Skip to main content
SpringerLink
Log in

Imatinib Mesylate

  • Chapter
  • First Online:
Book cover Small Molecules in Oncology

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 201))

Abstract

Imatinib mesylate (Gleevec, Glivec [Novartis, Basel, Switzerland], formerly referred to as STI571 or CGP57148B) represents the paradigm of a new class of anticancer agents, so-called small molecules. They have a high selectivity against a specific molecular target known to be the cause for the establishment and maintenance of the malignant phenotype. Imatinib is a rationally designed oral signal transduction inhibitor that specifically targets several protein tyrosine kinases, Abl, Arg (Abl-related gene), the stem cell factor receptor (c-KIT), platelet-derived growth factor receptor (PDGF-R), and their oncogenic forms, most notably BCR-ABL. Imatinib has been shown to have remarkable clinical activity in patients with chronic myeloid leukemia (CML) and malignant gastrointestinal stroma tumors (GIST) leading to its approval for treatment of these diseases. Treatment with imatinib is generally well tolerated with a low incidence of severe side effects. The most common adverse events include mild to moderate edema, muscle cramps, diarrhea, nausea, skin rashes, and myelosuppression. Several mechanisms of resistance have been identified. Clonal evolution, amplification, or overexpression of BCR-ABL as well as mutations in the catalytic domain, P-loop, and other mutations have been demonstrated to play a role in primary and secondary resistance to imatinib, respectively. Understanding of the underlying mechanisms of resistance has led to the development of new second- and third-generation tyrosine kinase inhibitors (see chapters on dasatinib, nilotinib, bosutinib, and ponatinib).

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 139.00
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Anafi M, Gazit A, Gilon C, Neriah YB, Levitzki A (1993a) Tyrphostin-induced differentiation of mouse erythroleukemia cells. FEBS Lett 330:260–264

    Article  CAS  PubMed  Google Scholar 

  • Anafi M, Gazit A, Zehavi A, Ben-Neriah Y, Levitzki A (1993b) Tyrphostin-induced inhibition of p210bcr-abl tyrosine kinase activity induces K562 to differentiate. Blood 82:3524–3529

    CAS  PubMed  Google Scholar 

  • Baccarani M, Russo D, Rosti G, Martinelli G (2003) Interferon-alfa for chronic myeloid leukemia. Semin Hematol 40:22–33

    Article  CAS  PubMed  Google Scholar 

  • Baccarani M, Martinelli G, Rosti G, Trabacchi E, Testoni N, Bassi S, Amabile M, Soverini S, Castagnetti F, Cilloni D et al (2004) Imatinib and pegylated human recombinant interferon-alpha2b in early chronic-phase chronic myeloid leukemia. Blood 104:4245–4251

    Article  CAS  PubMed  Google Scholar 

  • Baccarani M, Deininger MW, Rosti G, Hochhaus A, Soverini S, Apperley JF, Cervantes F, Clark RE, Cortes JE, Guilhot F et al (2013) European LeukemiaNet recommendations for the management of chronic myeloid leukemia: 2013. Blood 122:872–884

    Article  CAS  PubMed  Google Scholar 

  • Barnhill RL, Xiao M, Graves D, Antoniades HN (1996) Expression of platelet-derived growth factor (PDGF)-A, PDGF-B and the PDGF-alpha receptor, but not the PDGF-beta receptor, in human malignant melanoma in vivo. Br J Dermatol 135:898–904

    Article  CAS  PubMed  Google Scholar 

  • Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, Raymond AK, Bramwell VH, Baker LH, Maki RG et al (2008) Phase III randomized, intergroup trial assessing imatinib mesylate at two dose levels in patients with unresectable or metastatic gastrointestinal stromal tumors expressing the kit receptor tyrosine kinase: S0033. J Clin Oncol 26:626–632

