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Last updated: 14 Jan 2016

Mitoxantrone

Summary
Trade name: 
Novantrone
(14)
Novantrone
OSI Pharmaceuticals, 2012
Accessed on 13 Jan 2012 from http://www.osip.com/novantrone.
Class: 
Immunosuppressor
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Target: 
T cells
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
B cell proliferation
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Macrophages
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Antigen presenting cells
(18)
Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro.
Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stüve O, Hartung H-P
J Neuroimmunol. 2005 Nov; 168(1-2):128-37. PMID: 16171875. Abstract
Pro-inflammatory cytokines, including interleukin-10
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Microglia
(5)
Mitoxantrone exerts both cytotoxic and immunoregulatory effects on activated microglial cells.
Li J-M, Yang Y, Zhu P, Zheng F, Gong F-L, Mei Y-W
Immunopharmacol Immunotoxicol. 2012 Feb; 34(1):36-41. Epub 2011 Apr 26. PMID: 21517718. Abstract
DNA
(19)
DNA strand breakage by peroxidase-activated mitoxantrone.
Fisher GR, Patterson LH
J Pharm Pharmacol. 1991 Jan; 43(1):65-8. PMID: 1676068. Abstract
Status for MS: 
Approved in US, EU, and other countries for RRMS, SPMS, and PRMS
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Administration: 
Recommended administration is as a short intravenous infusion every 3 months, according to information from the US Food and Drug Administration
(16)
NOVANTRONE. mitoXANTRONE for injection concentrate
FDA, May 2010
Accessed on 13 Feb 2012 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019297s033s034lbl.pdf.
Cumulative lifetime dose should be limited
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Commercial: 
Marketed by EMD Serono, Inc.
(14)
Novantrone
OSI Pharmaceuticals, 2012
Accessed on 13 Jan 2012 from http://www.osip.com/novantrone.
Names
Name: 
Mitoxantrone
Trade name: 
Novantrone
(14)
Novantrone
OSI Pharmaceuticals, 2012
Accessed on 13 Jan 2012 from http://www.osip.com/novantrone.
Synonyms: 
MTX
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
1,4-Bis(2-(2-hydroxyethylamino)ethyl)amino)-5,8-dihydroxyanthraquinone
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
1,4-Dihydroxy-5,8-bis(2-((2-hydroxyethyl)amino)ethylamino)-9,10-anthracenedione
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
1,4-Dihydroxy-5,8-bis(5-hydroxy-3-azapentylamino)anthrachinon
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
5,8-Bis((2-((2-hydroxyethyl)amino)ethyl)amino)-1,4-dihydroxyanthraquinone
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
BRN 2795126
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
CCRIS 7604
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
DHAQ
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Dihydroxyanthraquinone
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Mitoxanthrone
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Mitoxantrona
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Mitoxantrona [INN-Spanish]
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Mitoxantronum
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Mitoxantronum [INN-Latin]
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
NSC 279836
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Novantron
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
UNII-BZ114NVM5P
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Mitoxantrone hydrochloride
(15)
Novantrone (mitoxantrone HCl) Injection February 2009
FDA, 19 Jun 2009
Accessed on 13 Feb 2012 from http://www.fda.gov/Safety/MedWatch/SafetyInformation/Safety-RelatedDrugLabelingChanges/ucm133055.htm.
Systematic name: 
9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2 hydroxyethyl)amino)ethyl)amino)- (9CI)
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Anthraquinone, 5,8-bis((2-((2- hydroxyethyl)amino)ethyl)amino)-1,4-dihydroxy-
(1)
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.
Physiology
Class: 
Immunosuppressor
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Target: 
T cells
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
B cell proliferation
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Macrophages
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Antigen presenting cells
(18)
Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro.
Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stüve O, Hartung H-P
J Neuroimmunol. 2005 Nov; 168(1-2):128-37. PMID: 16171875. Abstract
Pro-inflammatory cytokines, including interleukin-10
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Microglia
(5)
Mitoxantrone exerts both cytotoxic and immunoregulatory effects on activated microglial cells.
Li J-M, Yang Y, Zhu P, Zheng F, Gong F-L, Mei Y-W
Immunopharmacol Immunotoxicol. 2012 Feb; 34(1):36-41. Epub 2011 Apr 26. PMID: 21517718. Abstract
DNA
(19)
DNA strand breakage by peroxidase-activated mitoxantrone.
Fisher GR, Patterson LH
J Pharm Pharmacol. 1991 Jan; 43(1):65-8. PMID: 1676068. Abstract
Properties: 
Antineoplastic drug
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Crosslinks DNA
(13)
Mitoxantrone and ametantrone induce interstrand cross-links in DNA of tumour cells.
Skladanowski A, Konopa J
Br J Cancer. 2000 Apr; 82(7):1300-4. PMID: 10755405. Abstract
Exhibits extensive tissue distribution
(20)
Pharmacokinetics and metabolism of mitoxantrone. A review.
Ehninger G, Schuler U, Proksch B, Zeller KP, Blanz J
Clin Pharmacokinet. 1990 May; 18(5):365-80. PMID: 2185907. Abstract
Eliminated primarily via biliary excretion, and to a lesser extent in the urine
(20)
Pharmacokinetics and metabolism of mitoxantrone. A review.
Ehninger G, Schuler U, Proksch B, Zeller KP, Blanz J
Clin Pharmacokinet. 1990 May; 18(5):365-80. PMID: 2185907. Abstract
Half-life measurements in MS patients are available
(24)
Pharmacokinetics and pharmacodynamics of the interferon-betas, glatiramer acetate, and mitoxantrone in multiple sclerosis.
