Skip to main content
SpringerLink
Log in

Imatinib

A Review of its Use in the Management of Gastrointestinal Stromal Tumours

  • Adis Drug Evaluation
  • Published:
Drugs Aims and scope Submit manuscript

Summary

Abstract

Imatinib (Gleevec®, Glivec®) is a small molecule inhibitor of tyrosine kinase that has been evaluated for efficacy in patients with gastrointestinal stromal tumours (GIST). The drug is approved for the treatment of unresectable and/or metastatic, KIT-positive GIST in the US, Europe and many other countries.

Imatinib has had a significant impact on the management of advanced GIST, which has traditionally had a poor prognosis, and has quickly become the first choice of treatment in the medical therapy of unresectable and/or metastatic, KIT-positive GIST. In randomised, nonblind trials, imatinib 400–800 mg/day produced complete or partial responses in up to two-thirds of patients, with long-term efficacy, and substantially prolonged progression-free and overall survival. The drug was generally well tolerated in GIST patients, including during long-term treatment. Imatinib dosages higher than 400 mg/day (up to 800 mg/day) may improve progression-free survival, with an increase in dosage benefiting some patients who show disease progression at the lower dosage, particularly in those with exon 9 mutation; however, there is also a dose-related increase in imatinib toxicity. Mutational genotype and other, nonbiomolecular factors may aid in guiding imatinib therapy and predicting prognosis in GIST patients. Further data are required to evaluate the use of imatinib in adjuvant and neoadjuvant settings. Nevertheless, imatinib currently provides the most effective treatment option in the management of advanced GIST.

Pharmacological Properties

Imatinib acts by selectively and competitively inhibiting the protein-tyrosine kinase activity associated with KIT receptors and platelet-derived growth factor receptor-α. Inhibition of constitutively active KIT signalling by imatinib resulted in inhibition of cell proliferation and apoptosis induction in vitro in GIST cell lines, and arrest of tumour cell proliferation and decrease in tumour volume in vivo in a mouse model. Several pharmacodynamic and pharmacokinetic mechanisms of resistance, among the most common being secondary kinase mutations and constitutive KIT reactivation, have been proposed for the initial and late resistance to imatinib observed in clinical trials.

Imatinib is rapidly absorbed after oral administration with almost complete bioavailability. It is highly plasma protein bound and extensively distributed into body tissues. Cytochrome P450 (CYP) 3A4 is the main enzyme involved in imatinib metabolism, resulting in the formation of its major, active metabolite CGP 74588. The drug is eliminated mostly as metabolites, mainly via the faeces. Imatinib may interact with drugs that are inhibitors or inducers of, or substrate for, CYP3A4.

Therapeutic Efficacy

In randomised, nonblind, multicentre trials, imatinib 400–800 mg/day was associated with a complete or partial response in 48–58% of patients with advanced, unresectable and/or metastatic, KIT-positive GIST, with response rates in imatinib 400 mg/day recipients being similar to those in patients receiving imatinib 600 or 800 mg/day. Response rates were even higher (67%) during long-term follow-up in a phase II trial, most of them durable for >1 year. In a phase III trial, the median time to onset of response was 30 weeks, but occasional best responses required as long as 2 years of treatment.

The estimated progression-free and overall survival rates at 2 years were 44–52% and 69–76%. Imatinib 400mg twice daily appeared to provide greater benefit than imatinib 400mg once daily in terms of progression-free survival in one trial, but not in the other. During a 52-month follow-up in a phase II trial, the estimated median overall survival for all patients was 248 weeks.

Exploratory analyses of data from phase II/III trials showed that dosage escalation could be beneficial in some patients, particularly those harboring an exon 9 mutation, who had disease progression despite treatment with imatinib 400 mg/day; compared with continuous therapy, imatinib interruption was associated with a significant reduction in progression-free survival; dosage reductions did not appear to have an adverse impact on outcomes; and mutational genotype was the major predictor of clinical response to imatinib.

