Cancer Treatment Reviews
Volume 36, Issue 1 , Pages 63-68 , February 2010

Combined treatment strategies in gastrointestinal stromal tumors (GISTs) after imatinib and sunitinib therapy

  • Maria Abbondanza Pantaleo

      Affiliations

    • Department of Hematology and Oncological Sciences “L.A. Seragnoli”, S. Orsola-Malpighi Hospital, University of Bologna, Italy
    • Emergency Surgery and Transplant Department, S. Orsola-Malpighi Hospital, University of Bologna, Italy
    • Interdepartmental Centre of Cancer Research “G. Prodi”, University of Bologna, Italy
    • Corresponding Author InformationCorresponding author. Address: Department of Hematology and Oncological Sciences “L.A. Seragnoli”, University of Bologna, Sant’Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy. Tel.: +39 051 6364078; fax + 39 051 6364037.
  • ,
  • Margherita Nannini

      Affiliations

    • Department of Hematology and Oncological Sciences “L.A. Seragnoli”, S. Orsola-Malpighi Hospital, University of Bologna, Italy
  • ,
  • Monica Di Battista

      Affiliations

    • Department of Hematology and Oncological Sciences “L.A. Seragnoli”, S. Orsola-Malpighi Hospital, University of Bologna, Italy
  • ,
  • Fausto Catena

      Affiliations

    • Emergency Surgery and Transplant Department, S. Orsola-Malpighi Hospital, University of Bologna, Italy
  • ,
  • Guido Biasco

      Affiliations

    • Department of Hematology and Oncological Sciences “L.A. Seragnoli”, S. Orsola-Malpighi Hospital, University of Bologna, Italy
    • Emergency Surgery and Transplant Department, S. Orsola-Malpighi Hospital, University of Bologna, Italy
    • Interdepartmental Centre of Cancer Research “G. Prodi”, University of Bologna, Italy

Received 5 August 2009 ,Revised 14 October 2009 ,Accepted 19 October 2009.

