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GIST As the Model of Paradigm Shift Towards Targeted Therapy of Solid Tumors: Update and Perspective on Trial Design

  • Jaap Verweij
  • Caroline Seynaeve
  • Stefan Sleijfer
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 610)

Gastrointestinal Stroma Tumors — or GIST — are the most common gastrointestinal (GI) sarcomas, and were only recently identified as a distinct clinical and histopathologic entity (Corless, Fletcher and Heinrich 2004). GIST have an incidence of 14.5 per million annually (comparable with chronic myeloid leukemia), and a prevalence of 129 per million (Nilsson, Bumming, Meis-Kindblom, Odén, Dortok, Bengt, Sablinska and Kindblom 2005). They constitute 0.2 percent of all GI tumors, but 80 percent of GI sarcomas. Their highest incidence is in the 40- to 60- year age group.

Keywords

Chronic Myeloid Leukemia Soft Tissue Sarcoma Gastrointestinal Stromal Tumor Imatinib Mesylate Platelet Derive Growth Factor Receptor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Corless, C. L., Fletcher, J. A., Heinrich, M. C. (2004) Biology of Gastrointestinal stromal tumors. J. Clin. Oncol. 22, 3813–3825.PubMedCrossRefGoogle Scholar
  2. Debiec-Rychter, M., Sciot, R., Le Cesne, A., Schlemmer, M., Hohenberger, P., Van Oosterom, A., Blay, J.-Y., Leyvraz, S., Stul, M., Casali, P. (2006) KIT-mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumors. Eur. J. Cancer 42, 1093–1103.PubMedCrossRefGoogle Scholar
  3. Debiec-Rychter, M., Dumez, H., Judson, I., Wasag, B., Verweij, J., Brown, M., Dimitrijevic, S., Sciot, R., Stul, M., Vranck, H., Scurr, M., Hagemeijer, A., Van Glabbeke, M., and Van Oosterom, A. T. (2004) Use of c-KIT/PDGFRA mutational analysis to predict the clinical response to imatinib in patients with advanced gastrointestinal stromal tumors entered on phase I and II studies of the EORTC Soft Tissue and Bone Sarcoma Group. Eur. J. Cancer 40, 689–695.PubMedCrossRefGoogle Scholar
  4. Demetri, G. D., Von Mehren, M., Blanke, C. D., Van den Abbeele, A. D., Eisenberg, B., Roberts, P. J., Heinrich, M. C., Tuveson, D. A., Singer, S., Janicek, M., Fletcher, J. A., Silverman, S. G., Silberman, S. L., Capdeville, R., Kiese, B., Peng, B., Simitrijevic, S., Druker, B. J., Corless, C., Fletcher, C. D. M., Joensuu, H. (2002) Efficacy and safety of imatinib mesylate in advanced gastrointestinal stromal tumors. New. Engl. J. Med. 347, 472–480.PubMedCrossRefGoogle Scholar
  5. Demetri, G. D., Van Oosterom, A. T., Garrett, C. R., Blackstein, M. E., Shah, M. H., Verweij, J., McArthur, G., Judson, I. R., Heinrich, M. C., Morgan, J. A., Desai, J., Fletcher, C. D., George, S., Bello, C. L., Huang, X., Baum, C. M., Casali, P. G. (2006) Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumours after failure of imatinib: a randomized controlled trial. The Lancet 368, 1329–1338.CrossRefGoogle Scholar
  6. Heinrich, M. C., Corless, C. L., Demetri, G. D., Blanke, C. D., Von Mehren, M., Joensuu, H., McGreevy, L. S., Chen, C-J., Van den Abbeele, A. D., Bruker, B. J., Kiese, B., Eisenberg, B., Roberts, P. J., Singer, S., Fletcher, C. D. M., Silberman, S., Dimitrijevic, S., Fletcher, J. A. (2003) Kinase mutations and imatinib responses in patients with metastatic gastrointestinal stromal tumors. J. Clin. Oncol. 21, 4342–4349.PubMedCrossRefGoogle Scholar
  7. Heinrich, M. C., Maki R. G., Corless, C. L., Antonescu C. R., Fletcher, J. A., Fletcher, C. D., Huang, X., Baum, C. M., Demetri, G. D. (2006) Sunitinib response in imatinib-resistant GIST correlates with KIT and PDGFRA mutations. Proc. Am. Soc. Clin. Oncol. 24: abstract # 9502.Google Scholar
  8. Hirota, S., Isozaki, K., Moriyama, Y., Hashimoto, K., Nishida, T., Ishiguro, S., Kawano, K., Hanada, M., Kurata, A., Takeda, M., Muhammad, Tunio G., Matsuzawa, Y., Kanakura, Y., Shinomura, Y., Kitamura, Y. (1998) Gain-of-function mutations of c-KIT in human gastrointestinal tumors. Science 279, 577–580.PubMedCrossRefGoogle Scholar
  9. Le Cesne, A., Perol, D., Ray-Coquard, I., Bui, B., Duffaud, F., Rios, M., Coindre, J. M., Emile, J. F., Berthaud, P., Blay, J.-Y. (2005) Interruption of imatinib (IM) in GIST patients with advanced disease: updated results of the prospective French Sarcoma Group randomized phase III trial on survival and quality of life. Proc. Am. Soc. Clin. Oncol. 23, abstract # 9031.Google Scholar
