發(fā)布時間：2018-07-04 11:34

  本文選題：胃腸道間質(zhì)瘤 + 分子靶向治療��； 參考：《吉林大學(xué)》2017年碩士論文

【摘要】：背景與目的:胃腸道間質(zhì)瘤(GISTs)是消化道最常見的間葉源性腫瘤,伊馬替尼為晚期或轉(zhuǎn)移的GISTs一線藥物,隨著伊馬替尼耐藥和不耐受問題的出現(xiàn),舒尼替尼作為二線替代藥物被用于臨床。舒尼替尼尚未一線應(yīng)用于GISTs治療,本研究對56例2周內(nèi)出現(xiàn)不可耐受伊馬替尼副作用而應(yīng)用舒尼替尼治療的GISTs患者臨床資料進(jìn)行回顧性分析對比,以評估舒尼替尼一線用藥的臨床療效及安全性。方法:統(tǒng)計2012年1月至2015年1月間我校附屬醫(yī)院收治的GISTs患者病歷資料,并全程隨訪2年,填寫調(diào)查表。采用Choi標(biāo)準(zhǔn)對入組患者進(jìn)行客觀療效評價,對生存情況用1年OS、PFS,2年OS、PFS以及中位OS、PFS進(jìn)行比較,并分別記錄各組治療相關(guān)不良事件的發(fā)生情況,對所獲得的臨床資料依材料類別,分別行卡方檢驗、非參數(shù)檢驗以及Kaplan-Meier法繪制生存曲線等。結(jié)果:1.患者的基本狀況比較:共統(tǒng)計124例GISTs患者,舒尼替尼組共56例,男性34例,女性22例,中位年齡為57歲,初診高危組9人,中危組15人,低危組32人,Ⅲ期患者24例,Ⅳ期32例,ECOG體能評分為0分24人,1分26人,2分6人。伊馬替尼組共68例,其中男性42例,女性26例,中位年齡為54歲,初診高危組13人,中危組20人,低危組35人,Ⅲ期患者32例,Ⅳ期患者36例,ECOG體能評分為0分33人,1分22人,2分13人。2.客觀療效分析:用藥3個月時評估各組客觀療效,其中舒尼替尼組完全緩解(CR)3例(5.36%),部分緩解(PR)26人(46.43%),疾病穩(wěn)定(SD)17人(30.36%),疾病進(jìn)展(PD)10人(17.86%)。伊馬替尼組完全緩解(CR)1例(1.47%),部分緩解(PR)31人(45.59%),疾病穩(wěn)定(SD)22人(32.35%),疾病進(jìn)展(PD)14人(20.59%)。舒尼替尼組ORR(CR+PR)及DCR(CR+PR+SD)略高于伊馬替尼組,但兩者無顯著性差別,ORR分別為49.15%和47.05%,p=0.600,DCR分別是82.14%和79.41%,p=0.702。3.生存情況比較:舒尼替尼組的1年OS及PFS均略低于伊馬替尼組,但兩者間無顯著性差異。1年OS%分別為80.35%(45/56)及82.35%(56/68),P=0.776。1年P(guān)FS%分別為58.93%(33/56)及61.76%(42/68),p=0.748。舒尼替尼組的2年OS及PFS均明顯低于伊馬替尼組,具有顯著性差異。2年OS%分別為44.64%(25/56)及67.65%(46/68),p=0.010。2年P(guān)FS%分別為23.21%(13/56)及41.17%(28/68),p=0.010。截止到隨訪結(jié)束,舒尼替尼組中位OS為19.4個月,中位PFS13.9為,伊馬替尼組中位OS未達(dá)到,中位PFS為20.1個月。4.治療相關(guān)不良事件:舒尼替尼組所有患者(100%)均出現(xiàn)不同級別的治療相關(guān)不良事件(adverse events,AEs)。其中3-4級不良反應(yīng)發(fā)生率47.8%,主要表現(xiàn)為疲勞(10%),其次為高血壓(8%),其他為腹瀉(5%)、手足綜合征(5%)等,此外尚有一些不常見的AEs,如心臟不良事件(1%),甲狀腺功能減退(2%)等。伊馬替尼組97.3%患者出現(xiàn)不同級別的AEs,其中3-4級不良反應(yīng)發(fā)生率為20.5%,最常出現(xiàn)的是中性粒細(xì)胞減少(6.8%),其次為消化道出血(4.1%),其他比較常見的皮疹(2.7%)、肝功能損傷(2.7%)等。5.影響舒尼替尼組的生存因素:臨床分期及危險度分級與預(yù)后密切相關(guān)。(1)Ⅲ期患者1年OS、PFS及2年OS、FPS均高于Ⅳ期患者。1年OS%分別為91.67%(22/24)及71.88%(23/32),p=0.031。1年P(guān)FS%分別為70.83%(17/24)及50.00%(16/32),p=0.031。2年OS%分別為62.50%(15/24)及31.25%(10/32),p=0.020。2年P(guān)FS%分別為37.50%(9/24)及12.50%(4/32),p=0.029。(2)低危組患者1年OS、PFS均高于高危組及中危組患者。高、中、低危三組患者1年OS%分別為55.56%(5/9)、66.67%(10/15)及93.75%(30/32),高、低危組相較p=0.004,中、低危組相較p=0.015,均具有統(tǒng)計學(xué)差異。1年P(guān)FS%分別為22.22%(2/9)、40.00%(6/15)及78.13%(25/32),高、低危組相較p=0.002,中、低危組相較p=0.010,均具有統(tǒng)計學(xué)差異。低危組患者2年OS、PFS均高于高危組及低危組患者。高、中、低危三組患者2年OS%分別為11.11%(1/9)、26.67%(4/15)及62.50%(20/32),高、低危組相較p=0.006,中、低危組相較p=0.022,均具有統(tǒng)計學(xué)差異。2年P(guān)FS%分別為0%(0/9)、6.67%(1/15)及34.38%(11/32),高、低危組相較p=0.040,中、低危組相較p=0.028,均具有統(tǒng)計學(xué)差異。結(jié)論:1.舒尼替尼一線應(yīng)用于胃腸道間質(zhì)瘤的客觀控制率與伊馬替尼相近,2年生存率低于伊馬替尼。2.舒尼替尼一線治療胃腸道間質(zhì)瘤,Ⅲ期客觀控制率高于Ⅳ期,低危組高于中、高危組。3.舒尼替尼一線應(yīng)用于胃腸道間質(zhì)瘤不良事件較伊馬替尼發(fā)生率高,主要表現(xiàn)為疲勞、高血壓、腹瀉、手足綜合征等。
[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.
【學(xué)位授予單位】：吉林大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R735

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