舒尼替尼一线治疗胃肠道间质瘤56例的临床研究

发布时间：2018-07-04 11:34

本文选题：胃肠道间质瘤 + 分子靶向治疗　；参考：《吉林大学》2017年硕士论文

【摘要】：背景与目的:胃肠道间质瘤(GISTs)是消化道最常见的间叶源性肿瘤,伊马替尼为晚期或转移的GISTs一线药物,随着伊马替尼耐药和不耐受问题的出现,舒尼替尼作为二线替代药物被用于临床。舒尼替尼尚未一线应用于GISTs治疗,本研究对56例2周内出现不可耐受伊马替尼副作用而应用舒尼替尼治疗的GISTs患者临床资料进行回顾性分析对比,以评估舒尼替尼一线用药的临床疗效及安全性。方法:统计2012年1月至2015年1月间我校附属医院收治的GISTs患者病历资料,并全程随访2年,填写调查表。采用Choi标准对入组患者进行客观疗效评价,对生存情况用1年OS、PFS,2年OS、PFS以及中位OS、PFS进行比较,并分别记录各组治疗相关不良事件的发生情况,对所获得的临床资料依材料类别,分别行卡方检验、非参数检验以及Kaplan-Meier法绘制生存曲线等。结果:1.患者的基本状况比较:共统计124例GISTs患者,舒尼替尼组共56例,男性34例,女性22例,中位年龄为57岁,初诊高危组9人,中危组15人,低危组32人,Ⅲ期患者24例,Ⅳ期32例,ECOG体能评分为0分24人,1分26人,2分6人。伊马替尼组共68例,其中男性42例,女性26例,中位年龄为54岁,初诊高危组13人,中危组20人,低危组35人,Ⅲ期患者32例,Ⅳ期患者36例,ECOG体能评分为0分33人,1分22人,2分13人。2.客观疗效分析:用药3个月时评估各组客观疗效,其中舒尼替尼组完全缓解(CR)3例(5.36%),部分缓解(PR)26人(46.43%),疾病稳定(SD)17人(30.36%),疾病进展(PD)10人(17.86%)。伊马替尼组完全缓解(CR)1例(1.47%),部分缓解(PR)31人(45.59%),疾病稳定(SD)22人(32.35%),疾病进展(PD)14人(20.59%)。舒尼替尼组ORR(CR+PR)及DCR(CR+PR+SD)略高于伊马替尼组,但两者无显著性差别,ORR分别为49.15%和47.05%,p=0.600,DCR分别是82.14%和79.41%,p=0.702。3.生存情况比较:舒尼替尼组的1年OS及PFS均略低于伊马替尼组,但两者间无显著性差异。1年OS%分别为80.35%(45/56)及82.35%(56/68),P=0.776。1年PFS%分别为58.93%(33/56)及61.76%(42/68),p=0.748。舒尼替尼组的2年OS及PFS均明显低于伊马替尼组,具有显著性差异。2年OS%分别为44.64%(25/56)及67.65%(46/68),p=0.010。2年PFS%分别为23.21%(13/56)及41.17%(28/68),p=0.010。截止到随访结束,舒尼替尼组中位OS为19.4个月,中位PFS13.9为,伊马替尼组中位OS未达到,中位PFS为20.1个月。4.治疗相关不良事件:舒尼替尼组所有患者(100%)均出现不同级别的治疗相关不良事件(adverse events,AEs)。其中3-4级不良反应发生率47.8%,主要表现为疲劳(10%),其次为高血压(8%),其他为腹泻(5%)、手足综合征(5%)等,此外尚有一些不常见的AEs,如心脏不良事件(1%),甲状腺功能减退(2%)等。伊马替尼组97.3%患者出现不同级别的AEs,其中3-4级不良反应发生率为20.5%,最常出现的是中性粒细胞减少(6.8%),其次为消化道出血(4.1%),其他比较常见的皮疹(2.7%)、肝功能损伤(2.7%)等。5.影响舒尼替尼组的生存因素:临床分期及危险度分级与预后密切相关。(1)Ⅲ期患者1年OS、PFS及2年OS、FPS均高于Ⅳ期患者。1年OS%分别为91.67%(22/24)及71.88%(23/32),p=0.031。1年PFS%分别为70.83%(17/24)及50.00%(16/32),p=0.031。2年OS%分别为62.50%(15/24)及31.25%(10/32),p=0.020。2年PFS%分别为37.50%(9/24)及12.50%(4/32),p=0.029。(2)低危组患者1年OS、PFS均高于高危组及中危组患者。高、中、低危三组患者1年OS%分别为55.56%(5/9)、66.67%(10/15)及93.75%(30/32),高、低危组相较p=0.004,中、低危组相较p=0.015,均具有统计学差异。1年PFS%分别为22.22%(2/9)、40.00%(6/15)及78.13%(25/32),高、低危组相较p=0.002,中、低危组相较p=0.010,均具有统计学差异。低危组患者2年OS、PFS均高于高危组及低危组患者。高、中、低危三组患者2年OS%分别为11.11%(1/9)、26.67%(4/15)及62.50%(20/32),高、低危组相较p=0.006,中、低危组相较p=0.022,均具有统计学差异。2年PFS%分别为0%(0/9)、6.67%(1/15)及34.38%(11/32),高、低危组相较p=0.040,中、低危组相较p=0.028,均具有统计学差异。结论:1.舒尼替尼一线应用于胃肠道间质瘤的客观控制率与伊马替尼相近,2年生存率低于伊马替尼。2.舒尼替尼一线治疗胃肠道间质瘤,Ⅲ期客观控制率高于Ⅳ期,低危组高于中、高危组。3.舒尼替尼一线应用于胃肠道间质瘤不良事件较伊马替尼发生率高,主要表现为疲劳、高血压、腹泻、手足综合征等。
