Skip to main content
Erschienen in: Der Nervenarzt 10/2003

01.10.2003 | Aktuelles

Mitoxantron zur Therapie der Multiplen Sklerose

verfasst von: B. C. Kieseier, R. Gold, Prof. Dr. H.-P. Hartung

Erschienen in: Der Nervenarzt | Ausgabe 10/2003

Einloggen, um Zugang zu erhalten

Zusammenfassung

Die Veröffentlichung der MIMS-Studie (Mitoxantrone in Multiple Sclerosis), die Zulassung durch die deutschen Gesundheitsbehörden sowie die Empfehlungen der MS-Therapie-Konsenus-Gruppe (MSTKG) stützen den therapeutischen Einsatz von Mitoxantron bei Patienten mit aktiver Multipler Sklerose. Der vorliegende Artikel gibt eine Übersicht über relevante vorklinische und klinische Studien, diskutiert relevante unerwünschte Wirkungen der Substanz und definiert den Stellenwert von Mitoxantron im Arsenal der therapeutischen Möglichkeiten im Kampf gegen diese behindernde Erkrankung.
Literatur
1.
Zurück zum Zitat Bellosillo B, Colomer D, Pons G, Gil J (1998) Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol 100:142–6CrossRefPubMed Bellosillo B, Colomer D, Pons G, Gil J (1998) Mitoxantrone, a topoisomerase II inhibitor, induces apoptosis of B-chronic lymphocytic leukaemia cells. Br J Haematol 100:142–6CrossRefPubMed
2.
Zurück zum Zitat Boland MP, Fitzgerald KA, O'Neill LA (2000) Topoisomerase II is required for mitoxantrone to signal nuclear factor kappa B activation in HL60 cells. J Biol Chem 275:25231–8CrossRefPubMed Boland MP, Fitzgerald KA, O'Neill LA (2000) Topoisomerase II is required for mitoxantrone to signal nuclear factor kappa B activation in HL60 cells. J Biol Chem 275:25231–8CrossRefPubMed
3.
Zurück zum Zitat Cattaneo C, Almici C, Borlenghi E, Motta M, Rossi G (2003) A case of acute promyelocytic leukaemia following mitoxantrone treatment of multiple sclerosis. Leukemia 17:985–986CrossRefPubMed Cattaneo C, Almici C, Borlenghi E, Motta M, Rossi G (2003) A case of acute promyelocytic leukaemia following mitoxantrone treatment of multiple sclerosis. Leukemia 17:985–986CrossRefPubMed
4.
Zurück zum Zitat Chan A, Weilbach FX, Toyka KV, Gold R (2002) Mitoxantrone-induced immunological changes in mitoxantrone-induced immunological changes in peripheral blood leukocytes of MS-patients. Mult Scler 8:S69 Chan A, Weilbach FX, Toyka KV, Gold R (2002) Mitoxantrone-induced immunological changes in mitoxantrone-induced immunological changes in peripheral blood leukocytes of MS-patients. Mult Scler 8:S69
5.
Zurück zum Zitat Doroshow JH (1983) Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. Cancer Res 43:4543–5451 Doroshow JH (1983) Anthracycline antibiotic-stimulated superoxide, hydrogen peroxide, and hydroxyl radical production by NADH dehydrogenase. Cancer Res 43:4543–5451
6.
Zurück zum Zitat 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 62:112–118PubMed 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 62:112–118PubMed
7.
Zurück zum Zitat Edan G, Morrissey SP, Hartung HP (2002) Use of mitoxantrone to treat multiple sclerosis. In: Cohen JA, Rudick RA (eds) Multiple Sclerosis Therapeutics. Martin Dunitz, London, pp 403–426 Edan G, Morrissey SP, Hartung HP (2002) Use of mitoxantrone to treat multiple sclerosis. In: Cohen JA, Rudick RA (eds) Multiple Sclerosis Therapeutics. Martin Dunitz, London, pp 403–426
8.
Zurück zum Zitat Ehrke MJ, Maccubbin D, Ryoyama K, Cohen SA, Mihich E (1986) Correlation between adriamycin-induced augmentation of interleukin 2 production and of cell-mediated cytotoxicity in mice. Cancer Res 46:54–60PubMed Ehrke MJ, Maccubbin D, Ryoyama K, Cohen SA, Mihich E (1986) Correlation between adriamycin-induced augmentation of interleukin 2 production and of cell-mediated cytotoxicity in mice. Cancer Res 46:54–60PubMed
