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The safety profile of imatinib in CML and GIST: long-term considerations

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Abstract

Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST) by targeting BCR-ABL and c-KIT tyrosine kinases, respectively. Indeed, imatinib has substantially changed the clinical management and improved the prognosis of both diseases. Treatment with imatinib is generally well tolerated, and the risk for severe adverse effects is low, generally occurring during the early phase of treatment and correlating with imatinib dose, phase of disease and patient’s characteristics. This article summarises recent data on safety profile of imatinib for the treatment of CML and GIST, including long-term side effects. Prolonged treatment with imatinib in both diseases demonstrates excellent tolerability. There are few significant concerns and those that have emerged, like cardiotoxicity, have far turned out to be exaggerated.

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References

  • (MetaGIST) GSTM-AG (2010) Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors: a meta-analysis of 1,640 patients. J Clin Oncol 28(7):1247–53. doi:10.1200/JCO.2009.24.2099

  • Agostino N, Chinchilli VM, Lynch CJ et al (2010) Effect of the tyrosine kinase inhibitors (sunitinib, sorafenib, dasatinib, and imatinib) on blood glucose levels in diabetic and nondiabetic patients in general clinical practice. J Oncol Pharm Pract. doi:10.1177/1078155210378913

  • Atallah E, Durand J-B, Kantarjian H, Cortes J (2007) Congestive heart failure is a rare event in patients receiving imatinib therapy. Blood 110(17449798):1233–1237

    Article  PubMed  CAS  Google Scholar 

  • Baccarani M, Cortes J, Pane F et al (2009) Chronic myeloid leukemia: an update of concepts and management recommendations of European LeukemiaNet. J Clin Oncol 27(19884523):6041–6051

    Article  PubMed  CAS  Google Scholar 

  • Berman E, Nicolaides M, Maki RG et al (2006) Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med 354(19):2006–13. doi:10.1056/NEJMoa051140

    Google Scholar 

  • Blanke CD, Demetri GD, von Mehren M et al (2008a) Long-term results from a randomized phase II trial of standard- versus higher-dose imatinib mesylate for patients with unresectable or metastatic gastrointestinal stromal tumors expressing KIT. J Clin Oncol 26(18235121):620–625

    Article  PubMed  CAS  Google Scholar 

  • Blanke CD, Rankin C, Demetri GD et al (2008b) 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(4):626–32. doi:10.1200/JCO.2007.13.4452

  • Breccia M, Muscaritoli M, Aversa Z, Mandelli F, Alimena G (2004) Imatinib mesylate may improve fasting blood glucose in diabetic Ph+ chronic myelogenous leukemia patients responsive to treatment. J Clin Oncol 22(15542819):4653–4655

    Article  PubMed  CAS  Google Scholar 

  • Buchdunger E, Zimmermann J, Mett H et al (1996) Inhibition of the Abl protein-tyrosine kinase in vitro and in vivo by a 2-phenylaminopyrimidine derivative. Cancer Res 56(1):100–104

    PubMed  CAS  Google Scholar 

  • Chitteti BR, Cheng Y-H, Poteat B et al (2010) Impact of interactions of cellular components of the bone marrow microenvironment on hematopoietic stem and progenitor cell function. Blood 115(20154218):3239–3248

    Article  PubMed  CAS  Google Scholar 

  • Cortes J, Kim DW, Raffoux E et al (2008) Efficacy and safety of dasatinib in imatinib-resistant or -intolerant patients with chronic myeloid leukemia in blast phase. Leukemia 22(12):2176–83. doi:10.1038/leu.2008.221

    Google Scholar 

  • Cortes JE, Baccarani M, Guilhot F et al (2010) Phase III, randomized, open-label study of daily imatinib mesylate 400 mg versus 800 mg in patients with newly diagnosed, previously untreated chronic myeloid leukemia in chronic phase using molecular end points: tyrosine kinase inhibitor optimization and selectivity study. J Clin Oncol 28(20008622):424–430

    Article  PubMed  CAS  Google Scholar 

  • Dagher R, Cohen M, Williams G et al (2002) Approval summary: imatinib mesylate in the treatment of metastatic and/or unresectable malignant gastrointestinal stromal tumors. Clin Cancer Res 8(12374669):3034–3038

