Onkologie. 2015:9(2):88-92

Targeted therapy based treatment of gastrointestinal stromal tumors

Beatrix Bencsiková
Klinika komplexní onkologické péče, Masarykův onkologický ústav Brno

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of gastrointestinal tract. Oncogenic activating mutations

in the receptor tyrosine kinases, KIT (75–80 %) and platelet- derived growth factor receptor alpha (PDGFRA, 10 %) play a crucial

role in the molecular pathogenesis of GIST. Complete surgical resection is the standard treatment for localized GISTs, however, recurrence

is observed in approximately a third of patients 2 years following resection. Better treatment strategies and targeted therapies

have improved survival rates for patients with GIST significantly. Imatinib, the receptor tyrosine kinase inhibitor, has revolutionized the

therapeutic landscape for GIST patients and remains the mainstay first-line clinical option for both unresectable and advanced GISTs,

as well as for adjuvant treatment after resection of high risk GISTs. Sunitinib is indicated as second-line therapy. Regorafenib has been

approved recently as third-line treatment of patients who progressed on or are intolerant to prior imatinib and sunitinib. Early identification

of patients with suboptimal response to therapy and treatment failure, as well as intolerable toxicities, is an important issue of

a multidisciplinary personalized treatment of patients with GIST.

Keywords: gastrointestinal stromal tumors, targeted therapy, imatinib, sunitinib, regorafenib

Published: April 10, 2015  Show citation

ACS AIP APA ASA Harvard Chicago Chicago Notes IEEE ISO690 MLA NLM Turabian Vancouver
Bencsiková B. Targeted therapy based treatment of gastrointestinal stromal tumors. Onkologie. 2015;9(2):88-92.
Download citation

