Antioxidants in cancer therapy; their actions and interactions with oncologic therapies

Alternative Medicine Review

Volumn 4, Issue 5, 1999, Pages 304-329

  Lamson, Davis W ^a,b,c   Brignall, Matthew S ^a,b  

^a Tahoma Clinic   (United States)

^b BASTYR UNIVERSITY   (United States)

^c NONE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETYLCYSTEINE; ALPHA TOCOPHEROL; ALPHA2A INTERFERON; ANTINEOPLASTIC AGENT; ANTINEOPLASTIC ALKALOID; ANTINEOPLASTIC ANTIBIOTIC; ANTINEOPLASTIC ANTIMETABOLITE; ANTIOXIDANT; ASCORBIC ACID; BETA CAROTENE; BLEOMYCIN; CAMPTOTHECIN DERIVATIVE; CAROTENOID; CISPLATIN; DOXORUBICIN; EBSELEN; EPIRUBICIN; ETOPOSIDE; FLAVONOID; FLUOROURACIL; GLUTATHIONE; MELATONIN; METHOTREXATE; PACLITAXEL; PLATINUM DERIVATIVE; RETINOIC ACID; SELENIUM; TAMOXIFEN; UBIDECARENONE; UNINDEXED DRUG;

ALTERNATIVE MEDICINE; ANTIOXIDANT ACTIVITY; BONE MARROW TOXICITY; BREAST CANCER; CANCER; CANCER CHEMOTHERAPY; CANCER COMBINATION CHEMOTHERAPY; CANCER RADIOTHERAPY; CARDIOTOXICITY; DIET SUPPLEMENTATION; DRUG EFFICACY; GASTROINTESTINAL TOXICITY; HEAD AND NECK CANCER; HUMAN; INTRAPERITONEAL DRUG ADMINISTRATION; INTRAVENOUS DRUG ADMINISTRATION; LUNG CANCER; MELANOMA; NEPHROTOXICITY; NONHUMAN; ORAL DRUG ADMINISTRATION; REVIEW; TOPICAL DRUG ADMINISTRATION; UTERINE CERVIX CANCER; VITAMIN INTAKE;

ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; COMBINED MODALITY THERAPY; DRUG INTERACTIONS; DRUG THERAPY, COMBINATION; HUMANS; NEOPLASMS;

EID: 0032697363     PISSN: 10895159     EISSN: None     Source Type: Journal    
DOI: None     Document Type: Review

References (180)

1. VandeCreek L, Rogers E, Lester J. Use of alternative therapies among breast cancer outpatients compared with the general population. Altern Ther Health Med 1999;5:71-76.
2. Singh DK, Lippman SM. Cancer chemoprevention part 1: retinoids and carotenoids and other classic antioxidants. Oncology 1998;12:1643-1660.
3. Prasad KN, Kumar A, Kochupillai V, Cole WC. High doses of multiple antioxidant vitamins: essential ingredients in improving the efficacy of standard cancer therapy. J Am Coll Nutr 1999;18:13-25.
4. Weijl NI, Cleton FJ, Osanto S. Free radicals and antioxidants in chemotherapy induced toxicity. Cancer Treat Rev 1997;23:209-240.
5. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-1012.
6. Schmitt CA, Lowe SW. Apoptosis and therapy. J Pathol 1999;187:127-137.
7. Chinery R, Brockman JA, Peeler MO, et al. Antioxidants enhance the cytotoxicity of chemotherapeutic agents in colorectal cancer: a p53-independent induction of p21 via C/EBP-beta. Nat Med 1997;3:1233-1241.
8. Mediavilla MD, Cos S, Sanchez-Barcelo EJ. Melatonin increases p53 and p21 WAF1 expression in MCF-7 human breast cancer cells ib vitro. Life Sci 1999;65:415-420.
9. Seifter E, Rettura G, Padawer J. Vitamin A and beta-carotene as adjunctive therapy to tumour excision, radiation therapy and chemotherapy. In Prasad K, ed. Vitamins Nutrition and Cancer. New York: Karger Press; 1984:2-19.
10. Thatcher N, Blackledge G, Crowther D. Advanced recurrent squamous cell carcinoma of the head and neck. Cancer 1980;46:1324-1328.
11. Shimpo K, Nagatsu T, Yamada K, et al. Ascorbic acid and adriamycin toxicity. Am J Clin Nutr 1991;54:1298S-1301S.
12. Taper HS, de Gerlache J, Lans M, et al. Nontoxic potentiation of cancer chemotherapy by combined C and K3 vitamin pre-treatment. Int J Cancer 1987;40:575-579.
13. Sue K, Nakagawara A, Okuzono SI, et al. Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of murine neuroblastoma in vivo. Eur J Cancer Clin Oncol 1988;24:1751-1758.
