Omacetaxine mepesuccinate for the treatment of leukemia

Expert Opinion on Pharmacotherapy

Volumn 12, Issue 15, 2011, Pages 2381-2392

  Kim, Theo Daniel ^a   Frick, Mareike ^a   Le Coutre, Philipp ^a  

^a CHARITÉ UNIVERSITÄTSMEDIZIN BERLIN   (Germany)

Author keywords

Acute myeloid leukaemia; BCR ABL1; BCR ABL1 mutations; Cephalotaxine; Chronic myeloid leukaemia; Homoharringtonine; Omacetaxine mepesuccinate; Philadelphia chromosome; T315I

Indexed keywords

ALPHA INTERFERON; ANCITABINE; BCR ABL PROTEIN; CGX 653; CYCLOSPORIN A; CYTARABINE; DASATINIB; DAUNORUBICIN; GLYCOPROTEIN P; GRANULOCYTE COLONY STIMULATING FACTOR; HOMOHARRINGTONINE; IMATINIB; JANUS KINASE 2; MERCAPTOPURINE; METHOTREXATE; MITOXANTRONE; MULTIDRUG RESISTANCE PROTEIN 1; MYELOID CELL LEUKEMIA 1 PROTEIN; NILOTINIB; ONCOPROTEIN; PREDNISONE; STAT5 PROTEIN; TIOGUANINE; UNCLASSIFIED DRUG; VINCRISTINE;

ACUTE GRANULOCYTIC LEUKEMIA; ACUTE LYMPHOBLASTIC LEUKEMIA; ANASARCA; ANEMIA; ANOREXIA; APOPTOSIS; ARTICLE; ASTHENIA; BONE MARROW SUPPRESSION; CANCER COMBINATION CHEMOTHERAPY; CANCER RESISTANCE; CARDIOVASCULAR DISEASE; CEPHALOTAXUS; CHINESE MEDICINE; CHRONIC MYELOID LEUKEMIA; CONTINUOUS INFUSION; CYTOGENETICS; DIARRHEA; DRUG BLOOD LEVEL; DRUG CLEARANCE; DRUG DOSE REDUCTION; DRUG EFFICACY; DRUG ERUPTION; DRUG EXCRETION; DRUG HALF LIFE; DRUG MECHANISM; DRUG POTENTIATION; DRUG SAFETY; DRUG SYNTHESIS; DRUG TOLERABILITY; FEBRILE NEUTROPENIA; FEVER; GENE MUTATION; GRANULOCYTOPENIA; HEART OUTPUT; HEMATEMESIS; HEMATOMA; HUMAN; HYPERGLYCEMIA; HYPEROSMOLAR COMA; HYPOTENSION; IN VITRO STUDY; IN VIVO STUDY; INJECTION SITE ERYTHEMA; INJECTION SITE REACTION; LEUKEMIA REMISSION; LOADING DRUG DOSE; LUNG ASPERGILLOSIS; MULTIDRUG RESISTANCE; MULTIPLE CYCLE TREATMENT; MYELODYSPLASTIC SYNDROME; NAUSEA; NEUTROPENIA; PAIN; PHASE 1 CLINICAL TRIAL (TOPIC); PHASE 2 CLINICAL TRIAL (TOPIC); PHILADELPHIA 1 CHROMOSOME; POINT MUTATION; RASH; SIDE EFFECT; TACHYCARDIA; THORAX PAIN; THROMBOCYTOPENIA;

ANTINEOPLASTIC AGENTS, PHYTOGENIC; CLINICAL TRIALS AS TOPIC; DRUG RESISTANCE, NEOPLASM; HARRINGTONINES; HUMANS; LEUKEMIA, MYELOGENOUS, CHRONIC, BCR-ABL POSITIVE;

EID: 80052913190     PISSN: 14656566     EISSN: 17447666     Source Type: Journal    
DOI: 10.1517/14656566.2011.613378     Document Type: Article

References (90)

