Seminars in Oncology
Volume 36, Issue 4 , Pages 302-311 , August 2009

Gastrointestinal Stromal Tumors II: Medical Oncology and Tumor Response Assessment

  • Robert S. Benjamin

      Affiliations

    • Department of Sarcoma Medical Oncology, University of Texas M.D. Anderson Cancer Center, Houston, TX
    • These authors contributed equally to this work.
    • ,
  • Maria Debiec-Rychter

      Affiliations

    • Department of Human Genetics, Catholic University Leuven, Leuven, Belgium
    • These authors contributed equally to this work.
    • ,
  • Axel Le Cesne

      Affiliations

    • Institut Gustave Roussy, Villejuif, France
    • These authors contributed equally to this work.
    • ,
  • Stefan Sleijfer

      Affiliations

    • Department of Medical Oncology, Erasmus University Medical Center, Daniel den Hoed Cancer Center, Rotterdam, The Netherlands
    • These authors contributed equally to this work.
    • ,
  • George D. Demetri

      Affiliations

    • Dana-Farber Cancer Institute, Ludwig Center, Boston, MA
    • These authors contributed equally to this work.
    • ,
  • Heikki Joensuu

      Affiliations

    • Helsinki University Central Hospital, Department of Oncology, Helsinki, Finland
    • These authors contributed equally to this work.
    • ,
  • Patrick Schöffski

      Affiliations

    • University Hospitals Leuven, Department of General Medical Oncology and Laboratory of Experimental Oncology, Leuven Cancer Institute, Catholic University Leuven, Leuven, Belgium
    • These authors contributed equally to this work.
    • ,
  • Andrés Poveda

      Affiliations

    • Instituto Valenciano de Oncología, Valencia, Spain
    • These authors contributed equally to this work.
    • Corresponding Author InformationAddress correspondence to Andrés Poveda, MD, Instituto Valenciano de Oncología, Prof Baguena 19, Valencia 46009, Spain