14. Myers CE, McGuire WP, Liss RH, et al. Adriamycin: the role of lipid peroxidation in cardiac toxicity and tumor response. Science 1977;197:165-167.
15. Naganuma A, Satoh M, Imura N. Effect of selenite on renal toxicity and antitumor activity of cis-diamminedichloroplatinum in mice inoculated with ehrlich ascites tumor cell. J Pharm Dyn 1984;7:217-220.
16. Berry JP, Pauwella C, Tlouzeau S, et al. Effect of selenium in combination with cis-diamminedichloroplatinum(II) in the treatment of murine fibrosarcoma. Cancer Res 1984;44:2864-2868.
17. Jaakkola K, Lahteenmaki P, Laakso J, et al. Treatment with antioxidant and other nutrients in combination with chemotherapy and irradiation in patients with small-cell lung cancer. Anticancer Res 1992;12:599-606.
18. Lissoni P, Paolorossi F, Ardizzoia A. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res 1997;23:15-19.
19. Lissoni P, Barni S, Meregalli S, et al. Modulation of cancer endocrine therapy by melatonin: a phase II study on tamoxifen plus melatonin in metastatic breast cancer patients progressing under tamoxifen alone. Br J Cancer 1995;71:854-856.
20. Whelan RL, Horvath KD, Gleason NR, et al. Vitamin and calcium supplement use is associated with decrease adenoma recurrence in patients with a previous history of neoplasia. Dis Colon Rectum 1999;42:212-217.
21. Lamm DL, Riggs DR, Shriver JS, et al. Megadose vitamins in bladder cancer: a double-blind clinical trial. J Urol 1994;151:21-26.
22. Yoshida M, Sakai T, Hosokawa N, et al. The effect of quercetin on cell cycle progression and growth of human gastric cancer cells. FEBS Lett 1990;260:10-13.
23. th ed. Baltimore, MD: Williams and Wilkins; 1997.
24. Smith MA, Parkinson DR, Cheson BD, Friedman MA. Retinoids in cancer therapy. J Clin Oncol 1992;10:839-864.
25. Nikolaou AC, Fountazilas G, Daniilidis I. Treatment of unresectable recurrent head and neck carcinoma with 13-cis-retinoic acid and interferon-alpha. A phase II study. J Laryngol Orol 1996;110:857-861.
26. Chomienne C, Ballerini P, Balitrand N, et al. Retinoic acid therapy for promyelocytic leukemia. Lancet 1989;2:746-747.
27. Warrell RP, Frankel SR, Miller WH, et al. Differentiation therapy of acute promyelocytic leukemia with tretinoin (all-trans-retinoic acid). N Engl J Med 1991;324:1385-1393.
28. Meng-er H, Yu-chen Y, Shu-rong C, et al. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood 1988;72:567-572.
29. Castaigne S, Chomienne C, Daniel MT, et al. All-trans retinoic acid as a differentiation therapy for acute promyelocytic leukemia. I. Clinical Results. Blood 1990;76:1704-1709.
30. Breitman TR, Selonick SE, Collins SJ. Induction of differentiation of the human promyelocytic leukemia cell line (HL-60) by retinoic acid. Proc Natl Acad Sci 1980;77:2936-2940.
31. Meyskens FL, Graham V, Chvapil M, et al. A phase I trial of beta-all-trans-retinoic acid delivered via a collagen sponge and a cervical cap for mild or moderate intraepithelial cervical neoplasia. J Natl Cancer Inst 1983;71:921-925.
32. Meyskens FL, Surwit E, Moon TE, et al. Enhancement of regression of cervical intraepithelial neoplasia II (moderate dysplasia) with topically applied all-trans-retinoic acid: a randomized trial. J Natl Cancer Inst 1994;86:539-543.
33. Hong WK, Lippman SM, Itri LM, et al. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med 1990;323:795-801.
34. Doyle LA, Giangiulo D, Hussain A. Differentiation of human variant small cell lung cancer cell lines to a classic morphology by retinoic acid. Cancer Res 1989;49:6745-6751.
35. Pastorino U, Infante M, Maioli M, et al. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol 1993;11:1216-1222.
36. Grunberg SM, Itri LM. Phase II study of isotretinoin in the treatment of advanced non-small cell lung cancer. Cancer Treat Rep 1987;71:1097-1098.
37. Meyskens FL, Tuthill RJ, Sondak VK, et al. Randomized trial of vitamin A versus observation as adjuvant therapy in high-risk primary malignant melanoma: a Southwest Oncology Group study. J Clin Oncol 1994;12:2060-2065.
38. Culine S, Kramar A, Droz JP, Theodore C. Phase II study of all-trans retinoic acid administered intermittently for hormone refractory prostate cancer. J Urol 1999;161:173-175.