1. Dohner H, Estey EH, Amadori S, et al. Diagnosis and management of acute myeloid leukemia in adults: recommendations from an international expert panel, on behalf of the European LeukemiaNet. Blood 2010;115:453-74
2. Ofran Y, Rowe JM. Induction and postremission strategies in acute myeloid leukemia: what is new? Curr Opin Hematol 2011;18:83-8
3. Schiffer CA. "I am older, not elderly," said the patient with acute myeloid leukemia. J Clin Oncol 2010;28:521-3
4. Deininger M, Buchdunger E, Druker BJ. The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 2005;105:2640-53 (Pubitemid 40446252)
5. Baccarani M, Cortes J, Pane F, et al. Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 2009;27:6041-51
6. Hehlmann R, Hochhaus A, Baccarani M. Chronic myeloid leukaemia. Lancet 2007;370:342-50 (Pubitemid 47094995)
7. Apperley JF. Part I: mechanisms of resistance to imatinib in chronic myeloid leukaemia. Lancet Oncol 2007;8:1018-29 (Pubitemid 47629897)
8. Gorre ME, Mohammed M, Ellwood K, et al. Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 2001;293:876-80 (Pubitemid 32743979)
9. Quintas-Cardama A, Cortes J. Therapeutic options against BCR-ABL1 T315I-positive chronic myelogenous leukemia. Clin Cancer Res 2008;14:4392-9
10. Efferth T, Li PC, Konkimalla VS, et al. From traditional Chinese medicine to rational cancer therapy. Trends Mol Med 2007;13:353-61 (Pubitemid 47126989)
11. Powell RG, Weisleder D, Smith CR Jr, et al. Structures of harringtonine, isoharringtonine, and homoharringtonine. Tetrahedron Lett 1970;11:815-18
12. Powell RG, Weisleder D, Smith CR Jr. Antitumor alkaloids for Cephalataxus harringtonia: structure and activity. J Pharm Sci 1972;61:1227-30
13. Grem JL, Cheson BD, King SA, et al. Cephalotaxine esters: antileukemic advance or therapeutic failure? J Natl Cancer Inst 1988;80:1095-103
14. Robin J-P, Dhal R, Dujardin G, et al. The first semi-synthesis of enantiopure homoharringtonine via anhydrohomoharringtonine from a preformed chiral acyl moiety. Tetrahedron Lett 1999;40:2931-4 (Pubitemid 29156607)
15. Huang MT. Harringtonine, an inhibitor of initiation of protein biosynthesis. Mol Pharmacol 1975;11:511-19
16. Fresno M, Jimenez A, Vazquez D. Inhibition of translation in eukaryotic systems by harringtonine. Eur J Biochem 1977;72:323-30 (Pubitemid 8022231)
17. Gurel G, Blaha G, Moore PB, et al. U2504 determines the species specificity of the A-site cleft antibiotics: the structures of tiamulin, homoharringtonine, and bruceantin bound to the ribosome. J Mol Biol 2009;389:146-56
18. Baaske DM, Heinstein P. Cytotoxicity and cell cycle specificity of homoharringtonine. Antimicrob Agents Chemother 1977;12:298-300 (Pubitemid 8165802)
19. Chou TC, Schmid FA, Feinberg A, et al. Uptake, initial effects, and chemotherapeutic efficacy of harringtonine in murine leukemic cells sensitive and resistant to vincristine and other chemotherapeutic agents. Cancer Res 1983;43:3074-9 (Pubitemid 13061549)
20. Visani G, Russo D, Ottaviani E, et al. Effects of homoharringtonine alone and in combination with alpha interferon and cytosine arabinoside on in vitro growth and induction of apoptosis in chronic myeloid leukemia and normal hematopoietic progenitors. Leukemia 1997;11:624-8 (Pubitemid 27241237)
21. Tang R, Faussat AM, Majdak P, et al. Semisynthetic homoharringtonine induces apoptosis via inhibition of protein synthesis and triggers rapid myeloid cell leukemia-1 down-regulation in myeloid leukemia cells. Mol Cancer Ther 2006;5:723-31
22. Allan EK, Holyoake TL, Craig AR, et al. Omacetaxine may have a role in chronic myeloid leukaemia eradication through downregulation of Mcl-1 and induction of apoptosis in stem/progenitor cells. Leukemia 2011;25(6):985-94