    PubMed  CAS  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(4944):824–830

    Article  PubMed  CAS  Google Scholar 

  • Debiec-Rychter M, Sciot R, Le Cesne A et al (2006) KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 42(16624552):1093–1103

    Article  PubMed  CAS  Google Scholar 

  • Dematteo RP, Ballman KV, Antonescu CR et al (2009) Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373(9669):1097–104. doi:10.1016/S0140-6736(09)60500-6

    Google Scholar 

  • Demetri GD, von Mehren M, Blanke CD et al (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 347(12181401):472–480

    Article  PubMed  CAS  Google Scholar 

  • Dewar AL, Cambareri AC, Zannettino AC et al (2005) Macrophage colony-stimulating factor receptor c-fms is a novel target of imatinib. Blood 105(8):3127–32. doi:10.1182/blood-2004-10-3967

    Google Scholar 

  • Dewar AL, Farrugia AN, Condina MR et al (2006) Imatinib as a potential antiresorptive therapy for bone disease. Blood 107(16449525):4334–4337

    Article  PubMed  CAS  Google Scholar 

  • Dingli D, Wolf RC, Vella A (2007) Imatinib and type 2 diabetes. Endocr Pract 13(17490925):126–130

    PubMed  Google Scholar 

  • Druker BJ, Talpaz M, Resta DJ et al (2001) Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N Engl J Med 344(14):1031–7. doi:10.1056/NEJM200104053441401

    Google Scholar 

  • Druker BJ, Guilhot F, O’Brien SG et al (2006) Five-year follow-up of patients receiving imatinib for chronic myeloid leukemia. N Engl J Med 355(23):2408–17. doi:10.1056/NEJMoa062867

    Google Scholar 

  • El Hajj Dib I, Gallet M, Mentaverri R, Sevenet N, Brazier M, Kamel S (2006) Imatinib mesylate (Gleevec) enhances mature osteoclast apoptosis and suppresses osteoclast bone resorbing activity. Eur J Pharmacol 551(17049513):27–33

    Article  PubMed  CAS  Google Scholar 

  • Esmaeli B, Prieto VG, Butler CE et al (2002) Severe periorbital edema secondary to STI571 (Gleevec). Cancer 95(12209733):881–887

    Article  PubMed  Google Scholar 

  • Estabragh ZR, Knight K, Watmough SJ et al (2011) A prospective evaluation of cardiac function in patients with chronic myeloid leukaemia treated with imatinib. Leuk Res 35(1):49–51. doi:10.1016/j.leukres.2010.08.020

    Google Scholar 

  • Faderl S, Talpaz M, Estrov Z, O’Brien S, Kurzrock R, Kantarjian HM (1999) The biology of chronic myeloid leukemia. N Engl J Med 341(3):164–172. doi:10.1056/NEJM199907153410306

    Google Scholar 

  • Fernandez A, Sanguino A, Peng Z et al (2007) An anticancer C-Kit kinase inhibitor is reengineered to make it more active and less cardiotoxic. J Clin Invest 117(18060038):4044–4054

    Article  PubMed  CAS  Google Scholar 

  • Fitter S, Dewar AL, Kostakis P et al (2008) Long-term imatinib therapy promotes bone formation in CML patients. Blood 111(18042796):2538–2547

    Article  PubMed  CAS  Google Scholar 

  • Fitter S, Vandyke K, Schultz CG, White D, Hughes TP, Zannettino AC (2010) Plasma adiponectin levels are markedly elevated in imatinib-treated chronic myeloid leukemia (CML) patients: a mechanism for improved insulin sensitivity in type 2 diabetic CML patients? J Clin Endocrinol Metab 95(8):3763–3767. doi:10.1210/jc.2010-0086

    Google Scholar 

  • Gambacorti-Passerini CK, Kim DW, Mahon FX, Saglio G, Pane F, Guilhot F, Deininger MWN, Nagler A, Rambaldi A, Morra E, Antolini L, Kweon IY, Reiffers J, Tornaghi L, Valsecchi MG (2008) Imatinib Long Term Effects (ILTE) study: an independent, international study in CML patients In: 50th ASH Annual Meeting and Exposition. San Francisco, USA