39. Hennekens CH, Mayrent SL, Willett W. Vitamin A, carotenoids, and retinoids. Cancer 1986;58:1837-1841.
40. Murakoshi M, Takayasu J, Kimura O, et al. Inhibitory effects of alpha-carotene on proliferation of the human neuroblastoma cell line GOTO. J Natl Cancer Inst 1989;81:1649-1652.
41. The Alpha-Tocopherol, Beta Carotene Cancer Prevention Study Group. The effect of vitamin E and beta carotene on the incidence of lung cancer and other cancers in male smokers. N Engl J Med 1994;330:1029-1035.
42. Hennekens CH, Buring JE, Manson JE, et al. Lack of effect of long-term supplementation with beta carotene on the incidence of malignant neoplasms and cardiovascular disease. N Engl J Med 1996;334:1145-1149.
43. Gann PH, Ma J, Giovannucci E, et al. Lower prostate cancer risk in men with elevated plasma lycopene levels: results of a prospective analysis. Cancer Res 1999;59:1225-1230.
44. Amir H, Karas M, Giat J, et al. Lycopene and 1,25-dihyroxyvitamin D3 cooperate in the inhibition of cell cycle progression and induction of differentiation in HL-60 leukemic cells. Nutr Cancer 1999;33:105-112.
45. Levy J, Bosin E, Feldman B, et al. Lycopene is a more potent inhibitor of human cancer cell proliferation than either alpha-carotene or beta-carotene. Nutr Cancer 1995;24:257-266.
46. Duchesne GM, Hutchinson LK. Reversible changes in radiation response induced by all-trans retinoic acid. Int J Radiat Oncol Biol Phys 1995;33:875-880.
47. Park TK, Lee JP, Kim SN, et al. Interferon-alpha 2a, 13-cis-retinoic acid and radiotherapy for locally advanced carcinoma of the cervix: a pilot study. Eur J Gynaecol Oncol 1998;19:35-38.
48. Tannock IF, Suit HD, Marshall N. Vitamin A and the radiation response of experimental tumors: an immune mediated effect. J Natl Cancer Inst 1972;48:731-741.
49. Mills EED. The modifying effect of beta-carotene on radiation and chemotherapy induced oral mucositis. Br J Cancer 1988;57:416-417.
50. Kennedy AR, Krinsky NI. Effects of retinoids, beta-carotene, and canthaxanthin on UV- and X-ray induced transformation of C3H10T1/2 cells in vitro. Nutr Cancer 1994;22:219-232.
51. Doyle LA, Giangiulo D, Hussain A. Differentiation of human variant small cell lung cancer cell lines to a classic morphology by retinoic acid. Cancer Res 1989;49:6745-6751.
52. Adwankar M, Banerji A, Ghosh S. Differential response of retinoic acid pretreated human synovial sarcoma cell line to anticancer drugs. Tumori 1991;77:391-394.
53. Nagai Y, Horie T, Awazu S. Vitamin A, a useful biochemical modulator capable of preventing intestinal damage during methotrexate treatment. Pharmacol Toxicol 1993;73:69-74.
54. Weisman RA, Christen R, Los G, et al. Phase I trial of retinoic acid and cis-platinum for advanced squamous cell cancer of the head and neck based on experimental evidence of drug synergism. Otolaryngol Head Neck Surg 1998;118:597-602.
55. Kalemkerian GP, Jiroutek M, Ettinger DS, et al. A phase II study of all-trans-retinoic acid plus cisplatin and etoposide in patients with extensive stage small cell lung carcinoma. Cancer 1998;83:1102-1108.
56. Recchia F, Sica G, Casucci D, et al. Advanced carcinoma of the pancreas: phase II study of combined chemotherapy, beta-interferon, and retinoids. Am J Clin Oncol 1998;21:275-278.
57. Tsutani H, Ueda T, Uchida M, Nakamura T. Pharmacological studies of retinol palmitate and its clinical effect in patients with acute non-lymphocytic leukemia. Leukemia Res 1991;15:463-471.
58. Teicher BA, Schwartz JL, Holden SA, et al. In vivo modulation of several anticancer agents by beta-carotene. Cancer Chemother Pharmacol 1994;34:235-241.
59. Cameron E, Pauling L. Supplemental ascorbate in the supportive treatment of cancer: prolongation of survival times in terminal human cancer. Proc Natl Acad Sci 1976;73:3685-3689.
60. Cameron E. Protocol for the use of vitamin C in the treatment of cancer. Med Hypothesis 1991;36:190-194.
61. Creagan ET, Moertel CG, O'Fallon JR, 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.
62. Moertel CG, Fleming TR, Creagan ET, et al. High-dose vitamin C versus placebo in the treatment of patients with advanced cancer who have had no prior chemotherapy. N Engl J Med 1985;312:137-141.