23. Chen Y, Hu Y, Michaels S, et al. Inhibitory effects of omacetaxine on leukemic stem cells and BCR-ABL-induced chronic myeloid leukemia and acute lymphoblastic leukemia in mice. Leukemia 2009;23:1446-54
24. Kuroda J, Kamitsuji Y, Kimura S, et al. Anti-myeloma effect of homoharringtonine with concomitant targeting of the myeloma-promoting molecules, Mcl-1, XIAP, and beta-catenin. Int J Hematol 2008;87:507-15
25. Chen R, Guo L, Chen Y, et al. Homoharringtonine reduced Mcl-1 expression and induced apoptosis in chronic lymphocytic leukemia. Blood 2011;117:156-64
26. Robert F, Carrier M, Rawe S, et al. Altering chemosensitivity by modulating translation elongation. PLoS One 2009;4:e5428
27. Zhou JY, Chen DL, Shen ZS, et al. Effect of homoharringtonine on proliferation and differentiation of human leukemic cells in vitro. Cancer Res 1990;50:2031-5
28. Tong H, Ren Y, Zhang F, et al. Homoharringtonine affects the JAK2-STAT5 signal pathway through alteration of protein tyrosine kinase phosphorylation in acute myeloid leukemia cells. Eur J Haematol 2008;81:259-66
29. Cobb WR, Bogden AE, Reich SD, et al. Activity of two phase I drugs, homoharringtonine and tricyclic nucleotide, against surgical explants of human tumors in the 6-day subrenal capsule assay. Cancer Treat Rep 1983;67:173-8 (Pubitemid 13110652)
30. Takemura Y, Ohnuma T, Chou TC, et al. Biologic and pharmacologic effects of harringtonine on human leukemia-lymphoma cells. Cancer Chemother Pharmacol 1985;14:206-10 (Pubitemid 15118639)
31. Chen R, Gandhi V, Plunkett W. A sequential blockade strategy for the design of combination therapies to overcome oncogene addiction in chronic myelogenous leukemia. Cancer Res 2006;66:10959-66 (Pubitemid 44876995)
32. Kano Y, Akutsu M, Tsunoda S, et al. In vitro cytotoxic effects of a tyrosine kinase inhibitor STI571 in combination with commonly used antileukemic agents. Blood 2001;97:1999-2007 (Pubitemid 32239079)
33. Scappini B, Onida F, Kantarjian HM, et al. In vitro effects of STI 571-containing drug combinations on the growth of Philadelphia-positive chronic myelogenous leukemia cells. Cancer 2002;94:2653-62 (Pubitemid 34478080)
34. Tipping AJ, Mahon FX, Zafirides G, et al. Drug responses of imatinib mesylate-resistant cells: synergism of imatinib with other chemotherapeutic drugs. Leukemia 2002;16:2349-57 (Pubitemid 36054369)
35. Savaraj N, Lu K, Dimery I, et al. Clinical pharmacology of homoharringtonine. Cancer Treat Rep 1986;70:1403-7 (Pubitemid 17005119)
36. Ni D, Ho DH, Vijjeswarapu M, et al. Metabolism of homoharringtonine, a cytotoxic component of the evergreen plant Cephalotaxus harringtonia. J Exp Ther Oncol 2003;3:47-52 (Pubitemid 36722861)
37. Savaraj N, Feun LG, Lu K, et al. Central nervous system (CNS) penetration of homoharringtonine (HHT). J Neurooncol 1987;5:77-81 (Pubitemid 17089626)
38. Levy V, Zohar S, Bardin C, et al. A phase I dose-finding and pharmacokinetic study of subcutaneous semisynthetic homoharringtonine (ssHHT) in patients with advanced acute myeloid leukaemia. Br J Cancer 2006;95:253-9 (Pubitemid 44187584)
39. Institute of Materia Medica CAoMS. The antitumor effects and pharmacologic actions of harringtonine. Chin Med J (Engl) 1977;3:131-6
40. Jiang TL, Liu RH, Salmon SE. Comparative in vitro antitumor activity of homoharringtonine and harringtonine against clonogenic human tumor cells. Invest New Drugs 1983;1:21-5 (Pubitemid 14117517)
41. ODwyer PJ, King SA, Hoth DF, et al. Homoharringtonine-perspectives on an active new natural product. J Clin Oncol 1986;4:1563-8 (Pubitemid 17183582)