References

  1. Daum O, Sedivcova M. 2014. [Gastrointestinal stromal tumor (GIST): Advances in 2013]. Ceskoslovenska patologie 50: 76-80. Go to PubMed...
  2. Sircar K, Hewlett BR, Huizinga JD, Chorneyko K, Berezin I, Riddell RH. 1999. Interstitial cells of Cajal as precursors of gastrointestinal stromal tumors. The American journal of surgical pathology 23: 377-89. Go to original source... Go to PubMed...
  3. Lee HT, Hennig GW, Fleming NW, Keef KD, Spencer NJ, et al. 2007. The mechanism and spread of pacemaker activity through myenteric interstitial cells of Cajal in human small intestine. Gastroenterology 132: 1852-1865. Go to original source... Go to PubMed...
  4. Pappo AS, Janeway KA. 2009. Pediatric gastrointestinal stromal tumors. Hematology/oncology clinics of North America 23: 15-34. Go to original source... Go to PubMed...
  5. Miettinen M, Sobin LH, Lasota J. 2005. Gastrointestinal stromal tumors of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 1765 cases with long-term follow-up. The American journal of surgical pathology 29: 52-68. Go to original source... Go to PubMed...
  6. Corless CL, Heinrich MC. 2008. Molecular pathobiology of gastrointestinal stromal sarcomas. Annual review of pathology 3: 557-586. Go to original source... Go to PubMed...
  7. Heinrich MC, Corless CL, Demetri GD, Blanke CD, von Mehren M, et al. 2003. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 21: 4342-4349. Go to original source... Go to PubMed...
  8. Cameron S, Schaefer IM, Schwoerer H, Ramadori G. 2011. Ten Years of Treatment with 400 mg Imatinib per Day in a Case of Advanced Gastrointestinal Stromal Tumor. Case reports in oncology 4: 505-511. Go to original source... Go to PubMed...
  9. Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, et al. 2012. One vs three years of adjuvant imatinib for operable gastrointestinal stromal tumor: a randomized trial. Jama 307: 1265-1272. Go to original source... Go to PubMed...
  10. 2012. Gastrointestinal stromal tumors: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO 23 Suppl 7: vii49-55
  11. Dematteo RP, Ballman KV, Antonescu CR, Maki RG, Pisters PW, et al. 2009. Adjuvant imatinib mesylate after resection of localised, primary gastrointestinal stromal tumour: a randomised, double-blind, placebo-controlled trial. Lancet 373: 1097-1104. Go to original source... Go to PubMed...
  12. Joensuu H, Vehtari A, Riihimaki J, Nishida T, Steigen SE, et al. 2012. Risk of recurrence of gastrointestinal stromal tumour after surgery: an analysis of pooled population-based cohorts. The lancet oncology 13: 265-274. Go to original source... Go to PubMed...
  13. Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J. 2001. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. The American journal of surgical pathology 25: 1121-1133. Go to original source... Go to PubMed...
  14. Miettinen M, Kopczynski J, Makhlouf HR, Sarlomo-Rikala M, Gyorffy H, et al. 2003. Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. The American journal of surgical pathology 27: 625-641. Go to original source... Go to PubMed...
  15. Miettinen M, Makhlouf H, Sobin LH, Lasota J. 2006. Gastrointestinal stromal tumors of the jejunum and ileum: a clinicopathologic, immunohistochemical, and molecular genetic study of 906 cases before imatinib with long-term follow-up. The American journal of surgical pathology 30: 477-489. Go to original source... Go to PubMed...
  16. Huss S, Kunstlinger H, Wardelmann E, Kleine MA, Binot E, et al. 2013. A subset of gastrointestinal stromal tumors previously regarded as wild-type tumors carries somatic activating mutations in KIT exon 8 (p.D419del). Modern pathology: an official journal of the United States and Canadian Academy of Pathology, Inc 26: 1004-1012. Go to original source... Go to PubMed...
  17. Joensuu H, Roberts PJ, Sarlomo-Rikala M, Andersson LC, Tervahartiala P, et al. 2001. Effect of the tyrosine kinase inhibitor STI571 in a patient with a metastatic gastrointestinal stromal tumor. The New England journal of medicine 344: 1052-1056. Go to original source... Go to PubMed...
  18. Van Glabbeke M, Verweij J, Casali PG, Le Cesne A, Hohenberger P, et al. 2005. 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. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 23: 5795-5804. Go to original source... Go to PubMed...
  19. Zalcberg JR, Verweij J, Casali PG, Le Cesne A, Reichardt P, et al. 2005. 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 41: 1751-1757. Go to original source... Go to PubMed...
  20. Blay JY, Le Cesne A, Ray-Coquard I, Bui B, Duffaud F, et al. 2007. 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. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 25: 1107-1113. Go to original source... Go to PubMed...
  21. Corless CL, Fletcher JA, Heinrich MC. 2004. Biology of gastrointestinal stromal tumors. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 22: 3813-3825. Go to original source... Go to PubMed...
  22. Demetri GD, van Oosterom AT, Garrett CR, Blackstein ME, Shah MH, et al. 2006. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368: 1329-1338. Go to original source... Go to PubMed...
  23. George S, Blay JY, Casali PG, Le Cesne A, Stephenson P, et al. 2009. Clinical evaluation of continuous daily dosing of sunitinib malate in patients with advanced gastrointestinal stromal tumour after imatinib failure. Eur J Cancer 45: 1959-1968. Go to original source... Go to PubMed...
  24. Demetri GD, Reichardt P, Kang YK, Blay JY, Rutkowski P, et al. 2013. Efficacy and safety of regorafenib for advanced gastrointestinal stromal tumours after failure of imatinib and sunitinib (GRID): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 381: 295-302. Go to original source... Go to PubMed...
  25. Blanke CD, Demetri GD, von Mehren M, Heinrich MC, Eisenberg B, et al. 2008. 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. Journal of clinical oncology: official journal of the American Society of Clinical Oncology 26: 620-625. Go to original source... Go to PubMed...
  26. Demetri GD, Garrett CR, Schoffski P, Shah MH, Verweij J, et al. 2012. Complete longitudinal analyses of the randomized, placebo-controlled, phase III trial of sunitinib in patients with gastrointestinal stromal tumor following imatinib failure. Clinical cancer research: an official journal of the American Association for Cancer Research 18: 3170-3179. Go to original source... Go to PubMed...
  27. Schoffski P, Reichardt P, Blay JY, Dumez H, Morgan JA, et al. 2010. A phase I-II study of everolimus (RAD001) in combination with imatinib in patients with imatinib-resistant gastrointestinal stromal tumors. Annals of oncology: official journal of the European Society for Medical Oncology/ESMO 21: 1990-1998. Go to original source... Go to PubMed...
  28. Richardson AL, Iglehart JD. 2012. BEAMing up personalized medicine: mutation detection in blood. Clinical cancer research: an official journal of the American Association for Cancer Research 18: 3209-3211. Go to original source... Go to PubMed...
  29. Lasota J, Wang Z, Kim SY, Helman L, Miettinen M. 2013. Expression of the receptor for type i insulin-like growth factor (IGF1R) in gastrointestinal stromal tumors: an immunohistochemical study of 1078 cases with diagnostic and therapeutic implications. The American journal of surgical pathology 37: 114-119. Go to original source... Go to PubMed...




Oncology

Madam, Sir,
please be aware that the website on which you intend to enter, not the general public because it contains technical information about medicines, including advertisements relating to medicinal products. This information and communication professionals are solely under §2 of the Act n.40/1995 Coll. Is active persons authorized to prescribe or supply (hereinafter expert).
Take note that if you are not an expert, you run the risk of danger to their health or the health of other persons, if you the obtained information improperly understood or interpreted, and especially advertising which may be part of this site, or whether you used it for self-diagnosis or medical treatment, whether in relation to each other in person or in relation to others.

I declare:

  1. that I have met the above instruction
  2. I'm an expert within the meaning of the Act n.40/1995 Coll. the regulation of advertising, as amended, and I am aware of the risks that would be a person other than the expert input to these sites exhibited


No

Yes

If your statement is not true, please be aware
that brings the risk of danger to their health or the health of others.