Adriamycin
side effects, nutrient depletions, herbal interactions and health notes:
Data provided by Applied Health
• nutrient affected by drug: Vitamin B2 (Riboflavin) Doxorubicin can interfere with the normal metabolism and function of vitamin B2 and increase it urinary excretion. Doxorubicin has been shown to form a 1:1 stoichiometric complex with riboflavin, as well as to compete for binding to tissue proteins.1
• Research with rats has demonstrated riboflavin deficiency due to doxorubicin, even when dietary sources of riboflavin have been sufficient. Studies by Pinto et al has demonstrated that the increased levels in aldosterone associated with doxorubicin are the result of the drug's inhibition of flavin coenzyme biosynthesis. They concluded that their findings with rat studies suggest that flavins play a decisive role in regulating the levels of aldosterone and raise the possibility that the doxorubicin-induced increase in serum aldosterone may be part of the pathogenetic mechanisms of cardiovascular toxicity and overall muscular weakness. Research looking at adverse effects, especially doxorubicin-induced mortality, has indicated that supplementation with riboflavin may reduce adverse side effects and enhance survival rates.2
• Antioxidant action reduces cardiac toxicity. However, as a strong antioxiidant and as an effective promoter of glutathione activity, vitamin C could potentially inhibit the therapeutic mechanism of doxorubicin which relies upon the cytotoxic effect of free radical formation.3
• Animal studies, using mice and guinea pigs, indicated that vitamin C significantly increased life expectancy by reducing the cardiotoxicity of doxorubicin; this positive effect was gained without interfering with the drug's anticancer effects. However, the relationship between these findings based on animal studies and human clinical cardiac toxicity is uncertain. Supplementation of vitamin C at doses of one or more grams per day is prescribed by some practitioners as nutritional support for patients taking doxorubicin, even though the practice lacks conclusive data based on human studies4
• Initial research by Prasad et al suggested that supplementation with vitamin E might reduce cardiac and skin toxicity due to doxorubicin. Research studies with animals have found that vitamin E's potent antioxidant activity can protect against Adriamycin-induced cardiotoxicity; hence reducing the risk of heart failure which is a serious side effect associated with doxorubicin.5
• No conclusive evidence has come forth confirming the cardioprotective effect of vitamin E in human trials. Nevertheless, some evidence suggests that supplementation with vitamin E may allow use of higher doses of doxorubicin without correspondingly increasing toxicity.6
• Anecdotal reports indicate that very high doses of vitamin E (1600 IU) may reduce the amount of alopecia (hair loss) resulting from use of doxorubicin. (Wood LA. N Engl J Med 1985;312:1060 ) As of yet, no research on humans has duplicated the protective effect against hair loss found in one study with rabbits nutritional support: Supplementation of vitamin E at doses of 800 IU or more is prescribed by some practitioners as nutritional support for patients taking doxorubicin, even though no decisive evidence has emerged showing that the vitamin reduces drug toxicity or protects against hair loss.7
• In vitro evidence suggests that vitamin E enhances the growth inhibitory effect of doxorubicin, at least in a test tube.8
• Research has found that N-acetyl cysteine (NAC) exerts a protective effect from the cardiotoxicity of doxorubicin, at least in animals; no research with human has yet confirmed these results. The prescription of oral NAC for individuals receiving doxorubicin therapy is not a common practice among nutritionally-oriented physicians.9