References 

  1. 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;347:472–480
  2. Demetri GD, van Oosterom AT, Garrett CR, et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib a randomised controlled trial. Lancet. 2006;368:1329–1338
  3. Reichardt P. Novel approaches to imatinib- and sunitinib-resistant GIST. Curr Oncol Rep. 2008;10:344–349
  4. Weisberg E, Manley PW, Breitenstein W, et al. Characterization of AMN107, a selective inhibitor of native and mutant Bcr-Abl. Cancer Cell. 2005;7:129–141
  5. Montemurro M, Schöffski P, Reichardt P, et al. Nilotinib in the treatment of advanced gastrointestinal stromal tumours resistant to both imatinib and sunitinib. Eur J Cancer. 2009;[Epub ahead of print]
  6. Wiebe L, Kasza KE, Maki RG, et al. Activity of sorafenib (SOR) in patients (pts) with imatinib (IM) and sunitinib (SU)-resistant (RES) gastrointestinal stromal tumors (GIST): a phase II trial of the University of Chicago Phase II Consortium. J Clin Oncol. 2008;26:20;[suppl; abstr 10502]
  7. Reichardt P, Montemurro M, Gelderblom H, et al. Sorafenib fourth-line treatment in imatinib-, sunitinib-, and nilotinib-resistant metastatic GIST: a retrospective analysis. J Clin Oncol. 2009;27:15s;[suppl; abstr 10564]
  8. Heinrich MC, Carden R, Griffith D, et al. In vitro activity of sorafenib against imatinib- and sunitinib-resistant kinase mutations associated with drug-resistant GI stromal tumors. J Clin Oncol. 2009;27:15s;[suppl; abstr 10500]
  9. Heinrich MC, Corless CL, Demetri GD, et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumors. J Clin Oncol. 2003;21:4342–4349
  10. Debiec-Rychter M, Dumez H, Judson I, Wasag B, 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;40:689–695
  11. Heinrich MC, Owzar K, Corless CL, Hollis D, Borden EC, Fletcher CD, et al. Correlation of kinase genotype and clinical outcome in the North AmericanIntergroup 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. 2008;26(33):5360–5367
  12. Desai J, Shankar S, Heinrich MC, et al. Clonal evolution of resistance to imatinib in patients with metastatic gastrointestinal stromal tumors. Clin Cancer Res. 2007;13:5398–5405
  13. Heinrich MC, Corless CL, Duensing A, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–710
  14. 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;23:5357–5364
  15. Heinrich MC, Corless CL, Blanke CD, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006;24:4764–4774
  16. Maleddu A, Pantaleo MA, Nannini M, et al. Mechanisms of secondary resistance to tyrosine kinase inhibitors in gastrointestinal stromal tumours (Review). Oncol Rep. 2009;21:1359–1366
  17. Liegl B, Kepten I, Le C, et al. Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 2008;216:64–74
  18. Wardelmann E, Merkelbach-Bruse S, Pauls K, et al. Polyclonal evolution of multiple secondary KIT mutations in gastrointestinal stromal tumors under treatment with imatinib mesylate. Clin Cancer Res. 2006;12:1743–1749
  19. Bauer S, Duensing A, Demetri GD, Fletcher JA. KIT oncogenic signaling mechanisms in imatinib-resistant gastrointestinal stromal tumor: PI3-kinase/AKT is a crucial survival pathway. Oncogene. 2007;26:7560–7568
  20. Agaimy A, Terracciano LM, Dirnhofer S, et al. V600E BRAF mutations are alternative early molecular events in a subset of KIT/PDGFRA wild-type gastrointestinal stromal tumours. J Clin Pathol. 2009;62:613–616
  21. Agaram NP, Laquaglia MP, Ustun B, et al. Molecular characterization of pediatric gastrointestinal stromal tumors. Clin Cancer Res. 2008;14:3204–3215
  22. Braconi C, Bracci R, Bearzi I, et al. Insulin-like growth factor 1 and 2 help to predict disease outcome in GIST patients. Ann Oncol. 2008;19:1293–1298
  23. Tarn C, Rink L, Merkel E, et al. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci USA. 2008;105:8387–8392
  24. Pantaleo MA, Astolfi A, Di Battista M, et al. Insuline-like growth factor 1 receptor (IGF1r) expression in wild-type GISTs: a potential novel therapeutic target. Int J Cancer. 2009;125:2991–2994
  25. Yang J, Du X, Lazar AJ, et al. Genetic aberrations of gastrointestinal stromal tumors. Cancer. 2008;113:1532–1543
  26. Gunawan B, von Heydebreck A, Sander B, et al. An oncogenetic tree model in gastrointestinal stromal tumours (GISTs) identifies different pathways of cytogenetic evolution with prognostic implications. J Pathol. 2007;211:463–470
  27. Weisberg E, Wright RD, Jiang J, et al. Effects of PKC412, Nilotinib, and imatinib against GIST-associated PDGFRA mutants with differential imatinib sensitivity. Gastroenterology. 2006;131:1734–1742
  28. Reichardt P, Casali PG, Blay J, et al. A phase I study of AMN107 alone and in combination with imatinib in patients (pts) with imatinib-resistant gastrointestinal stromal tumors (GIST). J Clin Oncol. 2006;9545
  29. Blay JY, Casali PG, Reichardt P, et al. A phase I study of nilotinib alone and in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors (GIST): Study update. J Clin Oncol. 2008;26:[May 20 suppl; abstr 10553]
  30. Van Oosterom AT, Dumez H, Desai J, et al. Combination signal transduction inhibition: A phase I/II trial of the oral mTOR-inhibitor everolimus (E, RAD001) and imatinib mesylate (IM) in patients (pts) with gastrointestinal stromal tumor (GIST) refractory to IM. J Clin Oncol. 2004;3002
  31. Dumez H, Reichard P, Blay JY, et al. A phase I–II study of everolimus (RAD001) in combination with imatinib in patients (pts) with imatinib-resistant gastrointestinal stromal tumors (GIST). J Clin Oncol. 2008;26:[May 20 suppl; abstr 10519]
