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.
This is a preview of subscription content, log in via an institution to check access.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
Preview
Unable to display preview. Download preview PDF.
References
Corless, C. L., Fletcher, J. A., Heinrich, M. C. (2004) Biology of Gastrointestinal stromal tumors. J. Clin. Oncol. 22, 3813–3825.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2008 Springer
About this chapter
Cite this chapter
Verweij, J., Seynaeve, C., Sleijfer, S. (2008). GIST As the Model of Paradigm Shift Towards Targeted Therapy of Solid Tumors: Update and Perspective on Trial Design. In: Colotta, F., Mantovani, A. (eds) Targeted Therapies in Cancer. Advances in Experimental Medicine and Biology, vol 610. Springer, New York, NY. https://doi.org/10.1007/978-0-387-73898-7_11
Download citation
DOI: https://doi.org/10.1007/978-0-387-73898-7_11
Publisher Name: Springer, New York, NY
Print ISBN: 978-0-387-73897-0
Online ISBN: 978-0-387-73898-7
eBook Packages: Biomedical and Life SciencesBiomedical and Life Sciences (R0)