单中心单臂Ⅱ期临床研究:沙利度胺治疗一代TKI继发性耐药的晚期非小细胞肺癌的临床疗效及安全性

A Single-center, Single-arm Phase Ⅱ Trail:Efficacy and Safety of Thalidomide on Advanced NSCLC Patients with Secondary Drug Resistance of First Generation EGRF-TKI

目的 观察沙利度胺治疗一代表皮生长因子受体酪氨酸激酶抑制剂（epidermal growth factor receptor tyrosine kinase inhibitor,EGFR-TKI）继发性耐药的晚期非小细胞肺癌患者的临床疗效及安全性。方法 选择2010年1月至2015年12月黄山市人民医院肿瘤科的52例非小细胞肺癌住院患者为研究对象,对经一代TKI治疗后影像学证实病情进展的患者加用沙利度胺治疗,沙利度胺睡前1小时顿服,从100 mg起,每隔3天加量50 mg,最大量300 mg,对患者的有效率、毒副反应及生存进行分析。结果 所有患者经沙利度胺治疗后,部分有效（PR）4例,病情稳定（SD）16例,有效率为7.7%,疾病控制率38.5%。所有患者均未见严重的毒副反应;经治疗后,患者无疾病进展时间（PFS）在3~44周之间,中位PFS为7周,总生存时间（OS）为52~240周,中位OS为108周。在对性别和TKI治疗后PFS分组进行比较时发现,各组之间联合治疗后PFS的差异具有统计学意义（P〈0.05）。结论 沙利度胺对逆转一代TKI耐药具有一定的帮助。

Objective To observe the clinical efficacy and safety of thalidomide in treatment of advanced non-small cell lung cancer patients with secondary drug resistance to first generation epidermal growth factor receptor tyrosine kinase inhibitor （EGFR-TKID. Methods In this study, 52 cases of non-small cell lung cancer patients were recruited from January 2010 to December 2015 in Huangshan City People＇ s Hospital. Thalidomide was added for the treatment of patients with imaging-confirmed disease progression after taking first generation EGFR-TKI. Thalidomide was taken at a draught from 100 mg to 300 mg with an increase of 50 mg every four days, 1 h before bedtime. The efficiency and toxicity of thalidomide and the survival of patients were analyzed. Results In all patients, there were 4 cases of partial response （PR） and 16 cases of stability of disease （SD）. The effective rate was 7.7%, and the disease control rate was 38.5%. There was no serious adverse reaction in all patients. After treatment, the progress free survival （PFS） ranged between 3 weeks and 44 weeks, and the median PFS was 7 weeks. The overall survival （OS） was from 52 weeks to 240 weeks, and the median OS was 108 weeks. After thalidomide and TKI combination therapy, there was statistical difference to overall survival between subgroups （male vs. female and PFS 〈 44w vs. PFS ≥ 44w） （P〈0.05）. Conclusion Thalidomide is helpful in a certain extent to the reversal of first generation TK1 resistance.