    Article  CAS  PubMed  Google Scholar 

  • Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Regenass U, Lydon NB (1995) Selective inhibition of the platelet-derived growth factor signal transduction pathway by a protein-tyrosine kinase inhibitor of the 2-phenylaminopyrimidine class. Proc Natl Acad Sci U S A 92:2558–2562

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Buchdunger E, Zimmermann J, Mett H, Meyer T, Muller M, Druker BJ, Lydon NB (1996) Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 56:100–104

    CAS  PubMed  Google Scholar 

  • Buchdunger E, Cioffi CL, Law N, Stover D, Ohno-Jones S, Druker BJ, Lydon NB (2000) Abl protein-tyrosine kinase inhibitor STI571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 295:139–145

    CAS  PubMed  Google Scholar 

  • Buchdunger E, Matter A, Druker BJ (2001) Bcr-Abl inhibition as a modality of CML therapeutics. Biochim Biophys Acta 1551:M11–M18

    CAS  PubMed  Google Scholar 

  • Carlo-Stella C, Regazzi E, Sammarelli G, Colla S, Garau D, Gazit A, Savoldo B, Cilloni D, Tabilio A, Levitzki A, Rizzoli V (1999) Effects of the tyrosine kinase inhibitor AG957 and an Anti-Fas receptor antibody on CD34(+) chronic myelogenous leukemia progenitor cells. Blood 93:3973–3982

    CAS  PubMed  Google Scholar 

  • Cohen MH, Dagher R, Griebel DJ, Ibrahim A, Martin A, Scher NS, Sokol GH, Williams GA, Pazdur R (2002a) US Food and Drug Administration drug approval summaries: imatinib mesylate, mesna tablets, and zoledronic acid. Oncologist 7:393–400

    Article  CAS  PubMed  Google Scholar 

  • Cohen MH, Williams G, Johnson JR, Duan J, Gobburu J, Rahman A, Benson K, Leighton J, Kim SK, Wood R et al (2002b) Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia. Clin Cancer Res 8:935–942

    CAS  PubMed  Google Scholar 

  • Cohen MH, Johnson JR, Pazdur R (2005) U.S. Food and Drug Administration drug approval summary: conversion of imatinib mesylate (STI571; Gleevec) tablets from accelerated approval to full approval. Clin Cancer Res 11:12–19

    PubMed  Google Scholar 

  • Cohen MH, Farrell A, Justice R, Pazdur R (2009) Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Oncologist

    Google Scholar 

  • Cortes J, Giles F, O’Brien S, Thomas D, Garcia-Manero G, Rios MB, Faderl S, Verstovsek S, Ferrajoli A, Freireich EJ et al (2003) Result of high-dose imatinib mesylate in patients with Philadelphia chromosome-positive chronic myeloid leukemia after failure of interferon-alpha. Blood 102:83–86

    Article  CAS  PubMed  Google Scholar 

  • Dagher R, Cohen M, Williams G, Rothmann M, Gobburu J, Robbie G, Rahman A, Chen G, Staten A, Griebel D, Pazdur R (2002) Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 8:3034–3038

    CAS  PubMed  Google Scholar 

  • Daley GQ, Van Etten RA, Baltimore D (1990) Induction of chronic myelogenous leukemia in mice by the P210bcr/abl gene of the Philadelphia chromosome. Science 247:824–830

    Article  CAS  PubMed  Google Scholar 

  • Deininger MW, Goldman JM (1998) Chronic myeloid leukemia. Curr Opin Hematol 5:302–308

    Article  CAS  PubMed  Google Scholar 

  • Deininger MW, Goldman JM, Lydon N, Melo JV (1997) The tyrosine kinase inhibitor CGP57148B selectively inhibits the growth of BCR-ABL-positive cells. Blood 90:3691–3698

    CAS  PubMed  Google Scholar 

  • Deininger MW, Goldman JM, Melo JV (2000) The molecular biology of chronic myeloid leukemia. Blood 96:3343–3356