63. Riordan HD, Jackson JA, Riordan NH, Schultz M. High-dose intravenous vitamin C in the treatment of a patient with renal cell carcinoma of the kidney. J Orthomol Med 1998;13:72-73.
64. Riordan NH, Riordan HD, Meng X, et al. Intravenous ascorbate as a tumor cytotoxic chemotherapeutic agent. Med Hypotheses 1995;44:207-213.
65. Rivers JM. Safety of high-level vitamin C ingestion. Ann NY Acad Sci 1988;498:445-454.
66. Cameron E, Campbell A. The orthomolecular treatment of cancer. II. Clinical trial of high-dose ascorbic acid supplements in advanced human cancer. Chem Biol Interactions 1974;9:285-315.
67. Kakar SC, Wilson CWM, Moriarty MJ. The relationship between cancer, radiotherapy and vitamin C. Ir J Med Sci 1977;146:289-294.
68. Taper HS, Keyeux A, Roberfroid M. Potentiation of radiotherapy by nontoxic pretreatment with combined vitamins C and K3 in mice bearing solid transplantable tumor. Anticancer Res 1996;16:499-504.
69. Okunieff P. Interactions between ascorbic acid and the radiation of bone marrow, skin, and tumor. Am J Clin Nutr 1991;54:1281S-1283S.
70. Okunieff P, Suit HD. Toxicity, radiation sensitivity modification, and combined drug effects of ascorbic acid with misonidazole in vivo on FSall murine fibrosarcomas. J Natl Cancer Inst 1987;79:377-381.
71. Tewfik FA, Tewfik HH, Riley EF. The influence of ascorbic acid on the growth of solid tumors in mice and on tumor control by X-irradiation. Int J Vitam Nutr Res Suppl 1982;23:257-263.
72. Hanck AB. Vitamin C and cancer. Prog Clin Biol Res 1988;259:301-320.
73. Halperin EC, Gaspar L, George S, et al. A double-blind, randomized, prospective trial to evaluate topical vitamin C solution for the prevention of radiation dermatitis. Int J Rad Oncol Biol Phys 1993;26:413-416.
74. Wells WW, Rocque PA, Xu DP. Ascorbic acid and cell survival of adriamycin resistant and sensitive MCF-7 breast tumor cells. Free Rad Biol Med 1995;18:699-708.
75. Kurbacher CM, Wagner U, Kolster B, et al. Ascorbic acid (vitamin C) improves the antineoplastic activity of doxorubicin, cisplatin, and paclitaxel in human breast carcinoma cells in vitro. Cancer Lett 1996;103:183-189.
76. Chiang CD, Song EJ, Yang VC, Chao CCK. Ascorbic acid increases drug accumulation and reverses vincristine resistance of human non-small-cell lung-cancer cells. Biochem J 1994;301:759-764.
77. Turley JM, Funakoshi S, Ruscetti FW, et al. Growth inhibition and apoptosis of RL human B lymphoma cells by vitamin E succinate and retinoic acid: role for transforming growth factor beta. Cell Growth Differ 1995;6:655-663.
78. Turley JM, Fu TF, Ruscetti FW, et al. Vitamin E succinate induces Fas-mediated apoptosis in estrogen receptor-negative human breast cancer cells. Cancer Res 1997;57:881-890.
79. Elattar TMA, Virji AS. Biphasic action of vitamin E on the growth of human oral squamous carcinoma cells. Anticancer Res 1999;19:365-368.
80. Helson L. A phase I study of vitamin E and neuroblasoma. In: Prasad ed. Vitamins, Nutrition, and Cancer. New York: Karger Press; 1984:274-281.
81. Gogos CA, Ginopoulos P, Salsa B, et al. Dietary omega-3 polyunsaturated fatty acids plus vitamin E restore immunodeficiency and prolong survival for severely ill patients with generalized malignancy. Cancer 1998;82:395-402.
82. Kelloff GJ, Crowell JA, Boone CW. Clinical development plan: vitamin E. J Cell Biochem Suppl 1994;20:282-299.
83. Bendich A, Machlin LJ. Safety of oral intake of vitamin E. Am J Clin Nutr 1988;48:612-619.
84. Sakamoto K, Sakka M. Reduced effect of irradiation on normal and malignant cells irradiated in vivo in mice pretreated with vitamin E. Br J Radiology 1973;46:538-540.
85. Fonck K, Konings AWT. The effect of vitamin E on cellular survival after X irradiation of lymphoma cells. Br J Radiology 1978;51:832-833.
