Twenty-one patients with various advanced neoplasms were treated with 60 to 75 mg/m2 of doxorubicin every 3 to 4 weeks and monitored by ECG and systolic time intervals (PEP/LVET) with the aim to establish whether a pretreatment with beta-methyldigoxin, administered intermittently, could prevent doxorubicin-induced cardiotoxicity. It was found that until patients received digitalis pretreatment the PEP/LVET ratio did not change significantly from mean basal values even after the highest cumulative dosages of doxorubicin. However, after interruption of the therapy with both drugs, PEP/LVET increased reaching a value not significantly different from that observed in a comparable group of patients treated only with doxorubicin. Moreover, of 9 patients who reached the cumulative limiting dose, 2 developed congestive heart failure. These results question the possibility that digitalis administered according to an intermittent treatment scheme may prevent doxorubicin cardiomyopathy.
Get full access to this article
View all access options for this article.
References
1.
ArenaE.D'AlessandroN.DusonchetL.GebbiaN.GerbasiF.SanguedolceR.RausaL.: Influence of pharmacokinetic variations on the pharmacologic properties of adriamycin.In: International Symposium on Adriamycin, CarterS.K.Di MarcoA.GhioneM.KrakoffI.MathèG. (Eds.), pp. 96–116. New York, Springer, 1972.
2.
BachurN.R.ReiterW.ArenaE.: Cardiac uptake of adriamycin (NSC-123127) not affected by Strophanthin G (NSC-25485).Cancer Chemother. Rep., 59: 765–766, 1975.
3.
BalcuevaE.SchaibergerC.MasudK.DimitrovN.: Determination of early adriamycin-induced cardiotoxicity by impedance cardiography.In: Current Chemotheraphy, SiegenthalerA.LuthyR. (Eds.), pp. 1253–1255. Washington D.C.: American Society Microbiology, 1978.
4.
BeermannB.: The gastrointestinal uptake of methyldigoxin 12 a-3H in man.Eur. J. Clin. Pharmacol., 5: 28–35, 1972.
5.
BlumE.H.CarterS.K.: Adriamycin. A new anticancer drug wtih significant clinical activity.Ann. Intern. Med., 80: 249–254, 1974.
6.
BurnsJ.H.DowJ.W.: Daunorubicin-induced myocardial failure: Reversal by digoxin of an inability to use ATP for contraction.J. Mol. Cell. Cardiol., 12: 95–108, 1980.
7.
CaroniP.VillaniF.CarafoliE.: Inhibition of Na/Ca exchange in dog heart sarcolemmal vesicles by anthracycline analogs.FEBS Lett., 130: 184–186, 1981.
8.
GottliebJ.A.LefrakE.A.O'BryanR.M.: Total adriamycin cardiomyopathy. Prevention by dose limitation.Proc. Am. Ass. Cancer Res., 14: 88, 1973.
9.
GuthrieD.GibsonA.L.: Doxorubicin cardiotoxicity. Possible role of digoxin in its prevention.Br. Med. J., 2: 1447–1449, 1977.
10.
LefrakE.A.PithaJ.RosenheimS.GottliebJ.A.: A clinicopathologic analysis of adriamycin cardiotoxicity.Cancer, 32: 302–314, 1973.
11.
NeccoA.DasdiaT.Di FrancescoD.FerroniA.: Action of ouabain, oligomycin and glucagon on cultured heart cells treated with adriamycin.Pharmacol. Res. Commun., 8: 105–109, 1976.
12.
PragaC.BerettaG.VigoP.L.LenazG.R.PolliniC.BonadonnaG.Adriamycin cardiotoxicity. A survey of 1273 patients.Cancer Treat. Rep., 63: 827–834, 1979.
13.
RonchettiL.StramezziM.BertuzziA.RonchiE.Di FronzoG.: Action of deslanatoside C on adriamycin uptake by isolated rabbit atria.Pharmacol. Res. Commun., 9: 465–478, 1977.
14.
RoudatR.TaytardA.DallocchioM.FreòurP.BricaudH.: Myocardiopathies a l'adriamycine.Surveillance echocardiographique. Protection par la digoxine? VIII European Congress of Cardiology. Ab. 1758, p. 1754, 1980.
15.
SmithB.J.KunduD.: Digoxin does not prevent daunorubicin or adriamycin from binding to rat heart muscle.Br. J. Cancer, 33: 232–233, 1976.
16.
SombergJ.GaginN.LevittB.NounousH.ReadyP.LeonardD.AnagnostopoulosC.: Blockade of tissue uptake of the antineoplastic agent, doxorubicin.J. Pharmacol. Exp. Ther., 204: 226–229, 1977.
17.
VillaniF.BerettaG.PagnoniA.GuindaniA.: Adriamycin cardiotoxicity in man. Effect of pretreatment with beta-methyl-digoxin. A polygraphic study. In: Chemotherapy, Vol. 8, HellmannK.ConnorsT.A. (Eds.), pp. 491–499. New York, Plenum Press1976.
18.
VillaniF.PiccininiF.MerelliP.FavalliL.: Influence of adriamycin on calcium exchangeability in cardiac muscle and its modification by ouabain.Biochem. Pharmacol., 27: 985–987, 1978.
19.
VillaniF.BerettaG.GuindaniA.: Evaluation of early doxorubicin-induced cardiotoxicity by means of systolic time intervals.Cancer Chemother. Pharmacol., 3: 249–251, 1979.
20.
VillaniF.FavalliL.PiccininiF.: Relationship between the effect on calcium turnover and early cardiotoxicity of doxorubicin and 4'-epi-doxorubicin in guinea pig heart muscle.Tumori, 66: 689–697, 1980.
21.
VillaniF.GuindaniA.FavalliL.MontiE.ChiariM.C.PiccininiF.: Role of calcium in the early and delayed cardiotoxicity of anthracyclines: Experimental and clinical aspects.In: Organ-directed toxicity, chemical indices and mechanism, BrownS.S.DaviesD.S. (Eds.), pp. 327–333, Pergamon Press, Oxford and New York, 1981.
22.
WeisslerA.M.KamenA.R.BernsteinR.S.SchoenfeldD.C.CohenS.: The effect of deslanoside on the duration of the phases of ventricular systole in man.Am. J. Cardiol., 15: 153–169, 1965.
23.
WeisslerA.M.HarrisW.S.SchoenfeldD.C.: Bedside technic for the evaluation of ventricular function in man.Am. J. Cardiol., 23: 577–583, 1969.