    CAS  PubMed  Google Scholar 

  • Deininger M, Buchdunger E, Druker BJ (2005) The development of imatinib as a therapeutic agent for chronic myeloid leukemia. Blood 105:2640–2653

    Article  CAS  PubMed  Google Scholar 

  • Demetri GD (2002) Identification and treatment of chemoresistant inoperable or metastatic GIST: experience with the selective tyrosine kinase inhibitor imatinib mesylate (STI571). Eur J Cancer 38(Suppl 5):S52–S59

    Article  PubMed  Google Scholar 

  • Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, Heinrich MC, Tuveson DA, Singer S, Janicek M et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347:472–480

    Article  CAS  PubMed  Google Scholar 

  • Druker BJ (2008) Translation of the Philadelphia chromosome into therapy for CML. Blood 112:4808–4817

    Article  CAS  PubMed  Google Scholar 

  • Druker BJ, Lydon NB (2000) Lessons learned from the development of an abl tyrosine kinase inhibitor for chronic myelogenous leukemia. J Clin Invest 105:3–7

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Druker BJ, Tamura S, Buchdunger E, Ohno S, Segal GM, Fanning S, Zimmermann J, Lydon NB (1996) Effects of a selective inhibitor of the Abl tyrosine kinase on the growth of Bcr-Abl positive cells. Nat Med 2:561–566

    Article  CAS  PubMed  Google Scholar 

  • Druker BJ, Sawyers CL, Kantarjian H, Resta DJ, Reese SF, Ford JM, Capdeville R, Talpaz M (2001a) Activity of a specific inhibitor of the BCR-ABL tyrosine kinase in the blast crisis of chronic myeloid leukemia and acute lymphoblastic leukemia with the Philadelphia chromosome. N Engl J Med 344:1038–1042

    Article  CAS  PubMed  Google Scholar 

  • Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E, Ford JM, Lydon NB, Kantarjian H, Capdeville R, Ohno-Jones S, Sawyers CL (2001b) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344:1031–1037

    Article  CAS  PubMed  Google Scholar 

  • Druker BJ, Guilhot F, O’Brien SG, Gathmann I, Kantarjian H, Gattermann N, Deininger MW, Silver RT, Goldman JM, Stone RM et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355:2408–2417

    Article  CAS  PubMed  Google Scholar 

  • Gambacorti-Passerini C, Le Coutre P, Mologni L, Fanelli M, Bertazolli C, Marchesi E, Di Nicola M, Biondi A, Corneo GM, Belotti D et al (1997) Inhibition of the ABL kinase activity blocks the proliferation of BCR/ABL+ leukemic cells and induces apoptosis. Blood Cells Mol Dis 23:380–394

    Article  CAS  PubMed  Google Scholar 

  • Gardembas M, Rousselot P, Tulliez M, Vigier M, Buzyn A, Rigal-Huguet F, Legros L, Michallet M, Berthou C, Cheron N et al (2003) Results of a prospective phase 2 study combining imatinib mesylate and cytarabine for the treatment of Philadelphia-positive patients with chronic myelogenous leukemia in chronic phase. Blood 102:4298–4305

    Article  CAS  PubMed  Google Scholar 

  • Gorre ME, Mohammed M, Ellwood K, Hsu N, Paquette R, Rao PN, Sawyers CL (2001) Clinical resistance to STI-571 cancer therapy caused by BCR-ABL gene mutation or amplification. Science 293:876–880

    Article  CAS  PubMed  Google Scholar 

  • Gratwohl A, Hermans J, Goldman JM, Arcese W, Carreras E, Devergie A, Frassoni F, Gahrton G, Kolb HJ, Niederwieser D et al (1998) Risk assessment for patients with chronic myeloid leukaemia before allogeneic blood or marrow transplantation. Chronic leukemia working party of the European group for blood and marrow transplantation. Lancet 352:1087–1092