86. Kagreud A, Peterson HI. Tocopherol in irradiation of experimental neoplasms. Acta Radiol Oncol 1981;20:97-100.
87. Delanian S. Striking regression of radiation-induced fibrosis by a combination of pentoxifylline and tocopherol. Br J Radiology 1998;71:892-894.
88. Sonneveld R Effect of alpha-tocopherol on the cardiotoxicity of adriamycin in the rat. Cancer Treat Rep 1978;62:1033-1036.
89. Perez Ripoll EA, Rama BN, Webber MM. Vitamin E enhances the chemotherapeutic effects of adriamycin on human prostatic carcinoma cells in vitro. J Urol 1986;136:529-531.
90. Sue K, Nakagawara A, Okuzono SI, et al. Combined effects of vitamin E (alpha-tocopherol) and cisplatin on the growth of murine neuroblastoma in vivo. Eur J Cancer Clin Oncol 1988;24:1751-1758.
91. von Oefele F. Some remarks on the treatment of cancerous growths with selenium compounds. American Medicine 1912;18:216-219.
92. Watrach AM, Milner JA, Watrach MA. Effect of selenium on growth rate of canine mammary carcinoma cells in athymic nude mice. Cancer Lett 1982;15:137-143.
93. Watrach AM, Milner JA, Watrach MA, Poirier KA. Inhibition of human breast cancer cells by selenium. Cancer Lett 1984;25:41-47.
94. Pakdaman A. Symptomatic treatment of brain tumor patients with sodium selenite, oxygen, and other supportive measures. Biol Trace Elem Res 1998;62:1-6.
95. Ladas HS. The potential of selenium in the treatment of cancer. Holistic Med 1989;4:145-156.
96. Hehr T,Hoffmann W, Bamberg M. Role of sodium selenite as an adjuvant in radiotherapy of rectal carcinoma. Med Klin 1997;92:S48-S49.
97. Myers C, Katki A, Travis E. Effect of tocopherol and selenium on defenses against reactive oxygen species and their effect on radiation sensitivity. Ann NY Acad Sci 1982;393:419-425.
98. Ohkawa K, Tsukada Y, Dohzono H, et al. The effects of co-administration of selenium and cis-platin (CDDP) on CDDP-induced toxicity and antitumor activity. Br J Cancer 1988;58:38-41.
99. Hu YJ, Chen Y, Zhang YQ, et al. The protective role of selenium on the toxicity of cisplatin-contained chemotherapy regimen in cancer patients. Biol Trace Elem Res 1997;56:331-341.
100. Kappus H, Reinhold C. Inhibition of bleomycin-induced toxic effects by antioxidants in human malignant melanoma cells. Adv Exp Med Biol 1990;264:345-348.
101. Folkers K, Brown R, Judy W, Morita M. Survival of cancer patients on therapy with coenzyme Q10. Biochem Biophys Res Comm 1993;192:241-245.
102. Lockwood K, Moesgaard S, Yamamoto T, Folkers K. Progress on therapy of breast cancer with vitamin Q10 and the regression of metastases. Biochem Biophys Res Comm 1995;212:172-177.
103. Lockwood K, Moesgaard S, Hanioka T, Folkers K. Apparent partial remission of breast cancer in 'high-risk' patients supplemented with nutritional antioxidants, essential fatty acids and coenzyme Q10. Molec Aspects Med 1994;15:S231-S240.
104. Lund EL, Quistorff B, Spang-Thomsen M, Kristjansen PEG. Effect of radiation therapy on small-cell lung cancer is reduced by ubiquinone intake. Folia Microbiol 1998;43:505-506.
105. Tsubaki K, Horiuchi A, Kitani T, et al. Investigation of the preventive effect of CoQ10 against the side-effects of anthracycline antineoplastic agents. Gan To Kagaku Ryoho 1984;11:1420-1427.
106. Shaeffer J, El-Mahdi AM, Nichols RK. Coenzyme Q10 and adriamycin toxicity in mice. Res Commun Chem Pathol Pharmacol 1980;29;309-315.
107. Iarussi D, Auricchio U, Agretto A, et al. Protective effect of coenzyme Q10 on anthracyclines cardiotoxicity: control study in children with acute lymphoblastic leukemia and non-hodgkin lymphoma. Molec Aspects Med 1994;15:S207-S212.
108. Reiter RJ, Carneiro RC, Oh CS. Melatonin in relation to cellular antioxidative defense mechanisms. Horm Metab Res 1997;29:363-372.
109. Peller S. Clinical implications of p53: effect on prognosis, tumor progression and chemotherapy response. Semin Cancer Biol 1998;8:379-387.
110. Neri B, DeLeonardis V, Gemelli MT, et al. Melatonin as biological response modifier in cancer patients. Anticancer Res 1998;18:1329-1332.
