Background The 5-year survival rate for extensive-disease small-cell lung carcinoma (ED-SCLC) is only 1%. Recently, apatinib exerted promising effects on cancer patients after failure of first-line chemotherapy. Methods This study enrolled 24 ED-SCLC patients to study the efficacy and toxicity of apatinib in combination with chemotherapy and maintenance therapy. The primary endpoints were overall survival (OS) and progression-free survival (PFS). The secondary endpoints included toxicity and safety. Apatinib was given 250 mg/day during the chemotherapy interval, and as maintenance therapy after 4-6 cycles until the patient progressed, died, or was intolerant to drug toxicity. The study further evaluated the cytotoxicity, cell-cycle arrest and apoptotic induction of apatinib in A549 and H446 cells. Results There was no difference in short-term efficacy between combined and chemotherapy groups. Long-term efficacy showed that the median PFS was 7.8 months and 4.9 months in combination and chemotherapy groups, respectively [p = 0.002, HR(95%CI): 0.18(0.06-0.60)]. The median OS was 12.1 months and 8.2 months in combination and chemotherapy groups, respectively [p = 0.023, HR(95%CI): 0.38 (0.16-0.90)]. Multivariate Cox regression analysis showed that apatinib combined with chemotherapy was an independent prognostic factor for OS and PFS. The ECOG score was an independent prognostic factor affecting OS. In vitro analysis showed that apatinib inhibited cell proliferation and caused cell-cycle arrest and apoptosis. Conclusion Apatinib combination/maintenance therapy showed promising efficacy and safety to extend OS/PFS in ED-SCLC and will be a potent therapeutic option in future practice. Although the scale of this study is small, further research on large sample sizes is needed.
Keywords: Apatinib; Apoptosis; Cell cycle arrest; Extensive-disease small-cell lung carcinoma; Maintenance therapy.