In two groups of female patients with metastatic breast cancer who had all been pretreated with doxorubicin (350 mg/m2), acute cardiac effects following i.v. doxorubicin bolus injection (60 mg/m2) were recorded on the basis of systolic time intervals (STI). In six patients who received doxorubicin only the ratio between the heart-beat-corrected preejection period and left ventricular ejection time (PEPI:LVETI) as well as the PEP index were found to be significantly increased with a peak at 6 h following drug infusion (P<0.001). Another six patients received an identical chemotherapeutic regimen and, in addition, a combination of tocopherol (200 mg i.m. 6 h before treatment) and nifedipine (60 mg p.o. daily from 2 days before doxorubicin infusion). In the pretreatment group, the PEPI: LVETI ration and PEP index remained unchanged during the posttreatment period. Pharmacokinetic analysis of drug concentrations in the plasma revealed a significantly accelerated distribution and elimination of doxorubicin after combined tocopherol and nifedipine pretreatment, although no statistically significant differences could be found in calculated drug levels in the peripheral compartment between both treatment groups. Our results indicate that acute cardiac reactions reflected by changes in STI values can be prevented by combined tocopherol and nifedipine pretreatment.
This is a preview of subscription content, log in to check access.
Buy single article
Instant access to the full article PDF.
Price includes VAT for USA
Subscribe to journal
Immediate online access to all issues from 2019. Subscription will auto renew annually.
This is the net price. Taxes to be calculated in checkout.
Bristow MR, Mason JW, Billingham ME, Daniels JR (1981) Dose-effect and structure-function relationships in doxorubicin cardiomyopathy. Am Heart J 102:709–718
Benjamin RS, Mackay B, Ewer M, Wallace S, Valdivieso M, Rasmussen SL Blumenschein GR, Freireich EJ (1982) Reduction of doxorubicin cardiotoxicity by prolonged continuous intravenous infusion. Ann Intern Med 96:133–139
Bühner R, Biedert S, Miura D (1980) Erhöhung des frei-ionisierten zytoplasmatischen Calciums als Ursache der Adriamycin-Kardiomyopathie. Klin Wochenschr 58:747–748
Chan KK, Cohen JL, Gross JF, Himmelstein KJ, Bateman, JR, Tsu-Lee Y, Marlis AS (1978) Predicition of adriamycin disposition in cancer patients using a physiologic, pharmacokinetic model. Cancer Treat Rep 62:1161–1171
Di Fronzo G, Bertuzzi A, Ronchi E, Villani FP, Ronchetti L (1979) Evaluation of cardiac activity and pharmacokinetic analysis of 3H-adriamycin in patients pretreated with beta-methyldigoxin. Cancer Chemother Pharmacol 2:169–173
Domae N, Sawada H, Matsuyama E, Konishi T, Uchino H (1981) Cardiomyopathy and other chronic toxic effects induced in rabbits by doxorubicin and possible prevention by coenzyme Q10. Cancer Treat Rep 6579–91
Ehninger G, Stocker HJ, Proksch B, Wilms K (1980) Die Pharmakokinetik von Adriamycin und Adriamycin-Metaboliten. Klin Wochenschr 58:927–934
Fleckenstein A (1977) Specific pharmacology of calcium in myocardium, cardiac pace markers, and vascular smooth muscle. Ann Rev Pharmacol Toxicol 17:149–166
Gomeni C, Gomeni R (1978) IGPHARM: Interactive graphic package for pharmacokinetic analysis. Comput Biomed Res 11:345–361
Gosalvez M, Rossum G, Blanco MF (1979), Inhibition of sodium-potassium activated adenosine 5,4-triphosphatase and ion transport by adriamycin. Cancer Res 39:257–261
Khalil MA, Soto AP, Maroongroge D, Bekheit-Saad S, Buzdar AU, Blumenschein GR, Hortobagyi N, Tashima CK, Wiseman CL, Schullenberger CC (1979) Electrocardiographic changes after adriaycin chemotherapy. Cancer 43:465–471
Lefrak EA, Pitha J, Rosenheim S, Gottlieb JA (1973) A clinicopathologic analysis of adriamycin cardiotoxicity. Cancer 32:302–314
Lenaz L, Page JA (1976) Cardiotoxicity of adriamycin and related anthracyclines. Cancer Treat Rev 3:111–120
Lenzhofer R, Magometschnigg D, Dudczak, Czerni C, Bolebruch C, Moser K (1983a) Indication of reduced doxorubicin induced cardiac toxicity by additional treatment with antioxidative substances. Experientia 39:62–64
Lenzhofer R, Bolebruch C, Moser K (1983b) Experimental studies on the prevention of adriamycin induced cardiomyopathy. Z Krebsforsch Klin Onkol 105/2: Ex 13
Moore L, Landon EJ, Cooney DA (1977) Inhibition of the cardiac mitochondrial calcium pump by adriamycin in vitro. Biochem Med 18:131–138
Myers CE, McGuire WP, Liss RH, Ifrim J, Grotzinger K, Young RC (1977) Adriamycin: The role of lipid peroxidation in cardiac toxicity and tumor response. Science 197:165–167
Olson HM, Young DM, Prieur DJ, Le Roy AF, Reagan RL (1974) Electrolyte and morphologic alterations of myocardium in adriamycin-treated rabbits. Am J Pathol 77:439–454
Schildberg FW, Fleckenstein A, Klek J (1964) Die Bedeutung der extrazellulären Calziumkonzentration für die Spaltung von energiereichem Phosphat in ruhendem und tätigem Myokardgewebe. Pflügers Arch 283:137–150
Taylor D, Hochstein P (1978) Inhibition by adriamycin of a Metmyoglobin reductase from beef-heart. Biochem Pharmacol 27:2079–2082
Von Hoff DD, Layard MW, Basa P, Davis HL, Von Hoff AL, Rozencweig M, Muggia FM (1979) Risk factors for doxorubicin-induced congestive heart failure. Ann Intern Med 91710–717
Weissler AM, Harris WS, Schoenfeld CD (1969) Bedside technics for the evaluation of ventricular funtion in man. Am J Cardiol 23:577–583
Wortman JE, Lucas VS, Thiele D, Logue GL (1979) Sudden death during doxorubicin administration. Cancer 44:1588–1591
Zähringer J (1981) The regulation of protein synthesis in heart muscle under normal conditions and in the adriamycin-cardiomyopathy. Klin Wochenschr 59:1273–1287
Zunino F, Gambetta R, Di Marco A, Zaccara A (1972) Interactions of daunomycin and its derivatives with DNA. Biochem Biophys Acta 277:489–498
About this article
Cite this article
Lenzhofer, R., Ganzinger, U., Rameis, H. et al. Acute cardiac toxicity in patients after doxorubicin treatment and the effect of combined tocopherol and nifedipine pretreatment. J Cancer Res Clin Oncol 106, 143–147 (1983). https://doi.org/10.1007/BF00395393
- Acute cardiac toxicity