吉非替尼对非小细胞肺癌的疗效与T细胞亚群变化分析

目的观察吉非替尼治疗晚期非小细胞肺癌(NSCLC)临床疗效与外周T淋巴细胞亚群变化的关系。方法对组织或细胞病理证实的35例晚期NSCLC患者口服吉非替尼250 mg/d。采集全部患者治疗前及治疗后外周血标本,三色染色后流式细胞仪分析CD3+、CD4+、CD8+T淋巴细胞亚群变化。结果35例患者中部分缓解13例,稳定13例,进展9例,疾病控制率为74.2%。治疗前后T淋巴细胞亚群无显著差异。结论吉非替尼治疗晚期非小细胞肺癌疗效较好,毒副反应轻微。治疗后T淋巴细胞可以恢复到治疗前水平。     

中国的非小细胞肺癌Gefitinib分子靶向治疗

目的 探讨非小细胞肺癌gefitinib分子靶向治疗的国内经验。方法 收集国内7个医院未经正式发表的用gefitinib治疗晚期非小细胞肺癌的资料，重点分析广东省肺癌研究所的病例情况。结果 自2001年7月至2003年12月．共有282例晚期非小细胞肺癌接受gefitinib治疗。有效率为22．2％～47．7％，疾病控制率为62．6％～81．8％。没有观察到明显的毒副作用。结论 gefitinib可安全有效地用于国内的晚期非小细胞肺癌。     

吉非替尼联合培美曲塞治疗吉非替尼二线治疗进展后肺腺癌的疗效观察

目的观察吉非替尼联合培美曲塞治疗吉非替尼二线治疗进展后肺腺癌的疗效及安全性。方法选取2010年10月至2012年12月间74例一线化疗进展后给予吉非替尼治疗有效再次进展患者,随机分为观察组和对照组两组。观察组患者36例,采用培美曲塞500mg/m2,静脉滴注;吉非替尼250mg/d,口服,21d为1个周期;对照组患者38例,单用培美曲塞500mg/m2,静脉滴注,21d为1个周期。所有患者至少治疗2个周期。结果观察组近期治疗效果优于对照组,但两组差异无统计学意义;与对照组相比,观察组死亡率略低,中位进展时间和中位生存时间均更长,两组在死亡率、生存时间和进展时间方面比较,差异无统计学意义（P〉0.05）;两组不良反应差异无统计学意义（P〉0.05）。结论采用吉非替尼二线治疗进展后联合培美曲塞治疗非小细胞癌肺腺癌,其治疗效果明显,不良反应能耐受,有利于提高肺腺癌患者的生活质量,有望成为非小细胞肺癌（NSCLC）患者标准的三线治疗方案。     

Mir-7上调增强肺腺癌对吉非替尼敏感性的机制研究

目的:探索上调Mir-7的表达使肺腺癌A549细胞增强吉非替尼的敏感性及其机制。方法:用lipo-fectamine2000携带Mir-7对A549细胞进行瞬时转染。将A549细胞分为对照组、转染组、吉非替尼组与联合组。MTT法测各组细胞增殖率变化,Transwell检测细胞侵袭性,Real time PCR检测E-Cadherin及N-Cad-herin的mRNA表达的变化,Western blot检测他们的蛋白表达的变化。结果:上调A549细胞中Mir-7的表达与吉非替尼共同作用较单独吉非替尼作用有更显著的抑制作用。用Mir-7转染后,肺腺癌A549细胞的侵袭力下降。转染与吉非替尼联合组E-Cadherin的信使RNA及蛋白的表达变化不大,但N-Cadherin表达下降。结论:上调Mir-7的表达可以增强肺腺癌细胞对吉非替尼的敏感性,其机制可能是过量表达的Mir-7抑制了IGF-1R信号通路及肿瘤上皮细胞间质化。     

对256例服用吉非替尼非小细胞肺癌患者的药学监护体会

目的 探讨对256例服用吉非替尼非小细胞肺癌患者实施药学监护的过程、方法 及其作用。方法 选取2017年10月至2019年10月在我院肿瘤科住院的服用吉非替尼的非小细胞肺癌患者256例,对照组给予常规药物治疗,观察组在药物治疗基础上给予针对性药学监护措施,对其不良反应相应给予不同的应对方案,整理、归纳和分析两组的治疗总有效率、不良反应总发生率和因不良反应导致的总停药率。结果 观察组的治疗总有效率为48.44%,明显高于对照组的28.12%,差异有统计学意义(P0.05);两组不良反应总发生率比较,差异无统计学意义(P0.05);观察组因不良反应导致的总停药率为25.78%,明显低于对照组的40.63%,差异有统计学意义(P0.05)。结论 通过对吉非替尼不良反应的针对性药学监护,使其疗效显著升高、停药率显著降低,大大提高了患者的依从性。     