[Abstract]:Background and objective: gastrointestinal stromal tumor (GISTs) is the most common mesenchymal tumor in the digestive tract. Imatinib is a advanced or metastatic GISTs first-line drug. With the emergence of imatinib resistance and intolerance, sulonitinib is used as a second-line replacement drug. Sulonitinik is not used in GISTs treatment. This study is a study of 56 A retrospective analysis and comparison of the clinical data of GISTs patients with the side effect of imatinib intolerance to the side effect of imatinib in 2 weeks was performed to evaluate the clinical efficacy and safety of the first line of sulinitinib. Methods: the data of patients with GISTs in the Affiliated Hospital of our school from January 2012 to January 2015 were collected and the whole course of follow-up was 2. Year, fill out the questionnaire. Use the Choi standard to evaluate the objective effect of the patients, and compare the survival situation with 1 years OS, PFS, 2 year OS, PFS and the middle OS, PFS, and record the occurrence of the adverse events related to the treatment of each group respectively. The clinical data are checked by chi square test, non parameter test and Kaplan according to the material category. -Meier method of survival curve and so on. Results: the basic status of 1. patients: a total of 124 cases of GISTs patients, a total of 56 cases of suninib, 34 men, 22 women, 57 years of age, 9 at high risk group, 15 in the middle risk group, 32 in the low risk group, 24 in stage III, 32 in stage IV, ECOG physical score of 24, 1 cents, equalization. There were 68 cases of Tanei group, including 42 male and 26 female, 54 years old, 13 at high risk group, 20 in middle risk group, 35 in low risk group, 32 in low risk group, 32 in stage III and 36 in stage IV, ECOG physical energy score was 0, 33, 1 score 22 and objective curative effect of 2 divide people. CR (5.36%), partial remission (PR) 26 (46.43%), disease stability (SD) 17 (30.36%), disease progression (PD) 10 (17.86%), imatinib group complete remission (CR) 1 cases (1.47%), partial remission (PR) 31 (45.59%), disease stability (SD) 22 people (PD), ORR (CR+PR) and DCR (CR+PR+SD) slightly higher than ima There was no significant difference between the two groups, but the ORR was 49.15% and 47.05%, p=0.600, and DCR were 82.14% and 79.41%, respectively, and p=0.702.3. survival was compared. The 1 year OS and PFS of the sulanitinib group were slightly lower than the imatinib group, but there was no significant difference between the two groups of 80.35% (45/56) and 82.35% (56/68), respectively, and 58.93% (3 respectively) for P=0.776.1 year PFS%. 3/56) and 61.76% (42/68). The 2 year OS and PFS in the p=0.748. suneinib group were significantly lower than the imatinib group. There were significant differences in.2 year OS% of 44.64% (25/56) and 67.65% (46/68). P=0.010.2 PFS% was 23.21% (13/56) and 41.17%, respectively, to the end of the follow-up. The median of the sulitinib group was 19.4 months. The median of the sulnitinib group was 19.4 months. The median OS of the imatinib group was not reached, and the median PFS was 20.1 months of.4. treatment related adverse