9.
Zurück zum Zitat Faulds D, Balfour JA, Chrisp P, Langtry HD (1991) Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 41:400–449PubMed Faulds D, Balfour JA, Chrisp P, Langtry HD (1991) Mitoxantrone. A review of its pharmacodynamic and pharmacokinetic properties, and therapeutic potential in the chemotherapy of cancer. Drugs 41:400–449PubMed
10.
Zurück zum Zitat Fidler JM, DeJoy SQ, Gibbons JJ Jr (1986) Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function. J Immunol 137:727–732PubMed Fidler JM, DeJoy SQ, Gibbons JJ Jr (1986) Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function. J Immunol 137:727–732PubMed
11.
Zurück zum Zitat Fidler JM, DeJoy SQ, Smith FR, 3rd, Gibbons JJ Jr (1986) Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone-treated mice. J Immunol 136:2747–2754PubMed Fidler JM, DeJoy SQ, Smith FR, 3rd, Gibbons JJ Jr (1986) Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone-treated mice. J Immunol 136:2747–2754PubMed
12.
Zurück zum Zitat Gbadamosi J, Buhmann C, Tessmer W, Moench A, Haag F, Heesen C (2003) Effects of Mitoxantrone on Multiple Sclerosis Patients' Lymphocyte Subpopulations and Production of Immunoglobulin, TNF-alpha and IL-10. Eur Neurol 49:137–141CrossRefPubMed Gbadamosi J, Buhmann C, Tessmer W, Moench A, Haag F, Heesen C (2003) Effects of Mitoxantrone on Multiple Sclerosis Patients' Lymphocyte Subpopulations and Production of Immunoglobulin, TNF-alpha and IL-10. Eur Neurol 49:137–141CrossRefPubMed
13.
Zurück zum Zitat Ghalie RG, Edan G, Laurent M et al. (2002) Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology 59:909–913PubMed Ghalie RG, Edan G, Laurent M et al. (2002) Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology 59:909–913PubMed
14.
Zurück zum Zitat Ghalie RG, Mauch E, Edan G et al. (2002) A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis. Mult Scler 8:441–445CrossRefPubMed Ghalie RG, Mauch E, Edan G et al. (2002) A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis. Mult Scler 8:441–445CrossRefPubMed
15.
Zurück zum Zitat Gonsette RE, Demonty L (1990) Immunosuppression with mitoxantrone in multiple sclerosis: a pilot study for 2 years in 22 patients. Neurology 40:S261 Gonsette RE, Demonty L (1990) Immunosuppression with mitoxantrone in multiple sclerosis: a pilot study for 2 years in 22 patients. Neurology 40:S261
16.
Zurück zum Zitat Hartung HP, Gonsette R, Konig N et al. (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360:2018–2025CrossRefPubMed Hartung HP, Gonsette R, Konig N et al. (2002) Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial. Lancet 360:2018–2025CrossRefPubMed
17.
Zurück zum Zitat Heesen C, Bruegmann M, Gbdamosi J, Koch E, Monch A, Buhmann C (2003) Therapy-related acute myelogenous leukaemia (t-AML) in a patient with multiple sclerosis treated with mitoxantrone. Mult Scler 9:213–214CrossRefPubMed Heesen C, Bruegmann M, Gbdamosi J, Koch E, Monch A, Buhmann C (2003) Therapy-related acute myelogenous leukaemia (t-AML) in a patient with multiple sclerosis treated with mitoxantrone. Mult Scler 9:213–214CrossRefPubMed
18.
Zurück zum Zitat Herman EH, Zhang J, Rifai N et al. (2001) The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity. Cancer Chemother Pharmacol 48:297–304CrossRefPubMed Herman EH, Zhang J, Rifai N et al. (2001) The use of serum levels of cardiac troponin T to compare the protective activity of dexrazoxane against doxorubicin- and mitoxantrone-induced cardiotoxicity. Cancer Chemother Pharmacol 48:297–304CrossRefPubMed
19.
