| Part I Short-term efficacy of Anlotinib plus S-1 combined with radiation in patients with locoregional recurrence after radical esophagectomy for esophagus carcinomaBackground:Locoregional recurrence of EC is the most important reason for surgical failure.Radiotherapy combined with platinum-containing chemotherapy is the first choice.However,due to its high toxicity and poor safety,some elderly patients with poor physical conditions cannot tolerate intravenous chemotherapy,and thus cannot benefit from it.As a multi-target receptor tyrosine kinase inhibitor,Anlotinib inhibits angiogenesis by inhibiting VEGFR2,FDGFR and FGFR pathways to achieve anti-tumor,improve tumor oxygen content and increase the effect of radiotherapy.This study is mainly for the retrospective analysis of the short-term efficacy and adverse reactions of Anlotinib plus S-1 combined with radiotherapy in patients with locoregional recurrence of EC after surgery.Methods:Patients with locoregional recurrence after radical esophagectomy for EC of Second Affiliated Hospital of Nanchang University oncology department from June 2018 to February 2019 were followed up.A retrospective analysis of 7 patients who met the enrollment conditions and received Anlotinib plus S-1 combined with radiotherapy.The clinical data of the patients were recorded,including gender,age,PS score,smoking status,pathological type,degree of differentiation,type of recurrence,and treatment plan.Efficacy was evaluated according to RECIST1.1.And the toxic and side effects were evaluated according to RTOG and CTCAE4.0.Result:All 7 patients completed radiotherapy,with a median age of 71 years(60-76).The pathological types were esophageal squamous cell carcinoma.The efficacy was evaluated 4 weeks after the end of radiotherapy,of which CR2(28.6.7%),PR5(71.4%),SD0,PD0,ORR 100%,DCR 100%.The target lesion diameter andbaseline diameter were 23.7cm before treatment and 5.7cm 4 weeks after radiotherapy,which was 75.9% smaller than the baseline level.After 2 cycles of consolidation treatment,the efficacy was evaluated of which CR 2(28.6%),PR5(71.4%),SD 0,PD 0,ORR 100%,and DCR 100%.The side effects of radiotherapy mainly include radiation esophagitis(100%),myelosuppression(93.3%),and radiation pneumonitis(73.3%).Radiotherapy side effects mainly include myelosuppression(42.9%),radiation esophagitis(28.6%)and radiation pneumonitis(28.6%),and no radiotoxicity of grade 3 or above occurred.The side effects of chemotherapy include proteinuria(57.1%),digestive tract reaction(42.9%),fatigue(42.9%),hypertension(14.3%),hemoptysis(14.3%),hand-foot syndrome(14.3%),and liver function.Damage(14.3%).The third-grade chemotherapy side reaction has digestive tract reaction(14.3%),no grade 4 or higher chemotherapy toxicity occurred.Conclusions:The efficacy of Anlotinib plus S-1 combined with radiotherapy in the treatment of patients with locoregional recurrence of esophageal cancer after surgery has a good short-term effect.Patients can be resistant to radiotherapy and chemotherapy side effects.Part II Short-term efficacy evaluation of Anlotinib plus S-1 in the treatment of distant metastases for advanced esophagus carcinomaBackground:Remote metastasis of esophageal cancer is one of the main reasons for the failure of standard treatment.Systemic chemotherapy is the first choice,but the efficacy is poor,and the side effects are heavy.Some patients cannot tolerate combination chemotherapy.,and benefit of the long-term survival is not satisfactory.Anlotinib highly selectively blocks VEGFR2-mediated signaling to exert anti-tumor effects by inhibiting kinases such as PDGFR,FGFR and c-Kit.This study was retrospectively analyzed for the short-term efficacy and adverse effects of Anlotinib combined with S-1 versus S-1 in the treatment of metastatic advanced esophageal cancer.Methods:Patients with metastasis of esophageal cancer from June 2018 to February 2019 of Second Affiliated Hospital of Nanchang University oncology department were followed up.A total of 17 patients with advanced metastatic esophageal cancer who received Anlotinib plus S-1 were enrolled.The clinical data of the patients were recorded including gender,age,PS score,smoking status,pathological type,degree of differentiation,number of distant metastatic organs,first-course treatment,and treatment plan.After 2 cycles of treatment,the efficacy was evaluated according to the RECIST 1.1.The efficacy of different clinical features of the combination of Anlotinib and S-1 was performed by chi-square test.Toxic side reactions were evaluated according to the CTCAE 4.0.Result:All 17 patients completed at least 2 cycles of treatment,with a median age of 65years(43-82).Among them,10 patients were treated first-line and 7 patients were treated with second-line or above.(1)The efficacy was evaluated after 2 cycles of treatment,CR in 0,PR in 6(35.3%),SD in 8(47.1%),PD in 3(17.6%),ORR 35.3%,and DCR 82.4%.Among them,there were 10 patients with first-line treatment,CR in0,PR in 5(50%),SD in 3(30%),PD in 2(20%),ORR 50%,and DCR 80%.There were 7 patients with second-line and above treatment,CR in 0,PR in 1(14.3%),SDin 5(71.4%),PD in 1(14.3%),ORR 14.3%,and DCR 85.7%.(2)There were no significant differences in ORR,DCR and gender,age,PS score,smoking history,liver metastasis,brain metastasis,lung metastasis,distant lymph node metastasis,and organ metastasis(p>0.05).(3)The side effects of Anlotinib combined with S-1 were fatigue(58.8%),hypertension(47.1%),hemoptysis(29.4%),anemia(29.4%),nausea(23.5%),liver function damage(23.5%),proteinuria(17.6%),abdominal pain(17.6%),leukopenia(17.6%),neutropenia(11.8%),fever(11.8%),and hand-foot syndrome(11.8%).Grade 3 toxic side effects included nausea(5.9%),hypertension(5.9%),and no toxic side effects of grade 4 or above.Conclusions:For patients with metastatic advanced esophageal carcinoma,the combination of Anlotinib and S-1 significantly improved the objective response rate,and the clinical efficacy was exact.The toxicity of Anlotinib in combination with S-1 is controllable. |
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