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The Journal of Orthomolecular Medicine Vol. 12, 4th Quarter 1997

Nutritional and Lifestyle Modification toAugment Oncology Care: An Overview

- Charles B. Simone, M.D.;1 Nicole L. Simone, B.S.E.;1 Charles B. Simone, II

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Introduction

By the year 2000, cancer will emerge as the number one cause of death in the United States. Despite the enormous ef-fort to combat cancer, the number of new cases of nearly every form of cancer has increased annually over the last century. Still worse, from 1930 to the present, de-spite the introduction of radiation therapy, chemotherapy, and immunotherapy with biological response modifiers, despite CT scans, MR scans, and all the other new medical technology – lifespans for almost every form of adult cancer except cervical cancer and lung cancer have remained con-stant, which means that there has been no significant progress in cancer treatment. The successes in the treatment of cancer plateaued in the 1970s, and no real ad-vances have been made since then. Chemo-therapy and radiation therapy continue to have a role in cancer treatment but produce morbidity. Nutritional modification, in-cluding the use of certain nutrients, and proper lifestyle can dramatically decrease the morbidity and side effects of chemo-therapy and radiation therapy. There have even been some reports that nutritional and lifestyle modification actually increase survival. Numerous studies show that nu-trients used with chemotherapy and radia-tion therapy can enhance tumor killing and preserve normal tissue.

Vitamins and Minerals Used With Chemotherapy and Radiation Therapy

Do vitamins or minerals interfere with chemotherapy and/or radiation therapy? This is a question I am asked frequently by patients because they have been advised not to take supplements during treatment.

1. Simone Protective Cancer Center, 123 Franklin Corner Road, Lawrenceville, NJ 08648

Many studies have been done to address this. The early clinical studies were per-formed at the National Cancer Institute using an antioxidant called N-acetyl cysteine which was found to protect the heart from the cardiac toxicty of adria-mycin, but did not interfere with the tumor-killing capability of adriamycin.

A series of studies ensued to investigate the protective effects of antioxidants used concomitantly with adriamycin. An antioxi-dant called dexrasonane (formerly called ICRF-187) offered significant protection against cardiac toxicity caused by adriamycin without affecting the antitumor effect.1-6 Cellular studies,7-10 animal studies,11-21 and human studies22,23 demonstrate that vita-mins A, E, and C, as well as beta-carotene and selenium, as single agents or in com-bination, all protect against the toxicity of adriamycin and, at the same time, actually enhance its cancer-killing effects.

Animal Studies

Vitamins and minerals have also been studied with other chemotherapies and radiation. Studies using beta-carotene and other retinoids, vitamin C, or vitamin K show that normal tissue tolerance was improved in animals undergoing both chemotherapy and radiotherapy and that tumors regressed.24-33Vitamin E produced similar findings: Tumors in animals showed regression when either radiation or chemo-therapy was used concomitantly with vita-min E.17-21,34-41 Animals given both beta-caro-tene and vitamin A with radiation and chemotherapy had more tumor killing than with chemotherapy and radiation alone, normal tissues were more protected, and there was a longer period of time without tumor recurrence.42,43 Selenium and cysteine also heighten tumor killing by chemotherapy and radiation, and at the same time protect normal tissue.44,45

Cellular Studies

All cellular studies using vitamins (C, A, K, E, D, B6, B12), beta-carotene, minerals (selenium), or cysteine as single agents or in combination given concomitantly with chemotherapy, or tamoxifen, or interferon alpha-2b, or radiation, or combinations of these modalities show the same effect: in-creased tumor killing and increased protec-tion of the normal tissues.46-65

Human Studies

In human studies, vitamin E reduced the toxicity without affecting the cancer-killing performance of 13-cis-retinoic acid, used in the treatment of patients with head and neck, skin, and lung cancers.66 Vitamin E also reduced the toxicity of adriamycin and did not interfere with the cancer kill-ing ability of adriamycin.22,23,67 At 1,600 IU of vitamin E per day, hair loss in patients re-ceiving chemotherapy was reduced from the expected 30-90%.68 Treating 190 head and neck cancer patients with vitamin A, 5FU, and radiation resulted in more-than-ex-pected tumor killing while preserving nor-mal tissue.69 Vitamin A combined with chemotherapy for postmenopausal patients with metastatic breast cancers significantly increased the complete response rate.70 In thirteen patients with different cancers re-ceiving 42 different chemotherapies, vita-min K decreased tumor resistance.71 Vitamin B6 at 300 milligrams per day decreased radiation therapy toxicity.72 In twenty pa-tients receiving chemotherapy with vita-mins A, C, and E, there was a greater re-sponse rate.73 Glutathione, part of the sele-nium complex, protected 150 women with ovarian cancer against cisplatin toxicity with no loss of anticancer effects as shown in double-blind studies at nine British on-cology centers. In fact, more women treated with glutathione had an objective response (73% vs. 62%) and completed more cycles of cisplatin (58% vs. 39%) than those who were not so treated.74 Studies show that amifostine (WR-2721), an antioxidant, pro-tects against the harmful side effects of chemotherapy and radiation without the loss of antitumor activity.75-86

An increase in survival for cancer pa-tients, which is uncommon with any treat-ment, has been shown using antioxidants combined with chemotherapy or radiation. In fact, eleven patients who were given beta-carotene and anthaxanthin while un-dergoing surgery, chemotherapy and radia-tion lived longer with an increase in dis-ease-free intervals.87 Antioxidant treatment with chemotherapy and radiation pro-longed survival for patients with small cell lung cancer compared with patients who did not receive antioxidants.87,88

The effects of one chemotherapeutic agent, methotrexate, can be reversed with folinic acid, which is an analog of the vita-min folic acid. Folic acid itself does not re-verse methotrexate’s effects.89,90 In order to reverse the effects of methotrexate, folinic acid must be prescribed in high doses.