    Article  CAS  PubMed  Google Scholar 

  • Greco A, Roccato E, Miranda C, Cleris L, Formelli F, Pierotti MA (2001) Growth-inhibitory effect of STI571 on cells transformed by the COL1A1/PDGFB rearrangement. Int J Cancer 92:354–360

    Article  CAS  PubMed  Google Scholar 

  • Guilhot F (2004) Indications for imatinib mesylate therapy and clinical management. Oncologist 9:271–281

    Article  CAS  PubMed  Google Scholar 

  • Hahn EA, Glendenning GA, Sorensen MV, Hudgens SA, Druker BJ, Guilhot F, Larson RA, O’Brien SG, Dobrez DG, Hensley ML, Cella D (2003) Quality of life in patients with newly diagnosed chronic phase chronic myeloid leukemia on imatinib versus interferon alfa plus low-dose cytarabine: results from the IRIS Study. J Clin Oncol 21:2138–2146

    Article  CAS  PubMed  Google Scholar 

  • Hatfield A, Owen S, Pilot PR (2007) In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 13, 13: author reply 15–16

    Google Scholar 

  • Hehlmann R, Berger U, Pfirrmann M, Heimpel H, Hochhaus A, Hasford J, Kolb HJ, Lahaye T, Maywald O, Reiter A et al (2007a) Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia. Blood 109:4686–4692

    Article  CAS  PubMed  Google Scholar 

  • Hehlmann R, Hochhaus A, Baccarani M (2007b) Chronic myeloid leukaemia. Lancet 370:342–350

    Article  CAS  PubMed  Google Scholar 

  • Hehlmann R, Lauseker M, Jung-Munkwitz S, Leitner A, Muller MC, Pletsch N, Proetel U, Haferlach C, Schlegelberger B, Balleisen L et al (2011) Tolerability-adapted imatinib 800 mg/d versus 400 mg/d versus 400 mg/d plus interferon-alpha in newly diagnosed chronic myeloid leukemia. J Clin Oncol 29:1634–1642

    Article  CAS  PubMed  Google Scholar 

  • Heinrich MC, Blanke CD, Druker BJ, Corless CL (2002a) Inhibition of KIT tyrosine kinase activity: a novel molecular approach to the treatment of KIT-positive malignancies. J Clin Oncol 20:1692–1703

    Article  CAS  PubMed  Google Scholar 

  • Heinrich MC, Rubin BP, Longley BJ, Fletcher JA (2002b) Biology and genetic aspects of gastrointestinal stromal tumors: KIT activation and cytogenetic alterations. Hum Pathol 33:484–495

    Article  CAS  PubMed  Google Scholar 

  • Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, Joensuu H, McGreevey LS, Chen CJ, Van den Abbeele AD, Druker BJ et al (2003a) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21:4342–4349

    Article  CAS  PubMed  Google Scholar 

  • Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A et al (2003b) PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708–710

    Article  CAS  PubMed  Google Scholar 

  • Heinrich MC, Owzar K, Corless CL, Hollis D, Borden EC, Fletcher CD, Ryan CW, von Mehren M, Blanke CD, Rankin C et al (2008) Correlation of kinase genotype and clinical outcome in the North American Intergroup Phase III Trial of imatinib mesylate for treatment of advanced gastrointestinal stromal tumor: CALGB 150105 Study by Cancer and Leukemia Group B and Southwest Oncology Group. J Clin Oncol 26:5360–5367

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Heisterkamp N, Jenster G, ten Hoeve J, Zovich D, Pattengale PK, Groffen J (1990) Acute leukaemia in bcr/abl transgenic mice. Nature 344:251–253

    Article  CAS  PubMed  Google Scholar 

  • Hochhaus A, Druker B, Sawyers C, Guilhot F, Schiffer CA, Cortes J, Niederwieser DW, Gambacorti-Passerini C, Stone RM, Goldman J et al (2008) Favorable long-term follow-up results over 6 years for response, survival, and safety with imatinib mesylate therapy in chronic-phase chronic myeloid leukemia after failure of interferon-alpha treatment. Blood 111:1039–1043