events. All patients in the sulnitinib group (100%) had different levels of treatment related adverse events (adverse events, AEs). The 3-4 grade adverse reaction rate was 47.8%, the main manifestations were fatigue (10%), followed by hypertension (8%), and the others were diarrhea (5%). Foot syndrome (5%), in addition to some uncommon AEs, such as adverse cardiac events (1%), hypothyroidism (2%), and other 97.3% patients in the imatinib group, there were different levels of AEs, of which the incidence of grade 3-4 was 20.5%, the most frequent was neutrophils (6.8%), followed by gastrointestinal bleeding (4.1%), and the others were more common. The rash (2.7%), liver function injury (2.7%) and other.5. affected the survival factors of the sulnitinib group: the clinical stage and risk grade were closely related to the prognosis. (1) 1 years of OS, PFS and 2 year OS in stage III patients were higher than those of stage IV patients, OS% was 91.67% (22/24) and 71.88% (23/32) respectively, and p=0.031.1 PFS% was 70.83% (17/24) and 50%, respectively, respectively. For 1.2 years, OS% was 62.50% (15/24) and 31.25% (10/32), PFS% in p=0.020.2 was 37.50% (9/24) and 12.50% (4/32), p=0.029. (2) in low risk group was 1 years OS, and PFS was higher than that in high-risk group and middle risk group. High, middle, and low risk three groups were 55.56% (5/9), 66.67%, 93.75%, high, low risk group, middle and low risk group. Compared with p=0.015, there were statistical differences in.1 years PFS% 22.22% (2/9), 40% (6/15) and 78.13% (25/32), high, low risk group compared with p=0.002, low risk group compared with p=0.010, all with statistical difference. The low risk group patients 2 years OS, PFS are higher than the high-risk group and low risk group patients. High, middle, low risk three groups of 2 year OS% 11.11% (1/9), 26.67% ( 4/15) and 62.50% (20/32), high, low risk group compared with p=0.006, low risk group compared with p=0.022, all.2 PFS% was 0% (0/9), 6.67% (1/15) and 34.38% (11/32), high, lower risk group than p=0.040, middle, lower risk group than p=0.028, all have statistical difference. Conclusion: 1. suginib application in gastrointestinal stromal tumor objective control The rate of system was similar to imatinib. The 2 year survival rate was lower than the first line treatment of gastrointestinal stromal tumor with imatinib.2.. The objective control rate in stage III was higher than that in stage IV, and the low risk group was higher than that in the low risk group. The high risk group.3. suginib application in gastrointestinal stromal tumors was higher than imatinib, mainly characterized by fatigue, hypertension, diarrhea, and hands. Foot syndrome, etc.
【学位授予单位】：吉林大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735

【相似文献】