Studies of supplements all show that vitamins and minerals do not interfere with the antitumor effects of chemotherapy or radiation therapy. In fact, on the contrary, some vitamins and minerals used in con-junction with chemotherapy and/or radia-tion therapy have been shown to potentiate the destruction of cancer cells and also protect normal tissue.

Lifestyle modification to augment oncology care

Using Quality of Life Scales, fifty pa-tients with early staged breast cancer evalu-ated treatment side effects of radiation and/or chemotherapy while taking thera-peutic doses of nutrients.91,92 Quality of Life Scales are an acceptable way of evaluating any treatment or side effect not by the phy-sician, but rather by the patient. The pa-tient decides whether the treatment is ben-eficial or not in terms of side effects in-curred. These scales have been successfully used to evaluate treatments for cardiovas-cular disease, cancer, and other chronic ill-nesses.93-102

The scoring system for the Quality of Life Scales is simple. The patient decides if the nutrients used during the radiation and/ or chemotherapy treatments has improved, worsened, or has made no change in her life during the treatment period. The qualities of life tested were: physical symptoms, per-formance, general well being, cognitive abili-ties, sexual dysfunction, and life satisfaction. Fifty consecutive patients with early staged infiltrating ductal adenocarcinoma of the breast were treated with lumpectomy (re-excisional lumpectomy if indicated), axil-lary node dissection, and radiation therapy. Depending upon the nodal status, chemo-therapy was used. In Group I, twenty-five women with T1 or T2, N0, M0 were treated with primary radiation therapy, receiving 4500 cCy to the whole breast, and a total dose of 6000 cGy to the tumor bed. In Group II, twenty-five patients with T1 or T2, N1, MO were treated with primary ra-diation therapy to the same doses as with Group I and also received modified CMF chemotherapy consisting of cytoxan and 5-FU (methotrexate was omitted until radia-tion was completed). A total of six cycles of this modified regimen was given. Each pa-tient was instructed to follow the pertinent aspects of the Simone Ten-Point Plan as an adjunct to treatment. These points are:

1. Nutrition. Maintain an ideal weight—lose even five or seven pounds if needed. Low-fat (about 20 percent of calories), high-fiber (25 gm) diet. Eliminate salt, food additives, and caffeine. Nutrients taken 30 to 60 min-utes before oncological therapy: beta-carotene 30 mg vitamin A 5000 IU vitamin D 400 IU vitamin E 400 IU vitamin C 350 mg folic acid 400 mcg vitamin B1 10 mg vitamin B2 10 mg niacinamide 40 mg vitamin B6 10 mg vitamin B12 18 mcg biotin 150 mcg pantothenic acid 20 mg iodine 150 mcg copper 3 mg zinc 15 mg potassium 30 mg selenium (organic) 200 mcg chromium (organic) 125 mcg manganese 2.5 mg molybdenum 50 mcg inositol 10 mg L-cysteine 20 mg

In addition, the women took the fol-lowing at bedtime: calcium carbonate 1000 mg magnesium 280 mg potassium bicarbonate 100 mg boron 2 mg l-lysine 2 mg l-threonine 2 mg silicon 2 mg.

  1. Tobacco. Do not smoke, chew, snuff, or inhale other’s smoke.

  2. Alcohol. Avoid all alcohol.

  3. Radiation. Avoid unnecessary x-rays; sunscreens to be used. Avoid electromag-netic fields.

  4. Environment. Keep air, water, and work place clean.

  5. Hormones, Drugs. Avoid all estrogens and unnecessary drugs.

  6. Know the seven warning signs of can-cer: lump in breast; non-healing sore; change in wart/mole; change in bowel or bladder habits; persistant cough or hoarse-ness; indigestion or trouble swallowing; unusual bleeding.

  7. Exercise

  8. Stress modification, spirituality, and sexuality.

  9. Have executive physical annually.

Table 1 (p.200) presents the responses of the fifty patients. Most patients indicated improvement, a few indicated no change,

Table 1. Patient responses to Qualities of Life.

GROUP I* GROUP II*
Number Number
Life Quality Improve Change Worsen Improve Change Worsen
Physical symptoms† 25 24 1
Performance 23 2 23 2
General well-being 25 25
Cognitive abilities 25 22 3
Sexual dysfunction 25 15 10
Life satisfaction 25 25

* Group I patients had radiation only; Group II had radiation and chemotherapy.

† skin reaction; fatigue; mouth sores; nausea/vomiting; dizziness; vertigo; lightheadedness; muscle cramps

and none indicated worsening. This study demonstrates that patients who followed the Ten-Point Plan and used certain vitamins and minerals had few side effects from chemotherapy and radiation therapy.

The Hoffer-Pauling Study

Researchers Hoffer and Pauling asked whether therapeutic nutrition helped cancer patients.103 All 129 cancer patients in their study were to follow a low-fat diet supple-mented with therapeutic doses of vitamins C, E, A, niacin, and a multiple vitamin/min-eral supplement, in addition to following the advice and treatment of traditional oncology care. Those who did not follow nutritional modification (31 patients) lived an average of six months less. The other 98 patients fell into three categories: 32 patients with breast, ovar-ian, cervix, and uterus cancer had an average life span of over 10 years; 47 patients who had leukemia, lung, liver, and pancreas cancer had an average life span of over six years; and 19 patients with end-stage terminal cancer lived an average of 10 months.

