A comparison of the benefits of mitoxantrone and other recent therapeutic approaches in multiple sclerosis

Expert Opinion on Pharmacotherapy

Volumn 5, Issue 4, 2004, Pages 747-765

  Gonsette, Richard E ^a  

^a National Multiple Sclerosis Center   (Belgium)

Author keywords

Immunomodulation; Immunosuppression; Mitoxantrone; Multiple sclerosis; Pixantrone

Indexed keywords

ACETYLCYSTEINE; ALEMTUZUMAB; ALPHA TOCOPHEROL; ANTHRACYCLINE; ANTIEMETIC AGENT; ANTIINFLAMMATORY AGENT; ANTINEOPLASTIC AGENT; ANTIOXIDANT; AZATHIOPRINE; BETA1A INTERFERON; CARDIAC GLYCOSIDE; CORTICOSTEROID; CYCLOPHOSPHAMIDE; DIPEPTIDYL CARBOXYPEPTIDASE INHIBITOR; DIURETIC AGENT; DOXORUBICIN; FLUOROURACIL; GLATIRAMER; IMMUNOMODULATING AGENT; IMMUNOSUPPRESSIVE AGENT; INTERFERON BETA SERINE; METHOTREXATE; METHYLPREDNISOLONE; MITOXANTRONE; MONOCLONAL ANTIBODY; NATALIZUMAB; NEUROPROTECTIVE AGENT; PIXANTRONE; RAZOXANE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACUTE HEART FAILURE; ALOPECIA; AMENORRHEA; AMINO ACID SEQUENCE; BONE MARROW TOXICITY; CARDIOTOXICITY; CLINICAL FEATURE; CLINICAL TRIAL; CONGESTIVE HEART FAILURE; DISABILITY; DRUG APPROVAL; DRUG DELIVERY SYSTEM; DRUG EFFICACY; DRUG HALF LIFE; DRUG POTENTIATION; DRUG SAFETY; DRUG SYNTHESIS; DRUG TISSUE LEVEL; DRUG TOLERABILITY; FATIGUE; FOOD AND DRUG ADMINISTRATION; GENITAL SYSTEM DISEASE; GRAVES DISEASE; HAIR LOSS; HEART ARRHYTHMIA; HUMAN; IMMUNOMODULATION; IMMUNOTHERAPY; INFLAMMATION; LEUKEMIA; LONG TERM CARE; MULTIPLE SCLEROSIS; NAUSEA AND VOMITING; NONHUMAN; PATHOGENESIS; PATHOPHYSIOLOGY; RELAPSE; REVIEW; SODIUM CALCIUM EXCHANGE;

ADJUVANTS, IMMUNOLOGIC; ANTIOXIDANTS; CLINICAL TRIALS; COST-BENEFIT ANALYSIS; DRUG ADMINISTRATION SCHEDULE; HUMANS; IMMUNOSUPPRESSIVE AGENTS; ISOQUINOLINES; MITOXANTRONE; MULTIPLE SCLEROSIS; MULTIPLE SCLEROSIS, CHRONIC PROGRESSIVE; MULTIPLE SCLEROSIS, RELAPSING-REMITTING; NEUROPROTECTIVE AGENTS;

EID: 1842832790     PISSN: 14656566     EISSN: None     Source Type: Journal    
DOI: 10.1517/14656566.5.4.747     Document Type: Review

References (161)

1. GOODING DS, FROHMAN EM, GARMANY GP Jr et al.: Disease modifying therapies in multiple sclerosis. Report of Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology and the MS Council for Clinical Practice Guidelines. Neurology (2002) 58:169-178.
2. GOODIN DS, ARNASON BG, COYLE PK, FROHMAN EM, PATY DW: The use of mitoxantrone (Novantrone) for the treatment of multiple sclerosis. Report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology. Neurology (2003) 61:1332-1338.
3. LUBLIN FD, REINGOLD SC for the National Multiple Sclerosis Society (USA) Advisory Committee on Clinical Trials of New Agents in Multiple Sclerosis: Defining the clinical course of multiple sclerosis: results of an international survey. Neurology (1996) 46:907-911.
4. WEINSHENKER BG, BASS B, RICE GPA et al.: The natural history of multiple sclerosis: A geographically-based study. I. Clinical course and disability. Brain (1989) 112(Part 1):133-146.
5. GONSETTE RE, LISSOIR F, THEYS P, KETELAER P, DROISSART C, DEMONTY L: The natural history ofAMS in Belgium : a MS clinic based study. In: Multiple Sclerosis in Europe. An epidemiological update. Firnhaber W, Lauer K (Ed.), Leuchtturm-Verlag/LTV Press, Alsbach, Germany (1994):122-129.
6. KURTZKE JF: Rating neurologic impairment in multiple sclerosis: An expanded disability status scale (EDSS). Neurology (1983) 33:1444-1452.
7. HAWKINS SA, MCDONNELL GV: Benign multiple sclerosis? Clinical course, long term follow up, and assessment of prognostic factors. J. Neurol. Neurosurg. Psychiat. (1999) 67:148-152.