Zurück zum Zitat Kappos L, Gold R, Hofmann E, Keil W, Clauß R (1992) Multiple sclerosis: diagnostic criteria and the role of contrast-enhanced MRI. Medicom 127–135 Kappos L, Gold R, Hofmann E, Keil W, Clauß R (1992) Multiple sclerosis: diagnostic criteria and the role of contrast-enhanced MRI. Medicom 127–135
20.
Zurück zum Zitat Lenk H, Müller U, Tanneberger S (1987) Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. Anticancer Res 7:1257–1264PubMed Lenk H, Müller U, Tanneberger S (1987) Mitoxantrone: mechanism of action, antitumor activity, pharmacokinetics, efficacy in the treatment of solid tumors and lymphomas, and toxicity. Anticancer Res 7:1257–1264PubMed
21.
Zurück zum Zitat Levine S, Saltzman A (1986) Regional suppression, therapy after onset and prevention of relapses in experimental allergic encephalomyelitis by mitoxantrone. J Neuroimmunol 13:175–181CrossRefPubMed Levine S, Saltzman A (1986) Regional suppression, therapy after onset and prevention of relapses in experimental allergic encephalomyelitis by mitoxantrone. J Neuroimmunol 13:175–181CrossRefPubMed
22.
Zurück zum Zitat Lublin FD, Lavasa M, Viti C, Knobler RL (1987) Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin Immunol Immunopathol 45:122–128PubMed Lublin FD, Lavasa M, Viti C, Knobler RL (1987) Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin Immunol Immunopathol 45:122–128PubMed
23.
Zurück zum Zitat Mauch E, Kornhuber HH, Krapf H, Fetzer U, Laufen H (1992) Treatment of multiple sclerosis with mitoxantrone. Eur Arch Psychiatry Clin Neurosci 242:96–102PubMed Mauch E, Kornhuber HH, Krapf H, Fetzer U, Laufen H (1992) Treatment of multiple sclerosis with mitoxantrone. Eur Arch Psychiatry Clin Neurosci 242:96–102PubMed
24.
Zurück zum Zitat Millefiorini E, Gasperini C, Pozzilli C et al. (1997) Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol 244:153–159CrossRefPubMed Millefiorini E, Gasperini C, Pozzilli C et al. (1997) Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome. J Neurol 244:153–159CrossRefPubMed
25.
Zurück zum Zitat Mogenet I, Simiand-Erdociain E, Canonge JM, Pris J (2003) Acute myelogenous leukemia following mitoxantrone treatment for multiple sclerosis. Ann Pharmacother 37:747–748CrossRef Mogenet I, Simiand-Erdociain E, Canonge JM, Pris J (2003) Acute myelogenous leukemia following mitoxantrone treatment for multiple sclerosis. Ann Pharmacother 37:747–748CrossRef
26.
Zurück zum Zitat Noseworthy JH, Hopkins MB, Vandervoort MK et al. (1993) An open-trial evaluation of mitoxantrone in the treatment of progressive MS. Neurology 43:1401–1406PubMed Noseworthy JH, Hopkins MB, Vandervoort MK et al. (1993) An open-trial evaluation of mitoxantrone in the treatment of progressive MS. Neurology 43:1401–1406PubMed
27.
Zurück zum Zitat Pette M, Gold R, Pette DF, Hartung HP, Toyka KV (1995) Mafosfamide induces DNA fragmentation and apoptosis in human T-lymphocytes. A possible mechanism of its immunosuppressive action. Immunopharmacology 30:59–69CrossRefPubMed Pette M, Gold R, Pette DF, Hartung HP, Toyka KV (1995) Mafosfamide induces DNA fragmentation and apoptosis in human T-lymphocytes. A possible mechanism of its immunosuppressive action. Immunopharmacology 30:59–69CrossRefPubMed
28.
Zurück zum Zitat Pette M, Hartung HP (2003) Mitoxantrontherapie bei multipler Sklerose—Stand 2002. Akt Neurol 30:71–75CrossRef Pette M, Hartung HP (2003) Mitoxantrontherapie bei multipler Sklerose—Stand 2002. Akt Neurol 30:71–75CrossRef
29.
Zurück zum Zitat Ridge SC, Sloboda AE, McReynolds RA, Levine S, Oronsky AL, Kerwar SS (1985) Suppression of experimental allergic encephalomyelitis by mitoxantrone. Clin Immunol Immunopathol 35:35–42PubMed Ridge SC, Sloboda AE, McReynolds RA, Levine S, Oronsky AL, Kerwar SS (1985) Suppression of experimental allergic encephalomyelitis by mitoxantrone. Clin Immunol Immunopathol 35:35–42PubMed