Tolerability

Imatinib was generally well tolerated in patients with GIST in clinical trials, including the 52-month follow-up of a phase II trial; most of the adverse events were mild to moderate in severity. Anaemia and fatigue were the most common haematological and nonhaematological grade 3/4 adverse events. Overall, grade 3/4 adverse events were more common with imatinib 800 than 400 mg/day, although the incidence of serious adverse events was similar.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Table I
Table II
Table III
Fig. 1
Table IV
Fig. 2
Table V

Similar content being viewed by others

Notes

  1. The use of trade names is for product identification purposes only and does not imply endorsement.

References

  1. Sabah M, Leader M, Kay E. Gastrointestinal stromal tumours: an update. Curr Diagn Pathol 2005; 11 (6): 400–10

    Article  Google Scholar 

  2. Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST Consensus Conference of 20–21 March 2004, under the auspices of ESMO. Ann Oncol 2005 Apr; 16 (4): 566–78

    Article  PubMed  Google Scholar 

  3. van der Zwan SM, Dematteo RP. Gastrointestinal stromal tumor: 5 years later. Cancer 2005 Nov; 104 (9): 1781–8

    Article  PubMed  Google Scholar 

  4. Corless CL, Fletcher JA, Heinrich MC. Biology of gastrointestinal stromal tumors. J Clin Oncol 2004; 22 (18): 3813–25

    Article  PubMed  CAS  Google Scholar 

  5. Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 2001 Nov; 61 (22): 8118–21

    PubMed  CAS  Google Scholar 

  6. Corless CL, Schroeder A, Griffith D, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol 2005 Aug 10; 23 (23): 5357–64

    Article  PubMed  CAS  Google Scholar 

  7. Shinomura Y, Kinoshita H, Tsutsui S, et al. Pathophysiology, diagnosis, and treatment of gastrointestinal stromal tumors. J Gastroenterol 2005; 40: 775–80

    Article  PubMed  Google Scholar 

  8. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J Clin Oncol 2003 Dec 1; 21 (23): 4342–9

    Article  PubMed  CAS  Google Scholar 

  9. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science 2003 Jan 31; 299 (5607): 708–10

    Article  PubMed  CAS  Google Scholar 

  10. Moen MD, McKeage K, Plosker GL, et al. Imatinib: a review of its use in chronic myeloid leukaemia. Drugs 2007; 67 (2): 299–320

    Article  PubMed  CAS  Google Scholar 

  11. Curran MP, Croom KF, Goa KL. Imatinib mesylate: a review of its use in chronic myeloid leukemia. Am J Cancer 2003; 2 (6): 439–54

    Article  CAS  Google Scholar 

  12. Lyseng-Williamson K, Jarvis B. Imatinib. Drugs 2001; 61 (12): 1765–74; discussion 1775-6

    Article  PubMed  CAS  Google Scholar 

  13. Joensuu H, Roberts PJ, Sarlomo-Rikala M, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 2001 Apr 5; 344 (14): 1052–6

    Article  PubMed  CAS  Google Scholar 

  14. Croom KF, Perry CM. Imatinib mesylate: in the treatment of gastrointestinal stromal tumours. Drugs 2003; 63 (5): 513–22

    Article  PubMed  CAS  Google Scholar 

  15. Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet 2005; 44 (9): 879–94

    Article  PubMed  CAS  Google Scholar 

  16. Buchdunger E, Cioffi CL, Law N, et al. Abl protein-tyrosine kinase inhibitor ST1571 inhibits in vitro signal transduction mediated by c-kit and platelet-derived growth factor receptors. J Pharmacol Exp Ther 2000; 295 (1): 139–45

    PubMed  CAS  Google Scholar 

  17. Tuveson DA, Willis NA, Jacks T, et al. STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications. Oncogene 2001 Aug 16; 20 (36): 5054–8

    Article  PubMed  CAS  Google Scholar 

  18. Heinrich MC, Griffith DJ, Druker BJ, et al. Inhibition of c-kit receptor tyrosine kinase activity by STI 571, a selective tyrosine kinase inhibitor. Blood 2000; 96 (3): 925–32

    PubMed  CAS  Google Scholar 

  19. Prenen H, Deroose C, Vermaelen P, et al. Establishment of a mouse gastrointestinal stromal tumour model and evaluation of response to imatinib by small animal positron emission tomography. Anticancer Res 2006 Mar 30; 26 (2A): 1247–52