Other Clinical Studies

Patients who undergo conventional oncology therapy generally live longer and/ or have a lower recurrence rate if they modify their lifestyle, which includes diet changes, nutrient supplementation, and other lifestyle changes.104-109

The effect of vegetable consumption was examined over a period of six years in 675 patients with lung cancer. Those who lived longer ate more vegetables.104 In an-other study, 200 patients who made signifi-cant dietary changes, experienced regres-sion of their cancers without conventional treatment: 87 percent changed their diet dramatically to mainly vegetables, fruits, and whole grains; 65 percent consumed nutrient supplements; and 55 percent used a detoxification method.105

The effect of eating a macrobiotic diet on survival was studied in 1490 patients with pancreas cancer and 18 patients with prostate cancer.106 Twenty-three matched patients with pancreas cancer changed to a macrobiotic diet and 12 (52%) were alive after one year; 1467 continued their high-fat, low-fiber diet and of these, 146 (10%) were alive after one year. Similarly, nine patients with prostate cancer who ate a macrobiotic diet were matched to nine patients with prostate cancer who ate their “normal” high-fat diet. Those eating the macrobiotic diet lived longer (median sur-vival 228 months) than those who did not (median survival 45 months).

Tumor recurrence rate was decreased by 50 percent in patients with transitional cell bladder cancer who took higher than Recommended Dietary Intake (RDI) doses of certain vitamins compared to matched controls taking RDI doses.108 Sixty-five matched patients were randomized into two groups. The first group took a vitamin supplement providing the RDI doses, and the second group took that plus 40,000 IU vitamin A, 100 mg vitamin B6, 2000 mg vi-tamin C, 400 IU vitamin E, and 90 mg zinc. Tumor recurrence at 10 months was 80 percent in the first group (RDI supplement only) and 40 percent in the second group (RDI supplement plus the extra higher doses). The projected recurrence rate at 5 years was 91 percent for the controls and 41 percent for the second group taking the higher doses.

And finally, an increased survival was demonstrated for patients with small cell lung cancer who received antioxidants con-comitantly with chemotherapy and radia-tion therapy compared to matched controls who did not receive the antioxidants.109

It has also been found that patients who undergo chemotherapy develop lower serum levels of antioxidant vitamins and minerals.110,111 The decreased levels of these antioxidants result from lipid peroxidation.

Japanese Experience

The older generation of Japanese women rarely get breast cancer, but when these women do, they live longer than American women, stage for stage,112-119 because of only two reasons: (1) they are less obese, and (2) they eat a low-fat, high-fiber diet with vitamins and minerals. This is not necessarily true for younger Japanese women who have now adopted a more Western culture and diet.115

Obese breast cancer patients have a greater chance of early recurrence and a shorter life span compared to non-obese patients.120-124 And breast cancer patients who have a high-fat intake and an high serum cholesterol also have a shorter life span than patients with normal or low-fat intake and low serum cholesterol.125 Fat can initiate and also promote a cancer, espe-cially a dietary cancer like breast cancer. If cholesterol intake is dramatically limited, cancer cell growth is severely inhibited.126

U.S. National Cancer Institute Effort

Armed with this information, the US National Cancer Institute, National Insti-tutes of Health in Bethesda, Maryland con-ducted a research protocol in the mid 1980s to see if a low-fat diet would increase the life span of breast cancer patients. However, in January 1988, after only a brief time and an expenditure of about $90 million, the Board of Scientific Counselors of NCI’s Division of Cancer Prevention and Control decided to end the proposed ten year study because: (1) physicians did not “believe” that there was a relationship between breast cancer and fat or other nutritional factors and, subsequently, did not refer patients to the study; and (2) once a woman was enrolled in the protocol, she subse-quently “failed out” because she did not want to give up pizza, ice cream, and other high-fat foods. In 1991, NCI decided to try, in the near future, another low-fat cancer study in women aged 45 and 69.

Conclusion

Many of the nutrients used in the above studies are antioxidants. Antioxi-dants neutralize free radicals. Most cancer modalities exert their cancer killing effects by generating free radicals. Therefore it would seem inconsistent that these nutri-ents can help the cancer patient. However, in vitro and in vivo studies, including many clinical studies have repeatedly shown that certain vitamins and minerals can enhance the killing capabilities of cancer therapeu-tic modalities while at the same time can protect normal tissues and decrease side effects from these modalities.

Cancer cells accumulate excessive amounts of antioxidants due to a loss of the homeostasis control mechanism for the up-take of these nutrients. Normal cells do not have this membrane defect and do not accu-mulate large amounts of antioxidants. It has been postulated127 that the accumulation of excessive nutrients in cancer cells can:

  1. Shut down the oxidative reactions nec-essary for generating energy.

  2. Inhibit protein kinase C activity128 = which normally increases cell division and increases cell proliferation.

  3. Inhibit oncogene expression.129,130

  4. Increase the amount of growth inhibi-tory growth factors.131

With higher levels of cancer intracel-lular accumulation of nutrients, more of these cellular alterations occur. These changes can lead to a higher rate of cancer cell death, and a reduction in the rate of cell proliferation and induction of differ-entiation. These acquired changes of can-cer cells due to high doses of nutrients ac-tually override any protective action that antioxidants have against free radical dam-age on cancer cells.

Cancer patients should alter their life-styles (Ten Point Plan), which includes modifying nutritional factors and taking certain vitamins and minerals in doses outlined, especially if they receive chemo-therapy and/or radiation.

