Abstract
Mitoxantrone (MTX) is a synthetic antineoplastic cytotoxic drug, active both on proliferative and non-proliferative cells. The efficacy of MTX has been suggested by many open-label or observational studies and demonstrated in four randomized controlled clinical trials (RCTs). It is indicated for reducing neurological disability and the frequency of clinical relapses in patients with progressive relapsing and worsening relapsing–remitting MS patients. The short-term most frequent adverse events observed in RCTs have been nausea/vomiting, alopecia, an increased risk of urinary and respiratory tract infections, phlebitis, transitory leukopenia, amenorrhea in female patients and infertility. However, the most serious risks of the drug are represented by potential cardiotoxicity and leukaemia, whose incidence seems to be higher than previously reported. Therefore, all potential serious adverse events should be carefully considered against the potential relevant benefits of MTX treatment on every single MS patient.
Similar content being viewed by others
References
Lublin FD, Lavasa M, Viti C, Knobler RL (1987) Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin Immunol Immunopathol 45(1):122–128
Ehninger G, Proksch B, Heinzel G, Woodward DL (1986) Clinical pharmacology of mitoxantrone. Cancer Treat Rep 70(12):1373–1378
Hartung HP, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP et al (2002) A placebo-controlled, double-blind, randomised, multicentre trial of mitoxantrone in progressive multiple sclerosis. Lancet 360:2018–2025
Millefiorini E, Gasperini C, Pozzilli C, D’Andrea F, Bastianello S, Trojano M et al (1997) Randomized placebo-controlled trial of mitoxantrone in relapsing–remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol 244:153–159
Edan G, Miller D, Clanet M, Confavreux C, Lyon-Caen O, Lubetzki C 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
Van de Wyngaert FA, Beguin C, D’Hooghe MB, Dooms G, Lissoir F, Carton H, Sindic CJ (2001) A double-blind clinical trial of mitoxantrone versus methylprednisolone in relapsing, secondary progressive multiple sclerosis. Acta Neurol Belg 101(4):210–216
Martinelli Boneschi F, Rovaris M, Capra R, Comi G. (2005) Mitoxantrone for multiple sclerosis. Cochrane Database Syst Rev (4):CD002127
Fox EJ (2006) Management of worsening multiple sclerosis with mitoxantrone: a review. Clin Ther 28(4):461–474
Clerico M, Contessa G, Durelli L (2008) The therapy of multiple sclerosis with immune-modulating or immunosuppressive drug. A critical evaluation based upon evidence based parameters and published systematic reviews. Clin Neurol Neurosurg 110(9):878–885
Cocco E, Marchi P, Sardu C, Russo P, Paolillo A, Mascia M, Solla M, Frau J, Lorefice L, Massole S, Floris G, Marrosu M (2007) Mitoxantrone treatment in patients with early relapsing–remitting multiple sclerosis. Mult Scler 13(8):975–980
Le Page E, Leray E, Taurin G, Coustans M, Chaperon J, Morrissey SP, Edan G (2008) Mitoxantrone as induction treatment in aggressive relapsing remitting multiple sclerosis: treatment response factors in a 5 year follow-up observational study of 100 consecutive patients. J Neurol Neurosurg Psychiatry 79(1):52–56
Ramtahal J, Jacob A, Das K, Boggild M (2006) Sequential maintenance treatment with glatiramer acetate after mitoxantrone is safe and can limit exposure to immunosuppression in very active, relapsing remitting multiple sclerosis. J Neurol 253(9):1160–1164
Cohen BA, Mikol DD (2004) Mitoxantrone treatment of multiple sclerosis: safety considerations. Neurology 63(Suppl 6):S28–S32
Pattoneri P, Pelà G, Montanari E, Pesci I, Moruzzi P, Borghetti A (2007) Evaluation of the myocardial performance index for early detection of mitoxantrone-induced cardiotoxicity in patients with multiple sclerosis. Eur J Echocardiogr 8(2):144–150
Beaumont M, Sanz M, Carli PM, Maloisel F, Thomas X, Detourmignies L, Guerci A, Gratecos N, Rayon C, San Miguel J, Odriozola J, Cahn JY, Huguet F, Vekhof A, Stamatoulas A, Dombret H, Capote F, Esteve J, Stoppa AM, Fenaux P (2003) Therapy-related acute promyelocytic leukaemia. J Clin Oncol 21(11):2123–2137
Vicari AM, Ciceri F, Folli F, Lanzi R, Colombo B, Comi G, Camba L (1998) Acute promyelocytic leukemia following mitoxantrone as single agent for the treatment of multiple sclerosis. Leukemia 12(3):441–442
Ghalie RG, Mauch E, Edan G, Hartung HP, Gonsette RE, Eisenmann S, Le Page E, Butine MD, De Goodkin DE (2002) A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis. Mult Scler 8(5):441–445
Le Page E, Leray E, Brochet B et al (2006) Long term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: final report. ECTRIMS Madrid, September 2006, abstract Multiple Sclerosis
Ellis RJ, Boggild M (2009)Therapy-related acute leukemia with mitoxantrone: what is the risk and can we minimize it? Mult Scler 15(4):505–508
Rammohan K, Kita M, Lynn J, Dawson D, Bennet R, AL-Sabbagh A (2008) Post-marketing reports of acute leukemia in mitoxantrone-treated multiple sclerosis patients. Mult Scler 14:S175
Martinelli V, Amato MP, Bellantonio P (2008) Incidence of acute leukaemia in multiple sclerosis patients treated with mitoxantrone. Neurol Sci Suppl 29:S75
Conflict of interest statement
The authors declare that they have no conflict of interest related to the publication of this article.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Martinelli, V., Radaelli, M., Straffi, L. et al. Mitoxantrone: benefits and risks in multiple sclerosis patients. Neurol Sci 30 (Suppl 2), 167–170 (2009). https://doi.org/10.1007/s10072-009-0142-7
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10072-009-0142-7