本文選題：培美曲塞 + 吉非替尼　； 參考：《鄭州大學》2016年碩士論文

【摘要】：背景與目的表皮生長因子受體-酪氨酸激酶受體抑制劑(epidermal growth factor receptor-tyrosine kinase inhibitor, EGFR-TKI)廣泛應用于臨床,療效顯著,被NCCN指南推薦用于伴EGFR突變陽性的非小細胞肺癌的一線治療。但EGFR-TKI靶向治療在中位8-16個月后不可避免的出現(xiàn)耐藥進展,目前獲得性耐藥后的后續(xù)治療方法尚無標準方案。為探求更優(yōu)的后續(xù)治療策略,本文選取EGFR-TKI最終獲得性耐藥的晚期肺腺癌患者,后續(xù)治療采用培美曲塞或培美曲塞聯(lián)合吉非替尼,比較兩者臨床療效及安全性。方法1 入組我院2012年3月—2014年10月期間收治的伴EGFR突變陽性的晚期肺腺癌患者62例,既往一線行含鉑雙藥化療,接受EGFR-TKI一線維持或二線治療后獲得性耐藥,病情緩慢進展。2隨機分為聯(lián)合組和化療組,化療組30例給予培美曲塞500mg/m2,靜脈滴注,dl,每21天一個周期,直至腫瘤進展或不良反應無法耐受。聯(lián)合組32例給予培美曲塞500mg/m2,靜脈滴注,d1,每21天一個周期,吉非替尼250mg, qd,口服,直至腫瘤進展或不良反應無法耐受。3以客觀有效率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、不良反應、無進展生存期(progression-free survival, PFS)、總生存期(overallsurvival, OS)為評價指標,比較兩組間的差異。結(jié)果1近期療效全部入組62例病例均完成2個周期化療,可評價療效。聯(lián)合組ORR為63.3%,化療組ORR為33.3%,聯(lián)合組ORR高于化療組,差異有統(tǒng)計學意義(χ=4.218,P=0.040),聯(lián)合組DCR為84.4%,化療組DCR為80.0%,差異無統(tǒng)計學意義(χ2=0.203,P=0.652)。2遠期療效從接受本次治療第1日開始計算,隨訪時間截止至2015年7月。聯(lián)合組的中位PFS為8.0月,化療組中位PFS為6.3月,聯(lián)合組中位PFS高于化療組,差異有統(tǒng)計學意義(χ2=8.063,P=0.005),聯(lián)合組中位OS為12.7月,化療組中位OS為10.0月,差異無統(tǒng)計學意義(χ2=3.170,P=0.075)。3不良反應主要表現(xiàn)在血液系統(tǒng)毒性和胃腸道反應,1-2級多見,3-4級發(fā)生率低。與化療組相比,聯(lián)合組白細胞減少(χ2=4.089,P=0.043)、皮疹(χ2=5.858,P=0.027)發(fā)生率高。不良反應經(jīng)對癥處理緩解,未影響后續(xù)化療。結(jié)論晚期肺腺癌患者EGFR-TKI獲得性耐藥后,后續(xù)治療采用培美曲塞聯(lián)合吉非替尼治療較單用培美曲塞可獲得更高的ORR,中位PFS延長,不良反應可耐受,結(jié)果尚需大樣本資料驗證。
[Abstract]:Background & objective Epidermal growth factor receptor-tyrosine kinase receptor inhibitor (EGFR-TKI) has been widely used in clinical practice. It is recommended by NCCN guidelines for first-line treatment of non-small cell lung cancer with EGFR mutation positive. However, the progress of drug resistance is inevitable after the median 8-16 months of EGFR-TKI targeted therapy, and there is no standard protocol for subsequent treatment after acquired drug resistance. In order to find a better strategy for follow-up treatment, we selected advanced lung adenocarcinoma patients with EGFR-TKI final acquired drug resistance. The patients were treated with pemetrexed or pemetrexil combined with gefitinib. The clinical efficacy and safety of the two methods were compared. Methods from March 2012 to October 2014, 62 cases of advanced lung adenocarcinoma with EGFR mutation positive were treated in our hospital. The patients were treated with chemotherapy containing platinum and acquired drug resistance after first-line maintenance or second-line EGFR-TKI therapy. The patients in the chemotherapy group were treated with pemetrexil 500 mg / m ~ (2), intravenous drip of dl every 21 days, until tumor progression or adverse reactions were intolerable. 32 patients in the combined group were given pemetrexide 500 mg / m2, intravenous drip for d 1 every 21 days, gifitinib 250 mg, QD, oral, until tumor progression or adverse reactions could not tolerate 3. 3 to achieve objective effective rate of objective response rate.orr, disease control rate.DCRs, adverse reactions. Progression-free survival, PFSs, total survival time over survival (OS) were used to evaluate the difference between the two groups. Results 1 two cycles of chemotherapy were completed in all 62 patients, and the curative effect could be evaluated. The ORR of the combined group was 63.3 and the ORR of the chemotherapy group was 33.3. The ORR of the combined group was higher than that of the chemotherapy group (蠂 ~ (4) 218), the DCR of the combined group was 84.4m, and the DCR of the chemotherapy group was 80.00.There was no significant difference (蠂 ~ (2 +) 0.20 ~ (3) P 0.6522.2. the long-term curative effect was calculated from the first day of the treatment. The follow-up period ended in July 2015. The median PFS of the combined group was 8.0 months and the median PFS of the chemotherapy group was 6.3 months. The median PFS of the combined group was higher than that of the chemotherapy group, and the difference was statistically significant (蠂 ~ 2 / 8.063P ~ + 0.005). The median OS of the combined group was 12.7 months, and the median OS of the chemotherapy group was 10.0 months. There was no significant difference between them (蠂 ~ 2 / 3.170) (蠂 ~ 2 = 3.170). The main adverse reactions were blood system toxicity and gastrointestinal reaction in grade 1-2. The incidence rate of grade 3-4 was lower than that of grade 1-2. Compared with the chemotherapy group, the incidence of leukopenia and rash in the combined group was higher than that in the chemotherapy group (蠂 2 / 4.089 / P = 0.043 / P, 蠂 ~ 2 = 5.858 / P = 0.027). The adverse reaction was alleviated by symptomatic treatment and did not affect the follow-up chemotherapy. Conclusion after acquired drug resistance (EGFR-TKI) in patients with advanced lung adenocarcinoma, pemetrexil combined with gefitinib can obtain higher ORR than pemetrexil alone. The median PFS is longer and the adverse reaction is tolerable. The results need to be verified by large sample data.
【學位授予單位】：鄭州大學
【學位級別】：碩士
【學位授予年份】：2016
【分類號】：R734.2

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