References

  1. Speyer J, Green MD, Kramer E, Rey M, Sanger J, et al: Protective effect of ICRF-187 against doxorubicin induced cardiac toxicity in women with breast cancer. NEJM, 1988; 319: 745-752.

  2. Filippi and Enck: A review of ADR-529: A new cardioprotective agent. Clin Oncol, 1990: 16-18.

  3. Speyer, J, Green MD, Zeleniuh-Jacquotte A, Wernz JC, Rey M, Sanger J, et al: Cumulative dose-related doxorubicin cardiotoxicity can be prevented by ICRF-187. Cancer Invest, 1992: 10(1): 26-34.

  4. Speyer J, Green MD, Zeleniuh-Jacquotte A, et al: ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J Clin Oncol, 1992; 10: 117-127.

  1. Rhomberg W, Eiter H, Hergen K, et al: Inoper-able recurrent rectal cancer: Results of a pro-spective trial with radiation therapy and dexrazoxane. Int J Radiat Oncol Biol Phys. 1994; 30(2): 419-425.

  2. Carlson, R: Reducing the cardiotoxicity of the anthracyclincs. Oncology, 1992; 6(6) 95,108.

  3. Taper H, Roberfroid M, Janssens J, Bonte J, DeLoecker : Potentiation of chemotherapy in vivo in an ascitic mouse liver tumor, and growth inhi-bition in vitro in 3 lines of human tumors by com-bined vitamin C and K3 treatment. European As-sociation for Cancer Research Tenth Biennial Meeting R. Galway, Ireland. Sept 1989; 72.

  4. Shimpo, Nagatsu T, Yamada K, Sato T, Niimi H, et al: Ascorbic acid and adriamycin toxicity. Am J Clin Nutr, 1991; 54:1298S-1301S.

  5. Ripoll, EAP, Rama BN, Webber MM. Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro. J Urol, 1986; 136(2): 529-531.

  6. Pieters R, Huismans DR, Loonen AH, Hahlen K, Veerman AJ: Cytotoxic effects of vitamin A in combination with vincristine, daunorubicin and 6-thioguanine upon cells from lymphob-lastic leukemic patients. Jap J Cancer Res, 1991; 82(9): 1051-1055.

  7. Van Vleet, JF, Greenwood L, Ferands VJ, Rebar AH: Effect of selenium and vitamin E on adriamycin-induced cardiomyopathy in rab-bits. Am J Vit Res, 1980; 39:997-1010.

  8. Singal PK, Tong JG: Vitamin E deficiency accen-tuates adriamycin-induced cardiomyopathy and cell surface changes. Mol Cell Biochem, 1988; 84(2):163-171.

  9. Wang YM, Madanat FF, Kimball JC, Gleiser CA, Ali MK, et al: Effect of vitamin E against adriamycin-induced toxicity in rabbits. Cancer Res, 1980; 40: 1022-1027.

  10. Milei J, Boveris A, Llesuy S, Molina HA, Storino R, Ortega D, Milei SE: Amelioration of adriamycin-induced cardiotoxicity in rabbits by prenylamine and vitamins E and A. Am Heart J, 1986; 111: 95-102.

  11. Svingen, B., et al: Protection against adria-mycin-induced skin necrosis in the rat by dime-thyl sulfoxide and alpha-tocopherol. Cancer Res,1981; 41: 3395-3399.

  12. Fujita, K, Shinpo K, Sato T, Niime H, Shamoto M, et al: Reduction of adriamycin toxicity by ascorbate in mice and guinea pigs. Cancer Res, 1982; 42: 309-316.

  13. Sonnevald P: Effect of alpha-tocopherol on cardiotoxicity of adriamycin in the rat. Cancer Treat Rep, 1976; 62: 961-962.

  14. VanVleet JF, Greenwood L, Ferands VJ, Rebar AH. Effect of selenium-vitamin E on

adriamycin-induced cardiomyopathy in rab-bits. Am J Vit Res, 1978; 39:997-1010.

  1. Wang YM, Madanat FF, Kimball JC, Geiser CA, Ali MK, et al: Effect of vitamin E against adriamycin-induced toxicity in rabbits. Can-cer Res, 1980; 40:1022-1027.

  2. Svingen B, Powis A, Abbel PL, Scott M: Protec-tion against adriamycin-induced skin necrosis in the rat by dimethyl sulfoxide and alpha-toco-pherol. Cancer Res, 1981; 41: 3395-3399.

  3. Geetha A, Sankar R, Marar T, Devi CSS: Alpha to-copherol reduces doxorubicin-induced toxicity in rats – histological and biochemical evidences. Indian Physiol Pharmacol, 1990; 34: 94-98.

  4. Myers CE, McGuire W, Young R: Adriamycin amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep, 1976; 60: 961-962.

  5. Myers CE, McQuire WP Liss PH, Ifrim I: Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science 1977; 197: 165-167.

24.Mills EE: Retinoids and cancer. Soc R Radiotherap and Congress May 13, 1982.

  1. Okunieff, P: Interactions between ascorbic acid and the radiationof bone marrow, skin, and tumor. Am J Clin Nutr, 1991; 54:1281-1283S.

  2. Meadows G, Pierson HF, Abdallah RM: Ascor-bate in the treatment of experimental trans-planted melanoma. Am J Clin Nutr, 1991; 54: 1284S-1291S.

  3. Taper HS, Roberfroid M, Bonte J, et al. Non-toxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer, 1987; 40: 575-579.