42. Marin D, Kaeda JS, Andreasson C, et al. Phase I/II trial of adding semisynthetic homoharringtonine in chronic myeloid leukemia patients who have achieved partial or complete cytogenetic response on imatinib. Cancer 2005;103:1850-5 (Pubitemid 40563257)
43. Quintas-Cardama A, Kantarjian H, Garcia-Manero G, et al. Phase I/II study of subcutaneous homoharringtonine in patients with chronic myeloid leukemia who have failed prior therapy. Cancer 2007;109:248-55 (Pubitemid 46106239)
44. Kantarjian HM, Talpaz M, Santini V, et al. Homoharringtonine: history, current research, and future direction. Cancer 2001;92:1591-605
45. Feldman E, Arlin Z, Ahmed T, et al. Homoharringtonine in combination with cytarabine for patients with acute myelogenous leukemia. Leukemia 1992;6:1189-91
46. Ye JS, Wang XH, Feng GH, et al. Small-dose Harringtonine induces complete remission in patients with acute promyelocytic leukemia. Leukemia 1988;2:427-9
47. Hou CH, Zhang ZY. Intrathecal injection of harringtonine and homoharringtonine in treating central nervous system leukemia-clinical analysis of 26 cases (authors transl). Zhonghua Yi Xue Za Zhi 1981;61:530-2
48. Gu LF, Zhang WG, Wang FX, et al. Low dose of homoharringtonine and cytarabine combined with granulocyte colony-stimulating factor priming on the outcome of relapsed or refractory acute myeloid leukemia. J Cancer Res Clin Oncol 2011;137(6):997-1003
49. Huang BT, Zeng QC, Yu J, et al. High-dose homoharringtonine versus standard-dose daunorubicin is effective and safe as induction and postinduction chemotherapy for elderly patients with acute myeloid leukemia: a multicenter experience from China. Med Oncol 2011 Jan 22. [Epub ahead of print]
50. Jin J, Jiang DZ, Mai WY, et al. Homoharringtonine in combination with cytarabine and aclarubicin resulted in high complete remission rate after the first induction therapy in patients with de novo acute myeloid leukemia. Leukemia 2006;20:1361-7 (Pubitemid 44084048)
51. Mi Y, Xue Y, Yu W, et al. Therapeutic experience of adult acute myeloid leukemia in a single institution of China and its relationship with chromosome karyotype. Leuk Lymphoma 2008;49:524-30 (Pubitemid 351298337)
52. Wang J, Lu S, Yang J, et al. A homoharringtonine-based induction regimen for the treatment of elderly patients with acute myeloid leukemia: a single center experience from China. J Hematol Oncol 2009;2:32
53. Wu L, Li X, Su J, et al. Effect of low-dose cytarabine, homoharringtonine and granulocyte colony-stimulating factor priming regimen on patients with advanced myelodysplastic syndrome or acute myeloid leukemia transformed from myelodysplastic syndrome. Leuk Lymphoma 2009;50:1461-7
54. Zhang ZY, Hou CH, Zhu YF. A preliminary therapeutic analysis of 82 cases of chronic granulocytic leukemia treated with harringtonine. Zhonghua Nei Ke Za Zhi 1986;25:156-7.90
55. OBrien S, Kantarjian H, Keating M, et al. Homoharringtonine therapy induces responses in patients with chronic myelogenous leukemia in late chronic phase. Blood 1995;86:3322-6
56. OBrien S, Kantarjian H, Koller C, et al. Sequential homoharringtonine and interferon-alpha in the treatment of early chronic phase chronic myelogenous leukemia. Blood 1999;93:4149-53 (Pubitemid 29279257)
57. Li YF, Deng ZK, Xuan HB, et al. Prolonged chronic phase in chronic myelogenous leukemia after homoharringtonine therapy. Chin Med J (Engl) 2009;122:1413-17
58. OBrien S, Talpaz M, Cortes J, et al. Simultaneous homoharringtonine and interferon-alpha in the treatment of patients with chronic-phase chronic myelogenous leukemia. Cancer 2002;94:2024-32 (Pubitemid 34270056)