    PubMed  CAS  Google Scholar 

  20. Bono P, Krause A, von Mehren M, et al. Serum KIT and KIT ligand levels in patients with gastrointestinal stromal tumors treated with imatinib. Blood 2004 Apr 15; 103 (8): 2929–35

    Article  PubMed  CAS  Google Scholar 

  21. Ermer A, Huber V, Gilch S, et al. The anticancer drug imatinib induces cellular autophagy. Leukemia 2007 Mar 1 [Epub ahead of print]

  22. Demetri GD, von Mehren M, Blanke CD, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med 2002 Aug 15; 347 (7): 472–80

    Article  PubMed  CAS  Google Scholar 

  23. Van Glabbeke M, Verweij J, Casali PG, et al. Initial and late resistance to imatinib in advanced gastrointestinal stromal tumors are predicted by different prognostic factors: a European Organisation for Research and Treatment of Cancer-Italian Sarcoma Group-Australasian Gastrointestinal Trials Group study. J Clin Oncol 2005 Aug 20; 23 (24): 5795–804

    Article  PubMed  Google Scholar 

  24. Verweij J, Casali PG, Zalcberg J, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet 2004; 364 (9440): 1127–34

    Article  PubMed  CAS  Google Scholar 

  25. Fletcher JA, Corless CL, Dimitrijevic S, et al. Mechanisms of resistance to imatinib mesylate in advanced gastrointestinal stromal tumor [Abstract no. 3275]. Proc Am Soc Clin Oncol 2003; 22: 815

    Google Scholar 

  26. Debiec-Rychter M, Cools J, Dumez H, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology 2005 Feb 1; 128 (2): 270–9

    Article  PubMed  CAS  Google Scholar 

  27. Heinrich MC, Corless CL, Blanke CD, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol 2006 Oct 10; 24 (29): 4764–74

    Article  PubMed  CAS  Google Scholar 

  28. Thomas J, Wang L, Clark RE, et al. Active transport of imatinib into and out of cells: implications for drug resistance. Blood 2004 Dec 1; 104 (12): 3739–45

    Article  PubMed  CAS  Google Scholar 

  29. Judson I, Ma P, Peng B, et al. 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 2005 Apr; 55 (4): 379–86

    Article  PubMed  CAS  Google Scholar 

  30. Burger H, Nooter K. Pharmacokinetic resistance to imatinib mesylate: role of the ABC drug pumps ABCG2 (BCRP) and ABCB1 (MDR1) in the oral bioavailability of imatinib. Cell Cycle 2004 Dec; 3 (12): 1502–5

    Article  PubMed  CAS  Google Scholar 

  31. Hamada A, Miyano H, Watanabe H, et al. Interaction of imatinib mesilate with human p-glycoprotein. J Pharmacol Exp Ther 2003; 307 (2): 824–8

    Article  PubMed  CAS  Google Scholar 

  32. Delbaldo C, Chatelut E, Re M, et al. Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res 2006 Oct 15; 12 (20 Pt 1): 6073–8

    Article  PubMed  CAS  Google Scholar 

  33. Committee for Proprietary Medicinal Products. European public assessment report on Glivec (revision 1): scientific discussion. London: European Agency for the Evaluation of Medicinal Products, 2002; CPMP/2418/01

  34. Novartis Pharmaceuticals Corporation. Product information (US): Gleevec® (imatinib mesylate) tablets 100 and 400mg [online]. Available from URL: http://www.fda.gov/cder [Accessed 2007 Jan 22]

  35. Novartis Europharm Limited. Product information (EU): Glivec® (imatinib mesylate) tablets 100 and 400mg [online]. Available from URL: http://www.emea.eu.int/ [Accessed 2007 Jan 22]

  36. Glivec® GIST clinical monograph. Basel: Novartis Pharma AG, 2002

  37. Peng B, Hayes M, Resta D, et al. Pharmacokinetics and pharmacodynamics of imatinib in a phase I trial with chronic myeloid leukemia patients. J Clin Oncol 2004 Mar; 22 (5): 935–42