  4. Crary EJ, McCarty MF: Potential clinical appli-cations for high-dose nutritional antioxidants. Medical Hypothesis, 1984; 13(1): 77-98.

  5. Sprince H, Parker CM, Smith GG. Comparison of protection by L-ascorbic acid, L-cysteine, and adrenergic-blocking agents against acetal-dehyde, acrolein, and formaldehyde toxicity: implications in smoking. Agents Actions 1979; 9(4):407-414.

  6. Poydock, E. Am J Clin Nutr, 1984; 12: 813-817.

  7. Seifter E, Rettura A, Padawar J, et al: Vitamin A and beta-carotene as adjunctive therapy to tumor excision, radiation therapy and chemo-therapy. In: eds. Prasad KN: Vitamins, Nutrition and Cancer. Karger, Basel. 1984: 1-19.

  8. Trizna Z, Shantz SP, Lee JJ, Spitz MR, Goepfert H, et al: In vitro protective effect of chemo-pro-tective agents against bleomycin-induced genotoxicity in lymphoblastoid cell lines and pe-ripheral lymphocytes of head and neck cancer patients. Cancer Detect Prev, 1993; 17: 575-583.

  9. Sram RJ, Dobias L, Pastorkova A, et al. Effect of ascorbic acid prophylaxis on the frequency

of chromosome aberrations in the peripheral lymphocytes of coal-tar workers. Mutation Res, 1983; 120: 181-186.

  1. Sugiyama M, Lin X, Costa M: Protective effect of vitamin E against chromosomal aberration and mutation induced by sodium chromate in Chinese hamster V79 cells. Mutation Res, 1991; 260: 19-23.

  2. Holm G, Ferrogan AB, Kagerund A: Tocophe-rol in tumor irradiation and chemotherapy— experimental studies in the rat. Feb 12 Linderstrom-Lang Conference. Selenium, Vi-tamin E and Glutathioperoxidase. Icelandic Biochemical Society, June 25, 1982; p. 118.

  3. Kagerud, A, Peterson HI: Effect of tocopherol in irradiation of artificially hypoxic rat tumours. Sec-ond Rome International Symposium: Biological Bases and Clinical Implications. Sept. 21, 1980; 3-9.

  4. Kagerud A, Peterson HI: Tocopherol in tumour irradiation. Anticancer Res, 1981; 1: 35-38.

  5. Yamanaka N, Fukishima M, Koizumi K, Nishida K, Kato T, et al: Enhancement of DNA chain break-age by bleomycin and biological free radical pro-ducing systems. In: eds. DeDuve C, Hayashi T, Tocopherol, Oxygen and Biomembranes. New York. North Holland. 1978 59-69.

  6. Srinivasan V, Jacobs AL, Simpson SA, Weiss JF: Radioprotection by vitamin E effect on hepatic enzymes, delayed type hypersensitivity and post-irradiation survival in mice. In: In eds. Meyskens FL Jr, Prasad KN Modulations and Mediations of Cancer Cells by Vitamins. Karger, Basel. 1983. 119-131.

  7. Malick MA, Roy RM, Sternberg J: Effect of vita-min E on post irradiation death in mice. Experientia. 1978; 34: 1216-1217.

  8. Londer HM, Myers CE: Radioprotective effects of vitamin E. Am J Clin Nutr, 1978; 31: 705a.

  9. Shen RN, Mendecki J, Friedenthal E, Botstein C, et al: Antitumour activity of radiation and vitamin A used in combination on Lewis lung carcinoma. Thirty-first Annual Meeting of the Radiation Research Society. Feb. 27, 1983; San Antonio, p. 145.

  10. Seifter E , Rettura A, Padawar J, et al. C3HBA tumor therapy with radiation, beta-carotene and vitamin A. A two year follow-up. Fed Proc 1983; 42:768.

  11. Williamson JM, Boettcher B, Meister A. Intra-cellular cysteine delivery system that protects against toxicity by promoting glutathione syn-thesis. Proc Natl Acad Sci 1982; 79:6246-6249.

  12. Ohkawa K, Tsukada Y, Dohzono H, Koike K, Terashima Y. The effects of co-administra-tion of selenium and cisplatin on cisplatin in-duced toxicity and antitumour activity. Br J Cancer, 1988; 58(1): 38-41.

  13. Carini R, Poli G, Dianzani MU, Maddix SP, Slater

TF, Cheeseman KH: Comparative evaluation of the amount of the antioxidant activity of alpha-tocopherol, alpha-tocopherol polythylene glycol 1000 succinate and alpha tocopherol succinate in isolated hepatocytes and liver microsomal sus-pensions. Biochem Pharmacol, 1990; 39:1597.

  1. Waxman S, Brucjner H: The enhancement of 5-FU antimetabolic activity by Ieucovorin, me-nadione, and alpha-tocopherol. Eur J Cancer Clin Oncol, 1982; 18(7): 685-692.

  2. Watrach AM, Milner JA, Watrach MA, Poirier KA: Inhibition of human breast cancer cells. Cancer Letters, 1984; 25(1): 41-47.

  3. DeLoecker W, et al: Effects of vitamin C and vitamin K3 treatment on human tumor cell growth in vitro. Synergism with combined chemotherapy action. Anticancer Res, 1993; 13(1):103-106.

  4. Ferrero D, Carlesso N, Pregno P, Gallo E, Pileri A: Self-renewal inhibition of acute myeloid leukemia clonogenic cells by biological inducers of differ-entiation. Leukemia, 1992; 6(2): 100-106.

