| Theme |
The State of the Art in Chemotherapy for Gastrointestinal Cancer |
| Title |
Clinical Efficacy of Tyrosine Kinase Inhibitors in Gastrointestinal Stromal Tumor Treatment |
| Author |
Kazuya Matsumoto |
Department of Gastroenterology, Aichi Cancer Center Hospital / Department of Gastroenterology, Tottori University, Faculty of Medicine |
| Author |
Akira Sawaki |
Department of Gastroenterology, Tottori University, Faculty of Medicine |
| [ Summary ] |
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal malignancies of the gastrointestinal (GI) tract. These tumors exhibit positive immunohistochemical reactions to KIT or CD34. A new era in cancer therapy dawned when gain-of-function mutations of the c-kit gene were discovered in a majority of GISTs and the tyrosine kinase inhibitor(TKI)imatinib was introduced for clinical practice. This drug caused marked tumor response in most patients with advanced GISTs. In Japan, imatinib is also used in adjuvant settings after surgery because of the positive results observed in randomized phase III trials. With prolonged treatment imatinib resistance can develop, most likely due to secondary c-kit mutations. In this situation the second-line treatment TKI sunitinib is well suited for patients with c-kit exon 9 mutations, or for patients without KIT／PDGFRA mutations (wild-type GIST). Sunitinib shows a lot of toxicities because it is multitargeted drug. In our hospital, dose reduction was carried out when patients suffered from symptomatic toxicity. Based on time to treatment failure and tumor response, sunitinib demonstrated similar efficacy to that previously reported in a Japanese phaseⅠ/II trial. It is hoped that appropriate management of side effects will produce improved treatment. |