Neuhaus O, Kieseier BC, Hartung H-P
J Neurol Sci. 2007 Aug 15; 259(1-2):27-37. Epub 2007 Mar 27. PMID: 17391705. Abstract

Mechanisms/Effects

Human: 
Inhibits DNA replication and DNA-dependent RNA synthesis
(19)
DNA strand breakage by peroxidase-activated mitoxantrone.
Fisher GR, Patterson LH
J Pharm Pharmacol. 1991 Jan; 43(1):65-8. PMID: 1676068. Abstract
Interferes with DNA repair mechanisms in vitro
(19)
DNA strand breakage by peroxidase-activated mitoxantrone.
Fisher GR, Patterson LH
J Pharm Pharmacol. 1991 Jan; 43(1):65-8. PMID: 1676068. Abstract
Can cross the blood brain barrier, where it is thought to interact with cells in the central nervous system
(22)
Mechanism of action of mitoxantrone.
Fox EJ
Neurology. 2004 Dec 28; 63(12 Suppl 6):S15-8. PMID: 15623664. Abstract
Inhibits proliferation of activated peripheral blood mononuclear cells, B lymphocytes, and antigen-specific T cell lines in vitro in a dose-dependent manner
(18)
Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro.
Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stüve O, Hartung H-P
J Neuroimmunol. 2005 Nov; 168(1-2):128-37. PMID: 16171875. Abstract
Interferes with the antigen-presenting capability of dendritic cells in vitro
(18)
Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro.
Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stüve O, Hartung H-P
J Neuroimmunol. 2005 Nov; 168(1-2):128-37. PMID: 16171875. Abstract
Induces apoptosis of peripheral blood mononuclear cells, monocytes, and dendritic cells in vitro
(18)
Multiple sclerosis: Mitoxantrone promotes differential effects on immunocompetent cells in vitro.
Neuhaus O, Wiendl H, Kieseier BC, Archelos JJ, Hemmer B, Stüve O, Hartung H-P
J Neuroimmunol. 2005 Nov; 168(1-2):128-37. PMID: 16171875. Abstract
Induces cell membrane scrambling and suicidal death of human erythrocytes, effects that involve formation of reactive oxidant species and ceramide but not entry of extracellular Ca2+
(52)
Mitoxantrone-induced suicidal erythrocyte death.
Arnold M, Bissinger R, Lang F
Cell Physiol Biochem. 2014; 34(5):1756-67. Epub 2014 Nov 12. PMID: 25427644. Abstract
Suppresses B cells, enriches neutrophils and immunomodulatory CD8(low) T cells, and promotes natural killer (NK) cell enrichment and NK cell maturation in SPMS patients
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Generally does not influence intrathecal IgG production or oligoclonal IgG band patterns, as shown by a 2-year study of 22 individuals with MS
(44)
The influence of disease duration, clinical course, and immunosuppressive therapy on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis.
Axelsson M, Mattsson N, Malmeström C, Zetterberg H, Lycke J
J Neuroimmunol. 2013 Sep 18. PMID: 24125567. Abstract
Normalizes CXCL13, a chemokine that regulates B cells, in individuals with MS
(44)
The influence of disease duration, clinical course, and immunosuppressive therapy on the synthesis of intrathecal oligoclonal IgG bands in multiple sclerosis.
Axelsson M, Mattsson N, Malmeström C, Zetterberg H, Lycke J
J Neuroimmunol. 2013 Sep 18. PMID: 24125567. Abstract
Does not affect the activity of the antioxidant enzyme paraoxonase 1 in MS patients
(31)
Paraoxonase 1 activity in multiple sclerosis patients during mitoxantrone therapy.
Jamroz-Wisniewska A, Beltowski J, Stelmasiak Z, Bartosik-Psujek H
Acta Neurol Scand. 2012 Aug 11. PMID: 22881373. Abstract
Increases the concentration of the lipid peroxidation marker malondialdehyde in serum and cerebrospinal fluid in MS patients
(34)
Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients.
Adamczyk-Sowa M, Sowa P, Pierzchala K, Polaniak R, Labuz-Roszak B
J Physiol Pharmacol. 2012 Dec; 63(6):683-90. PMID: 23388485. Abstract
Decreases the activity of manganese superoxide dismutase in serum and cerebrospinal fluid (CSF), and of catalase and glutathione peroxidase in CSF, in MS patients
(34)
Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients.
Adamczyk-Sowa M, Sowa P, Pierzchala K, Polaniak R, Labuz-Roszak B
J Physiol Pharmacol. 2012 Dec; 63(6):683-90. PMID: 23388485. Abstract
Increases the activity of copper/zinc superoxide dismutase in serum in MS patients
(34)
Antioxidative enzymes activity and malondialdehyde concentration during mitoxantrone therapy in multiple sclerosis patients.
Adamczyk-Sowa M, Sowa P, Pierzchala K, Polaniak R, Labuz-Roszak B
J Physiol Pharmacol. 2012 Dec; 63(6):683-90. PMID: 23388485. Abstract
Reduces levels of soluble triggering receptor expressed on myeloid cells-2 in the cerebrospinal fluid, which are increased in individuals with RRMS, SPMS, or PPMS
(55)
Soluble TREM-2 in cerebrospinal fluid from patients with multiple sclerosis treated with natalizumab or mitoxantrone.
Öhrfelt A, Axelsson M, Malmeström C, Novakova L, Heslegrave A, Blennow K, Lycke J, Zetterberg H
Mult Scler. 2016 Jan 11. PMID: 26754805. Abstract
Appears to reduce axonal damage (as determined by measuring levels of the axonal damage biomarker neurofilament light protein in cerebrospinal fluid) in progressive MS (after 12 to 24 months of treatment)
(36)
Immunosuppressive therapy reduces axonal damage in progressive multiple sclerosis.