    Article  PubMed  CAS  Google Scholar 

  38. Peng B, Dutreix C, Mehring G, et al. Absolute bioavailability of imatinib (Glivec) orally versus intravenous infusion. J Clin Pharmacol 2004 Feb; 44 (2): 158–62

    Article  PubMed  Google Scholar 

  39. Gschwind HP, Pfaar U, Waldmeier F, et al. Metabolism and disposition of imatinib mesylate in healthy volunteers. Drug Metab Dispos 2005 Oct; 33 (10): 1503–12

    Article  PubMed  CAS  Google Scholar 

  40. Dutreix C, Peng B, Mehring G, et al. Pharmacokinetic interaction between ketoconazole and imatinib mesylate (Glivec) in healthy subjects. Cancer Chemother Pharmacol 2004 Oct; 54 (4): 290–4

    Article  PubMed  CAS  Google Scholar 

  41. Frye RF, Fitzgerald SM, Lagattuta TF, et al. Effect of St John’s wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004 Oct; 76 (4): 323–9

    Article  PubMed  CAS  Google Scholar 

  42. Bolton AE, Peng B, Hubert M, et al. Effect of rifampicin on the pharmacokinetics of imatinib mesylate (Gleevec, STI571) in healthy subjects. Cancer Chemother Pharmacol 2004 Feb; 53 (2): 102–6

    Article  PubMed  CAS  Google Scholar 

  43. O’Brien SG, Meinhardt P, Bond E, et al. Effects of imatinib mesylate (STI571, Glivec) on the pharmacokinetics of simvastatin, a cytochrome p450 3A4 substrate, in patients with chronic myeloid leukaemia. Br J Cancer 2003 Nov 17; 89 (10): 1855–9

    Article  PubMed  Google Scholar 

  44. Rankin C, Von Mehren M, Blanke C, et al. Dose effect of imatinib in patients with metastatic GIST: phase III Sarcoma Group Study S0033 [abstract no. 9005 plus oral presentation]. 40th Annual Meeting of the American Society of Clinical Oncology; 2004 Jun 5–8; New Orleans (LA)

  45. Blanke CD, Joensuu H, Demetri GD, et al. Outcome of advanced gastrointestinal stromal tumor patients treated with imatinib mesylate: four-year follow-up of a phase II randomized trial [Abstract no. 7 plus oral presentation]. The American Society of Clinical Oncology 3rd Annual Gastrointestinal Cancers Symposium; 2006 Jan 26–28; San Francisco (CA)

  46. van Oosterom AT, Judson IR, Verweij J, et al. Update of phase I study of imatinib (STI571) in advanced soft tissue sarcomas and gastrointestinal stromal tumours: a report of the EORTC soft tissue and bone sarcoma group. Eur J Cancer 2002; 38 Suppl. 5: S83–7

    Article  PubMed  Google Scholar 

  47. Verweij J, van Oosterom A, Blay JY, et al. 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 2003 Sep; 39 (14): 2006–11

    Article  PubMed  CAS  Google Scholar 

  48. Green S, Weiss GR. Southwest Oncology Group standard response criteria, endpoint definitions and toxicity criteria. Invest New Drugs 1992; 10: 239–53

    Article  PubMed  CAS  Google Scholar 

  49. Therasse P, Arbuck SG, Eisenhauer EA, et al. New guidelines to evaluate the response to treatment in solid tumors. J Natl Cancer Inst 2000; 92 (3): 205–16

    Article  PubMed  CAS  Google Scholar 

  50. Blanke CD, Demetri GD, Von Mehren M, et al. Efficacy of imatinib mesylate in advanced gastrointestinal stromal tumor (GIST) patients (pts) according to tumor bulk, [abstract no. 21]. The American Society of Clinical Oncology 4th Annual Gastrointestinal Cancers Symposium; 2007 Jan 19–21; Orlando (FL)

  51. Zalcberg JR, Verweij J, Casali PG, et al. 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 2005 Aug; 41 (12): 1751–7

    Article  PubMed  CAS  Google Scholar 

  52. Le Cesne A, Ray-Coquard I, Bui B, et al. Interruption of imatinib in responding patients after one year treatment does not influence overall survival of patients with advanced GIST: updated results of the French Sarcoma Group randomized phase III BFR14 trial. Eur J Cancer Suppl 2005 Oct; 3 (2): 202

