Skip to main content
Log in

Prospective study of left ventricular function using radionuclide scans in patients receiving mitoxantrone

  • Clinical
  • Published:
Investigational New Drugs Aims and scope Submit manuscript

Summary

A prospective Phase II study to evaluate the effects of mitoxantrone on left ventricular ejection fraction (LVEF) has been carried out in patients treated with 12 mg/m2 every three weeks. Gated radionuclide cardiac blood pool imaging with assessment of LVEF and wall motion prior to and during graded exercise was performed before the first and every other mitoxantrone course. Ten patients had either a minor response or tumour stabilization while receiving mitoxantrone treatment and underwent serial radionuclide scans during the course of therapy. Three patients who had received adriamycin as part of prior chemotherapy regimens showed no evidence of cardiotoxicity. Seven patients, who had had no prior adriamycin exposure, underwent serial radionuclide studies while receiving up to 204 mg/m2 of mitoxantrone. None of these patients showed evidence of clinically significant myocardial damage. One had a decline in LVEF from 70% to 50% at a maximum dose of 108 mg/m2. An additional patient whose LVEF rose from 57% at baseline to 62% at a total dose of 204 mg/m2 (17 courses) underwent endomyocardial biopsy which showed grade 2.5 anthracyclinetype cardiotoxicity. Serial endomyocardial biopsy studies are indicated in patients on longterm drug therapy to determine the incidence, dose-relationship and severity of potential mitoxantrone associated endomyocardial damage.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. Yap HY, Blumenschein GR, Schell FC, Buzdar AU, Valdivieso M, Brodey GP: Dihydroxyanthracenedione: a promising new drug in the treatment of metastatic breast cancer. Ann Int Med 95:694–697, 1981

    Google Scholar 

  2. deJager R, Cappelaere P, Earl H, Rubens R, Stuart-Harris R, Smith I, Carmichael J, Smythe J, Leiling R, Renard J, van Glabbeke M, Mathe G: Phase II clinical trial of mitoxantrone: 1,4-dihydroxy-5–8-bis((2-((2-hydroxyethyl)-amino)ethyl)amino)9,10 anthracenedione dihydrochloride in solid tumors and lymphomas (Abstract). Proc Am Soc Clin Onc 23:C345, 1982

    Google Scholar 

  3. Neidhart JA, Roach RW: A randomized study of mitoxantrone and adriamycin in breast cancer patients failing primary therapy (Abstract). Proc Am Soc Clin Onc 23:C331, 1982

    Google Scholar 

  4. Estey EH, Keating MJ, McCredie KB, Bodey GP, Freireich EJ: Phase II trial of dihydroxyanthracenedione in acute leukemia (Abstract). Proc Am Asoc Cancer Res 23:442, 1982

    Google Scholar 

  5. VanEcho DA, Shulman PN, Ferrari A, Budman D, Markus SD, Wiernik PH: A phase II trial of mitoxantrone (DHAD, NSC 301739) in adult acute leukemia (AL) (Abstract). Proc Am Soc Clin Onc 23:C513, 1982

    Google Scholar 

  6. Cheng CC, Zbinden G, Zee-Cheng RKY: Comparison of antineoplastic activity of aminoethylaminoanthraquinones and anthracycline antibiotics. J Pharm Sci 68:393–396, 1982

    Google Scholar 

  7. Henderson BM, Dougherty WJ, James VC, Tilley LP, Noble JF: Safety assessment of a new anticancer compound, mitoxantrone, in Beagle dogs: comparison with doxorubicin. I. Clinical observations. Cancer Treat Rep 66:1139–1143, 1982

    Google Scholar 

  8. Sparano BM, Gordon G, Hall C, Iatropoulos MJ, Noble JF: Safety assessment of a new anticancer compound, mitoxantrone, in Beagle dogs: comparison with doxorubicin. II. Histologic and ultrastructural pathology. Cancer Treat Rep 66:1145–1158, 1982

    Google Scholar 

  9. Kharasch ED, Novak RF: Anthracenedione activation by WADPH-cytochrome P-450 reductase; comparison with anthracyclines. Biochem Pharmacol 30:2881–2884, 1982

    Google Scholar 

  10. Alexander J, Dainiak N, Berger HJ, Goldman L, Johnstone D, Reduto L, Duffy T, Schwartz P, Gottschalk A, Zaret BL: Serial assessment of doxorubicine cardiotoxicity with quantitative radionuclide angiocardiography. N Engl J Med 300:278–283, 1979

    Google Scholar 

  11. Ritchie JL, Singer JW, Thorning D, Sorensen SG, Hamilton GW: Anthracycline cardiotoxicity: clinical and pathologic outcomes assessed by radionuclide ejection fraction. Cancer 46:1109–1116, 1980

    Google Scholar 

  12. Borer JS, Bacharach SL, Green MV, Kent KM, Epstein SE, Johnston GS: Real time radionuclide cineangiography in the noninvasive evaluation of global and regional left ventricular function at rest and during exercise in patients with coronary artery disease. N Engl J med 296:839–844, 1977

    Google Scholar 

  13. Borer JS, Kent KM, Bacharach SL, Green MV, Rosing DR, Seides SF, Epstein SE, Johnston GS: Sensitivity, specificity and predictive accuracy of radionuclide cineangiography during exercise in patients with coronary artery disease. Circulation 60:572–582, 1979

    Google Scholar 

  14. Berger HJ, Reduto LA, Johnstone DE Borkowski H, Sands JM, Cohen LS, Langou RA, Gottschalk A, Zaret HL: Global and regional left ventricular response to bicycle exercise in coronary artery disease. Assessment by quantitative radionclide angiocardiography. Am J Med 66:13–21, 1979

    Google Scholar 

  15. Brady TJ, Thrall JH, Clare JM, Rogers W, Ka Lo, Pitt B: Exercise radionuclide ventriculography: practical considerations and sensitivity of coronary artery disease detection. Radiology 132:697–702, 1979

    Google Scholar 

  16. Snedecor GW, Cochran WG, Statistical Methods, Iowa State University Press, 6th ed., Ames I.A., 1967

    Google Scholar 

  17. Billingham ME, Mason JW, Bristow MR, Daniels JR: Anthracycline cardiomyopathy monitored by morphologic changes. Cancer Treat Rep 62:865–872, 1978

    Google Scholar 

  18. Unverferth DV, Unverferth BJ, Balcerzak SP, Bashore TA, Neidhart JA: Cardiac evaluation of mitoxantrone. Cancer Treat Rep 67:343–350, 1983

    Google Scholar 

  19. Crossley RJ: Clinical safety and tolerance of Novantrone (Mitoxantrone). Proc 13th Int Congress Chemother 212 (Symposium Mitoxantrone):20–22, 1983

    Google Scholar 

  20. Fortuin NJ, Weiss JL: Exercise stress testing. Circulation 56:699–712, 1977

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Additional information

Presented in part at the May, 1982, meeting of the American Society of Clinical Oncology, St. Louis, MO.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Aapro, M.S., Alberts, D.S., Woolfenden, J.M. et al. Prospective study of left ventricular function using radionuclide scans in patients receiving mitoxantrone. Invest New Drugs 1, 341–347 (1983). https://doi.org/10.1007/BF00177420

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00177420

Key words

Navigation