  10. Le Cesne, A., Van Glabekke, M., Verweij, J., Casali, P., Zalcberg, J., Reichardt, P., Issels, R. D., Judson, I. R., Blay, J.-Y. (2006) Is a stable disease according to RECIST criteria a real stable disease in GIST patients treated with imatinib mesylate (IM) included in the intergroup EORTC/ISG/AGITG trial? Proc. Am. Soc. Clin. Oncol. 24, abstract # 9510.Google Scholar
  11. Mick, R., Crowley, J. J., Carroll, R. J. (2000) Phase II clinical trial design for non-cytotoxic anticancer agents for which time to disease progression is the primary endpoint. Control. Clin. Trials. 21, 343–359.PubMedCrossRefGoogle Scholar
  12. Nilsson, B., Bumming, P., Meis-Kindblom, J. M., Ode´ n, A., Dortok, A., Bengt, G., Sablinska, K., Kindblom, L-G. (2005) Gastrointestinal stromal tumors: the incidence, prevalence, clinical course, and prognostication in the preimatinib mesylate era. Cancer 103, 821–829.PubMedCrossRefGoogle Scholar
  13. Van Glabbeke, M., Verweij, J., Judson, I., Nielsen, O. S. (2002) Progression-free rate as the principal end point for phase II trials in soft tissue sarcomas. Eur. J. Cancer 38, 543–549.PubMedCrossRefGoogle Scholar
  14. Van Glabbeke, M., Verweij, J., Casali, P., Simes, J., Le Cesne, A., Reichardt, P., Issels, R., Judson, I., Van Oosterom, A., Blay, J.-Y. (2006) Predicting toxicities for patients with advanced gastrointestinal stromal tumors treated with imatinib: a study of the European Organisation for Research and Treatment of Cancer, the Italian Sarcoma Group, and the Australian Gastrointestinal trials group (EORTC-ISG-AGITG). Eur. J. Cancer 42, 2277–2285.PubMedCrossRefGoogle Scholar
  15. Van Glabbeke, M., Verweij, J., Casali, P. G., Le Cesne, A., Hohenberger, P., Ray-Coquard, I., Schlemmer, M., van Oosterom, A. T., Goldstein, D., Sciot, R., Hogendoorn, P., Brown, M., Bertulli, R., Judson, I. R. (2005) Initial and late resistance to Imatinib (IM) in advanced gastrointestinal stromal tumors (GIST) are predicted by different prognostic factors. An EORTC-AGITG study. J. Clin. Oncol. 23, 5795–5804.PubMedCrossRefGoogle Scholar
  16. Van Oosterom, A. T., Judson, I., Verweij J., Stroobants, S., Donato di Paola, E., Dimitrijevic, S., Martens, M., Webb, A., Sciot, R., Van Glabbeke, M., Silberman, S., Nielsen, O. S. (2001) Safety and efficacy of imatinib (STI571) in metastatic gastrointestinal stromal tumors: a phase I study. Lancet 358, 1421–1423.PubMedCrossRefGoogle Scholar
  17. Verweij, J., Van Oosterom, A., Blay, J.-Y., Judson, I., Rodenhuis, S., Van der Graaf, W., Radford, J., Le Cesne, A., Hogendoorn, P. C. W., Di Paola, E. D., Brown, M. and Nielsen, O. S. (2003) Imatinib mesylate (STI-571 Glivec, Gleevec) is an active agent for gastrointestinal stromal tumors, but does not yield responses in other soft tissue sarcomas that are unselected for a molecular target. Resultsfrom an EORTC Soft Tissue and Bone Sarcoma phase II study. Eur. J. Cancer 39, 2006–2011.PubMedCrossRefGoogle Scholar
  18. Verweij, J. and Van Glabbeke, M. (2006) Translating targets into treatment: Changes in trial methodology and treatment approaches for soft tissue sarcomas. ASCO Educational Book. pp 522–530.Google Scholar
  19. Verweij, J., Casali, P. G., Zalcberg, J., Le Cesne, A., Reichardt, P., Blay, J.-Y., Issels, R., Van Oosterom, A., Hogendoorn, P., Van Glabbeke, M., Bertulli, R. and Judson, I. (2004) Progression-free survival in gastrointestinal stromal tumors with high-dose imatinib: a randomized trial. Lancet 364, 1127–1134.PubMedCrossRefGoogle Scholar
  20. Zalcberg, J. R., Verweij, J., Casali, P. G., Le Cesne, A., Reichardt, P., Blay, J.-Y., Schlemmer, M., Van Glabbeke, M., Brown, M. and Judson, I. R. (2005) Outcome of patients with advanced gastrointestinal stromal tumors crossing over to a daily imatinib dose of 800 mg after progression on 400 mg. Eur. J. Cancer 41, 1751–1757.PubMedCrossRefGoogle Scholar

Copyright information

© Springer 2008

Authors and Affiliations

  • Jaap Verweij
    • 1
  • Caroline Seynaeve
    • 1
  • Stefan Sleijfer
    • 1
  1. 1.Daniel den Hoed Cancer Center, Department of Medical OncologyErasmus University Medical CenterThe Netherlands

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