59. Kantarjian HM, Talpaz M, Smith TL, et al. Homoharringtonine and low-dose cytarabine in the management of late chronic-phase chronic myelogenous leukemia. J Clin Oncol 2000;18:3513-21
60. Stone RM, Donohue KA, Stock W, et al. A phase II study of continuous infusion homoharringtonine and cytarabine in newly diagnosed patients with chronic myeloid leukemia: CALGB study 19804. Cancer Chemother Pharmacol 2009;63:859-64
61. OBrien S, Giles F, Talpaz M, et al. Results of triple therapy with interferon-alpha, cytarabine, and homoharringtonine, and the impact of adding imatinib to the treatment sequence in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in early chronic phase. Cancer 2003;98:888-93 (Pubitemid 37022086)
62. Ayoubi M, Kantarjian HM, Wierda W, et al. A Phase 2 study of the Combination of omacetaxine and imatinib in the treatment of patients with chronic myeloid leukemia (CML) in advanced stages or after failure to imatinib. Volume 114 ASH Annual Meeting Abstracts; 2009. p. 2193
63. Fang B, Li N, Song Y, et al. Standard-dose imatinib plus low-dose homoharringtonine and granulocyte colony-stimulating factor is an effective induction therapy for patients with chronic myeloid leukemia in myeloid blast crisis who have failed prior single-agent therapy with imatinib. Ann Hematol 2010;89:1099-105
64. Li YF, Liu X, Liu DS, et al. The effect of homoharringtonine in patients with chronic myeloid leukemia who have failed or responded suboptimally to imatinib therapy. Leuk Lymphoma 2009;50:1889-91
65. Cortes-Franco J, Raghunadharao D, Parikh P, et al. Safety and efficacy of subcutaneous-administered omacetaxine mepesuccinate in chronic myeloid Leukemia (CML) patients who are resistant or intolerant to two or more tyrosine kinase inhibitors -results of a multicenter phase 2/3 study. Volume 114 ASH Annual Meeting Abstracts; 861
66. Nicolini FE, Morisset S, Hochhaus A, et al. The presence of the BCR-ABL T315I mutation in chronic phase chronic myelogenous leukemia resistant to tyrosine kinase inhibitors profoundly compromises overall survival and progression free survival. preliminary results of a matched pair analysis. Volume 116 ASH Annual Meeting Abstracts; 2010. p. 3410
67. de Lavallade H, Khorashad JS, Davis HP, et al. Interferon-alpha or homoharringtonine as salvage treatment for chronic myeloid leukemia patients who acquire the T315I BCR-ABL mutation. Blood 2007;110:2779-80 (Pubitemid 47523217)
68. Legros L, Hayette S, Nicolini FE, et al. BCR-ABL(T315I) transcript disappearance in an imatinib-resistant CML patient treated with homoharringtonine: a new therapeutic challenge? Leukemia 2007;21:2204-6 (Pubitemid 47423816)
69. Nicolini FE, Chomel JC, Roy L, et al. The durable clearance of the T315I BCR-ABL mutated clone in chronic phase chronic myelogenous leukemia patients on omacetaxine allows tyrosine kinase inhibitor rechallenge. Clin Lymphoma Myeloma Leuk 2010;10:394-9
70. Cortes-Franco J, Khoury HJ, Nicolini FE, et al. Safety and efficacy of subcutaneous-administered omacetaxine mepesuccinate in imatinib-resistant Chronic myeloid leukemia (CML) patients who harbor the Bcr-Abl T315I mutation-results of an ongoing multicenter phase 2/3 Study. Volume 114 ASH Annual Meeting Abstracts; 644
71. ODAC Briefing Book: OMAPROTM (omacetaxine mepesuccinate). 2010 [cited; 1-71]. Available from: http://www.fda.gov/downloads/AdvisoryCommittees/ CommitteesMeetingMaterials/Drugs/OncologicDrugsAdvisoryCommittee/UCM204345.pdf
72. Berman E. Omacetaxine: the FDA decision. Clin Adv Hematol Oncol 2011;9:57-8