  • Gottschalk S, Anderson N, Hainz C, Eckhardt SG, Serkova NJ (2004) Imatinib (STI571)-mediated changes in glucose metabolism in human leukemia BCR-ABL-positive cells. Clin Cancer Res 10(15475456):6661–6668

    Article  PubMed  CAS  Google Scholar 

  • Grey A, O’Sullivan S, Reid IR, Browett P (2006) Imatinib mesylate, increased bone formation, and secondary hyperparathyroidism. N Engl J Med 355(23):2494–2495. doi:10.1056/NEJMc062388

    Google Scholar 

  • Gronchi A, Judson I, Nishida T et al (2009) Adjuvant treatment of GIST with imatinib: solid ground or still quicksand? A comment on behalf of the EORTC Soft Tissue and Bone Sarcoma Group, the Italian Sarcoma Group, the NCRI Sarcoma Clinical Studies Group (UK), the Japanese Study Group on GIST, the French Sarcoma Group and the Spanish Sarcoma Group (GEIS). Eur J Cancer 45(19286368):1103–1106

    Google Scholar 

  • Guetens G, De Boeck G, Highley M, Dumez H, Van Oosterom AT, de Bruijn EA (2003) Quantification of the anticancer agent STI-571 in erythrocytes and plasma by measurement of sediment technology and liquid chromatography-tandem mass spectrometry. J Chromatogr A 1020(14661754):27–34

    Article  PubMed  CAS  Google Scholar 

  • Guilhot F, Druker B, Larson RA et al (2009) High rates of durable response are achieved with imatinib after treatment with interferon alpha plus cytarabine: results from the International Randomized Study of Interferon and STI571 (IRIS) trial. Haematologica 94(12):1669–1675. doi:10.3324/haematol.2009.010629

    Google Scholar 

  • Hagerkvist R, Sandler S, Mokhtari D, Welsh N (2007) Amelioration of diabetes by imatinib mesylate (Gleevec): role of beta-cell NF-kappaB activation and anti-apoptotic preconditioning. FASEB J 21(17135364):618–628

    Article  PubMed  Google Scholar 

  • Hamberg P, de Jong FA, Boonstra JG, van Doorn J, Verweij J, Sleijfer S (2006) Non-islet-cell tumor induced hypoglycemia in patients with advanced gastrointestinal stromal tumor possibly worsened by imatinib. J Clin Oncol 24(16782905):30–31

    Article  Google Scholar 

  • Hatfield A, Owen S, Pilot PR (2007) In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 13(1):13; author reply 15–6. doi:10.1038/nm0107-13a

    Google Scholar 

  • Heinrich MC, Corless CL, Demetri GD et al (2003) Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 21(14645423):4342–4349

    Article  PubMed  CAS  Google Scholar 

  • Heinrich MC, Corless CL, Blanke CD et al (2006) Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 24(16954519):4764–4774

    Article  PubMed  CAS  Google Scholar 

  • Hirota S, Isozaki K, Moriyama Y et al (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279(5350):577–580

    Article  PubMed  CAS  Google Scholar 

  • Hochhaus A, Druker B, Sawyers C 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(17932248):1039–1043

    PubMed  CAS  Google Scholar 

  • Hughes TP, Branford S, White DL et al (2008) Impact of early dose intensity on cytogenetic and molecular responses in chronic- phase CML patients receiving 600 mg/day of imatinib as initial therapy. Blood 112(10):3965–73. doi:10.1182/blood-2008-06-161737

    Google Scholar 

  • Janeway KA, Liegl B, Harlow A et al (2007) Pediatric KIT wild-type and platelet-derived growth factor receptor alpha-wild-type gastrointestinal stromal tumors share KIT activation but not mechanisms of genetic progression with adult gastrointestinal stromal tumors. Cancer Res 67(17909012):9084–9088