  5. Schwartz JL, Tanaka J, Khandekar V, Herman TS, Teicher BA: Beta-carotene and/or vitamin E as modulators of alkylating agents in SCC-25 human squamous carcinoma cells. Cancer Chemother Pharmacol, 1992; 29(3): 207-213.

  6. Zhang L, Nakaya K, Yoshida T, Kuroiwa Y: In-duction by bufalin of differentiation on human leukemic cells HL60, U937, and ML1 toward macrophage/monocyte-like cells and its potent synergistic effect of the differentiation of hu-man leukemic cells in combination with other inducers. Cancer Res, 1992; 52(17):4634-4641,

  7. Hofsli and Waage: Effect of pyridoxine on tumor necrosis factor activities in vitro. Biotherapy, 1992; 5(4):285-290.

  8. Petrini M, Dastoli G, Valentini P, Mattii L, Trombi L, Testi R, et al: Synergistic effects of interferon and vitamin D3: preliminary evi-dence suggesting that interferon induces ex-pression of the vitamin receptor. Haema-tologica, 1991; 76(6): 467-471.

  9. Saunders CM, et al: Inhibition of ovarian car-cinoma cells by taxol combined with vitamin D and adriamycin. Proc Ann Meet Am Assoc Cancer Res, 1992; 33:A2641.

  10. Ermens AA, Kroes AC, Schoester M, et al. En-hanced effect of MTX and 5FU on folate me-tabolism of leukemic cells by B12. Proc Ann Meet Am Assoc Cancer Res, 1987; 28: 275.

    1. Prasad KN, Sinha PK, Ramanujam M, Sakamoto

    2. A: Sodium ascorbate potentiates the growth inhibitory effect of certain agents on neurob-lastoma cells in culture. Proc Natl Acad Sci USA. 1979; 76: 829-833.
  11. Prasad KN, Hernandez C, Edwards-Prasad J, et

al: Modification of the effect of tamoxifen, cisplatin, DTIC and interferon-alpha 2b on hu-man melanoma cells in culture by a mixture of vitamins. Nutr and Cancer 1994; 22: 233- 245.

  1. Josephy PD, Paleic B, Skarsgard LD: Ascorbic-enhanced cytotoxicity of misonidazole. Nature, (London) 1978; 271:370-372.

  2. O’Connor MK, Malone JF et al: A radioprotec-tive effect of vitamin C observed in Chinese ham-ster ovary cells. Brit J Radiol. 1977; 50: 587-591.

  3. Sarria A, Prasad KN: DL-alpha-tocopheryl suc-cinate enhances the effect of gamma-irridation on neuroblastoma cells in culture. Proc Soc Exp Biol Med. 1984; 175: 88.

  4. Prasad KN, Rama BN: Modification of the ef-fect of pharmacological agents, ionizing radia-tion and hyperthermia on tumor cells by vita-min E. In eds. Prasad KN: Vitamins, Nutrition and Cancer. Karger, Basel. 1984; 76.

  5. Ripole EAP, Rama BN, Webber MM: Vitamin E enhances the chemotherapeutic effects of adriamycin in human prostate carcinoma cells in vitro. J Urol, 1986; 136: 529.

  6. Seifter E, Rettura A, Padawar J, et al. Vitamin A and beta-carotene as adjunctive therapy to tumor excision, radiation therapy and chemo-therapy. In: eds. Prasad KN: Vitamins, Nutri-tion and Cancer. Karger, Basel. 1984; 1-19.

  7. Rutz HP, Little JB. Modification of radiosensi-tivity and recovery from X-ray damage in vitro by retinoic acid. Int J Radiat Oncol Biol Biophys, 1989; 16:1285-1289.

  8. Dimery IW, Lee JS et al: Reduction in toxicity of high-dose 13-cis-retinoic acid with vitamin E. Proc Ann Meet Am Soc Clin Oncol, 1992; 11: A399.

67. Kim JH, He SQ, Dragovic J, et al: Use of vitamins as adjunct to conventional cancer therapy. In eds. Prasad KN, Santamaria L, Williams RM: Nutrients in Cancer Prevention and Treatment. Humana Press, New Jersey. 1995; 363-372.

68. Wood LA: Possible prevention of adiramycin-induced alopecia by tocopherol. NEJM, 1985; 312(16):1060.

69 Komiyama S, Kudoh S, Yanagita T, Kuwano M: Synergistic combination of 5FU, vitamin A, and cobalt-60 radiation for head and neck tumors

antitumor combination therapy with vitamin
A.
Auris, Nasus, Larynx, 1985; 12; S2: S239-S243.

70. Israel L, Hajji O, Grefft-Alami A, Desmoulins D, et al: Vitamin A augmentation of the effects of chemotherapy in metastatic breast cancers after menopause. Randomized trial in 100 patients. Annles De Medecine Interne,1985; 136(7): 551-554.

71.Nagoumey, et al. Menadiol with chemotherapies: feasibility for resistance modification. Proc Ann Meet Am Soc Clin Oncol, 1987; 6: A132.

72.Ladner, HL, et al: In eds. F.L. Meyskens. Vita-mins and Cancer, Clifton, NJ. Humana Press. 1986; 429.

  1. Sakam A., et al. In: Medulation and Mediation of Cancer by Vitamins. Karger, Basel, 1983; 330.

  2. Smyth, J, et al: Glutathione may prevent cisplatin toxicity, raise response rates in ovar-ian cancer. Oncology News, 1995; 4(1): 1-4.

  3. Kemp G, Rose P, Lurain J, et al: Amifostine pre-treatment for protection against cyclophospha-mide-induced and cisplatin-induced toxicities: results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol, 1996; 14: 2101-2112.