111. Lissoni P, Paoorossi F, Tancini G, et al. Is there a role for melatonin in the treatment of neoplastic cachexia. Eur J Cancer 1996;32A:1340-1343.
112. Lissoni P, Barni S, Ardizzoia A, et al. Randomized study with the pineal hormone melatonin versus supportive care alone in advanced nonsmall cell lung cancer resistant to a first-line chemotherapy containing cisplatin. Oncology 1992;49:336-339.
113. Lissoni P, Barni S, Ardizzoia A, et al. A randomized study with the pineal hormone melatonin versus supportive care alone in patients with brain metastases due to solid neoplasms. Cancer 1994;73:699-701.
114. Lissoni P, Brivio O, Brivio F, et al. Adjuvant therapy with the pineal hormone melatonin in patients with lymph node relapse due to malignant melanoma. J Pineal Res 1996;21:239-242.
115. Lissoni P, Barni S, Crispino S, et al. Endocrine and immune effects of melatonin therapy in metastatic cancer patients. Eur J Cancer Clin Oncol 1989;25:789-795.
116. Anonymous. Evaluation of an unconventional cancer treatment (the Di Bella multitherapy): results of phase II trials in Italy. Italian Study Group for the Di Bella Multitherapy Trials. BMJ 1999;318:224-228.
117. Vijayalaxmi R, Meltz ML, Reiter RJ, et al. Melatonin and protection from whole-body irradiation: survival studies in mice. Mutat Res 1999;425:21-27.
118. Lissoni P, Meregalli S, Nosetto L, et al. Increased survival time in brain glioblastomas by a radioneuroendocrine strategy with radiotherapy plus melatonin compared to radiotherapy alone. Oncology 1996;53:43-46.
119. Lissoni P, Paolorossi F, Tancinin G, et al. A phase II study of tamoxifen plus melatonin in metastatic solid tumor patients. Br J Cancer 1996;74:1466-1468.
120. Lissoni P, Tancini G, Paolorossi F, et al. Chemoneuroendocrine therapy of metastatic breast cancer with persistent thrombocytopenia with weekly low-dose epirubicin plus melatonin: a phase II study. J Pineal Res 1999;26:169-173.
121. Lissoni P, Paolorossi F, Ardizzoia A. A randomized study of chemotherapy with cisplatin plus etoposide versus chemoendocrine therapy with cisplatin, etoposide and the pineal hormone melatonin as a first-line treatment of advanced non-small cell lung cancer patients in a poor clinical state. J Pineal Res 1997;23:15-19.
122. Ghielmini M, Pagani O, de Jong J. Double-blind randomized study on the myeloprotective effect of melatonin in combination with carboplatin and etoposide in advanced lung cancer. Br J Cancer 1999;80:1058-1061.
123. Lissoni P, Barni S, Tancini G. A randomized study with subcutaneous low-dose interleukin 2 alone vs. interleukin 2 plus the pineal neurohormone melatonin in advanced solid neoplasms other than renal cancer and melanoma. Br J Cancer 1994;69:196-199.
124. Lissoni P, Meregalli S, Fossati V, et al. A randomized study of immunotherapy with low-dose subcutaneous interleukin-2 plus melatonin vs. chemotherapy with cisplatin and etoposide as first-line therapy for advanced non-small cell lung cancer. Tumori 1994;80:464-467.
125. Miller LF, Rumack BH. Clinical safety of high oral doses of acetylcysteine. Sem Oncol 1983;10:S76-S85.
126. Maasilta P, Holsti LR, Blomqvist P, et al. N-Acetylcystine in combination with radiotherapy in the treatment of non-small cell lung cancer: a feasibility study. Radiother Oncol 1992;25:192-195.
127. Wanamarta AH, van Rijn J, Blank LECM, et al. Effect of N-acetylcysteine on the antiproliferative action of X-rays or bleomycin in cultured human lung cancer cells. J Cancer Res Clin Oncol 1989;115:340-344.
128. Kim JA, Baker DG, Hahn SS, et al. Topical use of N-acetylcysteine for reduction of skin reaction to radiation therapy. Sem Oncol 1983;10:S86-S88.
129. Levy L, Vredevoe DL. The effect of N-acetylcysteine on cyclophosphamide immunoregulation and antitumor activity. Semin Oncol 1983;10:S7-S16.
130. Harrison EF, Fuquay ME, Hunter HL. Effect of N-acetylcysteine on the antitumor activity of cyclophosphamide against Walker-256 carcinosarcoma in rats. Semin Oncol 1983;10:S25-S27.
131. Palermo MS, Olabuenaga SE, Giordano M, Isturiz MA. Immunomodulation exerted by cyclophosphamide is not interfered with by N-acetylcysteine. Int J Immunopharmac 1986;8:651-655.