8. WILLENBORG DO, PROWSE SJ: Immunoglobulin-deficient rats fail to develop experimental allergic encephalomyelitis. J. Neuroimmunol. (1983) 5:99-109.
9. MYERS KJ, SPRENT J, DOUGHERTY JP, RON Y: Synergy between encephalitogenic T cells and myelin basic protein-specific antibodies in the induction of experimental autoimmune encephalomyelitis. J. Neuroimmunol. (1992) 41:1-8.
10. BOYLAN MT, CROCKARD AD, MCDONNELL GV, ARMSTRONG MA, HAWKINS SA: CD80 (B7-1) and CD86 (B7-2) expression in multiple sclerosis patients: Clinical subtype specific variation in peripheral monocytes and B cells and lack of modulation by high dose methylprednisolone. J. Neurol. Sci. (1999) 167:79-89.
11. LIPSKY PE, ATTREP JF, GRAMMER AC, MCILRAITH MJ, NISHIOKA Y: Analysis of CD40-CD40 ligand interactions in the regulation of human B cell function. Ann. NY Acad. Sci. (1997) 815:372-383.
12. LITZENBURGER T, FASSLER R, BAUER J et al.: B lymphocytes producing demyelinating autoantibodies development and function in gene-targeted transgenic mice. J. Exp. Med. (1998) 188:169-180.
13. JAMES JA, HARLEY JB: B-cell epitope spreading in autoimmunity. Immunol. Rev. (1998) 164:185-200.
14. MAMULA MJ: EpTtope spreading: the role of self peptides and autoantigen processing by B lymphocytes. Immunol. Rev. (1998) 164:231-239.
15. ROBINSON WH, FONTOURA P, LEE BJ et al.: Protein microarrays guide tolerizing DNA vaccine treatment of autoimmune encephalomyelitis. Nat. Biotechnol. (2003) 21:1033-1039.
16. HUITINGA I, VAN ROOIJEN N, DE GROOT CJ, UITDEHAAG BM, DIJKSTRA CD: Suppression of experimental allergic encephalomyelitis in Lewis rats after elimination of macrophages. J. Exp. Med (1990) 172:1025-1033.
17. TRAN EH, HOEKSTRA K, VAN ROOIJEN N, DIJKSTRA CD, OWENS T: Immune invasion of the central nervous system parenchyma and experimental allergic encephalomyelitis, but not leukocyte extravasation from blood, are prevented in macrophage-depleted mice. J. Immunol. (1998) 161:3767-3775.
18. REDER AT, GENC K, BYSKOSH PV, PORRINI AM: Monocyte activation in multiple sclerosis. Mult. Scler. (1998) 4:162-168.
19. TAN J, TOWN T, PARIS D et al.: Activation of microglial cells by the CD40 pathway: Relevance to multiple sclerosis. J. Neuroimmunol. (1999) 97:77-85.
20. BENVENISTE EN: Role of macrophages/microglia in multiple sclerosis and experimental allergic encephalomyelitis. J. Mol. Med. (1997) 75:165-173.
21. SMITH KJ,TKAPOOR R, FELTS PA: Demyelination: the role of reactive oxygen and nitrogen species. Brain Pathol. (1999) 9:69-92.
22. SAMOILOVA EB, HORTON JL, ZHANG H, CHEN Y: CD40L blockade prevents autoimmune encephalomyelitis and hampers TH1 but not TH2 pathway of T cell differentiation. J. Mol. Med. (1997) 75:603-608.
23. BRÜCK W, SOMMERMEIER N, BERGMANN M et al.: Macrophages in multiple sclerosis. Immunobiology (1996) 195:588-600.
24. SRIRAM S, RODRIGUEZ M: Indictment of the microglia as the villain in multiple sclerosis. Neurology (1997) 48:464-470.
25. GENAIN P, CANNELLA B, HAUSER SL, RAINE CS: Identification of autoantibodies associated with myelin damage in multiple sclerosis. Nat. Med. (1999) 5:170-175.
26. CONFAVREUX C, VUKUSIC S, MOREAU T: Relapses and progression of disability in multiple sclerosis. N. Engl. J. Med. (2000) 343:1430-1438.
27. COLES A, COX A, LE PAGE E et al.: The window of therapeutic opportunity in multiple sclerosis: Evidence from monoclonal antibody therapy in relapsing-remitting and secondary progressive disease. Mult. Scler. (2003) 9(Suppl. 1):S17.
28. HENEGHAN C, BADENOCH D: Evidence-based Medicine ToolKit. Br. Med. J. Editors, London, UK (2002):65.
29. THE IFNB MULTIPLE SCLEROSIS STUDY GROUP: Interferon beta-1b is effective in relapsing-remitting multiple sclerosis. I. Clinical results of a multicenter, randomized, double- blind, placebo-controlled trial. Neurology (1993) 43:655-661.
30. JOHNSON KP, BROOKS BR, COHEN JA et al.: Copolymer 1 reduces relapse rate and improves disability in relapsing-remitting multiple sclerosis: Results of a Phase III multicenter, double-blind, placebo-controlled trial. Neurology (1995) 45:1268-1276.
31. JACOBS LD, COOKFAIR DL, RUDICK RA, HERNDON RM, RICHERT JR: Intramuscular interferon beta-1 alpha for disease progression in relapsing multiple sclerosis. Ann. Neurol. (1996) 39:285-295.
