving more extreme prohibitions, such as vegan-type diets, have also been popularized for cancer prevention. However, there is little evidence that vegetarian diets offer any advantage in risk reduction over the usual recommendations, and some reason to suspect that risks of dietary deficiencies are enhanced, especially when regimens such as macrobiotic diets, which include prohibitions against the use of vitamin-mineral supplements, are employed. Many questionable dietary therapies target cancer patients who are already ill. The proponents of these regimens recommend their use for many types and during all stages of the disease. Many of these therapies, including a number of dietary remedies, fail to meet usual medical criteria of efficacy and safety.M The major categories of questionable nutritionally oriented cancer treatments are well summarized in a new publication of the American Cancer Society. They include proprietary formulations and drugs that the proponents claim act as nutrients once they enter the body, such as hydrogen peroxide or laetrile, which are sold with the claim that they are foods rather than drugs. Food supplements consisting of vitamins, minerals, or various extracts of herbs, animal glands, or other foods are also common. Specific dietary regimens, include macrobiotic diets, wheatgrass supplements and enemas, and the Gerson therapy, which consists of a restrictive diet and coffee enemas, among other manipulations. Finally there are holistic and metabolic therapies of various sorts, which usually include a restricted diet, food supplements, proprietary drugs, and often other therapies as well. Questionable supplements for curing cancer have included, in the 1970s, vitamin B-17, laetrile, and related compounds, in the 1980s, megadoses of vitamin C and, in addition, vitamin A, many other vitamins, and selenium. There is little evidence that any of these therapies is curative in itself.% The macrobiotic diet as a cancer therapy was popularized by the book Recalled To The macrobiotic dietary regimen, while it has some elements that are similar to the recommendations of the American Cancer Society and the National Academy of Sciences for cancer prevention, is inappropriate for many patients with disseminated or metastatic cancers, particularly those
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of the head, neck, and gut, since the diet is high in bulk, low in several essential nutrients such as vitamins D, B,,, iron, and calcium, and relatively low in ca~ories.~ The Gerson therapy, a holistic regimen consisting of a vegetarian diet, and other elements, including supplements such as liver extracts, was recently reviewed by an expert group, and found to be ineffective. Other questionable nutritional therapies include the Hoxsey treatment, an herb-and-diet based regimen that has existed in one form or another since the 1920s. The diet excludes several processed foods, all carbonated beverages, and spicy foods, and stresses iron, calcium, vitamin C, yeast supplements, and grape juice along with herbally based medications that vary depending on the location of the cancer. Several reviews of the Hoxsey diet have been conducted by expert groups, including the National Cancer Institute and the American Cancer Society. They have concluded that the treatment, which costs thousands of dollars, is no more effective than no treatment at all. l 6 Thus there is no acceptable evidence that these therapies are efficacious by themselves. But there are few solid data on the effects of such special diets used in conjunction with conventional therapies, particularly at the later stages of cancer progression. Even if the questionable therapies do no good, some practitioners argue that they may have potent placebo effects which might help to improve patients psychological outlooks and quality of life. Dietary remedies are known to have strong placebo effects. l7 Abundant anecdotal evidence and convincing testimonials about their supposed efficacy are readily available, sometimes from caregivers. Patients are actively involved in treatment, the dietary treatment involves intimate contact, the use of dietary measures is currently culturally acceptable, and adherence to the diet engenders a sense of personal control in some patients. They often receive positive reinforcement from those they love or respect for fighting the disease with dietary measures. Also, individuals who choose dietary remedies may be more suggestible than those who do not. The lack of evidence on the efficacy of questionable dietary therapies derived from clinical trials of acceptable quality has made it difficult to definitively refute proponents claims that these treatments improve the quality of life and survival. A recent study of a well-known questionable cancer therapy which includes diet is therefore of great interest not only because of the findings, but also because it illustrates the difficulty of conducting such studies in a rigorous manner. The clinic chosen was an appropriate venue for such a study. It uses an unproven cancer therapy that involves an
