探讨阿帕替尼应用于二线以上进展期小细胞肺癌的临床疗效、不良反应、影响因素和生存分析。

收集二线以上化疗失败的小细胞肺癌患者30例，均给予甲磺酸阿帕替尼片500 mg/次/d口服，28 d为一疗程，有Ⅲ-Ⅳ级不良反应时减量至250 mg/次/d，至疾病进展或药物不良反应无法耐受则停药，观察服药2个疗程的临床疗效，及整个服药期间的不良反应。通过Kaplan-Meier法分析生存情况和影响因素，将有统计学意义的影响因素纳入多因素Cox比例风险模型进行分析。

30例患者经过2个疗程评估客观缓解率(ORR)为36.6%，疾病控制率(DCR)为66.6%，中位无疾病进展期(PFS)4.0个月(95%CI 2.864～5.136个月)，中位总生存期(OS)6.0个月(95%CI 4.555～7.445个月)。治疗期间主要不良反应为高血压发生率56.6%，蛋白尿发生率33.33%，血小板减少率56.6%，白细胞减少率86.6%，丙氨酸氨基转移酶升高16.6%，胃肠道反应10.0%，疲劳33.3%，手足综合证23.3%，无Ⅳ级以上不良反应。应用Kaplan-Meier法和多因素Cox回归模型分析低钠血症(HR＝3.693，95%CI为1.043～13.082，P＝0.043)、高血压(HR＝0.279，95%CI为0.090～0.869，P＝0.028)是PFS的独立影响因素，低钠血症(HR＝8.675，95%CI为2.284～32.947，P＝0.002)、分期(HR＝4.915，95%CI为1.151～20.978，P＝0.032)、高血压(HR＝0.128，95%CI为0.031～0.537，P＝0.005)是OS的独立影响因素。

阿帕替尼应用于二线以上进展期小细胞肺癌存在疗效，不良反应可耐受。治疗前期出现低钠血症及分期较高的患者预后不佳，不良反应出现高血压应用阿帕替尼可能存在生存优势。

To explore the clinical efficacy, toxicity, influence factors and survival analysis of apatinib in the patients with advanced small cell lung cancer (SCLC) after failure of beyond second-line treatment.

Thirty SCLC patients after failure of beyond second-line chemotherapy received oral administration of 500 mg of apatinib once a day, 28 days as a cycle, which was reduced to 250 mg once a day due to obvious adverse reactions or drug withdrawal due to disease progression or intolerance. The clinical efficacy of two courses of medication and the adverse reactions during the whole period of medication were observed. The survival and influencing factors were analyzed by Kaplan-Meier method, and the influencing factors with statistical significant difference were included in the multi-factor Cox proportional risk model.

The objective response rate was 36.66% and the disease control rate was 66.6% after two cycles of medication. The median progression free survival (PFS) was 4.0 months (95%CI 2.864~5.136), the median overall survival (OS) was 6.0 months (95%CI 4.555~7.445), and the main adverse reactions were hypertension (56.6%), proteinuria (33.3%), thrombocytopenia (56.6%), leukopenia (86.6%), abnormal liver function (16.6%), diarrhea (10.0%), fatigue (33.3%), and hand-foot syndrome (23.3%). Grade Ⅳ adverse reactions were not found. Hyponatremia (HR=3.693, 95%CI 1.043~13.082, P=0.043) and hypertension (HR=0.279, 95%CI 0.090~0.869, P=0.028) were independent influencing factors of PFS with Kaplan-Meier method and multivariate Cox regression model. Hyponatremia (HR=8.675, 95%CI 2.284~32.947, P=0.002), staging (HR=4.915, 95%CI 1.151~20.978, P=0.032) and hypertension (HR=0.128, 95%CI 0.031~0.537, P=0.005) were independent influencing factors of OS.

Apatinib is effective in the treatment of advanced SCLC above the second line. The prognosis of the patients with hyponatremia and higher stages before treatment is not good, and the patients with side effects of hypertension may have survival advantages by using apatinib.