32. PRISMS (PREVENTION OF RELAPSES AND DISABILITY BY INTERFERON BETA-1A SUBCUTANEOUSLY IN MULTIPLE SCLEROSIS) STUDY GROUP: Randomised double-blind placebo-controlled study of interferon beta-1a in relapsing/remitting multiple sclerosis. Lancet (1998) 352:1498-1504.
33. GALETTA SL, MARKOWITZ C, LEE AG: Immunomodulatory agents for the treatment of relapsing multiple sclerosis. a systematic review. Arch. Intern. Med. (2002) 162:2161-2169.
34. FILIPPINI G, INCORVAIA B: Is interferon effective and safe for relapsing-remitting multiple sclerosis? Neuroepidemiology (2002) 21:310.
35. O'CONNOR P, on behalf of the CANADIAN MULTIPLE SCLEROSIS WORKING GROUP: Key issues in the diagnosis and treatment of multiple sclerosis. An overview. Neurology (2002) 59(sup3):S1-S33.
36. COMI G, FILIPPI M, WOLINSKY JS, and the EUROPEAN/CANADIAN GLATIRAMER ACETATE STUDY GROUP: European/Canadian multicenter, double-blind, randomized, placebo-controlled study of the effects of glatiramer acetate on magnetic resonance imaging-measured disease activity and burden in patients with relapsing multiple sclerosis. Ann. Neurol. (2001) 49:290-297.
37. TRAPP BD, RANSOHOFF RM, FISHER E, RUDICK RA: Neurodegeneration in multiple sclerosis: Relationship to neurological disability. Neuroscientist (1999) 5:48-57.
38. THE IFNB MULTIPLE SCLEROSIS STUDY GROUP, and the UNIVERSITY OF BRITISH COLUMBIA MS/MRI ANALYSIS GROUP: Interferon beta-1b in the treatment of multiple sclerosis: Final outcome of the randomized controlled trial. Neurology (1995) 45:1277-1285.
39. JOHNSON KP, BROOKS BR, COHEN JA et al.: Extended use of glatiramer acetate (Copaxone) is well tolerated and maintains its clinical effect on multiple sclerosis relapse rate and degree of disability. Neurology (1998) 50:701-708.
40. EUROPEAN STUDY GROUP ON INTERFERON BETA-1B IN SECONDARY PROGRESSIVE MS: Placebo-controlled multicentre randomised trial of interferon beta-1b in treatment of secondary progressive multiple sclerosis. Lancet (1998) 352:1491-1497.
41. GOODKIN D, THE NORTH AMERICAN STUDY GROUP ON INTERFERON BETA-1b IN SECONDARY PROGRESSIVE MS: Interferon beta-1b in secondary progressive MS: Clinical and MRI results of a 3-year randomized controlled trial. Neurology (2000) 54:2352 (Abstract).
42. KILLIAN JM, BRESSLER RB, ARMSTRONG RM: Controlled pilot trial of monthly intravenous cyclophosphamide in multiple sclerosis. Arch. Neurol. (1988) 45:27-30.
43. GOBBINI MI, SMITH ME, RICHERT ND, FRANK JA, MCFARLAND HF. Effect of open label pulse cyclophosphamide therapy on MRI measures of disease activity in five patients with refractory relapsing-remitting multiple sclerosis. J. Neuroimmunol. (1999) 99:142-149.
44. MLLEFIORINI E, GASPERINI C, POZZILLI C et al.: Randomized placebo-controlled trial of mitoxantrone in relapsing- remitting multiple sclerosis: 24-month clinical and MRI outcome. J. Neurol. (1997) 244:153-159.
45. BASTIANELLO S, POZZILLI C, D'ANDREA F et al.: A controlled trial of mitoxantrone in multiple sclerosis: Serial MRI evaluation at one year. Can. J. Neurol. Sci. (1994) 21:266-270
46. EDAN G, MILLER D, CLANET M et al.: Therapeutic effect of mitoxantrone combined with methylprednisolone in multiple sclerosis: A randomized multicenter study of active disease using MRI and clinical criteria. J. Neurol. Neurosurg Pscyhiatry (1997) 62:112-118.
47. AMATO MP, PRACUCCI G, PONZIANI G, SIRACUSA G, FRATIGLIONI L: Long-term safety of azathioprine therapy in multiple sclerosis. Neurology (1993) 43:831-833.
48. PALACE J, ROTHWELL P: New treatments and azathioprine in multiple sclerosis. Lancet (1997) 350:261.
49. MARKOVIC-PLESE S, BIELEKOVA B, KADOM N et al.: Longitudinal magnetic resonance imaging study on the effect of azathioprine in relapsing-remitting multiple sclerosis patients refractory to the treatment with interferon β-1b. Neurology (2002) 58(Suppl. 3):A492.
50. MILLER DH, KHAN OA, SHEREMATA WA et al.: A controlled trial of Natalizumab for relapsing multiple sclerosis. N. Engl. J. Med. (2003) 348:15-23.