    Article  PubMed  CAS  Google Scholar 

  • Joensuu H, Roberts PJ, Sarlomo-Rikala M et al (2001) Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344(14):1052–1056. doi:10.1056/NEJM200104053441404

    Google Scholar 

  • Jonsson S, Olsson B, Ohlsson C, Lorentzon M, Mellstrom D, Wadenvik H (2008) Increased cortical bone mineralization in imatinib treated patients with chronic myelogenous leukemia. Haematologica 93(18508797):1101–1103

    Article  PubMed  Google Scholar 

  • Judson IDdP E, Verweij J, Van Glabbeke M, Ma P, Peng B, Dimitrijevic S, Van Oosterom A (2003) Population pharmacokinetic (PK) analysis and PK-pharmacodynamic (PD) correlations in Phase I/II trial of imatinib in gastrointestinal stromal tumours (GIST) conducted by the European Organisation for Research and Treatment of Cancer Soft Tissue and Bone Sarcoma Group. In: ASCO Annual Meeting Chicago, vol 22. USA

  • Judson I, Ma P, Peng B et al (2005) Imatinib pharmacokinetics in patients with gastrointestinal stromal tumour: a retrospective population pharmacokinetic study over time. EORTC Soft Tissue and Bone Sarcoma Group. Cancer Chemother Pharmacol 55(4):379–386. doi:10.1007/s00280-004-0876-0

  • Kantarjian H, Sawyers C, Hochhaus A et al (2002) Hematologic and cytogenetic responses to imatinib mesylate in chronic myelogenous leukemia. N Engl J Med 346(11870241):645–652

    Article  PubMed  CAS  Google Scholar 

  • Kantarjian HM, Giles F, Gattermann N et al (2007) Nilotinib (formerly AMN107), a highly selective BCR-ABL tyrosine kinase inhibitor, is effective in patients with Philadelphia chromosome-positive chronic myelogenous leukemia in chronic phase following imatinib resistance and intolerance. Blood 110(17715389):3540–3546

    Article  PubMed  CAS  Google Scholar 

  • Kerkela R, Grazette L, Yacobi R et al (2006) Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 12(8):908–916. doi:10.1038/nm1446

    Google Scholar 

  • Kindblom LG, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998) Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152(9588894):1259–1269

    PubMed  CAS  Google Scholar 

  • Komatsubara S, Mori S, Mashiba T et al (2003) Long-term treatment of incadronate disodium accumulates microdamage but improves the trabecular bone microarchitecture in dog vertebra. J Bone Miner Res: Off J Am Soc Bone Miner Res 18(3):512–520. doi:10.1359/jbmr.2003.18.3.512

    Google Scholar 

  • Langer C, Gunawan B, Schuler P, Huber W, Fuzesi L, Becker H (2003) Prognostic factors influencing surgical management and outcome of gastrointestinal stromal tumours. Br J Surg 90(12594669):332–339

    Article  PubMed  CAS  Google Scholar 

  • Le Cesne A, Ray-Coquard I, Bui BN et al (2010) Discontinuation of imatinib in patients with advanced gastrointestinal stromal tumours after 3 years of treatment: an open-label multicentre randomised phase 3 trial. Lancet Oncol 11(20864406):942–949

    Article  PubMed  CAS  Google Scholar 

  • Li B, Boast S, de los Santos K et al (2000) Mice deficient in Abl are osteoporotic and have defects in osteoblast maturation. Nat Genet 24(10700189):304–308

    Article  PubMed  CAS  Google Scholar 

  • Mahon F-X, Rea D, Guilhot J 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(20965785):1029–1035

    Article  PubMed  CAS  Google Scholar 

  • Mauro MJ, Deininger MW (2009) Management of drug toxicities in chronic myeloid leukaemia. Best Pract Res Clin Haematol 22(3):409–429. doi:10.1016/j.beha.2009.06.001

    Google Scholar 

  • Miettinen M, Sarlomo-Rikala M, Lasota J (1999) Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol 30(10):1213–1220

    Article  PubMed  CAS  Google Scholar 

  • Nishida T, Shirao K, Sawaki A et al (2008) Efficacy and safety profile of imatinib mesylate (ST1571) in Japanese patients with advanced gastrointestinal stromal tumors: a phase II study (STI571B1202). Int J Clin Oncol 13(18553235):244–251

