苹果酸舒尼替尼二线治疗胃肠间质瘤的临床观察

发布时间：2018-08-06 09:17

【摘要】：背景胃肠道间质瘤(Gastrointestinal Stromal Tumor,GIST)是目前临床上最常见的间叶源性的肿瘤,占全部胃肠道肿瘤的1%~3%,而其中的原发部位以胃部最为常见(约为60%~70%),其次为小肠(大约为20%~30%),肠系膜、网膜及腹盆腔较为少见。据目前临床资料统计,每年我国的一百万人口中大约有10~20个新发的胃肠道间质瘤的病例出现。手术切除是可切除胃肠道间质瘤的标准治疗方法,经过手术切除后,约有40%~80%的GIST患者出现局部复发或远处的转移,5年生存率只有45%,其中转移型的患者1年生存率不到30%。靶向治疗药物格列卫(甲磺酸伊马替尼)对胃肠道间质瘤具有良好的疗效,但在治疗过程中出现63%的耐药率。苹果酸舒尼替尼(索坦)是目前唯一被批准作用于伊马替尼耐药的患者的二线药物,但是国内对此类的研究报道非常的少。目的探讨格列卫(甲磺酸伊马替尼)临床治疗失败后,二线靶向治疗药物索坦(苹果酸舒尼替尼)临床治疗胃肠道间质瘤的疗效及安全性。方法回顾性分析,收集2010年1月至2016年5月在安徽医科大学第一附属医院普外科收治的经病理和免疫组化确诊的GIST患者32例,所有的胃肠道间质瘤患者均在格列卫临床治疗失败后,用二线靶向治疗药物舒尼替尼治疗,以37.5mg/d的剂量,连续性给药服用。观察评估舒尼替尼的不良反应及患者的生存时间。结果1、本组共32例患者,其中男性患者有22例,女性患者有10例,男性∶女性为2.2∶1,男性患者多见,中位发病年龄为64岁,平均发病年龄为55.6岁,其中40~60岁的患者较多见。2、32例患者约在使用甲磺酸伊马替尼12~24个月出现了病情的进展,且在出现病情进展后继续服用甲磺酸伊马替尼3~6个月后,病情进展不能得到控制。3、32例患者在服用苹果酸舒尼替尼后,部分患者的肿瘤病灶增长停止或逐渐缩小,绝大部分患者的病情得到了控制或逐渐缓解。4、入组的32例患者在服用甲磺酸伊马替尼后,出现的不良反应为:水钠潴留、皮肤色素减退、皮肤过敏、血液毒性、心血管毒性等;在服用苹果酸舒尼替尼后,除了甲磺酸伊马替尼常见的不良反应外还有些特殊的不良反应,包括手足综合征、甲状腺功能减退、心脏毒性和高血压等。5、32例胃肠道间质瘤患者的1年和2年生存率分别为78%和46.9%;中位pfs为55周,中位os为96周;其中存活时间最长的患者已存活5年以上。结论1胃肠道间质瘤是一种较少见的胃肠道间叶源性肿瘤,其发病年龄在40~60岁之间居多,男性患者多于女性患者。2对于胃肠道间质瘤患者,术后予以甲磺酸伊马替尼靶向治疗,可以明显改善或延缓患者病情的进展,但是随着药物的使用,患者逐渐出现了药物的耐受性增强,继续服用甲磺酸伊马替尼效果不佳。3对于对甲磺酸伊马替尼耐药的胃肠道间质瘤患者,二线应用苹果酸舒尼替尼,能明显控制病情的进展,早期应用对于胃肠道间质瘤是有效的。4胃肠道间质瘤患者,服用甲磺酸舒尼替尼会出现不同的不良反应,但是不良反应尚能耐受。在予以苹果酸舒尼替尼治疗后不良反应有:白细胞减少、肝功能损害、甲状腺功能减退、血小板减少、手足综合征、食欲减退、乏力、口腔黏膜炎和皮肤毒性等,不良反应多为1~2级,而3~4级较少,无因不良反应出现停药的患者,症状均可控制。5对甲磺酸伊马替尼治疗耐药或治疗失败的胃肠道间质瘤患者,予以苹果酸舒尼替尼继续治疗,对于部分患者是可以使病情得到缓解的,甚至得到完全控制,故本研究对于一线靶向药物治疗失败的应用二线药物治疗胃肠道间质瘤的治疗有重要的参考价值。
[Abstract]:Gastrointestinal Stromal Tumor (GIST) is the most common mesenchymal tumor in the clinic, which accounts for the 1%~3% of all gastrointestinal tumors. The primary site is the most common (about 60%~70%) in the stomach, followed by the small intestine (about 20%~ 30%), mesentery, omentum and abdominal pelvic cavity are rare. According to the present clinical practice, the mesenteric, omentum and abdominal pelvic cavity are rare. Data statistics show that about one million of the one million people of our country have new cases of gastrointestinal stromal tumors each year. Surgical excision is a standard treatment for excision of gastrointestinal stromal tumors. After surgical excision, about 40%~80% of GIST patients have local recurrence or distant metastasis, and the 5 year survival rate is only 45%. The 1 year survival rate was less than the 30%. target therapy drug Greve (imatinib mesylate) had a good effect on gastrointestinal stromal tumors, but there was a 63% resistance rate during the treatment. Sulanitinib (Sultan) was the only second-line drug approved for imatinib resistance in patients, but the domestic study of this kind of drug Objective to investigate the efficacy and safety of the second line targeted drug Sultan (sulonate) in the clinical treatment of gastrointestinal stromal tumors after the failure of the clinical treatment of gleevin (imatinib mesylate). Methods a retrospective analysis was carried out in the Department of general surgery, the First Affiliated Hospital of Medical University Of Anhui, from January 2010 to May 2016. 