Axelsson M, Malmeström C, Gunnarsson M, Zetterberg H, Sundström P, Lycke J, Svenningsson A
Mult Scler. 2013 May 23. PMID: 23702432. Abstract
Associated with a decrease in levels of the glial marker YKL-40 in the cerebrospinal fluid (CSF) from individuals with MS; CSF YKL-40 levels are increased in MS relative to healthy controls
(47)
CSF levels of YKL-40 are increased in MS and replaces with immunosuppressive treatment.
Malmeström C, Axelsson M, Lycke J, Zetterberg H, Blennow K, Olsson B
J Neuroimmunol. 2014 Feb 13. PMID: 24582001. Abstract
Therapeutic response to mitoxantrone in highly active MS (relapsing-progressive/SPMS) might be predicted by polymorphisms in genes encoding the ATP-binding cassette transporters ABCB1 and ABCG2, such that genotypes associated with decreased ABCB1/ABCG2 function are linked with increased clinical response rate, based on retrospective analysis
(50)
ABC-transporter gene-polymorphisms are potential pharmacogenetic markers for mitoxantrone response in multiple sclerosis.
Cotte S, von Ahsen N, Kruse N, Huber B, Winkelmann A, Zettl UK, Starck M, König N, Tellez N, Dörr J, et al.
Brain. 2009 Sep; 132(Pt 9):2517-30. Epub 2009 Jul 15. PMID: 19605531. Abstract
Therapeutic response to mitoxantrone in PPMS is not predicted by specific ABC transporter gene polymorphisms, based on retrospective analysis
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Less effective in individuals with PPMS than in those with relapsing-progressive/SPMS
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Animal: 
Reduces B cell number and inhibits B cell proliferation in mice in vivo and in vitro
(21)
Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function.
Fidler JM, DeJoy SQ, Gibbons JJ
J Immunol. 1986 Jul 15; 137(2):727-32. PMID: 3487580. Abstract
Reduces the immune response in experimental autoimmune encephalomyelitis rodents by depressing myelin-directed T- and B-cell responses 3- to 9-fold and inhibiting macrophage-mediated demyelination
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Appears to block inwardly rectifying K(+) channels in mouse osteoclast precursor cells that have been differentiated with lipopolysaccharide
(29)
Evidence for Mitoxantrone-induced Block of Inwardly Rectifying K Channels Expressed in the Osteoclast Precursor RAW 264.7 Cells Differentiated with Lipopolysaccharide.
Wang C-L, Tsai M-L, Wu S-N
Cell Physiol Biochem. 2012; 30(3):687-701. Epub 2012 Aug 01. PMID: 22854649. Abstract
Represses lipopolysaccharide induction of nitric oxide, tumor necrosis factor alpha, and interleukin-1 beta (which are pro-inflammatory, potentially cytotoxic molecules) by primary mouse astrocytes
(30)
Mitoxantrone repression of astrocyte activation: Relevance to multiple sclerosis.
Burns SA, Lee Archer R, Chavis JA, Tull CA, Hensley LL, Drew PD
Brain Res. 2012 Sep 14; 1473:236-41. Epub 2012 Aug 02. PMID: 22884503. Abstract
Represses lipopolysaccharide induction of MCP-1 (a chemokine that affects monocyte migration to inflammatory lesions in the central nervous system) by primary mouse astrocytes
(30)
Mitoxantrone repression of astrocyte activation: Relevance to multiple sclerosis.
Burns SA, Lee Archer R, Chavis JA, Tull CA, Hensley LL, Drew PD
Brain Res. 2012 Sep 14; 1473:236-41. Epub 2012 Aug 02. PMID: 22884503. Abstract
Represses lipopolysaccharide induction of interleukin-12 and -23 (which play a role in autoimmune encephalomyelitis pathogenesis by contributing to the development of Th1 and Th17 T cell lineages) by primary mouse astrocytes
(30)
Mitoxantrone repression of astrocyte activation: Relevance to multiple sclerosis.
Burns SA, Lee Archer R, Chavis JA, Tull CA, Hensley LL, Drew PD
Brain Res. 2012 Sep 14; 1473:236-41. Epub 2012 Aug 02. PMID: 22884503. Abstract
Represses lipopolysaccharide induction of C-reactive protein in primary mouse astrocytes
(30)
Mitoxantrone repression of astrocyte activation: Relevance to multiple sclerosis.
Burns SA, Lee Archer R, Chavis JA, Tull CA, Hensley LL, Drew PD
Brain Res. 2012 Sep 14; 1473:236-41. Epub 2012 Aug 02. PMID: 22884503. Abstract
Represses lipopolysaccharide induction of NF-kB DNA-binding activity in primary mouse astrocytes
(30)
Mitoxantrone repression of astrocyte activation: Relevance to multiple sclerosis.
Burns SA, Lee Archer R, Chavis JA, Tull CA, Hensley LL, Drew PD
Brain Res. 2012 Sep 14; 1473:236-41. Epub 2012 Aug 02. PMID: 22884503. Abstract
Regulatory and Commercial Status
Status for MS: 
Approved in US, EU, and other countries for RRMS, SPMS, and PRMS
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Highest status achieved (for any condition): 
Approved in US, EU, and other countries for RRMS, SPMS, and PRMS
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Other uses: 
Approved for acute non-lymphocyclophosphamidetic leukemia in 1987
(22)
Mechanism of action of mitoxantrone.
Fox EJ
Neurology. 2004 Dec 28; 63(12 Suppl 6):S15-8. PMID: 15623664. Abstract
Approved for breast, hormone-refractory prostatic, and hepatic cancer
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Decreased the frequency of relapses in neuromyelitis optica spectrum in an observational study
(32)
Efficacy of mitoxantrone in neuromyelitis optica spectrum: clinical and neuroradiological study.
Cabre P, Olindo S, Marignier R, Jeannin S, Merle H, Smadja D, Aegis of French National Observatory of Multiple Sclerosis
J Neurol Neurosurg Psychiatry. 2013 May; 84(5):511-6. Epub 2012 Nov 08. PMID: 23138769. Abstract
Administration: 
Recommended administration is as a short intravenous infusion every 3 months, according to information from the US Food and Drug Administration
(16)
NOVANTRONE. mitoXANTRONE for injection concentrate
FDA, May 2010
Accessed on 13 Feb 2012 from http://www.accessdata.fda.gov/drugsatfda_docs/label/2010/019297s033s034lbl.pdf.
Cumulative lifetime dose should be limited
(8)
Management of worsening multiple sclerosis with mitoxantrone: a review.
Fox EJ
Clin Ther. 2006 Apr; 28(4):461-74. PMID: 16750460. Abstract
Negative effects: 
Alopecia
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Amenorrhea
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Bilirubin
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Birth defects
(4)
A newborn with Pierre Robin sequence after preconceptional mitoxantrone exposure of a female with multiple sclerosis.
Hellwig K, Schimrigk S, Chan A, Epplen J, Gold R
J Neurol Sci. 2011 Aug 15; 307(1-2):164-5. Epub 2011 May 20. PMID: 21601225. Abstract
Cardiomyopathy
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Cardiotoxicity
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
(27)
Severe delayed heart failure in three multiple sclerosis patients previously treated with mitoxantrone.
Goffette S, van Pesch V, Vanoverschelde J L, Morandini E, Sindic CJM
J Neurol. 2005 Oct; 252(10):1217-22. Epub 2005 Apr 18. PMID: 15834643. Abstract
Associated with a risk of cardiotoxicity; plasma levels of N-terminal pro-brain natriuretic peptide (evaluated before, during, and after therapy in individuals with MS) appear useful for identifying those at risk for such cardiotoxicity
(48)
The N-terminal pro-brain natriuretic peptide as a marker of mitoxantrone-induced cardiotoxicity in multiple sclerosis patients.
Podlecka-Piętowska A, Kochanowski J, Zakrzewska-Pniewska B, Opolski G, Kwieciński H, Kamińska A M
Neurol Neurochir Pol. 2014 Mar-Apr; 48(2):111-5. Epub 2014 Jan 23. PMID: 24821636. Abstract
Mitoxantrone-associated cardiac dysfunction (milder forms; symptomatic congestive heart failure was not observed) occurred at a frequency of 4.1% in a German cohort of 639 MS patients, as seen in a retrospective study; the only relevant risk factor for this dysfunction was cumulative dose exposure
(49)
Cardiotoxicity of mitoxantrone treatment in a german cohort of 639 multiple sclerosis patients.
Fleischer V, Salmen A, Kollar S, Weyer V, Siffrin V, Chan A, Zipp F, Luessi F
J Clin Neurol. 2014 Oct; 10(4):289-95. Epub 2014 Oct 06. PMID: 25324877. Abstract
Hemorrhages in central nervous system
(3)
Increased incidence of central nervous system hemorrhages in patients with secondary acute promyelocytic leukemia after treatment of multiple sclerosis with mitoxantrone?
Taube F, Stölzel F, Thiede C, Ehninger G, Laniado M, Schaich M
Haematologica. 2011 Jun; 96(6):e31. PMID: 21632839. Abstract
Infertilty
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Leukemia
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Associated with the development of acute leukemia; when used to treat aggressive MS, the risk of therapy-related acute leukemia has been estimated to range from 0.07% to 0.81% in meta-analyses, and the estimated risk also varies by country (Italy, 0.93%; Germany and France, 0.25% to 0.41%)
(35)
Mitoxantrone-related acute leukemia in MS: An open or closed book?
Chan A, Lo-Coco F
Neurology. 2013 Apr 16; 80(16):1529-33. PMID: 23589639. Abstract
Risk of therapy-related acute leukemia is estimated as 1 in 139, based on a literature review covering 12,511 individuals with MS who had been treated with a mean dose of 90.1 mg per m[2] [[7962]]
Associated with lethal acute myeloid leukemia (with a 11q23 MLL gene rearrangement) in one child with MS
(53)
Fatal Acute Myeloid Leukemia With 11q23 MLL Gene Rearrangement Following Mitoxantrone Treatment in a Case of Childhood-onset Multiple Sclerosis.
Patejdl R, Krohn S, Murua Escobar H, Zettl UK
J Pediatr Hematol Oncol. 2015 Apr 3. PMID: 25851557. Abstract
Leukopenia
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Remote, standard-dose treatment may be associated with subclinical myocardial dysfunction (persistent diastolic dysfunction), based on an analysis of 50 consecutive MS patients treated in one center
(41)
Subclinical myocardial dysfunction in multiple sclerosis patients remotely treated with mitoxantrone: evidence of persistent diastolic dysfunction.
Joyce E, Mulroy E, Scott J, Melling J, Goggin C, McGorrian C, O'Rourke K, Lynch T, Mahon N
J Card Fail. 2013 Aug; 19(8):571-6. PMID: 23910587. Abstract
Nausea and vomiting
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Palpitations
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Phlebitis
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Respiratory tract infections
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Thrombocyclophosphamidetopenia
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Urinary tract infections
(2)
Mitoxantrone: benefits and risks in multiple sclerosis patients.
Martinelli V, Radaelli M, Straffi L, Rodegher M, Comi G
Neurol Sci. 2009 Oct; 30 Suppl 2:S167-70. PMID: 19882368. Abstract
Drastically reduced or eliminated the efficacy of vaccination against pandemic H1N1 (swine flu, in 2009) and seasonal influenza (in 2010)
(46)
Immunotherapies influence the influenza vaccination response in multiple sclerosis patients: an explorative study.
Olberg HK, Cox RJ, Nostbakken JK, Aarseth JH, Vedeler CA, Myhr K-M
Mult Scler. 2014 Jan 16. PMID: 24436455. Abstract
Commercial: 
Marketed by EMD Serono, Inc.
(14)
Novantrone
OSI Pharmaceuticals, 2012
Accessed on 13 Jan 2012 from http://www.osip.com/novantrone.
Key Clinical Trials
Placebo-controlled Trials: 
Trial name: 
Hartung et al., Lancet, December 2002 trial
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Phase: 
Phase III trial
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Study Design: 
Randomized, double-blind, placebo-controlled, multicenter trial to test the efficacy of mitoxantrone (5mg/m² or 12mg/m² intravenously every 3 months for 24 months), with the primary outcome a multivariate analysis of five clinical measures (change in expanded disability status scale, change in ambulation index, adjusted total number of treated relapses, time to first treated relapse, and change in standardised neurological status), comparing the 12mg/m² and placebo groups
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Disease Stage: 
Worsening RRMS (also known as progressive relapsing MS) or SPMS
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Enrollment/Number of Patients: 
194 enrolled, with 184 in the final analysis
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Duration: 
2 years
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Status/Outcome: 
Drug (12mg/m² dose) was associated with an overall benefit in the multivariate analysis of five clinical measures (0.30 difference overall)
(12)
Mitoxantrone in progressive multiple sclerosis: a placebo-controlled, double-blind, randomised, multicentre trial.
Hartung H-P, Gonsette R, König N, Kwiecinski H, Guseo A, Morrissey SP, Krapf H, Zwingers T, Mitoxantrone in Multiple Sclerosis Study Group(MIMS)
Lancet. 2002 Dec 21-28; 360(9350):2018-25. PMID: 12504397. Abstract
Trial name: 
Millefiorini et al., J. Neurol., March 1997 trial
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Phase: 
Phase II trial
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Study Design: 
Randomized, placebo-controlled, multicenter trial to determine the clinical efficacy of mitoxantrone (intravenous infusion of 8 mg/m² every month for 1 year), with the primary outcome disease progression and the secondary endpoints the growth and appearance of new brain lesions
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Disease Stage: 
RRMS
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Enrollment/Number of Patients: 
51 enrolled, with 42 completing the MRI examinations
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Duration: 
2 years
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Status/Outcome: 
Drug decreased the proportion of patients who showed confirmed disease progression, defined as a one point increase on the Kurtzke expanded disability scale (EDSS), but was not associated with a statistically significant benefit in the mean EDSS progression; drug reduced the mean number of brain lesions
(17)
Randomized placebo-controlled trial of mitoxantrone in relapsing-remitting multiple sclerosis: 24-month clinical and MRI outcome.
Millefiorini E, Gasperini C, Pozzilli C, D'Andrea F, Bastianello S, Trojano M, Morino S, Morra VB, Bozzao A, Calo' A, et al.
J Neurol. 1997 Mar; 244(3):153-9. PMID: 9050955. Abstract
Head-to-Head Trials: 
Trial name: 
Edan et al., J. Neurol. Neurosurg. Psychiatry, December 2011 trial
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Phase: 
Phase IV trial
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Study Design: 
Randomized, two-arm controlled trial to compare the effects of mitoxantrone [12 mg/m² (maximum 20 mg) monthly] combined with methylprednisolone (1 g intravenously each month for 6 months) followed 3 months later by interferon beta-1b (250 ug subcutaneously every other day for 27 months) or methylprednisolone (1 g intravenously each month during the first 6 months) and interferon beta-1b (250 ug every other day for 36 months), with the primary endpoint the time to worsen by one point on the expanded disability status scale (confirmed at 3 months) and the secondary endpoints the relapse rate and accumulation of new lesions
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Disease Stage: 
Aggressive RRMS
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Enrollment/Number of Patients: 
109
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Duration: 
3 years
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Status/Outcome: 
Mitoxantrone delayed disability by 18 months, as measured by the time to worsen by at least one point on the expanded disability status scale, and reduced the relapse rate, reduced the number of gadolinium-enhancing lesions, and slowed the accumulation of new T2 lesions
(6)
Mitoxantrone prior to interferon beta-1b in aggressive relapsing multiple sclerosis: a 3-year randomised trial.
Edan G, Comi G, Le Page E, Leray E, Rocca MA, Filippi M, French–Italian Mitoxantrone Interferon-beta-1b Trial Group
J Neurol Neurosurg Psychiatry. 2011 Dec; 82(12):1344-50. Epub 2011 Mar 24. PMID: 21436229. Abstract
Trial name: 
Vollmer et al., Mult. Schler., June 2008 trial
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
Phase: 
Phase II trial
(23)
A Study to Evaluate the Safety and Effectiveness of Novantrone Therapy Followed by Copaxone for Multiple Sclerosis
ClinicalTrials.gov, 13 Apr 2011
Accessed on 13 Feb 2012 from http://clinicaltrials.gov/ct2/show/NCT00203073.
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
Study Design: 
Multicenter, randomized, single-blind trial to compare the effects of glatiramer acetate (daily subcutaneous injections of 20 mg for 15 months) alone or mitoxantrone (monthly 12 mg/m² infusions for 3 months) followed by glatiramer acetate (daily subcutaneous injections of 20 mg for 12 months), with the primary outcome measure the incidence of adverse events and the secondary measures the number of gadolinium-enhancing lesions, the number of confirmed relapses, and changes in the expanded disability status scale
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
Disease Stage: 
RRMS
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
Enrollment/Number of Patients: 
40
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
Duration: 
15 months
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
Status/Outcome: 
Both treatments were well tolerated; combination therapy was associated with an 89% greater reduction in the number of gadolinium-enhancing lesions at 6 and 9 months, a 70% reduction at 12 and 15 months, and a reduction in the mean relapse rate as compared to glatiramer acetate alone
(25)
Glatiramer acetate after induction therapy with mitoxantrone in relapsing multiple sclerosis.
Vollmer T, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Campagnolo D, Deutsch F, Arnold DL
Mult Scler. 2008 Jun; 14(5):663-70. Epub 2008 Apr 18. PMID: 18424479. Abstract
(26)
Glatiramer acetate after mitoxantrone induction improves MRI markers of lesion volume and permanent tissue injury in MS.
Arnold DL, Campagnolo D, Panitch H, Bar-Or A, Dunn J, Freedman MS, Gazda SK, Vollmer T
J Neurol. 2008 Oct; 255(10):1473-8. Epub 2008 Oct 07. PMID: 18854910. Abstract
Trial name: 
Zipoli et al., J. Neurol. Sci., March 2008 study
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Phase: 
Open label comparative study
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Study Design: 
Study to compare the safety and efficacy of mitoxantrone (8 mg per square meter monthly for 3 months, then every 3 months to reach a dose of 120 mg per square meter) to that of cyclophosphamide (700 mg per square meter, monthly for 12 months and then bimonthly for another 24 months)
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Disease Stage: 
Active RRMS or SPMS
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Enrollment/Number of Patients: 
153
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Duration: 
Mean followup of 3.6 years
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Status/Outcome: 
No significant difference was seen between the time to first relapse in the two groups; time to disease progression was 3.8 years in the mitoxantrone group and 3.6 years in the cyclophosphamide group; discontinuation because of side effects occurred more frequently in the cyclophosphamide group, although both drug regimes were considered tolerable
(33)
Intravenous mitoxantrone and cyclophosphamide as second-line therapy in multiple sclerosis: an open-label comparative study of efficacy and safety.
Zipoli V, Portaccio E, Hakiki B, Siracusa G, Sorbi S, Amato M P
J Neurol Sci. 2008 Mar 15; 266(1-2):25-30. Epub 2007 Sep 17. PMID: 17870094. Abstract
Other Trials: 
Trial name: 
Tramacere et al., Cochrane Database Syst. Rev., September 2015 study
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Phase: 
Retrospective clinical trial analysis
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Study Design: 
Retrospective network meta-analysis to compare the benefits of alemtuzumab, azathioprine, daclizumab, dimethyl fumarate, fingolimod, glatiramer acetate, immunoglobulins, interferon beta-1a (Avonex, Rebif), pegylated interferon beta-1a, interferon beta-1b, laquinimod, mitoxantrone, natalizumab, and teriflunomide; data were extracted from 39 randomized controlled trials that compared one or more of the 15 drugs used as monotherapy to placebo or another drug
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Disease Stage: 
Adults with RRMS
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Enrollment/Number of Patients: 
25,113 individuals were randomized in the studies included in the analyses
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Duration: 
Median duration of studies, 24 months
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Status/Outcome: 
Alemtuzumab was found to be the most protective against relapses during the first 24 months of therapy (moderate quality evidence); the next most protective were found to be mitoxantrone (very low quality evidence), natalizumab (high quality evidence), and fingolimod (moderate quality evidence); mitoxantrone (low quality evidence) was found to be the most effective at delaying disability worsening, followed by alemtuzumab (low quality evidence) and natalizumab (moderate quality evidence); these results must be interpreted conservatively because few trials have been performed for most of the drugs
(54)
Immunomodulators and immunosuppressants for relapsing-remitting multiple sclerosis: a network meta-analysis.
Tramacere I, Giovane C D, Salanti G, D'Amico R, Filippini G
Cochrane Database Syst Rev. 2015 Sep 18; 9:CD011381. PMID: 26384035. Abstract
Trial name: 
Grey née Cotte et al., J. Neuroimmunol., November 2014 study
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Phase: 
Retrospective analysis
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Study Design: 
Multicenter, retrospective analysis to examine whether certain pharmacogenetic response markers (polymorphisms in genes encoding the ATP-binding cassette transporters ABCB1 and ABCG2), which are potentially relevant in relapsing-progressive MS (RPMS)/SPMS, might be useful in PPMS
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Disease Stage: 
PPMS and RP/SPMS
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Enrollment/Number of Patients: 
239
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Duration: 
N/A
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Status/Outcome: 
Only 53.7% of those with PPMS were responsive to mitoxantrone (and there was no correlation between genotype and treatment response), whereas 78.1% of those with RP/SPMS were responsive
(51)
Lack of efficacy of mitoxantrone in primary progressive Multiple Sclerosis irrespective of pharmacogenetic factors: A multi-center, retrospective analysis.
Grey Née Cotte S, Salmen Née Stroet A, von Ahsen N, Starck M, Winkelmann A, Zettl UK, Comabella M, Montalban X, Zipp F, Fleischer V, et al.
J Neuroimmunol. 2014 Nov 20. PMID: 25468777. Abstract
Trial name: 
Etemadifar et al., Eur. J. Paediatr. Neurol., October 2013 study
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Phase: 
Retrospective medical record review
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Study Design: 
Retrospective analysis to examine the safety and efficacy of mitoxantrone (20 mg) in pediatric patients
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Disease Stage: 
Aggressive MS
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Enrollment/Number of Patients: 
19
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Duration: 
30 months (median followup period)
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Status/Outcome: 
After mitoxantrone treatment, 73% of the patients were free of relapses, and, in 84.2% of the patients, Extended Disability Status scores decreased (by 0.5 or more) and gadolinium-enhancing lesion volume decreased
(45)
Safety and efficacy of mitoxantrone in pediatric patients with aggressive multiple sclerosis.
Etemadifar M, Afzali P, Abtahi S-H, Ramagopalan SV, Nourian S-M, Murray RT, Fereidan-Esfahani M
Eur J Paediatr Neurol. 2013 Oct 7. PMID: 24139067. Abstract
Trial name: 
Evdoshenko et al., ISRN Neurol., September 2013 study
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Phase: 
Observational/open-label study
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Study Design: 
Prospective, observational pilot study to examine the effects of combined rituximab and mitoxantrone therapy (consisting of an intravenous infusion of 1000 mg methylprednisolone, 1000 mg rituximab, and 20 mg mitoxantrone on day 1 and 1000 mg methylprednisolone and 1000 mg rituximab on day 14)
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Disease Stage: 
Active MS
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Enrollment/Number of Patients: 
28
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Duration: 
12 to 48 month observation period
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Status/Outcome: 
No relapses occurred during the observation period; CD19+ and CD19+/CD27+ B cells were depleted in all individuals in the peripheral blood and cerebrospinal fluid (CSF) at 6 months; the CD19+/CD27+ memory B cell subset was depressed over longer time periods than the CD19+ cells
(43)
Dynamics of B-Cell Populations in CSF and Blood in Patients Treated with a Combination of Rituximab and Mitoxantrone.
Evdoshenko E, Maslyanskiy A, Lapin S, Zaslavsky L, Dobson R, Totolian A, Skoromets A, Bar-Or A
ISRN Neurol. 2013; 2013:748127. Epub 2013 Sep 10. PMID: 24109519. Abstract
Trial name: 
Hadjigeorgiou et al., J. Clin. Pharm. Ther., August 2013 study
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Phase: 
Retrospective trial review
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Study Design: 
Study to examine the relative effectiveness and safety of marketed treatments for MS [interferon beta-1b (250 microg), interferon beta-1a (30 microg, 44 microg, or 22 microg), teriflunomide (7 mg or 14 mg), glatiramer acetate (20 mg), natalizumab (300 mg), fingolimod (0.5 mg), and mitoxantrone (12 mg per m[2])]; a network analysis that performed pairwise comparisons of these treatments, based on results from randomized controlled trials, was undertaken to examine 4 clinical outcomes: (i) patients free of relapse, (ii) patients without disease progression, (iii) patients without MRI progression, and (iv) patients with adverse events
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Disease Stage: 
Relapsing MS
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Enrollment/Number of Patients: 
20,455
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Duration: 
N/A
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Status/Outcome: 
Fingolimod was associated with a better response for 2 outcomes (patients free of relapse, patients without MRI progression) as compared with interferon beta-1a (Avonex); interferon beta-1b (Betaferon) was associated with a better response for 2 outcomes (patients without disease progression, patients without MRI progression) as compared with interferon beta-1a (Avonex); and natalizumab might be more effective than other treatments for 2 outcomes (patients free of relapse, patients without MRI progression); conclusions about patients with adverse events could not be reached because of a lack of data
(42)
A network meta-analysis of randomized controlled trials for comparing the effectiveness and safety profile of treatments with marketing authorization for relapsing multiple sclerosis.
Hadjigeorgiou GM, Doxani C, Miligkos M, Ziakas P, Bakalos G, Papadimitriou D, Mprotsis T, Grigoriadis N, Zintzaras E
J Clin Pharm Ther. 2013 Aug 20. PMID: 23957759. Abstract
Trial name: 
Registry to Evaluate Novantrone Effects in Worsening MS (RENEW) study (publ July 2013)
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Phase: 
Phase IV study
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Study Design: 
Multicenter study to examine the long-term safety profile of mitoxantrone (given every 3 months according to the package insert); patients received at least one infusion and were monitored every 3 months during treatment, after which they were monitored annually
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Disease Stage: 
SPMS, PRMS, and worsening RRMS
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Enrollment/Number of Patients: 
509, with 172 completing the study
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Duration: 
5 years
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Status/Outcome: 
Results were consistent with the previously-established safety profile; left ventricular ejection fraction reduction under 50% occurred in 5.3% of patients during treatment and in 5.6% during followup, indications of congestive heart failure occurred in 2.0% of patients, drug-related leukemia occurred in 0.6% of patients, and persistent amenorrhea occurred in 22% to 51% of women during treatment, depending on their menses history
(40)
Results from the 5-year, phase IV RENEW (Registry to Evaluate Novantrone Effects in Worsening Multiple Sclerosis) study.
Rivera VM, Jeffery DR, Weinstock-Guttman B, Bock D, Dangond F
BMC Neurol. 2013 Jul 11; 13(1):80. Epub 2013 Jul 11. PMID: 23841877. Abstract
Trial name: 
Filippini et al., Cochrane Database Syst. Rev., June 2013 study
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Phase: 
Retrospective trial review
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Study Design: 
Study that examined 44 randomized controlled trials of drugs used in MS to estimate the relative efficacy of interferon beta-1b (Betaseron), interferon beta-1a (Rebif and Avonex), glatiramer acetate, natalizumab, mitoxantrone, cyclophosphamide, and other treatments, using pairwise meta-analysis and network meta-analysis
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Disease Stage: 
RRMS and progressive MS
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Enrollment/Number of Patients: 
17401
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Duration: 
24 months (median duration of trials)
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Status/Outcome: 
Natalizumab and interferon beta-1a (Rebif) were determined to be better than other treatments for preventing relapses in RRMS over the short term (24 months), and these two drugs probably inhibited disability progression in RRMS in this time period, although they are linked with long-term adverse events; in RRMS, interferon beta-1b and mitoxantrone probably decreased the probability of relapses, whereas interferon beta-1a (Avonex) and cyclophosphamide lacked convincing efficacy data; none of the treatments effectively decreased disability progression in progressive MS
(37)
Immunomodulators and immunosuppressants for multiple sclerosis: a network meta-analysis.
Filippini G, Giovane C D, Vacchi L, D'Amico R, Di Pietrantonj C, Beecher D, Salanti G
Cochrane Database Syst Rev. 2013 Jun 6; 6:CD008933. PMID: 23744561. Abstract
Trial name: 
Martinelli et al., Cochrane Database Syst. Rev., May 2013 study
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Phase: 
Retrospective trial review
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Study Design: 
Study that examined 3 randomized, double-blinded, placebo-controlled trials to assess the efficacy of mitoxantrone (versus placebo) or mitoxantrone and steroids (versus placebo and steroids)
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Disease Stage: 
RRMS, PRMS, and SPMS
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Enrollment/Number of Patients: 
221
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Duration: 
2 years
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Status/Outcome: 
Mitoxantrone was associated with some reduction in the risk of MS progression and relapse frequency in worsening RRMS, PRMS, and SPMS over a 2-year span
(38)
Mitoxantrone for multiple sclerosis.
Martinelli Boneschi F, Vacchi L, Rovaris M, Capra R, Comi G
Cochrane Database Syst Rev. 2013; 5:CD002127. PMID: 23728638. Abstract
Trial name: 
Tabrizi et al., J. Res. Med. Sci., September 2012 study
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Phase: 
Observational/open-label study
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Study Design: 
Study to compare the efficacy of two treatment regimes: (i) monthly plasma exchange for three months, with mitoxantrone [12 mg per m(2)] given at the end of each course, followed by two doses of mitoxantrone [6 mg per m(2)] given at intervals of 3 months or (ii) the same treatment with mitoxantrone but without plasma exchange
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Disease Stage: 
Aggressive RRMS
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Enrollment/Number of Patients: 
40
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Duration: 
8 months
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Status/Outcome: 
Both treatment regimes were associated with a significant decrease in the Expanded Disability Status Scale score (which was affected similarly by the two regimes), but only mitoxantrone without plasma exchange therapy was associated with reduced numbers of demyelinating and gadolinium-enhancing plaques seen by MRI
(39)
Combination therapy with mitoxantrone and plasma exchange in aggressive relapsing remitting multiple sclerosis: A preliminary clinical study.
Tabrizi N, Etemadifar M, Ashtari F, Zahed A, Etemadifar F
J Res Med Sci. 2012 Sep; 17(9):828-33. PMID: 23826008. Abstract
Trial name: 
Chanvillard et al., PLoS One, June 2012 study
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Phase: 
Open-label study
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Study Design: 
Prospective, monocentric, single-arm, open-label study (partly funded by industry) to analyze the effects of mitoxantrone on immunological parameters; the treatment regime was 12 mg per m2 of body surface area given intravenously every three months, up to a cumulative dose of 140 mg per m2, unless reductions were required because of side effects
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Disease Stage: 
SPMS
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Enrollment/Number of Patients: 
19 patients were screened, 15 patients enrolled, and 12 patients completed the study
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Duration: 
12 months
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Status/Outcome: 
Mitoxantrone persistently suppressed B cells, enriched neutrophils and immunomodulatory CD8(low) T cells, and promoted natural killer (NK) cell enrichment and NK cell maturation; the drug-induced NK cell maturation occurred only in patients who responded to treatment
(28)
Mitoxantrone induces natural killer cell maturation in patients with secondary progressive multiple sclerosis.
Chanvillard C, Millward JM, Lozano M, Hamann I, Paul F, Zipp F, Dörr J, Infante-Duarte C
PLoS One. 2012; 7(6):e39625. Epub 2012 Jun 29. PMID: 22768101. Abstract
Trial name: 
Le Page et al., Mult. Scler., July 2011 study
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
Phase: 
Observational/open-label study
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
Study Design: 
Prospective, open-label study to examine the long-term safety profile of mitoxantrone, which was either given monthly for 6 months or every 3 months
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
Disease Stage: 
RRMS (308 individuals), SPMS (352), and PPMS (142)
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
Enrollment/Number of Patients: 
802
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
Duration: 
≥5 years
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
Status/Outcome: 
Negative effects included acute congestive heart failure (0.1% of study population), asymptomatic left ventricular ejection fraction reduction under 50% (4.9%), leukemia (0.25%), and amenorrhea (17.3% of women treated before age 45)
(7)
Long-term safety profile of mitoxantrone in a French cohort of 802 multiple sclerosis patients: a 5-year prospective study.
Le Page E, Leray E, Edan G, French Mitoxantrone Safety Group
Mult Scler. 2011 Jul; 17(7):867-75. Epub 2011 Feb 15. PMID: 21325016. Abstract
References
ChemIDplus Advanced
United States National Library of Medicine
Accessed on 29 Jul 2013 from http://chem.sis.nlm.nih.gov/chemidplus/chemidheavy.jsp.

Note: Compound name must be entered under "Substance Identification" and then "Names and Synonyms" selected to view synonyms.

Novantrone
OSI Pharmaceuticals, 2012
Accessed on 13 Jan 2012 from http://www.osip.com/novantrone.
DOI: 
doi/10.7493/msdf.10.547.1