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autogenous, immune enhancing vaccine of uncertain efficacy, made from bacille Calmete-Guerin, and combined with a vegetarian diet and coffee enemas. This prospective study compared terminally ill cancer patients receiving standard care at an academic center of excellence in cancer treatment to 78 similar patients who received standard medical care plus unconventional treatments at the clinic. The first hypothesis was that survival time would be similar in the two groups, since treatment in the end stages of these forms of cancer is unlikely to extend life regardless of what it is. A second hypothesis was that the clinic patients quality of life would be superior to that of the patients receiving conventional care: that patient involvement in self-care and the absence of toxicity associated with conventional chemotherapy might give the unconventional treatment an edge in terms of patient wellbeing. All of the patients had well-documented, extensive malignant disease which was severe enough to have a prognosis of a median survival time of not more than one year. The diagnoses included advanced, unresectable colorectal cancer, metastatic lung cancer, pancreatic cancer, and disseminated melanoma. As is the case in many studies of questionable therapies for cancer, the patients opting for them were relatively well educated, as were those in the academic cancer center comparison group to which they were Patients meeting study criteria who received treatment at the clinic were recruited with the cooperation of the clinic director. They were matched by age, sex, race, diagnosis, and time from diagnosis to metastatic or recurrent disease with patients who received only conventional treatments at a teaching hospitals cancer center. Patient charts were reviewed to verify the tissue biopsy evidence of diagnosis. The need to match on so many variables and the extended period of observation meant that over three years were devoted to recruitment alone. All the patients had very extensive disease. All were followed every two months until their demise. Outcomes of particular interest were quality of life and survival time. To measure quality of life in a way that is meaningful for patients many different domains of illness experience must be measured. Thus several indices were used. First was a performance status checklist that had been used in other studies. At enrollment and at approximately two-month intervals thereafter a 22-item self-report, the Functional Living Index-Cancer, was used. This is a scale that addresses functional issues.20 It provides a single quality of life score based on indices of perceived physical well-being, psychological state, sociability, effect on family members, and nausea. Follow107

up was done by phone and the same index was administered by phone. At the same time, a detailed list of treatments of both a conventional and an unorthodox sort was provided and patients reported the various autogenous vaccines, vitamins, minerals, enemas, special diets, and other unconventional and conventional remedies they employed. In addition, information on the side effects of all treatments, including nausea, vomiting, diarrhea, constipation, appetite, weight changes, performance status, pain, dyspnea, cough, and comorbidity were obtained. At enrollment, 91% of the patients treated at the clinic and 96% treated in the academic center were ambulatory. At the last telephone interview before death, 68% of the clinic and 75% of the academiccenter patients were still ambulatory. The hypothesis that quality of life would be better among the group of patients treated in the clinic was refuted. Quality-of-life scores were consistently better among the conventionally treated patients at the academic center, and these differences were apparent from enrollment onward. Quality of life deteriorated at an equal rate in the two groups, and differences over time were significant. Both groups reported adverse effects of the disease on quality of life, regardless of whether they experienced chemotherapy or not. Both groups had appetite problems: 79% among the clinic patients and 71% among the academic-center patients who were on chemotherapy, and 76% of the clinic patients and 52% among the academic-center patients with no chemotherapy. Quality of life was significantly and inversely related to appetite difficulties and pain among the clinic patients, and to nausea and pain in the academic-center patients. Both groups experienced many adverse effects. The patients at the clinic who underwent its therapy experienced appetite problems to a greater extent than controls, although both groups were anorectic. Pain and breathing difficulties were also more common among the patients who had opted for questionable over conventional therapy. Comparisons with a notreatment option other than palliative care could not be made, since such a group was not included in the study. The hypothesis that there would be no differences in survival time was confirmed in survival curves using three different statistical models that weighted observations differently in the analysis. Women lived slightly longer than men, 17 vs. 14 months, and these differences were significant. No differences were evident in survival times when patients were stratified by receipt of chemotherapy vs. radiotherapy or combinations of these. Those who had surgery lived slightly longer than those who did not. Survival time did not differ between

the patients treated at the clinic with questionable therapies and those who received only conventional therapies in the academic-center clinic. Median survival was 15 months, with a relative risk of 1.23, and a 95% confidence interval of 0.88 to 1.72. To rule out the possibility that differences in performance status prior to treatment were the cause of the finding of no difference, patient pairs that differed greatly in their initial performance status were excluded from the analyses. Nevertheless, differences between the patients seen at the clinic and the academic center were not significant. This study had several flaws, to which the investigators readily admit. By its very nature, random assignment of patients to treatments was not possible. This raises the issue of a self-selection bias. For example, poor quality of life may have pushed a person to seek treatment with the questionable therapy, or perhaps patients seeking such treatment had higher and unrealizable