132. Slavik M, Saiers JH. Phase I clinical study of acetylcysteine's preventing ifosfamide-induced hematuria. Semin Oncol 1983;10:S62-S65.
133. Holoye PY, Duelge J, Hansen RM, et al. Prophylaxis of ifosfamide toxicity with oral acetylcysteine. Semin Oncol 1983;10:S66-S71.
134. Myers C, Bonow R, Palmeri S, et al. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin Oncol 1983;10:S53-S55.
135. Unverferth DV, Jagadeesh JM, Unverferth BJ, et al. Attempt to prevent doxorubicin induced acute human myocardial morphologic damage with acetylcysteine. J Natl Cancer Inst 1983;71:917-920.
136. Olson RD, Stroo WE, Boerth RC. Influence of N-acetylcysteine on the antitumor activity of doxorubicin. Semin Oncol 1983;10:S29-S34.
137. Schmitt-Graff A, Scheulen ME. Prevention of adriamycin cardiotoxicity by niacin, isocitrate, or N-acetylcysteine in mice. Path Res Pract 1986;181:168-174.
138. Roller A, Weller M. Antioxidants specifically inhibit cisplatin cytotoxicity of human malignant glioma cells. Anticancer Res 1998;18:4493-4497.
139. Miyajima A, Nakashima J, Tachibana M, et al. N-acetylcysteine modifies cis-dichlorodiammineplatinum induced effects in bladder cancer cells. Jpn J Cancer Res 1999;90:565-570.
140. Sheikh-Hamad D, Timmins K, Jalali Z. Cisplatin-induced renal toxicity: possible reversal by N-acetylcysteine treatment. J Am Soc Nephrol 1997;8:1640-1644.
141. Witschi A, Reddy S, Stofer B, Lauterberg BH. The systemic availability of oral glutathione. Eur J Clin Pharmacol 1992;43:667-669.
142. Hagen TM, Wierzbicka GT, Sillau AH, et al. Bioavailability of dietary glutathione: effect on plasma concentration. Am J Physiol 1990;259:G524-G529.
143. Holroyd KJ, Buhl R, Borok Z, et al. Correction of glutathione deficiency in the lower respiratory tract of HIV seropositive individuals by glutathione aerosol treatment. Thorax 1993;48:985-989.
144. Hospers GAP, Eisenhauer EA, de Vries EGE. The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects. Br J Cancer 1999;80:629-638.
145. Dalhoff K, Ranek L, Mantoni M, Poulsen, HE. Glutathione treatment of hepatocellular carcinoma. Liver 1992;12:341-343.
146. Novi AM. Regression of aflatoxin B1-induced hepatocellular carcinomas by reduced glutathione. Science 1981;212:541-542.
147. Kidd PM. Glutathione: systemic protectant against oxidative and free radical damage. Altern Med Rev 1997;2:155-176.
148. DeMaria D, Falchi AM, Venturino P. Adjuvant radiotherapy of the pelvis with or without reduced glutathione: a randomized trial in patients operated on for endometrial cancer. Tumori 1992;78:374-376.
149. Meijer C, Mulder NH, de Vries EGE. The role of detoxifying systems in resistance of tumor cells to cisplatin and adriamycin. Cancer Treat Rev 1990;17:389-407.
150. Smyth JF, Bowman A, Parren T, et al. Glutathione reduces the toxicity and improves quality of life of women diagnosed with ovarian cancer treated with cisplatin: results of a double-blind, randomised trial. Ann Oncol 1997;8:569-573.
151. Bogliun G, Marzorati L, Marzola M, et al. Neurotoxicity of cisplatin +/- reduced glutathione in the first-line treatment of advanced ovarian cancer. Int J Gynaecol Cancer 1996;6:415-419.
152. Cascinu S, Cordelia L, Del Ferro E, et al. Neuroprotective effect of reduced glutathione on cisplatin-based chemotherapy in advanced gastric cancer: a randomized double-blind placebo-controlled trial. J Clin Oncol 1995;13:26-32.
153. Di Re F, Bohm S, Oriana S, et al. High-dose cisplatin and cyclophosphamide with glutathione in the treatment of advanced ovarian cancer. Ann Oncol 1993;4:55-61.
154. Locatelli MC, D'Antonia A, Lablanca R, et al. A phase II study of combination chemotherapy in advanced ovarian carcinoma with cisplatin and cyclophosphamide plus reduced glutathione as potential protective agent against cisplatin toxicity. Tumori 1993;79:37-39.
155. Bushman JL: Green tea and cancer in humans: a review of the literature. Nutr Cancer 1998;31:151-159.
156. Lian F, Li Y, Bhuiyan M, Sarkar FH. P-53-independent apoptosis induced by genestein in lung cancer cells. Nutr Cancer 1999;33:125-131.