References 

  1. Karnofsky DA. Meaningful clinical classification of therapeutic responses to anticancer drugs. Clin Pharmacol Ther. 1961;2:709–712
  2. Miller AB, Hoogstraten B, Staquet M, Winkler A. Reporting results of cancer treatment. Cancer. 1981;47:207–214
  3. World Health Organization. WHO handbook for reporting results of cancer treatment (Offset publication No. 48). Geneva: World Health Organization; 1979;
  4. Moertel CG, Hanley JA. The effect of measuring error on the results of therapeutic trials in advanced cancer. Cancer. 1976;38:388–394
  5. Therasse P, Arbuck SG, Eisenhauer EA, Wanders J, Kaplan RS, Rubinstein L, et al. New guidelines to evaluate the response to treatment in solid tumors (European Organization for Research and Treatment of Cancer, National Cancer Institute of the United States, National Cancer Institute of Canada). J Natl Cancer Inst. 2000;92:205–216
  6. Freireich EJ. Who took the clinical out of clinical research? (—Mouse versus man: seventh David A Karnofsky Memorial Lecture—1976). Clin Cancer Res. 1997;3:2711–2722
  7. Van den Abbeele AD, Badawi RD. Use of positron emission tomography in oncology and its potential role to assess response to imatinib mesylate therapy in gastrointestinal stromal tumors (GISTs). Eur J Cancer. 2002;38(Suppl 5):S60–S65
  8. Benjamin RS, Choi H, Macapinlac HA, Burgess MA, Patel SR, Chen LL, et al. We should desist using RECIST, at least in GIST. J Clin Oncol. 2007;25:1760–1764
  9. Choi H, Charnsangavej C, Faria SC, Macapinlac HA, Burgess MA, Patel SR, et al. Correlation of computed tomography and positron emission tomography in patients with metastatic gastrointestinal stromal tumor treated at a single institution with imatinib mesylate: proposal of new computed tomography response criteria. J Clin Oncol. 2007;25:1753–1759
  10. Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, Fletcher JA, et al. 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. 2008;26:620–625
  11. Eisenhauer EA, Therasse P, Bogaerts J, Schwartz LH, Sargent D, Ford R, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1). Eur J Cancer. 2009;45:228–247
  12. Debiec-Rychter M, Dumez H, Judson I, Wasag B, Verweij J, Brown M, 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
  13. Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, et al. PDGFRA activating mutations in gastrointestinal stromal tumors. Science. 2003;299:708–710
  14. Corless CL, Schroeder A, Griffith D, Town A, McGreevey L, Harrell P, et al. PDGFRA mutations in gastrointestinal stromal tumors: frequency, spectrum and in vitro sensitivity to imatinib. J Clin Oncol. 2005;23:5357–5364
  15. Dewaele B, Wasag B, Cools J, Sciot R, Prenen H, Vandenberghe P, et al. Activity of dasatinib, a dual SRC/ABL kinase inhibitor, and IPI-504, a heat shock protein 90 inhibitor, against gastrointestinal stromal tumor-associated PDGFRAD842V mutation. Clin Cancer Res. 2008;14:5749–5758
  16. Debiec-Rychter M, Cools J, Dumez H, Sciot R, Stul M, Mentens N, et al. Mechanisms of resistance to imatinib mesylate in gastrointestinal stromal tumors and activity of the PKC412 inhibitor against imatinib-resistant mutants. Gastroenterology. 2005;128:270–279
  17. Janeway KA, Matthews DC, Butrynski JE, D'Amato GZ, Agresta S, Garrett C, et al. Sunitinib treatment of pediatric metastatic GIST after failure of imatinib [abstract]. J Clin Oncol. 2006;24:9519
  18. Antonescu CR, Besmer P, Guo T, Arkun K, Hom G, Koryotowski B, et al. Acquired resistance to imatinib in gastrointestinal stromal tumor occurs through secondary gene mutation. Clin Cancer Res. 2005;11:4182–4190
  19. Heinrich MC, Corless CL, Blanke CD, Demetri GD, Joensuu H, Roberts PJ, et al. Molecular correlates of imatinib resistance in gastrointestinal stromal tumors. J Clin Oncol. 2006;24:4764–4774
  20. Wardelmann E, Thomas N, Merkelbach-Bruse S, Pauls K, Speidel N, Buttner R, et al. Acquired resistance to imatinib in gastrointestinal stromal tumours caused by multiple KIT mutations. Lancet Oncol. 2005;6:249–251
  21. Guo T, Agaram NP, Wong GC, Hom G, D'Adamo D, Maki RG, et al. Sorafenib inhibits the imatinib-resistant KITT670I gatekeeper mutation in gastrointestinal stromal tumor. Clin Cancer Res. 2007;13:4874–4881
  22. Prenen H, Cools J, Mentens N, Folens C, Sciot R, Schoffski P, et al. Efficacy of the kinase inhibitor SU11248 against gastrointestinal stromal tumor mutants refractory to imatinib mesylate. Clin Cancer Res. 2006;12:2622–2627