  4. Schein, P: Results of chemotherapy and radia-tion therapy protection trials with WR-2721. Cancer Invest, 1992; 10(1): 24-26.

  5. Schuchter LM, Luginbuhl WE, Meropol NJ: The current status of toxicity protectants in can-cer therapy. Semin Oncol, 1992; 19: 742-745.

  6. Coleman N, Bump E, Kramer R. Chemical modifiers of cancer treatment. J Clin Oncol, 1988; 6: 709-733.

  7. Yuhas JM, Spellman JM, Jordan SW: Treatment of tumors with the combination of WR-2721 and cis-dichlorodiammineplatinum(II) or cyclo-phosphamide. Br J Cancer, 1980; 42: 574-585.

  8. Yuhas JM, Spellman JM, Culo F: The role of WR-2721 in radiotherapy and/or chemotherapy. Cancer Clin Trials. 1980; 3: 211-216.

  9. Kligerman M, Glover D, Turrisi A, Simone CB, et al: Toxicity of WR-2721 administered in sin-gle and multiple doses. Int J Radiat Oncol Biol, Phys, 1984; 10: 1773-1776.

    1. Kemp G, Rose P, Lurain J, et al: Amifostine pre-treatment for protection against cyclophospha-mide- and cisplatin-induced toxicities: Results of a randomized control trial in patients with advanced ovarian cancer. J Clin Oncol, 1996;

    2. 14: 2101-2112.
  10. DiPaola R, Rodriguez R, Recio A, et al: A phase I study of amifostine and paclitazel in patients with advanced malignancies. Am Med Soc Clin Oncol, 1992; 15: 488-489.

  11. Liu T, Liu Y, He S, et al. Use of radiation with or without WR-2721 in advanced rectal cancer. Cancer, 1992; 69: 2820-2825.

85.Dousay L, Mu C, Giarratana MC, et al. Amifo-stine improves the antileukemic therapeutic index of mafosfamide: Implications for bone marrow purging. Blood, 1995; 88: 2849-2855.

86. Schiller JH, Storer B, Berlin J, et al: Amifostine, cisplatin and vinblastine in metastatic non-small cell lung cancer: A report of high response rates and prolonged survival. J Clin Oncol, 1996;

14: 1913-1921.

87. Santamaria, Benazzo, et al: First clinical case-report (1980-88) of cancer chemoprevention with beta-carotene plus canthaxanthin supple-mented to patients after radical treatment. In eds. Tryfiates GP, Prasad KN: Nutrition, Growth and Cancer. Alan R. Liss: New York. 1988.

  1. Jaakkola K, Lahteenmaki P, Laaksa J, Harju E, et al: Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small cell lung cancer. Anticancer Res, 1992; 12(3): 599-606.

  2. Henriksson, Rogo KO, Grankvist K:Interac-tion between cytostatics and nutrients. Med Oncol Tumor Pharmacother, 1991; 8(2):79-86.

    1. Leob BF. Folic acid does not interfere with methotrexate. Clin Exp Rheum. 1995; 13:459-

    2. 463.
  3. Simone CB: Use of therapeutic levels of nutri-ents to augment oncology care. In eds. Quillin P, Williams M: Adjuvant Nutrition in Cancer Treatment. Academic Press, Tulsa, OK, p. 72. 1992.

92. Simone CB: Cancer and Nutrition, A Ten Point Plan to Decrease Your Risk of Getting Cancer. Ney York, McGraw-Hill 1981; revised, Garden City Park, Avery 1992.

  1. Williams CH: Quality of life and its impact on hypertensive patients. Am J Med, 1987; 82:9-105.

  2. Selby PJ, et al: The development of a method for assessing the quality of life of cancer pa-tients. Br J Cancer, 1981; 50: 13-22.

  3. Aaronson NK: Quality of Life: What is it? How should it be measured? Oncology, 1988;2(5): 69-76.

  4. Tchekmedyian NS, Cella DF: Quality of Life in Current Oncology Practice and Research, 1990: 4(5): 11-234.

  5. Cassileth B, Lusk EJ, DuPont G, Blake AD, Walsh WP, et al: Survival and quality of life among pa-tients receiving unproven as compared with con-ventional cancer therapy. NEJM, 1991; 324 (17): 1180-1185.

  6. Hopwood P, Thatcher N: Currentstatus of quality of life measurement in lung cancer pa-tients. Oncology, 1991; 5(5): 159-164.

  7. Gelber RD, Goldhirsch A, Cavalli F: Quality of life adjusted evaluation of adjuvant therapies for operable breast cancer. The International Breast Cancer Study Group. Ann Intern Med 1991;114(8): 621-628.

  8. Gotay CC, Korn EL, McCabe MS, Moore TD, Cheson BD . Building quality of life assessment into cancer treatment studies. Oncology, 1992; 6(6): 25-28.

101.Tchekmedyian NS, Cella DF, Mooradian AD: Care of the older cancer patient: clinical and quality of life issues. Oncology, 1992; 6(2) Suppl: l-160.

102. Sensky T: Measurement of the quality of life in end-stage renal failure Lancet, 1988; 319(20): 1353-1354.

  1. Hoffer A, Pauling L: Hardin Jones bio-statis-tical analysis of mortality data for cohorts of cancer patients with a large surviving fraction surviving at the termination of the study using vitamin C and other nutrients. J Orthomolecu-lar Medicine, 1990; 5(3): 143.