    Google Scholar 

  53. Blay JY, Berthaud P, Perol D, et al. Continuous vs intermittent imatinib treatment in advanced GIST after one year: a prospective randomized phase III trial of the French Sarcoma Group. [Abstract no. 9006 plus oral presentation]. 40th Annual Meeting of the American Society of Clinical Oncology; 2004 Jun 5–8; New Orleans (LA)

  54. Debiec-Rychter M, Dumez H, Judson I, et al. Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumours entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur J Cancer 2004 Mar; 40 (5): 689–95

    Article  PubMed  CAS  Google Scholar 

  55. Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer 2006 May; 42 (8): 1093–103

    Article  PubMed  CAS  Google Scholar 

  56. Kerkelä R, Grazette L, Yacobi R, et al. Cardiotoxicity of the cancer therapeutic agent imatinib mesylate. Nat Med 2006 Aug; 12 (8): 908–16

    Article  PubMed  Google Scholar 

  57. Force T. In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’ [letter]. Nat Med 2007 Jan; 13 (1): 15–6

    Article  CAS  Google Scholar 

  58. Hatfield A, Owen S, Pilot PR. In reply to ‘Cardiotoxicity of the cancer therapeutic agent imatinib mesylate’. Nat Med 2007 Jan; 13 (1): 13

    Article  PubMed  CAS  Google Scholar 

  59. Berman E, Nicolaides M, Maki RG, et al. Altered bone and mineral metabolism in patients receiving imatinib mesylate. N Engl J Med 2006 May 11; 354 (19): 2006–13

    Article  PubMed  CAS  Google Scholar 

  60. National Comprehensive Cancer Network (NCCN) soft tissue sarcoma panel. NCCN clinical practice guidelines in oncology: soft tissue sarcoma (version 3.2006) [online]. Available from URL: http://www.nccn.org [Accessed 2007 Jan 22]

  61. Blanke C, Eisenberg BL, Heinrich M. Epidemiology of GIST [letter]. Am J Gastroenterol 2005 Oct; 100 (10): 2366

    Article  PubMed  Google Scholar 

  62. Goettsch WG, Bos SD, Breekveldt-Postma N, et al. Incidence of gastrointestinal stromal tumours is underestimated: results of a nation-wide study. Eur J Cancer 2005 Dec; 41 (18): 2868–72

    Article  PubMed  Google Scholar 

  63. DeMatteo RP, Lewis J, Leung D, et al. Two hundred gastrointestinal stromal tumors: recurrence patterns and prognostic factors for survival. Ann Surg 2000; 231 (1): 51–8

    Article  PubMed  CAS  Google Scholar 

  64. Blackstein ME, Blay JY, Corless C, et al. Gastrointestinal stromal tumours: consensus statement on diagnosis and treatment. Can J Gastroenterol 2006 Mar; 20 (3): 157–63

    PubMed  Google Scholar 

  65. Dileo P, Rankin CJ, Benjamin RS, et al. Incidence and reasons for dose modification of standard-dose vs high-dose imatinib mesylate in the phase III intergroup study S0033 of patients with unresectable or metastatic gastrointestinal stromal tumor [abstract no. 9032]. J Clin Oncol 2005 Jun; 23 Suppl. 16S Pt 1: 824. Plus oral presentation made at the 41st Annual Meeting of the American Society of Clinical Oncology; 2005 May 13–17; Orlando (FL)

    Google Scholar 

  66. Scaife CL, Hunt KK, Patel SR, et al. Is there a role for surgery in patients with “unresectable” cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate? Am J Surg 2003 Dec; 186 (6): 665–9

    Article  PubMed  Google Scholar 

  67. GIST Support International. Current trials [online]. Available from URL: http://www.gistsupport.org/ [Accessed 2006 Aug 23]

  68. Blackstein ME, Rankin C, Fletcher C, et al. Clinical benefit of imatinib in patients with metastatic gastrointestinal stromal tumors negative for the expression of CD117 in the SOO33 trial [abstract no. 9010]. J Clin Oncol 2005 Jun; 23 Suppl. 16S Pt 1: 818