  23. Heinrich MC, Maki RG, Corless CL, Antonescu CR, Harlow A, Griffith D, et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol. 2008;26:5352–5359
  24. Heinrich MC, Maki RG, Corless CL, Antonescu CR, Fletcher JA, Fletcher CD, et al. Sunitinib response in imatinib-resistant GIST correlates with KIT and PDGFRA mutation status [abstract]. J Clin Oncol. 2006;24:9502
  25. Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, Tuveson D, et al. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med. 2001;344:1052–1056
  26. Blanke CD, Rankin C, Demetri GD, Ryan CW, von Mehren M, Benjamin RS, et al. 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. 2008;26:626–632
  27. Demetri GD, von Mehren M, Blanke CD, Van den Abbeele AD, Eisenberg B, Roberts PJ, et al. Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. N Engl J Med. 2002;347:472–480
  28. van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, et al. Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumours: a phase I study. Lancet. 2001;358:1421–1423
  29. Verweij J, Casali PG, Zalcberg J, LeCesne A, Reichardt P, Blay JY, et al. Progression-free survival in gastrointestinal stromal tumours with high-dose imatinib: randomised trial. Lancet. 2004;364:1127–1134
  30. Verweij J, van Oosterom A, Blay JY, Judson I, Rodenhuis S, van der Graaf W, 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;39:2006–2011
  31. Van Glabbeke MM, Owzar K, Rankin C, Simes J, Crowley J. Comparison of two doses of imatinib for the treatment of unresectable or metastatic gastrointestinal stromal tumors (GIST): a meta-analyis based on 1,640 patients [abstract]. J Clin Oncol. 2007;25
  32. von Mehren M, Wang Y, Joensuu H, Blanke CD, Wehrle E, Demetri GD. Imatinib pharmacokinetics and its correlation with clinical response in patients with unresectable/metastatic gastrointestinal stromal tumor [abstract]. J Clin Oncol. 2008;26:4523
  33. Larson RA, Druker BJ, Guilhot F, O'Brien SG, Riviere GJ, Krahnke T, et al. Imatinib pharmacokinetics and its correlation with response and safety in chronic-phase chronic myeloid leukemia: a subanalysis of the IRIS study. Blood. 2008;111:4022–4028
  34. Forrest DL, Trainor S, Brinkman RR, Barnett MJ, Hogge DE, Nevill TJ, et al. Cytogenetic and molecular responses to standard-dose imatinib in chronic myeloid leukemia are correlated with Sokal risk scores and duration of therapy but not trough imatinib plasma levels. Leuk Res. 2009;33:271–275
  35. Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, Blay JY, 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;41:1751–1757
  36. Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, Delbaldo C, et al. Prospective multicentric randomized phase III study of imatinib in patients with advanced gastrointestinal stromal tumors comparing interruption versus continuation of treatment beyond 1 year: the French Sarcoma Group. J Clin Oncol. 2007;25:1107–1113
  37. Le Cesne A, Ray-Coquard I, Bui B, Rios M, Adenis A, Bertucci F, et al. Continuous versus interruption of imatinib in responding patients with advanced GIST after three years of treatment: a prospective randomized phase III trial of the French Sarcoma Group [abstract]. J Clin Oncol. 2007;25:10005
  38. DeMatteo RP, Maki RG, Singer S, Gonen 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
  39. Gronchi A, Fiore M, Miselli F, Lagonigro MS, Coco P, Messina A, et al. Surgery of residual disease following molecular-targeted therapy with imatinib mesylate in advanced/metastatic GIST. Ann Surg. 2007;245:341–346
  40. Raut CP, Posner M, Desai J, Morgan JA, George S, Zahrieh D, 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
  41. Rutkowski P, Nowecki Z, Nyckowski P, Dziewirski W, Grzesiakowska U, Nasierowska-Guttmejer A, 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
  42. Peng B, Lloyd P, Schran H. Clinical pharmacokinetics of imatinib. Clin Pharmacokinet. 2005;44:879–894
  43. Burger H, van Tol H, Brok M, Wiemer EA, de Bruijn EA, Guetens G, et al. Chronic imatinib mesylate exposure leads to reduced intracellular drug accumulation by induction of the ABCG2 (BCRP) and ABCB1 (MDR1) drug transport pumps. Cancer Biol Ther. 2005;4:747–752
  44. Delbaldo C, Chatelut E, Re M, Deroussent A, Seronie-Vivien S, Jambu A, et al. Pharmacokinetic-pharmacodynamic relationships of imatinib and its main metabolite in patients with advanced gastrointestinal stromal tumors. Clin Cancer Res. 2006;12:6073–6078
