低剂量阿帕替尼联合替莫唑胺治疗复发小细胞肺癌的单臂临床疗效观察

目的 探讨低剂量阿帕替尼联合替莫唑胺治疗复发小细胞肺癌的客观反应、临床疗效和不良反应。 方法 本研究为前瞻性非盲单臂研究，选取2016年6月—2019年1月间中国人民解放军联勤保障部队第九〇一医院收治的15例进入二线治疗的复发小细胞肺癌患者，经纤维支气管镜、CT引导下肺穿刺活检或者胸水找脱落细胞病理诊断为依据。治疗方案为口服低剂量阿帕替尼+替莫唑胺:阿帕替尼250 mg，1次/d；替莫唑胺200 mg/(m2·d)，连续服用5 d，每28 d为1个周期。其中阿帕替尼剂量根据患者不良反应情况可适当调整为125 mg。用药至疾病进展或出现不可耐受的不良反应。每2个周期复查CT评价治疗效果，记录不良反应、肿瘤出现进展时间及患者生存时间。 结果 15例患者中位无进展生存时间(mPFS)为7.0个月，中位总生存期(mOS)为10.5个月，近期客观缓解率(ORR)为46.7%，疾病控制率(DCR)为66.7%，其中4例患者6个月内出现新发病灶，所有患者均耐受治疗，不良反应主要表现为骨髓抑制、消化道反应、口腔黏膜炎、手足综合征等，但Ⅲ~Ⅳ级严重不良反应少，经有效处理均可控。 结论 低剂量阿帕替尼联合替莫唑胺治疗复发小细胞肺癌疗效较好，且耐受性好。 

Single arm clinical observation of low-dose apatinib combined with temozolomide in the treatment of relapsed small cell lung cancer

Objective To investigate the objective response, clinical efficacy and adverse reactions of low dose apatinib combined with temozolomide in the treatment of relapsed small cell lung cancer (SCLC). Methods This study was a prospective, unblinded, one-arm study. Fifteen patients with pathological diagnosis of recurrent SCLC were enrolled from June 2016 to January 2019. All patients were diagnosed with SCLC by biopsy guided by fiberoptic bronchoscope, CT or exfoliating cell biopsy by pleural effusion. The fifteen patients were treated by apatinib (125-250 mg/d) and temozolomide[200 mg/(m2·d), continuously for 5 d, one cycle every 28 d]. The dosage of apatinib can be adjusted to 125 mg according to the patient's adverse reaction. These patients were treated until the disease progressed or an intolerable adverse reaction occurred. CT was reexamined every 2 cycles to evaluate the treatment effect, and progression free survival (PFS), overall survival (OS) time and adverse events (AEs) were recorded. Results The median PFS was 7.0 months, the median OS was 10.5 months, the objective remission rate was 46.7%, and the disease control rate was 66.7% within 6 months. AEs were mainly manifested as myelosuppression, digestive tract reaction, oral mucositis, and hand-foot syndrome. Serious AEs were less. Conclusion Low dose apatinib combined with temozolomide is effective and well tolerated in the treatment of relapsed small cell lung cancer.