  32. Palassini E, Fumagalli E, Coco P, et al. Combination of PKC412 and sirolimus in a metastatic patient with PDGFRA-D842V gastrointestinal stromal tumor (GIST). J Clin Oncol. 2008;26:[May 20 suppl; abstr 21515]
  33. Piovesan C, Fumagalli E, Coco P, et al. Response to sirolimus in combination to tirosine kinase inhibitors (TKI) in three cases of PDGFRA-D842V metastatic gastrointestinal stromal tumor (GIST). J Clin Oncol. 2009;27:15s;[suppl; abstr 10565]
  34. Conley P, Araujo D, Ludwig J, et al. A randomized phase II study of perifosine (P) plus imatinib for patients with imatinib-resistant gastrointestinal stromal tumor (GIST). J Clin Oncol. 2009;27:15s;[suppl; abstr 10563]
  35. Schoffski P, Floris G, Sciot R, et al. Assessment of the heat shock protein 90 (HSP90) inhibitor IPI504 alone or in combination with the tyrosine kinase inhibitor (TKI) imatinib in mice carrying xenografts of human gastrointestinal stromal tumors (GIST). J Clin Oncol. 2009;27:15s;[suppl; abstr 10534]
  36. Fabbro D, Ruetz S, Bodis S, et al. PKC412 – a protein kinase inhibitor with a broad therapeutic potential. Anticancer Drug Des. 2000;15:17–28
  37. Prenen H, Guetens G, de Boeck G, et al. Cellular uptake of the tyrosine kinase inhibitors imatinib and AMN107 in gastrointestinal stromal tumor cell lines. Pharmacology. 2006;77:11–16
  38. Wang L, Giannoudis A, Lane S, Williamson P, Pirmohamed M, Clark RE. Expression of the uptake drug transporter hOCT1 is an important clinical determinant of the response to imatinib in chronic myeloid leukemia. Clin Pharmacol Ther. 2008;83:258–264
  39. Bonvalot S, Eldweny H, Pechoux CL, et al. Impact of surgery on advanced gastrointestinal stromal tumors (GIST) in the imatinib era. Ann Surg Oncol. 2006;13:1596–1603
  40. Andtbacka RH, Ng CS, Scaife CL, et al. Surgical resection of gastrointestinal stromal tumors after treatment with imatinib. Ann Surg Oncol. 2007;14:14–24
  41. Raut CP, Posner M, Desai J, et al. Surgical management of advanced gastrointestinal stromal tumors after treatment with targeted systemic therapy using kinase inhibitors. J Clin Oncol. 2006;24:2325–2331
  42. Gronchi A, Fiore M, Miselli F, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–346
  43. DeMatteo RP, Maki RG, Singer S, Gonene M, Brennan MF, Antonescu CR. Results of tyrosine kinase inhibitor therapy followed by surgical resection for metastatic gastrointestinal stromal tumor. Ann Surg. 2007;245:347–352
  44. Scaife CL, Hunt KK, Patel SR, et al. Is there a role for surgery in patients with unrespectable cKIT+ gastrointestinal stromal tumors treated with imatinib mesylate?. Am J Surg. 2003;186:665–669
  45. Wu PC, Langerman A, Ryan CW, Hart J, Swiger S, Posner MC. Surgical treatment of gastrointestinal stromal tumors in the imatinib era. Surgery. 2003;134:665–666
  46. Rutkowski P, Nowecki Z, Nyckowski P, et al. Surgical treatment of patients with initially inoperable and/or metastatic gastrointestinal stromal tumors (GIST) during therapy with imatinib mesylate. J Surg Oncol. 2006;93:304–311
  47. Haller F, Dekten S, Schulten H-J, et al. Surgical management after neoadjuvant imatinib therapy in gastrointestinal stromal tumors (GIST) with respect to imatinib resistance caused by secondary KIT mutations. Ann Surg Oncol. 2007;14:526–532
  48. Fiore M, Palassini E, Fumagalli E, et al. Preoperative imatinib mesylate for unresectable or locally advanced primary gastrointestinal stromal tumors (GIST). Eur J Surg Oncol. 2009;35:739–745
  49. Katz D, Segal A, Alberton Y, et al. Neoadjuvant imatinib for unresectable gastrointestinal stromal tumor. Anticancer Drugs. 2004;15:599–602
  50. Al-Batran SE, Hartmann JT, Heidel F, et al. Focal progression in patients with gastrointestinal stromal tumors after initial response to imatinib mesylate: a three-center-based study of 38 patients. Gastric Cancer. 2007;10:145–152
  51. Hasegawa J, Kanda T, Hirota S, et al. Surgical interventions for focal progression of advanced gastrointestinal stromal tumors during imatinib therapy. Int J Clin Oncol. 2007;12:212–217
  52. Bauer S, Hartmann JT, de Wit M, et al. Resection of residual disease in patients with metastatic gastrointestinal stromal tumors responding to treatment with imatinib. Int J Cancer. 2005;117:316–325
  53. Pantaleo MA, Di Battista M, Catena F, et al. Surgical debulking of gastrointestinal stromal tumors: is it a reasonable option after second-line treatment with sunitinib?. J Cancer Res Clin Oncol. 2008;134:625–630
  54. Choi WH, Kim S, Hyung WJ, et al. Long-surviving patients with recurrent GIST after receiving cytoreductive surgery with imatinib therapy. Yonsei Med J. 2009;50:437–440
  55. Pantaleo MA, Landuzzi L, Nicoletti G, et al. Advances in preclinical therapeutics development using small animal imaging and molecular analyses: the gastrointestinal stromal tumors model. Clin Exp Med. 2009;9:199–205
  56. Pantaleo MA, Nannini M, Maleddu A, et al. Conventional and novel PET tracers for imaging in oncology in the era of molecular therapy. Cancer Treat. 2008;34:103–121
  57. Kil KE, Ding YS, Lin KS, et al. Synthesis and positron emission tomography studies of carbon-11-labeled imatinib (Gleevec). Nucl Med Biol. 2007;34:153–163

PII: S0305-7372(09)00157-1

doi: 10.1016/j.ctrv.2009.10.004

Cancer Treatment Reviews
Volume 36, Issue 1 , Pages 63-68 , February 2010