吉非替尼与5－氟尿嘧啶、紫杉醇联合对胃癌细胞MKN－45的抑制作用

目的：探讨吉非替尼与5－氟尿嘧啶（5－FU）、紫杉醇（ Paclitaxel）联合序贯对人胃癌细胞MKN－45的抑制作用,筛选出体外对胃癌有效的联合用药方案。方法采用免疫组化法鉴定MKN－45细胞内EGFR相关抗原,采用MTT法测定5－FU、紫杉醇与吉非替尼联合对 MKN－45细胞的抑制作用。利用combidrug软件分析联合用药的作用效果。结果表明MKN－45细胞内 EGFR相关抗原表达阳性。先用化疗药物24h序贯吉非替尼48h方式给药时,5－氟尿嘧啶,紫杉醇与吉非替尼均有协同作用,CI值＜1;先用吉非替尼48h序贯化疗药物24h方式给药时,5－氟尿嘧啶,与吉非替尼有协同作用,CI值＜1,紫杉醇与吉非替尼在fa＞0．85时,CI值＞1,呈拮抗作用。结论5－氟尿嘧啶与吉非替尼具有协同作用,联合效果不受序贯给药顺序的影响。先用紫杉醇24h序贯吉非替尼48h具有协同作用,联合效果优于其余两种给药方案。     

Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma

AIM: To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). METHODS: Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib at daily dose of 100 mg/kg body weight (BW) or lecithin liquid was given by gastrogavage once a day for 5 or 10 successive days. CDDP or normal saline (NS) was administered intraperitoneally (i.p.) once a day for 5 successive days. Mice were randomly divided into control group (lecithin, or NS, i.p.), CDDP group (daily dose, 1.2 mg/kg BW; d1-5, or d6-10), Gefitinib (d1-5, or d6-10, or d1-10), and Gefitinib combined with CDDP groups. The inhibitory rate (IR) of tumor, net BW, spleen index (SI), thymus index (TI) and the amount of peripheral blood cells of mice were detected on the 12th experiment day. RESULTS: The growth of HCC in mice was inhibited by Gefitinib alone (IR: 41% in d1-10 group and 30% in d1-5 group, respectively) or CDDP alone (IR: 32-54% in d1-5 group or d6-10 group). The highest inhibitory effect (IR: 56%) on HCC growth was observed in Gefitinib (d1-10) combined with CDDP (d1-5) group. Higher inhibition was also observed in CDDP (d1-5) followed by Gefitinib (d6-10) group than that in Gefitinib (d1-5) followed by CDDP (d6-10) group (IR: 61% vs 36%, P<0.01) in the independent study. Net BW, SI, TI and the amount of blood cells of mice in Gefitinib alone group were not significantly different from those in control groups. CONCLUSION: Gefitinib can significantly inhibit the growth of murine H22 hepatocellular carcinoma. If Gefitinib is used after CDDP treatment in animal experiments, the inhibitory effect could be enhanced.     

吉非替尼不同序贯培美曲塞联合卡铂化学治疗晚期EGFR突变型肺腺癌临床效果观察

目的对比分析吉非替尼不同序贯培美曲塞联合卡铂化学治疗晚期表皮生长因子受体(epidermal growth factor receptor,EGFR)突变型肺腺癌的临床效果。方法选取晚期EGFR突变型肺腺癌98例,根据吉非替尼不同序贯化学治疗方案将其分为A组(48例)和B组(50例)两组。A组采用吉非替尼序贯培美曲塞联合卡铂化学治疗,B组采用培美曲塞联合卡铂序贯吉非替尼化学治疗。观察比较两组治疗结束后临床效果,治疗期间毒副反应发生情况,以及随访3年无疾病进展时间(PFS)。结果治疗结束后,两组完全缓解(CR)、部分缓解(PR)、稳定(SD)及有效(RR)率比较差异无统计学意义(P>0.05);B组进展(PD)率低于A组,疾病控制(DCR)率高于A组,差异有统计学意义(P<0.01)。两组治疗期间不良反应以肝功能异常、皮疹、中性粒细胞减少、贫血、恶心、血小板减少、白细胞减少和脱发多见。A组恶心Ⅰ或Ⅱ度发生率高于B组,差异有统计学意义(P<0.05)。两组随访时间为3年或死亡,A组中位PFS为9.79个月,B组中位PFS为19.21个月,两组中位PFS比较差异有统计学意义(P<0.01)。结论培美曲塞联合卡铂序贯吉非替尼化学治疗晚期EGFR突变型肺腺癌可提高DCR率,且在改善患者PFS中作用明显。     

Post-Progression Survival in Patients with Non-Small Cell Lung Cancer with Clinically Acquired Resistance to Gefitinib

Most patients with tyrosine kinase inhibitor (TKI)-sensitive non-small cell lung cancer (NSCLC) eventually develop acquired resistance to TKIs. Factors that affect TKI-sensitive patient survival after progression during TKI treatment remain unknown. We attempted to identify factors that affected post-progression survival. We retrospectively reviewed 81 advanced NSCLC patients with disease progression following tumor response and durable (≥ 6 months) disease stabilization with first-line or second-line gefitinib. Post-progression survival (PPS) and characteristics were investigated and compared in patients who did (n = 16) and did not (n = 65) resume TKIs. Most patients were female never-smokers with adenocarcinoma. Median overall PPS was 10.3 months (95% confidence interval [CI], 7.458-13.142). Age, gender, smoking history, histology, Eastern Cooperative Oncology Group performance status at gefitinib initiation, initial stage, and platinum-based chemotherapy after gefitinib were not significant predictors of PPS. Pemetrexed use after gefitinib significantly improved PPS (18.5 vs 8.6 months; hazard ratio [HR], 0.45; P = 0.008). Gefitinib reuse tended to lengthen PPS but was insignificant in multivariate analysis (27.4 vs 8.8 months; HR, 0.53; P = 0.095). NSCLC patients assumed to have clinically acquired resistance to TKIs had relatively long PPS. TKIs reuse or pemetrexed use after progression with gefitinib may improve PPS.