分阶段中药内服联合外洗治疗晚期非小细胞肺癌EGFR-TKIs相关皮疹的临床研究

[目的]观察中医辨证论治联合中药外洗治疗晚期非小细胞肺癌表皮生长因子受体酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinaseinhibitor,EGFR-TKI)相关皮疹的临床疗效。[方法]入组出现EGFR-TKI相关皮疹的晚期非小细胞肺癌患者63例,随机分为中医治疗组32例和对照组31例,中医治疗组根据皮疹发展的不同阶段及表现,中医辨证分为风热型(初期)、湿热型(中期)、阴虚型(晚期),分别予消风散、萆薢渗湿汤、沙参麦冬汤内服1剂/日,同时予中药外洗2次/日;对照组予红霉素软膏外用2次/日,合并感染予米诺环素100mg 2次/日口服。治疗疗程均为6周。观察治疗前后皮疹分级与中医临床症状的变化。[结果]中医治疗组有效25例,稳定4例,无效3例,有效率78.13%;对照组有效7例,稳定11例,无效13例,有效率22.6%,中医治疗组较对照组EGFR-TKIs相关皮疹改善明显,差异有统计学意义(P0.05)。中医治疗组与对照组治疗前肺癌中医症状评分分别为35.38±3.69与34.38±4.21,差异无统计学意义(P0.05);中医治疗组治疗后中医症状评分为29.59±3.06,较治疗前降低,差异有统计学意义(P0.05);对照组治疗后中医症状评分为33.29±4.08,较治疗前差异无统计学意义(P0.05);治疗后中医治疗组中医症状评分优于对照组,差异有统计学意义(P0.05)。[结论]中医分阶段辨证治疗联合中药外洗能显著改善晚期非小细胞肺癌患者EGFR-TKIs治疗相关皮疹,改善患者的中医临床症状。     

奥希替尼致间质性肺病1例并文献复习

报道1例65岁表皮生长因子受体19外显子缺失突变（E746_A750del）的右下肺腺癌患者,在服用奥希替尼100天后出现间质性肺病。停药后给予吸氧、糖皮质激素治疗后好转,尝试使用盐酸厄洛替尼片,未再发生间质性肺病。     

表皮生长因子受体酪氨酸激酶抑制剂对骨组织的影响研究进展

表皮生长因子受体（EGFR）是原癌基因c-erbB-1的表达产物,具有酪氨酸激酶活性。EGFR与配体结合可以激活下游信号通路并导致肿瘤细胞的增殖及侵袭。在肿瘤细胞中,EGFR过度表达可以激活骨吸收过程,导致肿瘤骨转移。表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKI）主要包括吉非替尼、厄洛替尼、阿法替尼、奥希替尼等,这些药物可以抑制骨吸收和肿瘤骨转移,但也会导致骨形成障碍。联合用药可以解决耐药等问题,并改善药物对骨组织的影响。本文对常见的EGFR-TKIs在骨形成、骨吸收和肿瘤骨转移等过程中对骨组织的影响及其机制进行综述,对不同EGFR-TKIs联合用药的优点及其对骨组织的影响进行归纳,并就EGFR-TKIs对骨组织负面影响的解决方案进行展望。     

Comparing the effectiveness of different EGFR-TKIs in patients with EGFR mutant non–small-cell lung cancer: A retrospective cohort study in Taiwan

The study was to compare the effectiveness of different epidermal growth factor receptor—tyrosine kinase inhibitors (EGFR-TKIs) in patients with advanced non-small-cell lung cancer (NSCLC) and received EGFR-TKIs as first-line therapy. This retrospective cohort study was conducted using data from real-world settings. Patients with stage IIIB and IV NSCLC and first received gefitinib, erlotinib, or afatinib between 2011 and 2015 were included. The date of the first claim for EGFR-TKIs was set as the index date. Study endpoints were all-cause death and treatment failure that was defined when patients added on or switched to chemotherapy or terminal care. A total of 5,940 patients, including 3,982 (67.0%) receiving gefitinib, 1,207 (20.3%) receiving erlotinib, and 751 (12.7%) receiving afatinib, were eligible for this study. The 1-year overall survival (OS) rates for gefitinib, erlotinib, and afatinib groups were 74% (95% confidence interval [CI]: 72–75%), 75% (95% CI: 73–77%), and 80% (95% CI: 77–83%), respectively. Compared to gefitinib, afatinib was associated with a lower risk of all-cause death (adjusted hazard ratio [aHR] = 0.82, 95% CI: 0.72–0.93) but not erlotinib (aHR = 0.95, 95% CI: 0.86–1.05). Similar results were also found regarding the effectiveness of treatment. All the three EGFR-TKIs showed no differences for both outcomes among patients with an Eastern Cooperative Oncology Group Performance Score of 2. The real-world data exhibited afatinib was more likely to be used for younger patients in a better condition than other EGFR inhibitors, and observed prolonged OS and treatment effectiveness compared to gefitinib after performing a multivariate Cox regression analysis.     

