Surgical resection of recurrent gastrointestinal stromal tumor after interruption of long-term nilotinib therapy.

Surg Case Rep 2016 Dec 19;2(1):137. Epub 2016 Nov 19.

Department of Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita, Osaka, 565-0871, Japan.

Background: Nilotinib inhibits the tyrosine kinase activities of ABL1/BCR-ABL1, KIT, and platelet-derived growth factor receptors (PDGFRs). The results of a phase III clinical trial indicated that nilotinib could not be recommended for broad use as first-line therapy for gastrointestinal stromal tumor (GIST). However, some clinical studies have reported the effectiveness of nilotinib. We report here the cases of two patients who underwent surgical resections of nilotinib-resistant lesions after long-term nilotinib administration.

Case Presentation: Two Japanese female patients, aged 66 and 70 years, experienced peritoneal recurrence of intestinal GIST several years after surgery. Both were registered in the ENESTg1 trial and received nilotinib therapy. Although they continued nilotinib administration with a partial response according to the protocol, nilotinib-resistant lesions, which were diagnosed as focally progressive disease, developed and complete surgical resection was performed. Pathological examination revealed that the tumors were composed of viable KIT-positive spindle cells, and the recurrent tumors were diagnosed as nilotinib-resistant GIST. In gene mutation analysis, a secondary KIT gene mutation was detected in one case. Both patients have survived more than 5 years after the first surgery.

Conclusions: Of patients who were registered in this trial, we have encountered two patients with long-term effects after nilotinib administration. Moreover, secondary mutations in the KIT gene, similar to those involved in resistance to imatinib, might be involved in resistance to nilotinib.

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http://dx.doi.org/10.1186/s40792-016-0266-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5116018PMC
December 2016
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