32 patients with GIST were confirmed by pathology and immunohistochemistry. All the patients with gastrointestinal stromal tumors were treated with the second line target therapy, sulnitinib, with the dose of 37.5mg/d and continuous administration after the failure of gleguard's clinical treatment. The adverse reaction of sulninib and the patient's survival time were observed and evaluated. Results 1, 32 cases in this group. In the patients, there were 22 male patients, 10 female patients, male: 2.2: 1, male patients, the median age of 64 years and the average age of 55.6 years old, among which 40~60 years of age were seen in.2,32 patients about 12~24 months in the use of imatinib mesylate. After taking imatinib methanesulfonate for 3~6 months, the progression of the disease could not be controlled in.3,32 patients after taking suoninib malate, the tumor growth of some patients was stopped or gradually reduced, and the most of the patients were controlled or gradually relieved.4. The 32 patients in the group entered after taking imatinib mesylate. The adverse reactions are: water and sodium retention, skin pigmentation, skin allergy, hematological toxicity, cardiovascular toxicity, and some special adverse reactions, including hand foot syndrome, hypothyroidism, cardiac toxicity and hypertension, in addition to the common adverse reactions of imatinib methanesulfonate after taking sulonate malate, including hand foot syndrome, hypothyroidism, cardiac toxicity and hypertension. The 1 and 2 year survival rates of patients with stromal tumors were 78% and 46.9% respectively, median PFS was 55 weeks and median OS was 96 weeks; the longest surviving patients had survived for more than 5 years. Conclusion 1 gastrointestinal stromal tumors were a rare gastrointestinal lobar tumor with the majority of the age between 40~60 years, and the male patients were more than the female patients with.2. In patients with gastrointestinal stromal tumors, imatinib methanesulfonate targeted therapy after operation can significantly improve or delay the progression of the patient's condition, but with the use of the drug, the patient has gradually increased the tolerance of the drug, and the continued use of imatinib mesylate.3 for the imatinib mesylate resistant gastrointestinal stroma The tumor patients, the second line application of sulonnioil, can obviously control the progress of the disease. Early application of the gastrointestinal stromal tumor is an effective.4 gastrointestinal stromal tumor, taking suloninionate may have different adverse reactions, but the adverse reactions are still tolerable. Cytopenia, impairment of liver function, hypothyroidism, thrombocytopenia, hand foot syndrome, anorexia, asthenia, oral mucositis and skin toxicity and so on. Adverse reactions are mostly 1~2, and 3~4 is less, and there are no patients who have been stopped by adverse reactions, and the symptoms are controlled by.5 against imatinib in the treatment of drug resistance or the failure of the gastrointestinal tract. The patients with stromal tumors are treated with sugate malate, which can be relieved and even completely controlled for some patients. Therefore, this study is of important reference value for the treatment of gastrointestinal stromal tumors by the second line drugs for the failure of the first line targeting drug therapy.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735

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