157. Miodini P, Fioravanti L, DiFronzo G, Cappelletti V. The two phyto-oestrogens genistein and quercetin exert different effects on oestrogen receptor function. Br J Cancer 1999;80:1150-1155.
158. Sriganth INP, Premalatha B. Dietary curcumin with cisplatin administration modulates tumour marker indices in experimental fibrosarcoma. Pharmacol Res 1999;39:175-179.
159. Zi X, Agarwal R. Silibinin decreases prostate-specific antigen with cell growth inhibition via G1 arrest, leading to differentiation of prostate carcinoma cells: implications for prostate cancer intervention. Proc Natl Acad Sci 1999;96:7490-7495.
160. van Rijn J, van den Berg J. Flavonoids as enhancers of x-ray-induced cell damage in hepatoma cells. Clin Cancer Res 1997;3:1775-1779.
161. Fritz-Niggli H, Rao KR. Rutosides and radiation induced regression of experimental tumors. Arzn Forsch 1977;27:1057-1064.
162. Robert J. Multidrug resistance in oncology: diagnostic and therapeutic approaches. Eur J Clin Invest 1999;29:536-545.
163. Sadzuka Y, Sugiyama T, Hirota S. Modulation of cancer chemotherapy by green tea. Clin Cancer Res 1998;4:153-156.
164. Sugiyama T, Sadzuka Y. Enhancing effects of green tea components on the antitumor activity of adriamycin against M5076 ovarian sarcoma. Cancer Lett 1998;133:19-26.
165. Scambia G, Ranelletti FO, Panici PB, et al. Quercetin potentiates the effect of adriamycin in a multidrug-resistant MCF-7 human breast cancer cell line: P-glycoprotein as a possible target. Cancer Chemother Pharmacol 1994;34:459-464.
166. Critchfield JW, Welsh CJ, Phang JM, Yeh GC. Modulation of adriamycin accumulation and efflux by flavonoids in HCT-15 colon cells. Biochem Pharm 1994;48:1437-1445.
167. Versantvoort CHM, Schuurhuis GJ, Pinedo HM, et al. Genistein modulates the decreased drug accumulation in non-P-glycoprotein mediated multidrug resistant tumour cells. Br J Cancer 1993;68:939-946.
168. Marverti G, Andrews PA. Stimulation of cis-diamminedichloroplatinum(II) accumulation by modulation of passive permeability with genistein: an altered response in accumulation-defective resistant cells. Clin Cancer Res 1996;2:991-999.
169. Hofmann J, Fiebig HH, Winterhalter BR, et al. Enhancement of the antiproliferative activity of cis-diamminedichloroplatinum(II) by quercetin. Int J Cancer 1990;45:536-539.
170. Scambia G, Ranelletti FO, Panici PB, et al. Inhibitory effect of quercetin on primary ovarian and endometrial cancers and synergistic activity with cis-diamminedichloroplatinum (II). Gynecol Oncol 1992;45:13-19.
171. Bracke ME, Depypere HT, Boterberg T, et al. Influence of tangeretin on tamoxifen's therapeutic benefit in mammary cancer. J Natl Cancer Inst 1999;91:354-359.
172. Schwartz JA, Liu G, Brooks SC. Genistein-mediated attenuation of tamoxifen-induced antagonism from estrogen receptor-regulated genes. Bioch Biophys Res Comm 1998;253:38-43.
173. Shen F, Xue X, Weber G. Tamoxifen and genistein synergistically down-regulate signal transduction and proliferation in estrogen receptor-negative human breast carcinoma MDA-MB-435 cells. Anticancer Res 1999;19:1657-1662.
174. Shklar G, Schwartz J, Trickler D, Reid S. Regression of experimental cancer by oral administration of combined alpha-tocopherol and beta-carotene. Nutr Cancer 1989;12:321-325.
175. Wagdi P, Fluri M, Aeschbacher B, et al. Cardioprotection in patients undergoing chemo- and/or radiotherapy for neoplastic disease. Jpn Heart J 1996;37:353-359.
176. Braverman A. Medical oncology in the 1990's. Lancet 1991;337:901-902.
177. Braverman A. Chemotherapeutic failure: resistance or insensitivity? Lancet 1980;2:1343-1346.
178. Greenberg DM. The vitamin fraud in cancer quackery. West J Med 1975;122:345-348.
179. Benade L, Howard T, Burk D. Synergistic killing of Ehrlich ascites carcinoma cells by ascorbate and 3-amino-1,2,4,-triazole. Oncology 1969;23:33-43.
180. Oberley TD, Oberley LW. Antioxidant enzyme levels in cancer. Histol Histopathol 1997;12:525-535.