| Background:Small cell lung cancer(SCLC)grows rapidly and can metastasize at an early stage.Although it is sensitive to radiotherapy and chemotherapy,it remains an aggressive tumor with a short survival due to its limited treatment options.The treatment of SCLC is mainly chemotherapy.After the failure of first-line chemotherapy,the choice of treatment is ineffective and prone to drug resistance.Therefore,it is urgent to find new treatment modes to prolong survival.Beginning with bevacizumab,some anti-angiogenic drugs have attracted more and more attention in recent years by targeting vascular endothelial cells and inhibiting tumor growth.Inhibition of tumor angiogenesis by regulating vascular endothelial growth factor(VEGF)and its signal transduction pathway has been clinically validated as a feasible treatment for cancer.Apatinib is a small molecule tyrosine kinase inhibitor(TKI)that selectively inhibits vascular endothelial growth factor receptor 2(VEGFR-2),thereby achieving anti-angiogenic and anti-tumor effects.It has been shown to have a positive effect in advanced gastric adenocarcinoma,colorectal cancer and non-small cell lung cancer(NSCLC),but its effect in patients with SCLC has not been determined.Methods:Eligible for inclusion in this study were patients with advanced SCLC whose disease had progressed after prior treatment.Patients received 500 mg/d of apatinib orally in combination with 4 cycles of chemotherapy,followed by maintenance therapy with 500 mg/d of apatinib orally until PD,death,intolerance or withdrawal.If grade 3/4 AE occurs,the dose of apatinib can be reduced to 250 mg/d.If grade 3/4 AE occurs again,the dose of apatinib can be further adjusted to 250 mg every other day.The primary endpoint was progression free survival(PFS).Secondary endpoints were objective response rate(ORR),disease control rate(DCR),overall survival(OS),and treatment-related adverse events(AE).Results:A total of 18 patients were enrolled,including 10 patients with limited stage SCLC and 8 patients with extensive stage SCLC.In this study,16 patients received second-line treatment and 2 patients received third-line treatment.At the data cutoff date(March 1,2021),2 patients remained unenrolled and 16 patients were excluded from the group,of which 13 patients died.Of the 16 patients who were excluded from the group,12 patients were excluded due to PD and 4 patients due to death.Of the 12 patients who were excluded from the group due to PD,9 patients received follow-up chemotherapy and 3 patients did not receive any follow-up antitumor therapy.Tumor response was assessed in all 18 patients,no patients achieved a complete response(CR),5 patients achieved a partial response(PR),and 13 patients were assessed as having stable disease(SD).ORR and DCR were 27.8% and 100%,respectively.The median PFS and OS were 6.54 months and 13.23 months,respectively.Safety was evaluated in 18 patients,the most common AE was neutropenia,followed by leukopenia.The apatinib-associated AE in this study were proteinuria,diarrhea,hypertension,and hand-foot syndrome.When apatinib was administered at 500mg/d,all patients developed varying degrees of AE,and the incidence of grade 3-4 AE was 94.44%.After 250mg/d reduction,52.94% of patients developed AE,and the incidence of grade 3-4 AE was 11.76%.During the course of treatment,22.22% of patients had discontinued the medication,94.44% of patients reduced the dose of apatinib to 250 mg/d,with a median reduction time of 0.89 month.After the reduction,AE was significantly reduced and basically tolerated by the patients.No treatment-related deaths or unexpected toxic reactions were found.Conclusions:The combination of apatinib(500 mg/d)and monotherapy has a good efficacy for advanced SCLC patients,but the tolerance of patients is poor.The reduction to low dose apatinib(250 mg/d)may be a new choice for the treatment of advanced SCLC,but a larger sample size is still needed for further verification. |
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