    Article  PubMed  CAS  Google Scholar 

  • O’Brien SG, Guilhot F, Larson RA et al (2003) Imatinib compared with interferon and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia. N Engl J Med 348(12637609):994–991004

    Article  PubMed  Google Scholar 

  • Osorio S, Noblejas AG, Duran A, Steegmann JL (2007) Imatinib mesylate induces hypophosphatemia in patients with chronic myeloid leukemia in late chronic phase, and this effect is associated with response. Am J Hematol 82(5):394–395. doi:10.1002/ajh.20778

    Google Scholar 

  • O’Sullivan S, Naot D, Callon K et al (2007) Imatinib promotes osteoblast differentiation by inhibiting PDGFR signaling and inhibits osteoclastogenesis by both direct and stromal cell-dependent mechanisms. J Bone Miner Res 22(17663639):1679–1689

    Article  PubMed  Google Scholar 

  • O’Sullivan S, Horne A, Wattie D et al (2009) Decreased bone turnover despite persistent secondary hyperparathyroidism during prolonged treatment with imatinib. J Clin Endocrinol Metab 94(19174494):1131–1136

    Article  PubMed  Google Scholar 

  • Peng B, Hayes M, Resta D et al (2004) Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol 22(14990650):935–942

    Article  PubMed  CAS  Google Scholar 

  • Perik PJ, Rikhof B, de Jong FA, Verweij J, Gietema JA, van der Graaf WT (2008) Results of plasma N-terminal pro B-type natriuretic peptide and cardiac troponin monitoring in GIST patients do not support the existence of imatinib-induced cardiotoxicity. Ann Oncol: Off J Eur Soc Med Oncol/ESMO 19(2):359–361. doi:10.1093/annonc/mdm468

    Google Scholar 

  • Ramanathan RK, Egorin MJ, Takimoto CHM et al (2008) Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of liver dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. J Clin Oncol 26(18235115):563–569

    Article  PubMed  CAS  Google Scholar 

  • Rousselot P, Huguet F, Rea D et al (2007) Imatinib mesylate discontinuation in patients with chronic myelogenous leukemia in complete molecular remission for more than 2 years. Blood 109(16973963):58–60

    Article  PubMed  CAS  Google Scholar 

  • Rubin BP, Fletcher JA, Fletcher CDM (2000) Molecular insights into the histogenesis and pathogenesis of gastrointestinal stromal tumors. Int J Surg Pathol 8(11493959):5–10

    Article  PubMed  CAS  Google Scholar 

  • Sawyers CL (1999) Chronic myeloid leukemia. N Engl J Med 340(17):1330–1340. doi:10.1056/NEJM199904293401706

    Google Scholar 

  • Sawyers CL, Hochhaus A, Feldman E 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(11986204):3530–3539

    Article  PubMed  CAS  Google Scholar 

  • Scheinfeld N (2006) Imatinib mesylate and dermatology part 2: a review of the cutaneous side effects of imatinib mesylate. J Drugs Dermatol 5(3):228–231

    PubMed  Google Scholar 

  • Schellings MWM, Baumann M, van Leeuwen REW et al (2006) Imatinib attenuates end-organ damage in hypertensive homozygous TGR(mRen2)27 rats. Hypertension 47(16432052):467–474

    Article  PubMed  CAS  Google Scholar 

  • Talpaz M, Silver RT, Druker BJ 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(6):1928–1937

    Article  PubMed  CAS  Google Scholar 

  • Tarn C, Skorobogatko YV, Taguchi T, Eisenberg B, von Mehren M, Godwin AK (2006) Therapeutic effect of imatinib in gastrointestinal stromal tumors: AKT signaling dependent and independent mechanisms. Cancer Res 66(16707477):5477–5486

    Article  PubMed  CAS  Google Scholar 

  • Trent JC, Patel SS, Zhang J et al (2010) Rare incidence of congestive heart failure in gastrointestinal stromal tumor and other sarcoma patients receiving imatinib mesylate. Cancer 116(19885836):184–192

