Surgical resection of recurrent gastrointestinal stromal tumor after interruption of long-term nilotinib therapy.
Surgical resection of recurrent gastrointestinal stromal tumor after interruption of long-term nilotinib therapy.
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DOI：
10.1186/s40792-016-0266-y
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发表时间：
2016-12
影响因子：
0.8
通讯作者：
Doki Y
中科院分区：
文献类型：
--
作者：
Sugase T;Takahashi T;Ishikawa T;Ichikawa H;Kanda T;Hirota S;Nakajima K;Tanaka K;Miyazaki Y;Makino T;Kurokawa Y;Yamasaki M;Takiguchi S;Wakai T;Mori M;Doki Y
尼洛替尼抑制ABL 1/BCR-ABL 1、KIT和血小板衍生生长因子受体（PDGFR）的酪氨酸激酶活性。一项III期临床试验结果表明，尼洛替尼不能被推荐作为胃肠道间质瘤（GIST）的一线治疗药物广泛使用。然而，一些临床研究报告了尼洛替尼的有效性。我们在此报告了2例长期使用尼洛替尼后接受手术切除尼洛替尼耐药病变的患者。两名日本女性患者，年龄分别为66岁和70岁，在手术后数年发生了肠GIST腹膜复发。两人均在ENESTg 1试验中注册并接受尼洛替尼治疗。尽管他们根据方案继续尼洛替尼给药并获得部分缓解，但发生了尼洛替尼耐药病变（诊断为局灶性进展性疾病），并进行了完全手术切除。病理检查显示肿瘤由活的KIT阳性梭形细胞组成，复发肿瘤被诊断为尼洛替尼耐药GIST。在基因突变分析中，在1例病例中检测到继发性KIT基因突变。两名患者在首次手术后均存活了5年以上。在本试验登记的患者中，我们遇到了2例尼洛替尼给药后出现长期效应的患者。此外，与伊马替尼耐药相关的KIT基因继发突变可能与尼洛替尼耐药相关。
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. 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. 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.