    Article  CAS  PubMed  Google Scholar 

  • Hochhaus A, La Rosee P, Muller MC, Ernst T, Cross NC (2011) Impact of BCR-ABL mutations on patients with chronic myeloid leukemia. Cell Cycle 10:250–260

    Article  CAS  PubMed  Google Scholar 

  • Hoeper MM, Barst RJ, Bourge RC, Feldman J, Ghofrani HA, Galié N, Gómez-Sánchez MA, Grimminger F, Grünig E, Hassoun PM et al (2013) Imatinib mesylate as add-on therapy for pulmonary arterial hypertension results of the randomized IMPRES study. Circulation 127(10):1128–1138

    Google Scholar 

  • Hughes TP, Kaeda J, Branford S, Rudzki Z, Hochhaus A, Hensley ML, Gathmann I, Bolton AE, van Hoomissen IC, Goldman JM, Radich JP (2003) Frequency of major molecular responses to imatinib or interferon alfa plus cytarabine in newly diagnosed chronic myeloid leukemia. N Engl J Med 349:1423–1432

    Article  CAS  PubMed  Google Scholar 

  • Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schutte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE et al (2012) One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. JAMA 307:1265–1272

    Article  CAS  PubMed  Google Scholar 

  • Jovanovic JV, Score J, Waghorn K, Cilloni D, Gottardi E, Metzgeroth G, Erben P, Popp H, Walz C, Hochhaus A et al (2007) Low-dose imatinib mesylate leads to rapid induction of major molecular responses and achievement of complete molecular remission in FIP1L1-PDGFRA-positive chronic eosinophilic leukemia. Blood 109:4635–4640

    Article  CAS  PubMed  Google Scholar 

  • Kantarjian H, Sawyers C, Hochhaus A, Guilhot F, Schiffer C, Gambacorti-Passerini C, Niederwieser D, Resta D, Capdeville R, Zoellner U et al (2002a) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346:645–652

    Article  CAS  PubMed  Google Scholar 

  • Kantarjian HM, O’Brien S, Cortes JE, Smith TL, Rios MB, Shan J, Yang Y, Giles FJ, Thomas DA, Faderl S et al (2002b) Treatment of philadelphia chromosome-positive, accelerated-phase chronic myelogenous leukemia with imatinib mesylate. Clin Cancer Res 8:2167–2176

    CAS  PubMed  Google Scholar 

  • Kerkela R, Grazette L, Yacobi R, Iliescu C, Patten R, Beahm C, Walters B, Shevtsov S, Pesant S, Clubb FJ et al (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12:908–916

    Article  PubMed  Google Scholar 

  • Konopka JB, Watanabe SM, Witte ON (1984) An alteration of the human c-abl protein in K562 leukemia cells unmasks associated tyrosine kinase activity. Cell 37:1035–1042

    Article  CAS  PubMed  Google Scholar 

  • Larsen RA, Druker BJ, Guilhot F, O’Brien SG, Riviere GJ, Krahnke T, Gathmann I, Wang Y et al (2008) Imatinib pharmacokinetics and its correlation with response and safety in chronic phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood 111:4022–4028

    Google Scholar 

  • Le Coutre P, Mologni L, Cleris L, Marchesi E, Buchdunger E, Giardini R, Formelli F, Gambacorti-Passerini C (1999) In vivo eradication of human BCR/ABL-positive leukemia cells with an ABL kinase inhibitor. J Natl Cancer Inst 92:163–168

    Article  Google Scholar 

  • Levitzky A, Gazit A (1995) Tyrosine kinase inhibition: an approach to drug development. Science 267:1782–1788