51. COLES AJ, WING MG, MOLYNEUX P, PAOLILLO A, DAVIE CM, HALE G: Monoclonal antibody treatment exposes three mechanisms underlying the clinical course of multiple sclerosis. Ann. Neurol. (1999) 46:296-305.
52. COLES AJ, WING N, SMITH S et al.: Pulsed monoclonal antibody treatment and autoimmune thyroid disease in multiple sclerosis. Lancet (1999) 354:1691-1696.
53. GOODKIN DE, PLENCNER S, PALMER-SAXERUD J, TEETZEN M: Cyclophosphamide in chronic progressive multiple sclerosis: Maintenance versus nonmaintenance therapy. Arch. Neurol. (1987) 44:823-827.
54. COOK SD, DEVEREUX C, TROIANO R et al.: Effect of total lymphoïd irradiation in chronic progressive multiple sclerosis. Lancet (1986) 1:1405-1408.
55. WEINER HL, COHAN JA: Treatment of multiple sclerosis with cyclophosphamide: Critical review of clinical and immunological effects. Mult. Scler. (2002) 8:142-154.
56. FIDLER JM, QUINN DEJOY S, GIBBONS JJ Jr: Selective immunomodulation by the antineoplastic agent mitoxantrone. I. Suppression of B lymphocyte function. J. Immunol. (1986) 137:727-732.
57. MUSTAFA M, DIENER P, SUN JB, LINK H, OLSSON T: Immunopharmacologic modulation of experimental allergic encephalomyelitis: Low-dose cyclosporin-A treatment causes disease relapse and increased systemic T and B cell mediated myelin-directed autoimmunity. Scand. J. Immunol. (1993) 38:499-507.
58. LEVINE S, GHERSON J: Morphologic effects of mitoxantrone and a related anthracenedione on lymphoid tissues. Int. J. Immunopharmacol. (1986) 8:999-1007.
59. WANG BS, LUMANGLAS AL, SILVA J, RUSZALA-MALLON VM, DURR FE: Inhibition of the induction of alloreactivity with miroxantrone. Int. J. Immunopharmacol. (1987) 8:967-973.
60. NEUMANN H, MEDANA IM, BAUER J, LASSMANN H: Cytotoxic T lymphocytes in autoimmune and degenerative CNS diseases. Trends Neurosci. (2002) 25:313-319.
61. GIULIANI F, GOODYER CG, ANTEL JP, YONG VW: Vulnerability of human neurons to T cell-mediated cytotoxicity. J. Immunol. (2003) 171:368-379.
62. FIDLER JM, DEJOY SQ, SMITH FR 3rd, GIBBONS JJ Jr: Selective immunomodulation by the antineoplastic agent mitoxantrone. II. Nonspecific adherent suppressor cells derived from mitoxantrone-treated mice. J. Immunol. (1986) 136:2747-2754.
63. WATSON CM, DAVISON AN, BAKER D, O'NEILL JK, TURK JL: Suppression of demyelination by mitoxantrone. Int. J. Immunopharmacol. (1991) 13:923-930.
64. EHNINGER G, PROKSCH B, HEINZEL G, WOODWARD DL: Clinical pharmacology of mitoxantrone. Cancer Treat. Rep. (1986) 70:1373-1378.
65. VAN BELLE SJP, DE PLANQUE MM, SMITH IE et al.: Pharmacokinetics of mitoxantrone in humans following single-agent infusion or intra-arterial injection therapy or combined-agent infusion therapy. Cancer Chemother. Pharmacol. (1986) 18:27-32.
66. ROBOZ J, PACIUCCI PA, SILIDES D, GREAVES J, HOLLAND JF: Detection and quantification of mitoxantrone in human organs. A case report. Cancer Chemother. Pharmacol. (1984) 13:67-68.
67. STEWART DJ, GREEN RM, MIKHAEL NZ, MONTPETIT V, THIBAULT M, MAROUN JA: Human autopsy tissue concentrations of mitoxantrone. Cancer Treat Rep (1986) 70:1255-1261.
68. LU K, SAVARAJ N, LOO TL: Pharmacological disposition of 1,4-dihydroxy-5-8-bis 2[(2-hydroxyethal)amino]ethyl]amino]-9,10-anthracenedione dihydrochloride in the dog. Cancer Chemother. Pharmacol. (1984) 13:63-66.
69. ALBERTS DS, PENG YM, BOWDEN GT, DALTON WS, MACKEL C: Pharmacology of mitoxantrone: Mode of action and pharmacokinetics. Invest. New Drugs (1985) 3:101-107.
70. GREIDANUS J, DE VRIES EG, MULDER NH et al.: A Phase I pharmacokinetic study of 21-day continuous infusion mitoxantrone. J. Clin. Oncol. (1989) 7:790-797.
71. RIDGE SC, SLOBODA AE, MCREYNOLDS RA et al.: Suppression of experimental allergic encephalomyelitis by mitoxantrone. Clin. Immunol. Immunopathol. (1985) 35:35-42.
72. LEVINE S, SALTZMAN A: Regional suppression, therapy after onset and prevention of relapses in experimental allergic encephalomyelitis by mitoxantrone. J. Neuroimmunol. (1986) 13:175-181.