• Coenzyme Q10 reduces free radical formation induced by doxorubicin. Studies with both animals and humans have found that pretreating with coenzyme Q10, at levels of 100 mg per day, reduces cardiac toxicity caused by doxorubicin. Coenzyme Q10 reduces free radical formation induced by doxorubicin.10
• Individuals taking doxorubicin (Adriamycin) may benefit from supplementation with coenzyme Q10 at some point in their treatment protocol. However, such supplementation should only be started after consultation with and under the close supervision of the prescribing physician and/or a nutritionally trained healthcare professional. Nutrients with antioxidant potential should generally be avoided during the course of treatment with doxorubicin as there is concern that the effectiveness of the medication might be diminished since it relies upon free radical formation for its cytotoxic effect. Should use of coenzyme Q10 be agreed upon a dosage in the range of 50-100 mg three times daily would be in the range many nutritionally oriented healthcare professionals would use.11
• One of the vital roles of ascorbic acid (vitamin C) is to act as an antioxidant to protect cellular components from free radical damage. Ascorbic acid has been shown to scavenge free radicals directly in the aqueous phases of cells and the circulatory system. Ascorbic acid has also been proven to protect membrane and other hydrophobic compartments from such damage by regenerating the antioxidant form of vitamin E. In addition, reduced coenzyme Q, also a resident of hydrophobic compartments, interacts with vitamin E to regenerate its antioxidant form. The mechanism of vitamin C antioxidant function, the myriad of pathologies resulting from its clinical deficiency, and the many health benefits it provides, are reviewed12
• nutrient affecting drug toxicity: N-acetyl Cysteine (NAC), a precursor to Glutathione. Antioxidant action reduces cardiac toxicity of doxorubicin13
• There are no Herbal considerations at this time14
References1 Pinto J, et al. Cancer 1986 Oct 15;58(8 Suppl):1911-1914
2 Ogura R, et al. J Nutr Sci Vitaminol (Tokyo). 1991 Oct;37(5):473-477; Raiczyk GB, et al. Proc Soc Exp Biol Med 1988 Sep;188(4):495-499; Pinto JT, et al. Endocrinology 1990 Sep;127(3):1495-1501
3 Labriola D, Livingston R. Oncology (Huntingt). 1999 Jul;13(7):1003-1008.
4 Fujita, K, et al. Cancer Res 1982;42:309-316; Shimpo K, et al. Am J Clin Nutr 1991 Dec;54(6 Suppl):1298S-1301S; Ellison, NM, Londer H. 1981
5 Prasad KN, et al. Proc Soc Exp Biol Med 1980 Jun;164(2):158-163; Ellison NM. Cancer Bull 1985;37(3):112-113; Am Heart J 1986;lll:95; Myers C, et al. Cancer Treat Rep 1976;60:961-962; Sonneveld P. Cancer 1978;62:1033-1036
6 Ellison, NM, Londer H. 1981; Weiji NI, et al. Cancer Treatment Rev 1997,23:209-210
7 Weiji NI, et al. Cancer Treatment Rev 1997;23:209-240.
8 Ripoll EAP, et al. J Urol 1986;136:529-531
8 Ellison, NM. Relationship between vitamin E and cancer - facts, not fancy. Cancer Bull 1985;37(3):112-113
8 Ellison, NM, Londer H. Vitamin E and C and their relatiuonship to cancer. In: Newell GR, Ellison NM, eds. Nutrition and Cancer: Etiology and Treatment. New York: Raven Press, 1981.
9 Schmitt-Graff A, et al. Pathol Res Pract. 1986 May;181(2):168-74; Martinez E, Domingo P. Lancet 1991;338:249; Doroshow JH, et al. J Clin Invest 1981;68:1053-1064; Meyers C, et al. Semin Oncol 1983;10:53-55
10 Gaby, AR.1987; Judy WV, et al. 1984,231-241; Ogura R, et al. J Appl Biochem 1979,1:325;
10 Folkers K. 1985; Gaby, AR. 1987; Anonymous. Nutr Rev 1988;46:1367; Beyer RE. Biochem Cell Biol 1992 70(6):390-403
10 Shinozawa S, et al. Biol Pharm Bull. 1993 Nov;16(11):1114-1117; Shinozawa S, et al. Acta Med Okayama. 1991 Jun;45(3):195-199; Shinozawa S, et al. Acta Med Okayama.