    Article  Google Scholar 

  • Lugo TG, Pendergast AM, Muller AJ, Witte ON (1990) Tyrosine kinase activity and transformation potency of bcr-abl oncogene products. Science 247:1079–1082

    Article  CAS  PubMed  Google Scholar 

  • Lux ML, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri GD, Xiao S, Singer S, Fletcher CD, Fletcher JA (2000) Kit extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 156:791–795

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Lyseng-Williamson K, Jarvis B (2001) Imatinib. Drugs 61:1765–1774

    Article  CAS  PubMed  Google Scholar 

  • Mahon FX, Rea D, Guilhot J, Guilhot F, Huguet F, Nicolini F, Legros L, Charbonnier A, Guerci A, Varet B et al (2010) 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 11:1029–1035

    Article  CAS  PubMed  Google Scholar 

  • Marangon E, Citterio M, Sala F, Barisone E, Lippi AA, Rizzari C, Biondi A, D’Incalci M, Zucchetti M (2009) Pharmacokinetic profile of imatinib mesylate and N-demethyl-imatinib (CGP74588) in children with newly diagnosed Ph+ acute leukemias. Cancer Chemother Pharmacol 63:563–566

    Article  PubMed  Google Scholar 

  • Mauro MJ, O’Dwyer M, Heinrich MC, Druker BJ (2002) STI571: a paradigm of new agents for cancer therapeutics. J Clin Oncol 20:325–334

    Article  CAS  PubMed  Google Scholar 

  • Moinzadeh P, Hunzelmann N, Krieg T (2013) Pharmacology and rationale for imatinib in the treatment of scleroderma. J Exp Pharmacol 5:15–22

    Article  CAS  Google Scholar 

  • Mueller BA (2009) Imatinib and its successors: how modern chemistry has changed drug development. Curr Pharm Design 15:120–133

    Article  CAS  Google Scholar 

  • NCCN Practice Guidelines in Oncology, v.1.2014. (http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf)

  • NCCN_Practice_Guidelines_in_Oncology, v.3.2008. http://www.nccn.org/professionals/physician_gls/PDF/cml.pdf

  • Nowell PC, Hungerford DA (1960) A minute chromosome in human chronic granulocytic leukemia. Science 132:1497

    Google Scholar 

  • O’Brien SG, Guilhot F, Goldman J, Hochhaus A, Hughes T, Radich J, Rudoltz M, Filian J, Gathmann I, Druker B et al (2008) International randomized study of interferon versus STI571 (IRIS) 7-year follow-up: sustained survival, low rate of transformation and increased rate of major molecular response (MMR) in patients (pts) with newly diagnosed chronic myeloid leukemia in chronic phase (CML-CP) treated with imatinib (IM). Blood 112:76

    Google Scholar 

  • O’Brien S, Giles F, Talpaz M, Cortes J, Rios MB, Shan J, Thomas D, Andreeff M, Kornblau S, Faderl S et al (2003a) 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 98:888–893

    Article  PubMed  Google Scholar 

  • O’Brien SG, Guilhot F, Larson RA, Gathmann I, Baccarani M, Cervantes F, Cornelissen JJ, Fischer T, Hochhaus A, Hughes T et al (2003b) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348:994–1004

    Article  PubMed  Google Scholar 

  • Okuda K, Weisberg E, Gilliland DG, Griffin JD (2001) ARG tyrosine kinase activity is inhibited by STI571. Blood 97:2440–2448

    Article  CAS  PubMed  Google Scholar 

  • Ottmann OG, Druker BJ, Sawyers CL, Goldman JM, Reiffers J, Silver RT, Tura S, Fischer T, Deininger MW, Schiffer CA et al (2002) A phase 2 study of imatinib in patients with relapsed or refractory Philadelphia chromosome-positive acute lymphoid leukemias. Blood 100:1965–1971