    Google Scholar 

  69. Medeiros F, Corless CL, Duensing A, et al. KIT-negative gastrointestinal stromal tumors: proof of concept and therapeutic implications. Am J Surg Pathol 2004 Jul; 28 (7): 889–94

    Article  PubMed  Google Scholar 

  70. Huse DM, von Mehren M, Lenhart G, et al. Cost effectiveness of imatinib mesylate in the treatment of advanced gastrointestinal stromal tumors. Clin Drug Invest 2007; 27 (2): 85–93

    Article  CAS  Google Scholar 

  71. Huse D, Finkelstein S, Glendenning A, et al. Cost-effectiveness of imatinib in the treatment of gastrointestinal stromal tumors [abstract no. MO-1800-1900-40.144-2]. 5th World Congress of the International Health Economics Association; 2005 Jul 9–13; Barcelona

  72. Finketstein SN, Huse DM, Glendenning GA, et al. Imatinib: cost-effective in the treatment of gastrointestinal stromal tumors [abstract no. 762P]. Ann Oncol 2004; 15 Suppl. 3: 201

    Google Scholar 

  73. De Abreu Lourenco R, Wonder M. The cost effectiveness of imatinib for the treatment of patients with gastrointestinal stromal tumours [abstract no. PCSC3]. 1st Asia-Pacific meeting of the International Society for Pharmacoeconomics and Outcomes Research; 2003 Sep 1–3; Kobe

Download references

Author information

Authors and Affiliations

  1. Wolters Kluwer Health / Adis, 41 Centorian Drive, Private Bag 65901, Mairangi Bay, Auckland, 1311, New Zealand

    M. Asif A. Siddiqui & Lesley J. Scott

  2. Wolters Kluwer Health, Conshohocken, Pennsylvania, USA

    M. Asif A. Siddiqui & Lesley J. Scott

Authors
  1. M. Asif A. Siddiqui
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Lesley J. Scott
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to M. Asif A. Siddiqui.

Additional information

Various sections of the manuscript reviewed by: C. Blanke, Division of Hematology and Medical Oncology, Oregon Health and Science University, Portland, Oregon, USA; T. Kubota, Center for Comprehensive and Advanced Medicine, Keio University Hospital, Tokyo, Japan; M. Lopez, Department of Medical Oncology B, Regina Elena Institute for Cancer Research, Rome, Italy; P. Reichardt, Division of Medical Oncology, Hematology, and Tumour Immunology, Robert Roessle Hospital and Tumour Institute, Charite University Hospital, The Humboldt University at Berlin, Berlin, Germany; M. Schubert, Division of Gastroenterology, Department of Medicine, Virginia Commonwealth University’s Medical College of Virginia and McGuire Veterans Affairs Medical Center, Richmond, Virginia, USA; J.R. Zalcberg, Department of Medical Oncology and Haematology, Peter MacCallum Cancer Centre, Melbourne, Australia.

Data Selection

Sources: Medical literature published in any language since 1980 on ‘imatinib’, identified using MEDLINE and EMBASE, supplemented by AdisBase (a proprietary database of Wolters Kluwer Health | Adis). Additional references were identified from the reference lists of published articles. Bibliographical information, including contributory unpublished data, was also requested from the company developing the drug.

Search strategy: MEDLINE, EMBASE and AdisBase search terms were ‘imatinib’ and (‘GIST’ or ‘gastrointestinal stromal tumours’). Searches were last updated 5 March 2007.

Selection: Studies in patients with gastrointestinal stromal tumours who received imatinib. Inclusion of studies was based mainly on the methods section of the trials. When available, large, well controlled trials with appropriate statistical methodology were preferred. Relevant pharmacodynamic and pharmacokinetic data are also included.

Index terms: Imatinib, gastrointestinal stromal tumours, pharmacodynamics, pharmacokinetics, therapeutic use, resistance, tolerability.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Siddiqui, M.A.A., Scott, L.J. Imatinib. Drugs 67, 805–820 (2007). https://doi.org/10.2165/00003495-200767050-00012

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2165/00003495-200767050-00012

Keywords

Search

Navigation