Medizinische Universität Graz - Research portal
Selected Publication:
Ruehlinger, D.
Sequential treatment of a patient with metastatic gastrointestinal stromal tumor (GIST): A case report
[ Diplomarbeit ] Medical University of Graz; 2011. pp. 95
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- Authors Med Uni Graz:
- Advisor:
- Bauernhofer Thomas
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- Abstract:
- Until recently the prognosis for patients diagnosed with an unresectable GIST was very poor, as conventional chemotherapy and radiotherapy were inefficient in the treatment of this disease. Oncogenic mutations in genes encoding the two closely related tyrosine kinases c-KIT and PDGFRA have been recognized as the initiating features in 85-90% of GIST tumourigenesis. By targeting these auto-activated oncoproteins, imatinib and sunitinib are effective agents for the GIST treatment. Both compounds have been approved for the first- and second-line treatment, respectively. However, at some point of sequential GIST treatment, secondary mutations and consequent resistance to imatinib and sunitinib are likely to occur and present a major therapeutic challenge. Thus, novel multi-TKIs that target alternative spots in oncogenic KIT/PDGFRA become more and more important to sustain subsequent disease control in patients with advanced GIST. In the first segment of this diploma thesis, the pathology, a historical overview, relevant cyto-pathogenetic aspects, diagnosis, prognostic parameters of GIST as well as established and novel treatment options are presented in detail, according to the latest literature. The second segment of this diploma thesis demonstrates the case of a female patient first diagnosed with a c-KIT exon 9 mutated GIST in 2005. This patient received TKI treatment for three and a half years. Imatinib and sunitinib were effectively used as first- and second-line therapy. After disease progression, sequential treatment with nilotinib, sorafenib and, to our knowledge for the first time, with pazopanib has been initiated subsequently. While sorafenib and pazopanib resulted in disease stabilisation, nilotinib failed to do so. Observed adverse events were mild to moderate and the patient continued to work until 1 month before decease. In the following, epidemiologic and general information about GIST is presented as opening part of the first section of this thesis.