expectations. Possible interviewer biases were probably ruled out by interviewer training and standardization of interviews. Because of the design, comparisons with a palliative-care-only option could not be made. Finally, the questionable therapy that was evaluated was only one of many possible options, and the patients were only those with extensive and incurable disease. Nevertheless, both the proponents and the foes of questionable methods will study these findings with profit. Treatment and its side effects did not determine quality of life in these patients: treatment was only one influence in the larger array of variables. However, this particular questionable therapy did not improve quality of life, and thus in and of itself it could not be justified on these grounds, or on the basis of improvements in survival. What lessons can be learned from this study? A caring attitude on the health professionals part, encompassing concerns and communication not only about purely medical matters but also about the patients human dilemmas and problems, is critical. Anticipatory guidance from the time of diagnosis onward is helpful; patients who have become convinced that unorthodox methods are efficacious may abandon conventional treatment. Strategies for helping cancer patients deal with questionable remedies have recently been summarized.21*22 The newly updated preventively oriented cancer risk reduction guidelines of the American Cancer Society (ACS)23 provide useful principles, all of which are consistent with the Dietary Guidelines for Americans24and the Diet and Health Report of the National Academy of Sciences, for individuals seeking guidance about ways to eat to minimize cancer risks. The documents emphasize these dicta: maintain desirable weight; eat a varied diet; include
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a variety of both vegetables and fruits daily; eat more high-fiber foods, such as whole-grain cereals, legumes, vegetables, and fruits; cut total fat intake; limit consumption of salt-cured, smoked, and nitrite-preserved foods, and alcohol, if a person drinks. Areas regarded as still under study and for which no specific quantitative recommendations were made include intakes of food additives, artificial sweeteners, coffee, cholesterol, cooking at high temperatures, and taking supplements of vitamins E or selenium larger than those suggested in the Recommended Dietary Allowances.26 More quantitative goals have recently been suggested as well; these are an amalgam of the ACS guidelines and recommendations to reduce chronic disease risk from the Committee on Diet and Health of the National Academy of Sciences. For example, they suggest cutting dietary fat to less than 25-30% of total calories, and eating five or more servings of fruits and vegetables and six or more servings of grains and legumes daily. All of the above-cited reports sensibly suggest moderation, rather than avoidance, of any food or food group, and consideration of diet in the context of overall cancer-risk reduction. For symptomatic cancer patients, nutritional support of curative therapies provided by welltrained oncologists offers the best hope.28
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9. Wittes RE. Vitamin C and cancer. N Engl J Med 1985;312:17&9 10. Committee on the Health Education of the Public, California Medical Association, Sampson W et al. The professionals guide to health and nutrition fraud. San Francisco, CA: California Medical Association, 1987 11. Moertel CG, Fleming TR, Rubin J, et al. A clinical trial of amygdalin (Laetrile) in the treatment of human cancer. New Engl J Med 1982;306:201-6 12. Sattilaro AJ, Monte T. Recalled by Life. New York: Avon, 1984 13. Raso J. A Kushi seminar for professionals. Nutrition Forum 1990;7:17-21 14. Dwyer J. The macrobiotic diet: no cancer cure. Nutrition Forum 1990;7:%11 15. American Cancer Society. Unproven methods of cancer management: Gerson method. CA 1990; 40 :252-6 16. American Cancer Society. Unproven methods of cancer management: Hoxsey method/Bio-medical center. CA 1990;40:51-5 17. Dwyer JT, Bye RL, Holt PL, Lauze SR. Unproven nutrition therapies for AIDS: what is the evidence? Nutr Today 1988;23:25-33 18. Cassileth BR, Lusk EJ, Guerry D, et al. Survival and quality of life among patients receiving unproven as compared with conventional cancer therapy. N Engl J Med 1991;324:1180-5 19. Cassileth BR. Unorthodox cancer medicine. Cancer Invest 1986;4:591-8 20. Schipper H, Clinch J, Mc Murray A, Levitt M. Measuring the quality of life in cancer patients: the Functional Living Index-cancer: development and validation. J Clin Oncol 1984;2:472-83 21. American Cancer Society Questionable Methods of Cancer Management. American Cancer Society, Atlanta, Georgia, 1991 22. Durant J. If it quacks.. . . Cancer 1991;67:2225-6 23. Work Study Group on Diet, Nutrition, and Cancer. American Cancer Society Guidelines on Diet, Nutrition, and Cancer. CA 1991;41:334-8 24. US Department of Agriculture and U.S. Department of Health and Human Services. Dietary Guidelines for Americans, 3rd ed. Washington D.C.: US. Government Printing Office, 1990 25. Committee on Diet and Health, Diet and Health: Recommendations to Reduce Chronic Disease Risk. Washington DC: National Academy Press, 1989 26. Subcommittee on the Tenth Edition of the RDAs. Recommended Dietary Allowances, Tenth Edition. Washington DC: National Academy Press, 1989 27. Bal DG, Foerster SB. Changing the American diet: impact on cancer prevention policy-recommendations and program implications for the American Cancer Society. Cancer 1991;67:267180 28. De Vita VT, Hellman S, Rosenberg SA, eds. Cancer: Principles and Practice of Oncology, 3rd ed. Philadelphia, PA: JB Lippincott, 1989
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