73. LUBLIN FD, LAVASA M, VITI C, KNOBLER RL: Suppression of acute and relapsing experimental allergic encephalomyelitis with mitoxantrone. Clin. Immunol. Immunopathol. (1987) 45:122-128.
74. GONSETTEARE, DEMONTY L: Mitoxantrone: a new immunosuppressive agent in multiple sclerosis. In: Recent advances in multiple sclerosis therapy. Gonsette RE Delmotte P (Ed.), Elsevier Science Publishers BV (1989):11-164.
75. GONSETTE RE, DEMONTY L: Immunosuppression with mitoxantrone in multiple sclerosis: A pilot study for 2 years in 22 patients. Neurology (1990) 40(Suppl. 1):261.
76. KAPPOS L, GOLD R, KUNSTLER E, ROHRBACH E, HEUN R, STADT D: Mitoxantrone (Mx) in the treatment of rapidly progressive MS: A pilot study with serial gadolinum (Gd)-enhanced MRI. Neurology (1990) 40(Suppl. 1):261.
77. NOSEWORTHY JH, LEE D, PENMAN M et al.: A Phase II evaluation of mitoxantrone HCl in the treatment of progressive multiple sclerosis. Neurology (1991) 41(Suppl. 1):146.
78. RUTTINGER H, MARTIN J: Demonstration of MS-plaques activated during immunosuppression with mitoxantrone by gadolinium-enhanced MRI. Akt Neurol. (1992) 19:13-15.
79. MAUCH E, KORNHUBER HH: Die immunsuppressive Therapie der multiplen Sklerose mit Mitoxantron. Fortschr. Neurol. Psych. (1993) 61:410-417.
80. KRAPF H, MAUCH E, FETZER U, LAUFEN H: Serial gadolinium-enhanced magnetic resonance imaging in patients with multiple sclerosis treated with mitoxantrone. Neuroradiology (1995) 37:113-120.
81. NOSEWORTHY JH, HOPKINS MB, VANDERVOORT MK et al.: An open-trial evaluation of mitoxantrone in the treatment of progressive MS. Neurology (1993) 43:1401-1406.
82. GONSETTE RE: Mitoxantrone immunotherapy in multiple sclerosis. Mult. Scler. (1996) 1:329-332.
83. HARTUNG HP, GONSETTE R, KÖNIG N et al.: Mitoxantrone in progressive multiple sclerosis: A placebo-controlled, double blind, randomised, multicentre trial. Lancet (2002) 360:2018-2025.
84. JEFFERY DR, LEFKOWITZ DS, CRITTENDEN JP: Treatment of Marburg variant multiple sclerosis with mitoxantrone. J. Neuroimaging (2004) 14:58-62.
85. LA MANTIA L, EOLI M, SALMAGGI A, TORRI V, MILANESE C: Cyclophosphamide in chronic progressive multiple sclerosis: A comparative study. Ital. J. Neurol. Sci. (1998) 19:32-36.
86. SHENKENBERG TD, VON HOFF DD: Possible mitoxantrone-induced amenorrhea. Cancer Treat. Rep. (1986) 70:659-661.
87. DE CASTRO S, CARTONI D, MILLEFIORINI E et al.: Noninvasive assessment of mitoxantrone cardiotoxicity in relapsing remitting multiple sclerosis. J. Clin. Pharmacol. (1995) 35:627-632.
88. GHALIE RG, EDAN G, LAURENT M et al.: Cardiac adverse effects associated with mitoxantrone (Novantrone) therapy in patients with MS. Neurology (2002) 59:909-913.
89. ACEVEDO AR, NAVA C, ARRIADA V, VIOLANTE A, CORONA T: Cardiovascular dysfunction in multiple sclerosis. Acta Neurol. Scand. (2000) 101:85-88.
90. OLINDO S, GUILLON B, HELIAS J, PHILLIBERT B, MAGNE C, FEVE JR: Decrease in heart ventricular ejection fraction during multiple sclerosis. Eur. J. Neurol. (2002) 9:287-291.
91. STROTMANN JM, SPINDLER M, WEILBACH FX, GOLD R, ERTL G, VOELKER W: Myocardial function in patients with multiple sclerosis treated with low-dose mitoxantrone. Amer J. Cardiol. (2002) 89:1222-1225.
92. SPINDLER M, WEILBACH F, BEER M et al.: Non-invasive functional and biochemical assessment of mitoxantrone cardiotoxicity in patients with multiple sclerosis. J. Cardiovasc. Pharmacol. (2003) 42:680-687.
93. AVASARALA JR, CROSS AH, CLIFFORD DB, SINGER BA, SIEGEL BA, ABBEY E: Rapid onset mitoxantrone-induced cardiotoxicity in secondary progressive multiple sclerosis. Mult. Scler. (2003) 9:59-62.
94. GBADAMOSI J, MUNCHAU A, WEILLER C, SCHAFER H: Severe heart failure in a young multiple sclerosis patient. J. Neurol. (2003) 250:241-242.
95. JENSEN BV, SKOVSGAARD T, NIELSEN SL: Functional monitoring of anthracycline cardiotoxicity: A prospective, blinded, long-term observational study of outcome in 120 patients. Ann. Oncol. (2002) 13:699-709.