    Article  CAS  PubMed  Google Scholar 

  • Pardanani A, Tefferi A (2004) Imatinib targets other than bcr/abl and their clinical relevance in myeloid disorders. Blood 104:1931–1939

    Article  CAS  PubMed  Google Scholar 

  • Preudhomme C, Guilhot J, Nicolini FE, Guerci-Bresler A, Rigal-Huguet F, Maloisel F, Coiteux V, Gardembas M, Berthou C, Vekhoff A et al (2010) Imatinib plus peginterferon alfa-2a in chronic myeloid leukemia. N Engl J Med 363:2511–2521

    Article  CAS  PubMed  Google Scholar 

  • Rowley JD (1973) A new consistent abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–293

    Article  CAS  PubMed  Google Scholar 

  • Sawyers CL (1999) Chronic myeloid leukemia. N Engl J Med 340:1330–1340

    Article  CAS  PubMed  Google Scholar 

  • Sawyers CL, Hochhaus A, Feldman E, Goldman JM, Miller CB, Ottmann OG, Schiffer CA, Talpaz M, Guilhot F, Deininger MW et al (2002) Imatinib induces hematologic and cytogenetic responses in patients with chronic myelogenous leukemia in myeloid blast crisis: results of a phase II study. Blood 99:3530–3539

    Article  CAS  PubMed  Google Scholar 

  • Schiffer CA (2007) BCR-ABL tyrosine kinase inhibitors in chronic myelogenous leukemia. N Engl J Med 357:258–265

    Article  CAS  PubMed  Google Scholar 

  • Shah NP, Sawyers CL (2003) Mechanisms of resistance to STI571 in Philadelphia chromosome-associated leukemias. Oncogene 22:7389–7395

    Article  CAS  PubMed  Google Scholar 

  • Shah NP, Kantarjian HM, Kim DW, Rea D, Dorlhiac-Llacer PE, Milone JH, Vela-Ojeda J, Silver RT, Khoury HJ, Charbonnier A et al (2008) Intermittent target inhibition with dasatinib 100 mg once daily preserves efficacy and improves tolerability in imatinib-resistant and intolerant chronic-phase chronic myeloid leukemia. J Clin Oncol 26:3204–3212

    Article  CAS  PubMed  Google Scholar 

  • Talpaz M, Silver RT, Druker BJ, Goldman JM, Gambacorti-Passerini C, Guilhot F, Schiffer CA, Fischer T, Deininger MW, Lennard AL et al (2002) Imatinib induces durable hematologic and cytogenetic responses in patients with accelerated phase chronic myeloid leukemia: results of a phase 2 study. Blood 99:1928–1937

    Article  CAS  PubMed  Google Scholar 

  • von Bubnoff N, Peschel C, Duyster J (2003) Resistance of Philadelphia-chromosome positive leukemia towards the kinase inhibitor imatinib (STI571, Glivec): a targeted oncoprotein strikes back. Leukemia 17:829–838

    Article  Google Scholar 

  • Voncken JW, Kaartinen V, Pattengale PK, Germeraad WT, Groffen J, Heisterkamp N (1995) BCR/ABL P210 and P190 cause distinct leukemia in transgenic mice. Blood 86:4603–4611

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Hematology and Oncology, University of Freiburg Medical Center, Hugstetter Street 55, 79106, Freiburg, Germany

    Cornelius F. Waller

Authors
  1. Cornelius F. Waller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Cornelius F. Waller .

Editor information

Editors and Affiliations

  1. Cancer Center Heilbronn-Franken, SLK-Kliniken Heilbronn GmbH Medizinische Klinik III, Heilbronn, Germany

    Uwe M. Martens

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Waller, C.F. (2014). Imatinib Mesylate. In: Martens, U. (eds) Small Molecules in Oncology. Recent Results in Cancer Research, vol 201. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-54490-3_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-54490-3_1

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-54489-7

  • Online ISBN: 978-3-642-54490-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation