Skip to main content
SpringerLink
Log in

Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone

  • ORIGINAL COMMUNICATION
  • Published:
Journal of Neurology Aims and scope Submit manuscript

Abstract

Mitoxantrone is an approved drug for patients with worsening relapsing–remitting, secondary progressive and progressive relapsing multiple sclerosis (MS). From a cohort of 820 MS patients, 52 (6%) were treated with this drug between December 1991 and April 2003. Mitoxantrone was administered at a dose of 12 mg/m2 once a month for three months and then at three–month intervals to reach a total cumulative dose of 144 mg/m2. The left ventricular ejection fraction was checked by radionuclide ventriculography prior to treatment and every six months. Treatment was stopped if the ejection fraction was below 50% in two consecutive ventriculographies performed one to three months apart. Cardiotoxicity during the course of the treatment was not observed. However, three patients developed congestive heart failure 24, 39 and 80 months after the last dose of mitoxantrone. Other cardiac causes were excluded. Two of these patients had been treated previously with cyclophosphamide. All patients first recovered on medical treatment, but two worsened a few months later. One patient remained severely symptomatic in spite of optimal medical treatment. Although mitoxantrone is generally well tolerated and reduces progression of disability and clinical exacerbations, our observation of a delayed cardiotoxicity makes necessary a long–term follow–up of MS patients treated with this drug.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Posner LE, Dukart G, Goldberg J, et al. (1985) Mitoxantrone: an overview of safety and toxicity. Invest New Drugs 3:123–132

    Article  PubMed  Google Scholar 

  2. Gonsette RE, Demonty L (1990) Immunosuppression with mitoxantrone in multiple sclerosis: a pilot study for two years in 22 patients. Neurology 40(Suppl 1):261. Abstract. (537 P)

    PubMed  Google Scholar 

  3. Mauch E, Kornhuber HH, Krapf H, Fetzer U, Laufen H (1992) Treatment of Multiple Sclerosis with Mitoxantrone. Eur Arch Psychiatry Clin Neurosci 242:96–102

    Article  PubMed  Google Scholar 

  4. Kappos L, Gold R, Kündtler E, et al. (1990) Mitoxantrone in the treatment of rapidly progressive MS: a pilot study with serial gadolinium-enhanced MRI. Neurology 40(Suppl 1): 261. Abstract. (539 P)

    PubMed  Google Scholar 

  5. Noseworthy JH, Hopkins MB, Vandervoort MK, et al. (1993) An open-trial evaluation of mitoxantrone in the treatment of progressive MS. Neurology 43:1401–1406

    PubMed  Google Scholar 

  6. Millefiorini E, Gasperini C, Pozzilli C, et al. (1997) Randomized placebo-controlled trial mitoxantrone in relapsingremitting multiple sclerosis: a 24- month clinical and MRI outcome. J Neurol 244:153–159

    Article  PubMed  Google Scholar 

  7. Edan G, Miller D, Clanet M, et al. (1997) Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: A randomised multicentre study of active disease using MRI and clinical criteria. J Neurol Neurosurg Psychiatry 62:112–118

    PubMed  Google Scholar 

  8. van de Wyngaert FA, Beguin C, D’Hooghe MB, et al. (2001) A doubleblind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis. Acta Neurol Belg 101: 210–216

    PubMed  Google Scholar 

  9. Hartung HP, Gonsette R, König N, et al. (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360:2018–2025

    Article  PubMed  Google Scholar 

  10. Gonsette RE (1996) Mitoxantrone immunotherapy in multiple sclerosis. Mult Scler 1:329–332

    PubMed  Google Scholar 

  11. Edan G, Brochet B, Clanet M, et al. (2004) Safety profile of mitoxantrone in a cohort of 802 MS patients. A for year follow-up study. Neurology 62(Suppl 5): P 06093 Abstract

    Google Scholar 

  12. Pai VB, Nahata MC (2000) Cardiotoxicity of chemotherapeutic agents. Drug Safety 22:263–302

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  14. Keefe DL (2001) Anthracycline-induced cardiomyopathy. Semin Oncol 28(4 Suppl 12):2–7

    Article  Google Scholar 

  15. Herman EH, Zhang J, Hasinoff BB, Clark JR, Ferrans VJ (1997) Comparison of the structural changes induced by doxorubicin and mitoxantrone in the heart, kidney and intestine and characterization of the Fe (III)-mitoxantrone complex. J Mol Cell Cardiol 29:2415–2430

    Article  PubMed  Google Scholar 

  16. Andersson BS, Eksborg S, Vidal RF, Sundberg M, Carlberg M (1999) Anthraquinone- induced cell injury: acute toxicity of carminomycin, epirubicin, idarubicin and mitoxantrone in isolated cardiomyocytes. Toxicology 135:11–20

    Article  PubMed  Google Scholar 

  17. Gonsette RE (2003) Mitoxantrone in progressive multiple sclerosis: when and how to treat? J Neurol Sci 206:203–208

    Article  PubMed  Google Scholar 

  18. Steinherz LJ, Steinherz PG, Mangiacasale D, et al. (1981) Cardiac changes with cyclophosphamide. Med Pediatr Oncol 9:417–422

    PubMed  Google Scholar 

  19. Cazin B, Gorin NC, Laporte JP, et al. (1986) Cardiac complications after bone marrow transplantation. A report on a series of 63 consecutive transplantations. Cancer 57:2061–2069

    PubMed  Google Scholar 

  20. Feuillet L, Guedj E, Eusibio A, et al. (2003) Insuffisance cardiaque aiguë chez une patiente traitée par mitoxantrone pour sclérose en plaques. Rev Neurol (Paris) 159:1169–1172

    PubMed  Google Scholar 

  21. McDougall AJ, McLeod JG (2003) Autonomic nervous system function in multiple sclerosis. J Neurol Sci 215:79–85

    Article  PubMed  Google Scholar 

  22. Olindo S, Guillon B, Helias J, Phillibert B, Magne C, Fève JR (2002) Decrease in heart ventricular ejection fraction during multiple sclerosis. Eur J Neurol 9:287–291

    Article  PubMed  Google Scholar 

  23. Beer M, Sandstede J, Weilbach F, et al. (2001) Cardiac metabolism and function in patients with multiple sclerosis: a combined 31P-MR-spectroscopy and MRI study. Rofo Fortschr Geb Rontgenstr Neuen Bildgeb Verfahr 173:399–404

    Article  PubMed  Google Scholar 

  24. Mauch E, Eisenmann S, Hahn A (1999) Mitoxantrone in the treatment of patients with multiple sclerosis(MS): a large single-center experience. Mult Scler 5(Suppl 1):S94

    Article  Google Scholar 

  25. Ghalie RG, Edan G, Laurent M, et al. (2002) Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology 59:909–913

    PubMed  Google Scholar 

  26. The Euro Heart Failure Survey Programme (2003) A survey on the quality of care among patients with heart failure in Europe. Eur Heart J 24:422–474

    Google Scholar 

  27. Aviles A, Arevila N, Diaz Maqueo JC, Gomez T, Garcia R, Jesus Nambo MA (1993) Late cardiac toxicity of doxorubicin, epirubicin, and mitoxantrone therapy for Hodgkin’s disease in adults. Leuk Lymphoma 11:275–279

    PubMed  Google Scholar 

  28. Ritchie JL, Singer JW, Thorning D, Sorensen SG, Hamilton GW (1980) Anthracycline cardiotoxicity: clinical and pathological outcomes assessed by radionuclide ejection fraction. Cancer 46:1109

    PubMed  Google Scholar 

  29. Avasarala JR, Cross AH, Clifford DB, Singer BA, Siegel BA, Abbey EE (2003) Rapid onset mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis. Mult Scler 9:59–62

    Article  PubMed  Google Scholar 

  30. De Castro S, Cartoni D, Millefiorini E, et al. (1995) Noninvasive assessment of mitoxantrone cardiotoxicity in relapsing- remitting multiple sclerosis. J Clin Pharmacol 35:627–632

    PubMed  Google Scholar 

  31. Villani F, Galimberti M, Crippa F (1989) Evaluation of ventricular function by echography and radionuclide angiography in patients treated with mitoxantrone. Drugs Exp Clin Res 15:501–506

    Google Scholar 

  32. Strotmann JM, Spindler M, Weilbach FX, Gold R, Ertl G, Voelker W (2002) Myocardial function in patients with multiple sclerosis treated with lowdose mitoxantrone. Am J Cardiol 89:1222–1225

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Service de Neurologie, Cliniques Universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium

    S. Goffette MD, V. van Pesch MD, PhD & C. J. M. Sindic MD, PhD

  2. Service de Neurologie, Cliniques Universitaires Saint Luc, UCL, 10 Avenue Hippocrate, 1200, Brussels, Belgium

    S. Goffette MD

  3. Service de Cardiologie, Cliniques universitaires Saint Luc, Université catholique de Louvain, Brussels, Belgium

    J. L. Vanoverschelde MD, PhD

  4. Service de Cardiologie, Centre Hospitalier de l’Ardenne, Libramont, Belgium

    E. Morandini MD

Authors
  1. S. Goffette MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. V. van Pesch MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J. L. Vanoverschelde MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. E. Morandini MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C. J. M. Sindic MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to S. Goffette MD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Goffette, S., van Pesch, V., Vanoverschelde, J.L. et al. Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone. J Neurol 252, 1217–1222 (2005). https://doi.org/10.1007/s00415-005-0839-3

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00415-005-0839-3

Key words

Search

Navigation