  2. Goodman MT, Kolonel LN, Wilkens LR, Yoshizawa CN, LeMarchand L, Hankin JH: Di-etary factors in lung cancer prognosis. Euro-pean J Cancer, 1992; 28(2-3): 495-501.

  3. Foster HD: Lifestyle influences on spontane-ous cancer regression. Intl J Biosocial Research, 1988; 10(1): 17-20.

  4. Carter JP: Macrobiotic diet and cancer sur-vival. J Am College Nutr, 1993; 12(3): 209-215.

  5. Sakamoto G, Hartmann WH. et al. In: Modu-lation and Mediation of Cancer by Vitamins. Karger, Basel. 1983; p. 330.

    1. Lamm DL: Megadose vitamins in bladder can-cer: a double blind clinical trial. J Urol, 1994;

    2. 151: 21-26.
  6. Jaakkola K, Lahteenmaki P, Laaksa J, Harju E, et al: Treatment withantioxidant and other nu-trients in combination with chemotherapy and irradiation in patients with small cell lung can-cer. Anticancer Res, 1992; 12(3): 599-606.

    1. Henquin N, Havivi E, Reshef A, Barak F, Horn

    2. Y: Nutritional monitoring and counselling for cancer patients during chemotherapy. Oncol-ogy, 1989; 46(3): 173-177.
  7. Basu TK: Significance of vitamins in cancer. Oncology, 1976; 33:183-186.

  8. Wynder E, Kajitani T, Kuno J, Lucas J, Palo A, Farrow J: A comparison of survival rates between American and Japanese patients with breast can-cer. Surg Gyn Obstet, 1963; 8: 196-200.

  9. Nemoto T, Tominago T, Chamberlain A, Iwasza Z, et al: Differences in breast cancer between Japan and the U.S. JNCI, 1977;58:193-197.

  10. Sakamoto G, Sugano H, Hartmann WH: Com-parative clinicopathological study of breast cancer among Japanese and American females. Jpn J Cancer Clin, 1979; 25: 161-170.

    1. Ward-Hinds M, Kolonel LN, Nomura AM, Lee

    2. J. Stage-specific breast cancer incidence rates by age among Japanese and Caucasian women in Hawaii. Br J Cancer, 1982; 45: 118-123.
  11. Kolonel LN, Hankin JH, Lee J, Chu SY, Nomura AMY, Ward-Hinds M: Nutrient intakes in re-lation to cancer incidence in Hawaii. Br J Can-cer 1981; 44: 332-339.

  12. Armstrong and Doll: Environmental factors and cancer incidence and mortality in differ-ent countries with special reference to dietary practices. Int J Cancer 1975; 15:617-631.

  13. Morrison AS, Lowe CR, MacMahon B, Ravnihar B, Yuassa S: Some international dif-

ferences in treatment and survival in breast cancer. Int J Cancer, 1976; 18: 269-273.

  1. Morrison AS, Lowe CR, MacMahon B, et al: Incidence, risk factors and survival in breast cancer: report on five years of follow-up obser-vation. Europ J Cancer, 1977; 13: 209-214.

  2. Donegan WL, Hartz AJ, Rimm AA: The asso-ciation of body weight with recurrent cancer of the breast. Cancer, 1978; 41: 1590-1594.

  3. Abe R, Kumagai N, Kimura M, Hirosaki A, Nakamura T: Biological characteristics of breast cancer in obesity. Tohoku J Exp Med, 1976; 120: 351-359.

  4. Donegan WL, Rimm AA. The prognostic im-plications of obesity for surgical cure of breast cancer. Breast 1978; 4:14-17.

  5. Sohrabi A, Sandoz J, Spratt JS, Polk HC: Re-currence of breast cancer. Obesity, tumor size, and axillary lymph node metatstases. JAMA, 1980; 244: 261-265.

  6. Boyd NF, Campbell JE, Germanson T, Thom-son DB, Sutherland DJ, Meakin JW: Body weight and prognosis in breast cancer. JNCI, 1981; 67: 785-789.

  7. Tartter PI, Papatestas AE, Ioannovich J, Mul-vihill MN, Lesnick G, Aifees AH: Cholesterol and obesity as prognostic factors in breast can-cer. Cancer, 1981; 47: 2222-2227.

  8. Buchwald, H: Cholesterol inhibition, cancer, and chemotherapy. Lancet,1992; 339:1154-1156.

  9. Prasad KN, personal communication, 1997.

  10. Gopalakrishna R, Gundimeda U, and Chen Z: Vitamin E succinate inhibits protein kinase C: correlation with its unique inhibitory effects on cell growth and transformation. In eds. Prasad KN, Santamaria L and Williams RM: Nutrients in Cancer Prevention and Treatment. Humana Press: New Jersey. 1995; 21-37.

  11. Prasad KN, Cohrs RJ, Sharma OK: Decreased expression of c-myc and H-ras oncogenes in vitamin E succinate induced differentiation murine B-16 melanoma cells in culture. Biochem Cell Biol, 1990; 68: 1250-1255.

  12. Cohrs RJ, Torelli S, Prasad KN, Edwards-Prasad J, et al: Effect of vitamin E succinate and a cAMP stimulating agent on the expres-sion of c-myc and H-ras in murine neurob-lastoma cell. Int J Dev Biol Neurosci. 1991; 9: 187-194.

  13. Kline K, Yu W, Zhao B: Vitamin E succinate: mechanisms of action as tumor cell growth in-hibitor. In esd. Prasad KN, Santamaria L, Wiliams RM: Nutrients in Cancer Prevention and Treatment. Humana Press: New Jersey. 1995; 39-55.


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