Imatinib was proven to be effective for the adjuvant treatment of localized, surgically excised, gastrointestinal stromal tumors (GIST). Currently, there is proof that it is able to delay relapse and prolong survival. An effect on cure rate of localized GIST is still to be proven, given the shape of relapse-free survival curves, which apparently tend to overlap after 2-3 years from completion of the adjuvant period. Although observation for a longer follow-up is needed, attempts to prolong adjuvant therapy beyond the currently standard 3 years have been made and the results are awaited. However, the impact of more prolonged adjuvant intervals on secondary resistance is unknown, so that standard practice is still 3 years in most institutions. The adjuvant choice should be based on a rather precise identification of the relapse risk of the single patient, reserving treatment to the high-risk subgroups. The choice also should be personalized on the basis of genotype: generally, PDGFRA D842V mutated and wild-type GIST are excluded. Additional results from completed trials on a longer follow-up are awaited to further refine such "precision" decision-making. There are several instances in which part of the "adjuvant" treatment may be administered preoperatively, even on the face of a surgically resectable GIST, to make surgery more limited and/or safer.
"Based on this risk classification, all the patients with tumour rupture should be considered at high risk for recurrence  . Imatinib mesylate, a tyrosine kinase inhibitor, has been found to be beneficial after radical resective surgery of high-risk GISTs  . More recently, adjuvant therapy with imitinab has been used with wider indications, such as intermediate-risk tumours with size > 3 cm and primary tumours with rupture or perforation . "
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumor of the gastrointestinal tract. Soon after GIST was recognized as a tumor driven by a KIT or platelet-derived growth factor receptor mutation, it became the first solid tumor target for tyrosine kinase inhibitor therapies. More recently, alternative molecular mechanisms for GIST pathogenesis have been discovered. These are related to deficiencies in the succinate dehydrogenase complex, NF1-gene alterations in connection with neurofibromatosis type 1 tumor syndrome, and mutational activation of the BRAF oncogene in very rare cases.
Gastroenterology clinics of North America 06/2013; 42(2):399-415. DOI:10.1016/j.gtc.2013.01.001 · 2.82 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Introduction:
Epithelial ovarian cancer (EOC) is the leading cause of gynaecologic cancer death. Although in some cases initial treatment is effective, most of the women diagnosed with EOC will probably need medical treatment for their disease. There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent EOC, and targeted therapy with tyrosine kinase inhibitors (TKIs) has continued to be an area of active research and development in this setting.
This review summarises the available evidence on the use of TKIs in the clinical management of women with EOC. This article consists of material obtained via Medline, PubMed and EMBASE literature searches up to March 2013.
Several Phase I/II and III trials evaluated TKIs in EOC; however, it is difficult to draw conclusions on the efficacy of TKI regimens in these patients. TKIs seem to be better tolerated than conventional chemotherapy with a different toxicity profile. A better understanding of the signalling pathways, the toxicity profiles, the potential pharmacokinetic interactions as well as the identification of predictive biomarkers are needed to better identify a targeted patient population before these agents become part of routine treatment.
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