mPRα mediates P4/Org OD02-0 to improve the sensitivity of lung adenocarcinoma to EGFR-TKIs via the EGFR-SRC-ERK1/2 pathway

The discovery of epidermal growth factor receptor (EGFR) mutations has made EGFR tyrosine kinase inhibitors (EGFR-TKIs) a milestone in the treatment for advanced non–small cell lung cancer (NSCLC). However, patients lacking EGFR mutations are not sensitive to EGFR-TKI treatment and the emergence of secondary resistance poses new challenges for the targeted therapy of lung cancer. In this study, we identified that the expression of membrane progesterone receptor α (mPRα) was associated with EGFR mutations in lung adenocarcinoma patients and subsequently affected the efficacy of EGFR-TKIs. Progesterone (P4) or its derivative Org OD02-0 (Org), which is mediated by mPRα, increases the function of EGFR-TKIs to suppress the proliferation, migration, and invasion of lung adenocarcinoma cells in vitro and in vivo. In addition, the mPRα pathway triggers delayed resistance to EGFR-TKIs. Mechanistic investigations demonstrated that the mPRα pathway can crosstalk with the EGFR pathway by activating nongenomic effects to inhibit the EGFR-SRC-ERK1/2 pathway, thereby promoting antitumorigenic effects. In conclusion, our data describe an essential role for mPRα in improving sensitivity to EGFR-TKIs, thus rationalizing its potential as a therapeutic target for lung adenocarcinomas.     

表皮生长因子受体非热点突变型非小细胞肺癌一线应用表皮生长因子受体酪氨酸激酶抑制剂及化疗的疗效对比研究

背景 表皮生长因子受体酪氨酸激酶抑制剂（EGFR-TKIs）是晚期表皮生长因子受体（EGFR）突变型非小细胞肺癌（NSCLC）患者个体化靶向治疗方案之一,可显著改善患者的预后。然而不同类型EGFR的突变对EGFR-TKIs治疗的反应不同。 目的 比较EGFR非热点突变型NSCLC一线应用EGFR-TKIs及化疗的疗效。 方法 选取2012年4月—2019年6月在河北医科大学第四医院接受治疗的术后复发或晚期NSCLC患者,并确认为EGFR非热点突变型患者共90例。以患者一线治疗方案将患者分为一线EGFR-TKIs治疗组和一线化疗组。收集患者的一般资料及EGFR基因突变情况。所有患者通过电话进行随访或复查住院及门诊病例获得患者预后情况,随访截止时间为2024-03-31。观察并比较患者疗效及无进展生存期（PFS）和总生存期（OS）。 结果 90例患者中一线EGFR-TKIs治疗组52例,一线化疗组38例。术后复发转移患者16例,初诊分期为ⅢB~Ⅳ期患者74例。EGFR非热点突变患者中,单基因突变51例,复合突变39例。一线EGFR-TKIs治疗进展后二线EGFR-TKIs治疗患者8例,二线化疗患者9例。一线化疗进展后二线EGFR-TKIs治疗患者8例,二线化疗患者16例,免疫治疗患者1例。EGFR非热点突变不同亚型接受一线EGFR-TKIs治疗的患者PFS比较,差异有统计学意义（χ2=24.26,P<0.001）。一线EGFR-TKIs治疗组与一线化疗组的PFS、OS比较,差异有统计学意义（P<0.05）。在单突变亚型患者中,一线EGFR-TKIs治疗组与一线化疗组的PFS、OS比较,差异有统计学意义（P<0.05）。在复合位点突变患者中,一线EGFR-TKIs治疗组与一线化疗组的PFS比较,差异有统计学意义（P<0.05）;一线EGFR-TKIs治疗组与一线化疗组的OS比较,差异无统计学意义（P>0.05）。在一线化疗进展后的患者中,二线EGFR-TKIs治疗（8例）与化疗（16例）的中位PFS分别为11.3个月和5.6个月,二线EGFR-TKIs治疗与化疗患者PFS比较,差异有统计学意义（χ2=7.487,P=0.006）。 结论 在EGFR非热点突变型术后复发或晚期NSCLC中,EGFR ex20ins和E20 S768I突变患者与其他突变类型患者接受一线EGFR-TKIs治疗后的生存期存在差异。而在各突变亚型中,与一线化疗相比,一线EGFR-TKIs治疗均明显延长了患者的生存时间。     

EGFR-TKIs在NSCLC中的耐药机制及治疗策略研究进展

表皮生长因子受体（EGFR）抑制剂是目前临床治疗非小细胞肺癌（NSCLC）的一线小分子靶向药物,随着EGFR酪氨酸激酶抑制剂（EGFR-TKI）的广泛使用,其耐药现象也日趋明显,已成为其治疗NSCLC的巨大挑战。本文总结了EGFR-TKIs在NSCLC中的主要耐药机制,并对相关逆转策略的研究进展进行综述。