  45. Prenen H, Guetens G, De Boeck G, Highley M, van Oosterom AT, de Bruijn EA. Everolimus alters imatinib blood partition in favour of the erythrocyte. J Pharm Pharmacol. 2006;58:1063–1066
  46. Ramanathan RK, Egorin MJ, Takimoto CH, Remick SC, Doroshow JH, LoRusso PA, et al. 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. 2008;26:563–569
  47. Gibbons J, Egorin MJ, Ramanathan RK, Fu P, Mulkerin DL, Shibata S, et al. Phase I and pharmacokinetic study of imatinib mesylate in patients with advanced malignancies and varying degrees of renal dysfunction: a study by the National Cancer Institute Organ Dysfunction Working Group. J Clin Oncol. 2008;26:570–576
  48. Gardner ER, Burger H, van Schaik RH, van Oosterom AT, de Bruijn EA, Guetens G, et al. Association of enzyme and transporter genotypes with the pharmacokinetics of imatinib. Clin Pharmacol Ther. 2006;80:192–201
  49. de Kogel CE, Schellens JH. Imatinib. Oncologist. 2007;12:1390–1394
  50. van Erp NP, Gelderblom H, Karlsson MO, Li J, Zhao M, Ouwerkerk J, et al. Influence of CYP3A4 inhibition on the steady-state pharmacokinetics of imatinib. Clin Cancer Res. 2007;13:7394–7400
  51. Judson I, Ma P, Peng B, Verweij J, Racine A, di Paola ED, 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;55:379–386
  52. Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural basis for activation of the receptor tyrosine kinase KIT by stem cell factor. Cell. 2007;130:323–334
  53. Liegl B, Kepten I, Le C, Zhu M, Demetri GD, Heinrich MC, et al. Heterogeneity of kinase inhibitor resistance mechanisms in GIST. J Pathol. 2008;216:64–74
  54. Taldone T, Gozman A, Maharaj R, Chiosis G. Targeting Hsp90: small-molecule inhibitors and their clinical development. Curr Opin Pharmacol. 2008;8:370–374
  55. Wagner AJ, Morgan JA, Chugh R, Rosen LS, George S, Gordon MS, et al. Results from phase 1 trial of IPI-504, a novel HSP90 inhibitor, in tyrosine kinase inhibitor-resistant GIST and other sarcomas [abstract]. J Clin Oncol. 2008;26:10503
  56. Prakash S, Sarran L, Socci N, DeMatteo RP, Eisenstat J, Greco AM, et al. Gastrointestinal stromal tumors in children and young adults: a clinicopathologic, molecular, and genomic study of 15 cases and review of the literature. J Pediatr Hematol Oncol. 2005;27:179–187
  57. Tarn C, Rink L, Merkel E, Flieder D, Pathak H, Koumbi D, et al. Insulin-like growth factor 1 receptor is a potential therapeutic target for gastrointestinal stromal tumors. Proc Natl Acad Sci U S A. 2008;105:8387–8392
  58. Bui BN, Blay J, Duffaud F, Hermine O, Hermine O, Le Cesne A. Preliminary efficacy and safety results of Masitinib administered front line in patients with advanced GIST (A phase II study [abstract]). J Clin Oncol. 2007;25:10025
  59. Joensuu H, De Braud F, Coco P, De Pas T, Putzu C, Spreafico C, et al. Phase II, open-label study of PTK787/ZK222584 for the treatment of metastatic gastrointestinal stromal tumors resistant to imatinib mesylate. Ann Oncol. 2008;19:173–177
  60. Von Mehren M, Reichardt P, Casali PG, Blay J, Debiec-Rychter M, Dumez H, et al. A phase I study of nilotinib alone and in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors—study update [abstract]. J Clin Oncol. 2007;25:10023
  61. Wiebe L, Kasza KE, Maki RG, D'Adamo DR, Chow WA, Wade JL, et al. Activity of sorafenib in patients with imatinib and sunitinib-resistant gastrointestinal stromal tumors: a phase II trial of the University of Chicago Phase II Consortium [abstract]. J Clin Oncol. 2008;26:10502

Disclosures R.S. Benjamin: Novartis (consulting, speaker's bureau)M. Debiec-Rychter: Novartis (research support)A. Le Cesne: Novartis (honoraria)S. Sleijfer: Pfizer, Novartis (research support)G.D. Demetri: Novartis, Pfizer, Ariad, Johnson & Johnson, Genentech, Plexxikon, Bristol Meyers Squibb Research, Infinity Pharmaceuticals, Ziopharm, Alnylam, Idera, Bayer, Serono, Amgen (research support, consulting)H. Joensuu: Novartis, Bayer-Schering Pharma (honoraria), testimony (Pfizer)P. Schöffski: Novartis (research funding and honoraria); Pfizer (research funding and honoraria)A. Poveda: none

PII: S0093-7754(09)00103-1

doi: 10.1053/j.seminoncol.2009.06.003

Seminars in Oncology
Volume 36, Issue 4 , Pages 302-311 , August 2009

Article Tools

* Image Usage & Resolution