    PubMed  CAS  Google Scholar 

  • Van den Abbeele AD (2008) The lessons of GIST–PET and PET/CT: a new paradigm for imaging. Oncologist 13(Suppl 2):8–13. doi:10.1634/theoncologist.13-S2-8

    Google Scholar 

  • Van Glabbeke M, Verweij J, Casali PG et al (2006) Predicting toxicities for patients with advanced gastrointestinal stromal tumours treated with imatinib: a study of the European Organisation for Research and Treatment of Cancer, the Italian Sarcoma Group, and the Australasian Gastro-Intestinal Trials Group (EORTC-ISG-AGITG). Eur J Cancer 42(14):2277–2285. doi:10.1016/j.ejca.2006.03.029

  • van Oosterom AT, Judson I, Verweij J et al (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet 358(11705489):1421–1423

    Article  PubMed  Google Scholar 

  • Vandyke K, Fitter S, Dewar AL, Hughes TP, Zannettino ACW (2010) Dysregulation of bone remodeling by imatinib mesylate. Blood 115(19890095):766–774

    Article  PubMed  CAS  Google Scholar 

  • Veneri D, Franchini M, Bonora E (2005) Imatinib and regression of type 2 diabetes. N Engl J Med 352(15758023):1049–1050

    Article  PubMed  CAS  Google Scholar 

  • Verweij J, van Oosterom A, Blay JY et al (2003) Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumours, but does not yield responses in other soft-tissue sarcomas that are unselected for a molecular target. Results from an EORTC Soft Tissue and Bone Sarcoma Group phase II study. Eur J cancer 39(14):2006–2011

    Google Scholar 

  • Verweij J, Casali PG, Zalcberg J et al (2004) Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 364(9440):1127–1134. doi:10.1016/S0140-6736(04)17098-0

    Google Scholar 

  • Verweij J, Casali PG, Kotasek D et al (2007) Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: analysis of EORTC-ISG-AGITG study 62005. Eur J Cancer 43(17336514):974–978

    Article  PubMed  CAS  Google Scholar 

  • Wolf A, Couttet P, Dong M et al (2010) Imatinib does not induce cardiotoxicity at clinically relevant concentrations in preclinical studies. Leuk Res 34(9):1180–1188. doi:10.1016/j.leukres.2010.01.004

    Google Scholar 

  • Wu JY, Scadden DT, Kronenberg HM (2009) Role of the osteoblast lineage in the bone marrow hematopoietic niches. J Bone Mineral Res: Off J Am Soc Bone Miner Res 24(5):759–764. doi:10.1359/jbmr.090225

    Google Scholar 

  • Yamauchi T, Kamon J, Minokoshi Y et al (2002) Adiponectin stimulates glucose utilization and fatty-acid oxidation by activating AMP-activated protein kinase. Nat Med 8(12368907):1288–1295

    Article  PubMed  CAS  Google Scholar 

  • Yang WS, Lee WJ, Funahashi T et al (2001) Weight reduction increases plasma levels of an adipose-derived anti-inflammatory protein, adiponectin. J Clin Endocrinol Metab 86(8):3815–3819

    Article  PubMed  CAS  Google Scholar 

  • Zalcberg JR, Verweij J, Casali PG et al (2005) Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur J cancer 41(12):1751–1757. doi:10.1016/j.ejca.2005.04.034

  • Zhu J, Yang Y, Zhou L, Jiang M, Hou M (2010) A long-term follow-up of the imatinib mesylate treatment for the patients with recurrent gastrointestinal stromal tumor (GIST): the liver metastasis and the outcome. BMC Cancer 10(20465813):199

    Article  PubMed  Google Scholar 

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Acknowledgments

Eirini Thanopoulou is a scholarship recipient of the Hellenic Society of Medical Oncologists (HeSMO).

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    Eirini Thanopoulou & Ian Judson

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Thanopoulou, E., Judson, I. The safety profile of imatinib in CML and GIST: long-term considerations. Arch Toxicol 86, 1–12 (2012). https://doi.org/10.1007/s00204-011-0729-7

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