96. AUNER HW, TINCHON C, LINKESCH W et al.: Prolonged monitoring of troponin T for the detection of anthracycline cardiotoxicity in adults with hematological malignancies. Ann. Hematol. (2003) 82:218-222.
97. WILSTERMANN AM, OSHEROFF N: Stabilization of eukaryotic topoisomerase II-DNA cleavage complexes. Curr. Top. Med. Chem. (2003) 3:321-338.
98. ANDOH T: Mechanism of occurrence of secondary tumors by antitumor drugs. Gan To Kagaku Ryoho (1999) 26:1988-1998.
99. CHAPLAIN G, MILAN C, SGRO C, CARLI PM, BONITHON-KOPP C: Increased risk of acute leukemia after adjuvant chemotherapy for breast cancer: A population-based study. J. Clin. Oncol. (2000) 18:2836-2842.
100. BEAUMONT M, SANZ M, CARLI PM: Therapy related acute promyelocytic leukemia. J. Clin. Oncol. (2003) 21:2123-2137.
101. DASSONNEVILLE L, BAILLY C: Chromosome translocations and leukemias induced by inhibitors of topoisomerase II anticarcinogenic drugs. Bull. Cancer (1998) 85:254-261.
102. VICARI AM, CICERI F, FOLLI F: Acute promyelocytic leukemia following mitoxantrone as single agent for the treatment of multiple sclerosis. Leukemia (1998) 12:441-442.
103. BRASSAT D, RECHER C, WAUBANT E et al.: Therapy-related acute myeloblastic leukemia after mitoxantrone treatment in a patient with MS. Neurology (2002) 59:954-955.
104. RADU TD, MARC D, HEVE V: Acute myeloid leukaemia (AML) induced by mitoxantrone. Mult. Scler. (2002) 8(Suppl. 1):S127.
105. HEESEN C, BRUEGMANN M, GBDAMOSI J, KOCH E, MONCH A, BUHMANN C: Therapy-related acute myelogenous leukaemia (t-AML) in a patient with multiple sclerosis treated with mitoxantrone. Mult. Scler. (2003) 9:213-214.
106. CATTANEO C, ALMICI C, BORLENGHI E, MOTTA M, ROSSI G: A case of acute promyelocytic leukaemia following mitoxantrone treatment of multiple sclerosis. Leukemia (2003) 17:985-986.
107. MOGENET I, SIMIAND-ERDOCIAIN E, CANONGE JM, PRIS J: Acute myelogenous leukemia following mitoxantrone treatment for multiple sclerosis. Ann. Pharmacother. (2003) 37:747-748.
108. DELISSE B, DE SEZE J, MACKOWIAK A et al.: Therapy-related acute myeloblastic leukaemia after mitoxantrone treatment in a patient with multiple sclerosis. Mult. Scler. (2003) 9(Suppl. 1):S121.
109. LINASSIER C, BARIN C, CALAIS C et al.: Early secondary acute myelogenous leukemia in breast cancer patients after treatment with mitoxantrone, cyclophosphamide, fluorouracil and radiation therapy. Ann. Oncol. (2000) 11:1289-1294.
110. GHALIE RG, MAUCH E, EDAN G et al.: A study of therapy-related acute leukaemia after mitoxantrone therapy for multiple sclerosis. Mult. Scler. (2002) 8:441-445.
111. ANDERSSON BS, EKSBORG S, VIDAL RF, SUNDBERG M, CARLBERG M: Anthraquinone-induced cell injury: Acute toxicity of carminomycin, epirubicin, idarubicin and mitoxantrone in isolated cardiomyocytes. Toxicology (1999) 135:11-20.
112. KAHLES H, BASTIAN HJ, SCHIFFMANN O, GECK M, HELMKE FR, GOLZ N: Mitoxantrone-induced acute left heart failure after intrapleural administration. Herz (1997) 22:217-220.
113. FRISHMAN WH, SUNG HM, YEE HC et al.: Cardiovascular toxicity with cancer chemotherapy. Curr. Probl. Cancer (1997) 21:301-360.
114. PAI VB, NAHATA MC: Cardiotoxicity of chemotherapeutic agents: incidence, treatment and prevention. Drug Saf. (2000) 22:263-302.
115. HORTOBAGYI GN, FRUYE D, BUZDAR AU et al.: Decreased cardiac toxicity of doxorubicin administered by continuous intravenous infusion in combination chemotherapy for metastatic breast carcinoma. Cancer (1989) 63:37-45.
116. GOKHALE PC, PEI J, ZHANG C, AHMAD I, RAHMAN A, KASID U: Improved safety, pharmacokinetics and therapeutic efficacy profiles of a novel liposomal formulation of mitoxantrone. Anti-Cancer Res. (2001) 21:3313-3321.
117. VENDITTI P, BALESTRIERI M, DE LEO T, DI MEO S: Free radical involvement in doxorubicin-induced electrophysiological alterations in rat papillary muscle fibres. Cardiovasc. Res. (1998) 38:695-702.
118. WEILBACH FX, CHAN A, TOYKA KV, GOLD R: The cardioprotector dexrazoxane augments therapeutic efficacy of mitoxantrone in experimental autoimmune encephalomyelitis. Clin. Exp. Immunol. (2004) 135:49-55.
119. HERMAN EH, FERRANS VJ, MYERS CE, VAN VLEET JF: Comparison of the effectiveness of (+/-)-1,2-bis(3,5-dioxopiperazinyl-l-yl)propane (ICRF-187) and N-acetylcysteine in preventing chronic doxorubicin cardiotoxicity in beagles. Cancer Res. (1985) 45:276-281.
120. SPEYER JL, GREEN MD, ZELENIUCH-JACQUOTTE A et al.: ICRF-187 permits longer treatment with doxorubicin in women with breast cancer. J. Clin. Oncol. (1992) 10:117-127.
121. SEYMOUR L, BRAMWELL V, MORAN LA: 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 (1999) 3:145-159.
122. ALDERTON PM, GROSS J, GREEN MD: Comparative study of doxorubicin, mitoxantrone, and epirubicin in combination with ICRF-187 (ADR-529) in a chronic cardiotoxicity animal model. Cancer Res. (1992) 52:194-201.
123. KOUTINOS G, STATHOPOULOS GP, DONTAS I et al.: The effect of doxorubicin and its analogue mitoxantrone on cardiac muscle and on serum lipids: An experimental study. Anti-Cancer Res. (2002) 22:815-820.
124. HERMAN EH, ZHANG J, HASINOFF BB, CLARK JR Jr, FERRANS VJ: Comparison of the structural changes induced by doxorubicin and mitoxantrone in the heart, kidney and intestine and characterization of the Fe(III)-mitoxantrone complex. J. Mol. Cell. Cardiol. (1997) 29:2415-2430.
125. KITA M, GOODKIN DE, OLSON M, CAMPBELL J: A pilot study of mitoxantrone plus dexrazoxane versus mitoxantrone in patients with relapsing remitting, secondary progressive and progressive relapsing MS. Neurology (2003) 60(Suppl. 1):A149.
126. FADILLIOGLU E, ERDOGAN H, SOGUT S, KUKU I: Protective effects of erdosteine against doxorubicin-induced cardiomyopathy in rats. J. Appl. Toxicol. (2003) 23:71-74.
127. KRAPCHO AP, LANDI JJ Jr, HACKER MP, McCORMACK JJ. Synthesis of antineoplastic evaluations of 5,8-bis[(aminoalkyl)amino]-1-azaanthracene-9,10-diones. J. Med. Chem. (1985) 28:1124-1126.
128. KRAPCHO AP, MARESCH MJ, HACKER MP et al.: Anthracene-9,10-diones and Aza Bioisosteres as antitumor agents. Curr Med Chem (1995) 2:803-824.
129. BEGGIOLIN G, CRIPPA L, MENTA E et al.: BBR2778, an aza-anthracenedione endowed with preclinical anticancer activity and lack of delayed cardiotoxicity. Tumori (2001) 87:407-416.
130. CAVALLETTI E, CRIPPA L, BELLINI O, MENTA E, CAVAGNOLI R, DELBO D: 9-Aza-anthrapyrazoles devoid of cardiotoxic effects. Proc. Am. Assoc. Cancer Res. (1996) 37:aBstr 2662.
131. DUBOIS B, GONSETTE R, DILLEN C, BILLIAU A: Efficacy of a novel non-cardiotoxic aza-anthracenedione (BBR2778) in acute EAE. Mult. Scler. (2001) 7(Suppl. 1):S20(P-010).
132. CAVALETTI G, FRIGO M, ROTA S et al.: BBR2778, a new non-cardiotoxic drug structurally related to mitoxantrone, reduces the severity of rat acute and chronic experimental allergic encephalomyelitis. Mult. Scler. (2002) 8(Suppl. 1):S68.
133. BBR2778. Investigator Drug Brochure, July (2002) edition 6.
134. DAWSON LK, JODRELL DI, BOWMAN A et al.: A clinical Phase I and pharmacokinetic study of BBR2778, a novel anthracenedione analogue, administered intravenously, 3 weekly. Eur. J. Cancer (2000) 36:2353-2359.
135. FAIVRE S, RAYMOND E, BOIGE V et al.: A Phase I and pharmacokinetic study of the novel aza-anthracenedione compound BBR2778 in patients with advanced solid malignancies. Clin. Cancer Res. (2001) 7:43-50.
136. BORCHMANN P, SCHNELL R, KNIPPERTZ R: Phase I study of BBR2778, a new aza-anthracenedione, in advanced or refractory non-Hodgkin's lymphoma. Ann. Oncol. (2001) 12:661-667.
137. LEPAGE E, LERAY, DEBOUVERIE M et al.: Induction treatment with mitoxantrone in worsening relapsing remitting multiple sclerosis: A 'rescue therapy' for sub-optimal responders to interferon beta? A pilot study. Neurology (2003) 60(Suppl. 1):A149.
138. PERINI P, GALLO P: Cyclophosphamide is effective in stabilizing rapidly deteriorating secondary progressive multiple sclerosis. J. Neurol. (2003) 250:834-838.
139. GOTTESMAN M, FRIEDMAN-UREVICH S: Results from the IDEAS study: High-dose interferon beta-1b in MS treatment. Mult. Scler. (2003) 9(Suppl. 1):S95.