10 Acta Med Okayama. 1991 Jun;45(3):195-199; Shinozawa S, et al. Acta Med Okayama. 1987 Feb;41(1):11-17; Shinozawa S, et al. Acta Med Okayama. 1984 Feb;38(1):57-63; Labriola D, Livingston R. Oncology (Huntingt). 1999 Jul;13(7):1003-1008
11 Anonymous. Vitamin E and cell injury. Nutr Rev 1988;46:1367.
11 Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine. J Clin Invest 1981 Oct;68(4):1053-1064
11 Beyer RE. An analysis of the role of coenzyme Q in free radical generation, and as an antioxidant. Biochem Cell Biol 1992 70(6):390-403
11 Doroshow JH, Locker GY, Ifrim I, Myers CE. Prevention of doxorubicin cardiac toxicity in the mouse by N-acetylcysteine. J Clin Invest 1981 Oct;68(4):1053-1064.
11 Ellison, NM. Relationship between vitamin E and cancer - facts, not fancy. Cancer Bull 1985;37(3):112-113.
11 Ellison, NM, Londer H. Vitamin E and C and their relatiuonship to cancer. In: Newell GR, Ellison NM, eds. Nutrition and Cancer: Etiology and Treatment. New York: Raven Press, 1981.
11 Folkers K. Basic chemical research on coenzyme Q10 and integrated clinical research on therapy of diseases. In: Lenaz G, ed. Coenzyme Q. John Wiley and Sons, 1985.
11 Fujita K, Shinpo K, Yamada K, Sato T, Niimi H, Shamoto M, Nagatsu T, Takeuchi T, Umezawa H. Reduction of Adriamycin toxicity by ascorbate in mice and guinea pigs. Cancer Res 1982 Jan;42(1):309-316.
11 Judy, WV, Hall, JH, Dugan, W, et al. Coenzyme Q10 reduction of Adriamycin cardiotoxicity. In Biomedical and Clinical Aspects of Coenzyme Q, vol.4, ed. Folkers, K, Yamamura, Y. Amsterdam: Elsevier/North Holland Biomedical Press, 1984,231-241.
11 Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology (Huntingt). 1999 Jul;13(7):1003-1008; discussion 1008, 1011-1012.
11 Martinez, E, Domingo, P. N-acetylcysteine as chemoprotectant in cancer chemotherapy. Lancet 1991 Jul 27;338(8761):249. (Letter)
11 Myers C, Bonow R, Palmeri S, Jenkins J, Corden B, Locker G, Doroshow J, Epstein S. A randomized controlled trial assessing the prevention of doxorubicin cardiomyopathy by N-acetylcysteine. Semin Oncol 1983 Mar;10(1 Suppl 1):53-55.
11 Myers, C, McQuire, W, Young, R. Adriamycin amelioration of toxicity by alpha-tocopherol. Cancer Treat Rep 1976 Jul;60(7):961-962.
11 Ogura R, Ueta H, Hino Y, Hidaka T, Sugiyama M. Riboflavin deficiency caused by treatment with adriamycin. J Nutr Sci Vitaminol (Tokyo). 1991 Oct;37(5):473-477
11 Ogura R, Toyama H, Shimada T, Murakami M. The role of ubiquinone (Coenzyme Q10) in preventing Adriamycin-induced mitochondrial disorders in rat heart. J Appl Biochem 1979,1:325.
11 Okamoto K, Ogura R. Effects of vitamins on lipid peroxidation and suppression of DNA synthesis induced by adriamycin in Ehrlich cells. J Nutr Sci Vitaminol (Tokyo) 1985 Apr;31(2):129-137.
11 Pinto JT, Delman BN, Dutta P, Nisselbaum J. Adriamycin-induced increase in serum aldosterone levels: effects in riboflavin-sufficient and riboflavin-deficient rats. Endocrinology 1990 Sep;127(3):1495-1501.
11 Pinto J, Raiczyk GB, Huang YP, Rivlin RS. New approaches to the possible prevention of side effects of chemotherapy by nutrition. Cancer 1986 Oct 15;58(8 Suppl):1911-1914.
11 Prasad KN, Edwards-Prasad J, Ramanujam S, Sakamoto A. Vitamin E increases the growth inhibitory and differentiating effects of tumor therapeutic agents on neuroblastoma and glioma cells in culture. Proc Soc Exp Biol Med 1980 Jun;164(2):158-163.