30.
Zurück zum Zitat Rieckmann P, Toyka KV (2002) Immunmodulatorische Stufentherapie der Multiplen Sklerose. Nervenarzt 73:556–563CrossRefPubMed Rieckmann P, Toyka KV (2002) Immunmodulatorische Stufentherapie der Multiplen Sklerose. Nervenarzt 73:556–563CrossRefPubMed
31.
Zurück zum Zitat Robison TW, Giri SN (1986) Effects of chronic administration of doxorubicin on myocardial beta-adrenergic receptors. Life Sci 39:731–736CrossRefPubMed Robison TW, Giri SN (1986) Effects of chronic administration of doxorubicin on myocardial beta-adrenergic receptors. Life Sci 39:731–736CrossRefPubMed
32.
Zurück zum Zitat Seymour L, Bramwell V, Moran LA (1999) Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group. Cancer Prev Control 3:145–159PubMed Seymour L, Bramwell V, Moran LA (1999) Use of dexrazoxane as a cardioprotectant in patients receiving doxorubicin or epirubicin chemotherapy for the treatment of cancer. The Provincial Systemic Treatment Disease Site Group. Cancer Prev Control 3:145–159PubMed
33.
Zurück zum Zitat Singal PK, Deally CM, Weinberg LE (1987) Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol 19:817–828PubMed Singal PK, Deally CM, Weinberg LE (1987) Subcellular effects of adriamycin in the heart: a concise review. J Mol Cell Cardiol 19:817–828PubMed
34.
Zurück zum Zitat Singal PK, Pierce GN (1986) Adriamycin stimulates low-affinity Ca2+ binding and lipid peroxidation but depresses myocardial function. Am J Physiol 250:H419–425PubMed Singal PK, Pierce GN (1986) Adriamycin stimulates low-affinity Ca2+ binding and lipid peroxidation but depresses myocardial function. Am J Physiol 250:H419–425PubMed
35.
Zurück zum Zitat Spindler M, Weilbach FX, Beer M et al. (2003) Non-invasive functional and biochemical assessment of mitroxantrone cardiotoxicity in patients with multiple sclerosis. J Cardiovasc Pharmacol. In press Spindler M, Weilbach FX, Beer M et al. (2003) Non-invasive functional and biochemical assessment of mitroxantrone cardiotoxicity in patients with multiple sclerosis. J Cardiovasc Pharmacol. In press
36.
Zurück zum Zitat 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 12:441–442CrossRefPubMed 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 12:441–442CrossRefPubMed
37.
Zurück zum Zitat Weilbach FX, Toyka KV, Gold R (2000) Combination therapy with the iron chelator dexrazoxane augments therapeutic efficacy of mitoxantone in experimental autoimmune encephalomyelitis in Lewis rats. Rev Neurol 156:127PubMed Weilbach FX, Toyka KV, Gold R (2000) Combination therapy with the iron chelator dexrazoxane augments therapeutic efficacy of mitoxantone in experimental autoimmune encephalomyelitis in Lewis rats. Rev Neurol 156:127PubMed
38.
Zurück zum Zitat Wiendl H, Kieseier BC (2003) Disease-modifying therapies in multiple sclerosis: an update on recent and ongoing trials and future strategies. Expert Opin Investig Drugs 12:689–712PubMed Wiendl H, Kieseier BC (2003) Disease-modifying therapies in multiple sclerosis: an update on recent and ongoing trials and future strategies. Expert Opin Investig Drugs 12:689–712PubMed
Metadaten
Titel
Mitoxantron zur Therapie der Multiplen Sklerose
verfasst von
B. C. Kieseier
R. Gold
Prof. Dr. H.-P. Hartung
Publikationsdatum
01.10.2003
Verlag
Springer-Verlag
Erschienen in
Der Nervenarzt / Ausgabe 10/2003
Print ISSN: 0028-2804
Elektronische ISSN: 1433-0407
DOI
https://doi.org/10.1007/s00115-003-1566-6

Weitere Artikel der Ausgabe 10/2003

Der Nervenarzt 10/2003 Zur Ausgabe

Übersicht

Chemokine

Neu in den Fachgebieten Neurologie und Psychiatrie