140. HURWITZ B, ARNASON BG, GILEY GK et al.: Betaseron®/Betaferon® efficacy yielding outcomes of a new dose (BEYOND) - safety and tolerability of 500 mcg versus 250 mcg of interferon beta-1b. Mult. Scler (2003) 9(Suppl. 1):S40.
141. GOGGIN T, VIGNA E, NEUTEBOOM B, TRINCHARD-LUGAN I, KLETZL H: Non-covalent complex of interferon beta-1a and recombinant human Type I interferon receptor subunit 2 a: Preclinical and Phase I results. Mult. Scler. (2003) 9(Suppl. 1):S138.
142. MACHKHAS H, HARATI Y: Side effects of immunosuppressant therapies used in neurology. Neurol. Clin. (1998) 16:171-188.
143. CONNELL WR, KAMM MA, RITCHIE JK, LENNARD-JONES JE: Bone marrow toxicity caused by azathioprine in inflammatory bowel disease: 27 years of experience. Gut (1994) 34:1081-1085.
144. CONNELL WR, KAMM MA, DICKSON M, BALKWILL AM, RITCHIE JK, LENNARD-JONES JE: Long-term neoplasia risk after azathioprine treatment in inflammatory bowel disease. Lancet (1994) 343:1249-1252.
145. CONFAVREUX C, SADDIER P, GRIMAUD J, MOREAU T, ADELEINE P, AIMARD G: Risk of cancer from azathioprine therapy in multiple sclerosis: a case-control study. Neurology (1996) 46:1607-1612.
146. DE RIDDER D, VAN POPPEL H, DEMONTY L et al.: Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide. J. Urol. (1998) 159:1881-1884.
147. GONSETTE RE: Mitoxantrone in progressive multiple sclerosis: when and how to treat? J. Neurol. Sci. (2003) 206:203-208.
148. STARZL TE, MURASE N, ABU-ELMAGD K et al.: Tolerogenic immunosuppression for organ transplantation. Lancet (2003) 361:1502-1510.
149. TRAVIS LB, CURTIS RE, GLIMELIUS B et al.: Bladder and kidney cancer following cyclophosphamide therapy for non-Hodgkin's lymphoma. J. Natl. Cancer Inst. (1995) 87:524-530.
150. SISSI C, MORO S, RICHTER S: DNA-interactive anticancer Aza-anthrapyrazoles: Biophysical and biochemical studies relevant to the mechanism of action. Mol. Pharmacol. (2001) 59:96-103.
151. PARKIN D, JACOBY A, MCNAMEE P, MILLER P, THOMAS S, BATES D: Treatment of multiple sclerosis with interferon beta: In appraisal of cost-effectiveness and quality of life. J. Neurol. Neursurg. Psych. (2000) 68:144-149.
152. BROWN MG, MURRAY TJ, SKETRIS IS et al.: Cost-effectiveness of interferon beta-1b in slowing multiple sclerosis disability progression. First estimates. Int. J. Technol. Assess. Health Care (2000) 16:751-767.
153. COYLE PK, VOLLMER T, LEPEN C et al.: Long-term cost-effectiveness of interferon beta-1a (Rebif 44 μg tiw) in the treatment of relapsing-remitting multiple sclerosis: An econometric model. J. Neurol. (2002) 249(Suppl. 1):201-202.
154. FORBES RB, LEES A, WAUGH N, SWINGLER RJ: Population based cost utility study of interferon beta-1b in secondary progressive multiple sclerosis. Br. Med. J. (2000) 319:1529-1533.
155. KOBELT G, JONSSON L, HENRIKSSON F, FREDRIKSON S, JONSSON B: Cost-utility analysis of interferon beta-1b in secondary progressive multiple sclerosis. Int. J. Technol. Assess. Health Care (2000) 16:768-780.
156. NUIJTEN MJ, HUTTON J: Cost-effectiveness analysis of interferon beta in multiple sclerosis: A Markov process analysis. Value Health (2002) 5:44-54.
157. CHILCOTT J, MCCABE C, TAPPENDEN P et al.: Modelling the cost effectiveness of interferon beta and glatiramer acetate in the management of multiple sclerosis. Commentary: Evaluating disease modifying treatments in multiple sclerosis. Br. Med. J. (2003) 326:522.
158. TOUCHETTE DR, DURGIN TL, WANKE LA, GOODKIN DE: A cost-utility analysis of mitoxantrone hydrochloride and interferon beta-1b in the treatment of patients with secondary progressive or progressive relapsing multiple sclerosis. Clin. Ther. (2003) 25:611-634.
159. KOBELT G, JONSSON L, MILTENBURGER C, JONSSON B: Cost-utility analysis of interferon beta-1B in secondary progressive multiple sclerosis using natural history disease data. Int. J. Technol. Assess. Health Care (2002) 18:127-138.
160. LAUPACIS A, FEENY D, DETSKY AS, TUGWELL PX: How attractive does a new technology have to be to warrant adoption and utilization? Tentative guidelines for using clinical and economic evaluations. CMAJ (1992) 146:473-481.
161. FLACHENECKER P, RIECKMANN P: Early intervention in multiple sclerosis: Better outcomes for patients and society? Drugs (2003) 63:1525-1533.