11 Ripoll, EAP, Rama, BN, Webber, MM. Vitamin E enhances the chemotherapeutic effects of Adriamycin on human prostatic carcinoma cells in vitro. J Urol 1986 Aug;136(2):529-531.
11 Raiczyk GB, Rivlin RS, Pinto J. Enhancement of adriamycin-induced mortality during riboflavin administration and riboflavin deficiency in rats. Proc Soc Exp Biol Med 1988 Sep;188(4):495-499.
11 Shinozawa S, Kawasaki H, Gomita Y. [Effect of biological membrane stabilizing drugs (coenzyme Q10, dextran sulfate and reduced glutathione) on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice]. Gan To Kagaku Ryoho. 1996 Jan;23(1):93-98. [Article in Japanese]
11 Shinozawa S, Gomita Y, Araki Y. Protective effects of various drugs on adriamycin (doxorubicin)-induced toxicity and microsomal lipid peroxidation in mice and rats. Biol Pharm Bull. 1993 Nov;16(11):1114-1117.
11 Shinozawa S, Gomita Y, Araki Y. Tissue concentration of doxorubicin (adriamycin) in mouse pretreated with alpha-tocopherol or coenzyme Q10. Acta Med Okayama. 1991 Jun;45(3):195-199.
11 Shinozawa S, Gomita Y, Araki Y. Protection against adriamycin (doxorubicin)-induced toxicity in mice by several clinically used drugs. Acta Med Okayama. 1987 Feb;41(1):11-17.
11 Shinozawa S, Etowo K, Araki Y, Oda T. Effect of coenzyme Q10 on the survival time and lipid peroxidation of adriamycin (doxorubicin) treated mice. Acta Med Okayama. 1984 Feb;38(1):57-63.
11 Schmitt-Graff A, Scheulen ME. Prevention of adriamycin cardiotoxicity by niacin, isocitrate or N-acetyl-cysteine in mice. A morphological study. Pathol Res Pract. 1986 May;181(2):168-74.
11 Shimpo K, Nagatsu T, Yamada K, Sato T, Niimi H, Shamoto M, Takeuchi T, Umezawa H, Fujita K. Ascorbic acid and adriamycin toxicity. Am J Clin Nutr 1991 Dec;54(6 Suppl):1298S-1301S
11 Sonneveld, P. Effect of alpha-tocopherol on the cardiotoxicity of Adriamycin in the rat. Cancer 1978 Jul;62(7):1033-1036.
11 Weiji NI, Cleton, F.T, Osanto S. Free radicals and antioxidants in chemotherapy-induced toxicity. Cancer Treatment Rev 1997 Jul;23(4):209-240. (Review)
11 Wood, LA. Possible prevention of Adriamycin-induced alopecia by tocopherol. N Engl J Med 1985;312:1060. (Letter)
12 J Bioenerg Biomembr. 1994 Aug;26(4):349-58
12 Department of Biology, University of Michigan, Ann Arbor 48109
12 PMID: 7844109 [PubMed - indexed for MEDLINE
13 Schmitt-Graff A, et al. Pathol Res Pract. 1986 May;181(2):168-74; Martinez E, Domingo P. Lancet 1991;338:249; Doroshow JH, et al. J Clin Invest 1981;68:1053-1064; Meyers C, et al. Semin Oncol 1983;10:53-55
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The information in Drug Watch is provided as a courtesy to NewsTarget readers by Applied Health Solutions in cooperation with Healthway Solutions. Although the information is presented with scientific references, we do not wish to imply that this represents a comprehensive list of considerations about any specific drug, herb or nutrient. Nor should this information be considered a substitute for the advice of your doctor, pharmacist, or other healthcare practitioner. Please read the disclaimer about the intentions and limitations of the information provided on these pages. It is important to tell your doctor and pharmacist about all other drugs and nutritional supplements that you are taking if they are recommending a new medication. Copyright © 2007 by Applied Health Solutions, Inc. All rights reserved.
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