73. Nanda N, Cortes C, Lipton J, et al. Treatment of chronic phase (CP) chronic myeloid leukemia (CML) patients who harbor the BCR-ABL T315I mutation with subcutaneous omacetaxine results in improved survival compared to historical data. Haematologica 2011;96(s2):1012
74. Wilkoff LJ, Dulmadge DA, Laster WR Jr, et al. Effect of homoharringtonine on the viability of murine leukemia P388 cells resistant to either adriamycin, vincristine, or 1-beta-D-arabinofuranosylcytosine. Cancer Chemother Pharmacol 1989;23:145-50 (Pubitemid 19076597)
75. Russo D, Michelutti A, Melli C, et al. MDR-related P170-glycoprotein modulates cytotoxic activity of homoharringtonine. Leukemia 1995;9:513-16
76. Tebbi CK, Chervinsky D, Baker RM. Modulation of drug resistance in homoharringtonine-resistant C-1300 neuroblastoma cells with cyclosporine A and dipyridamole. J Cell Physiol 1991;148:464-71 (Pubitemid 21926083)
77. Zhou DC, Ramond S, Viguie F, et al. Sequential emergence of MRP-and MDR1-gene over-expression as well as MDR1-gene translocation in homoharringtonineselected K562 human leukemia cell lines. Int J Cancer 1996;65:365-71
78. Kantarjian HM, Keating MJ, Walters RS, et al. Phase II study of low-dose continuous infusion homoharringtonine in refractory acute myelogenous leukemia. Cancer 1989;63:813-17 (Pubitemid 19063182)
79. Sylvester RK, Lobell M, Ogden W, et al. Homoharringtonine-induced hyperglycemia. J Clin Oncol 1989;7:392-5 (Pubitemid 19075022)
80. Druker BJ, Guilhot F, OBrien SG, et al. Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 2006;355:2408-17 (Pubitemid 44903745)
81. Kantarjian H, Shah NP, Hochhaus A, et al. Dasatinib versus imatinib in newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 2010;362:2260-70
82. Saglio G, Kim DW, Issaragrisil S, et al. Nilotinib versus imatinib for newly diagnosed chronic myeloid leukemia. N Engl J Med 2010;362:2251-9
83. Branford S, Melo JV, Hughes TP. Selecting optimal second-line tyrosine kinase inhibitor therapy for chronic myeloid leukemia patients after imatinib failure: does the BCR-ABL mutation status really matter? Blood 2009;114:5426-35
84. Mahadeo KM, Cole PD. Successful treatment using omacetaxine for a patient with CML and BCR-ABL1 [corrected] 35INS. Blood 2010;115:3852
85. Mahon FX, Rea D, Guilhot J, et al. Discontinuation of imatinib in patients with chronic myeloid leukaemia who have maintained complete molecular remission for at least 2 years: the prospective, multicentre Stop Imatinib (STIM) trial. Lancet Oncol 2010;11:1029-35
86. Bhatia R, Holtz M, Niu N, et al. Persistence of malignant hematopoietic progenitors in chronic myelogenous leukemia patients in complete cytogenetic remission following imatinib mesylate treatment. Blood 2003;101:4701-7 (Pubitemid 36857723)
87. Graham SM, Jorgensen HG, Allan E, et al. Primitive, quiescent, Philadelphia-positive stem cells from patients with chronic myeloid leukemia are insensitive to STI571 in vitro. Blood 2002;99:319-25
88. Holtz MS, Slovak ML, Zhang F, et al. Imatinib mesylate (STI571) inhibits growth of primitive malignant progenitors in chronic myelogenous leukemia through reversal of abnormally increased proliferation. Blood 2002;99:3792-800 (Pubitemid 34534553)
89. Xu WL, Jin J, Qian WB. Homoharringtonine in combination with cytarabine and aclarubicin as induction therapy improves remission and survival of patients with higher risk myelodysplastic syndromes. Chin Med J (Engl) 2010;123:108-10
90. Eckelbarger JD, Wilmot JT, Epperson MT, et al. Synthesis of antiproliferative Cephalotaxus esters and their evaluation against several human hematopoietic and solid tumor cell lines: uncovering differential susceptibilities to multidrug resistance. Chemistry (Easton) 2008;14:4293-306