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| 1 | Phase II clinical trial using camrelizumab combined with apatinib and chemotherapy as the first-line treatment of advanced esophageal squamous cell carcinoma显示文摘Background:Effective therapeutic options are limited for patients with advanced esophageal squamous cell carcinoma(ESCC).The incorporation of an immune checkpoint inhibitor and a molecular anti-angiogenic agent into the commonly adopted chemotherapy may produce synergistic effects.Therefore,we aimed to investigate the efficacy and safety of camrelizumab plus apatinib combined with chemotherapy as the first-line treatment of advanced ESCC.Methods:In this single-arm prospective phase II trial,patients with unresectable locally advanced or recurrent/metastatic ESCC received camrelizumab 200 mg,liposomal paclitaxel 150 mg/m2,and nedaplatin 50 mg/m2 on day 1,and apatinib 250 mg on days 1-14.The treatments were repeated every 14 days for up to 9 cycles,followed by maintenance therapy with camrelizumab and apatinib.The primary endpoint was objective response rate(ORR)according to the Response Evaluation Criteria in Solid Tumors(version 1.1).Secondary endpoints included disease control rate(DCR),progression-free survival(PFS),overall survival(OS),and safety.Results:We enrolled 30 patients between August 7,2018 and February 23,2019.The median follow-up was 24.98 months(95%confidence interval[CI]:23.05-26.16 months).The centrally assessed ORR was 80.0%(95%CI:61.4%-92.3%),with a median duration of response of 9.77 months(range:1.54 to 24.82+months).The DCR reached 96.7%(95%CI:82.8%-99.9%).The median PFS was 6.85 months(95%CI:4.46-14.20 months),and the median OS was 19.43 months(95%CI:9.93 months–not reached).The most common grade 3-4 treatmentrelated adverse events(AEs)were leukopenia(83.3%),neutropenia(60.0%),and increased aspartate aminotransferase level(26.7%).Treatment-related serious AEs included febrile neutropenia,leukopenia,and anorexia in one patient(3.3%),and single cases of increased blood bilirubin level(3.3%)and toxic epidermal necrolysis(3.3%).No treatment-related deaths occurred.Conclusions:Camrelizumab plus apatinib combined with liposomal paclitaxel and nedaplatin as first-line treatment demonstrated feasible anti-tumor activity and manageable safety in patients with advanced ESCC.Randomized trials to evaluate this new combination strategy are warranted.Trial registration:This trial was registered on July 27,2018,at ClinicalTrials.gov(identifier:NCT03603756). | Bo Zhang Ling Qi Xi Wang Jianping Xu Yun Liu Lan Mu Xingyuan Wang Lidan Bai Jing Huang | 2020 | Cancer Communications2020，40，12： | 38 |
| 2 | 小分子酪氨酸激酶抑制剂Apatinib对白血病HL-60细胞株抑制增殖作用及机制显示文摘目的探讨新型小分子酪氨酸激酶抑制剂apatinib体外对白血病HL-60细胞增殖的影响及机制。方法分别采用MTT法、流式细胞仪检测apatinib对白血病HL-60细胞株的细胞毒IC50值、细胞周期、凋亡的影响,Western Blot法观察apatinib对白血病细胞Erk1/2和Akt磷酸化的影响。结果 Apatinib对白血病细胞株HL-60增殖有明显抑制作用,IC50值为4.96±0.32μmol/L;apatinib能增加HL-60细胞凋亡率,并呈浓度依赖性;与对照组相比,经不同浓度apatinib处理的HL-60细胞,其细胞周期分布无明显改变(P>0.05);Western Blot结果显示,经apatinib处理48h后的HL-60细胞,其P-Erk1/2及P-Akt蛋白表达降低。结论 apatinib可通过下调P-Erk1/2及P-Akt蛋白表达诱导HL-60细胞凋亡,抑制其增殖。 | 粱树 童秀珍 符立悟 | 2011 | 南方医科大学学报2011，31，5： | 17 |
| 3 | Extraordinary response of metastatic pancreatic cancer to apatinib after failed chemotherapy: A case report and literature review显示文摘Chemotherapy has limited efficacy in the treatment of advanced and metastatic pancreatic cancer(PC), and has serious side effects. The development of novel effective agents, especially targeted therapy, is essential for patients with PC. We present a 58-year-old Chinese woman initially diagnosed with locally advanced PC. As the disease progressed to Stage Ⅳ, the patient was unable to tolerate chemotherapy after the fourth-line treatment. She was then treated with apatinib, a novel and highly selective tyrosine kinase inhibitor of vascular endothelial growth factor receptor-2 and achieved a progression-free-survival of 7 mo. All drug-related side effects were well controlled with medication. To the best of our knowledge, this is the first case of PC which responded to apatinib. Considering this remarkable response, apatinib may be a promising agent in the treatment of PC. We also reviewed the literature on chemotherapy and targeted therapy, especially the anti-angiogenesis therapy for patients with PC, and investigated the effect of apatinib in other solid tumors as well. | Cheng-Ming Li Zhi-Chao Liu You-Ting Bao Xin-Dong Sun Lin-Lin Wang | 2017 | World Journal of Gastroenterology2017，23，41： | 14 |
| 4 | Apatinib, a selective VEGFR2 inhibitor, improves the delivery of chemotherapeutic agents to tumors by normalizing tumor vessels in LoVo colon cancer xenograft mice显示文摘Tumor vascular normalization has been proposed as a therapeutic strategy for malignant neoplasms, which can also interpret the synergistic effect of anti-angiogenesis agents combined with chemotherapy. Apatinib (Apa), a highly selective VEGFR2 inhibitor, attracts much attentions due to its encouraging anticancer activity, especially in the clinical trials of combined treatment. In this study, we investigated whether Apa could promote vascular normalization in tumor in a certain time window. Mice bearing LoVo colon cancer xenograft were orally administrated Apa (150 mg kg^-1 per day) for 5, 7, 10, or 12 days. Apa significantly inhibited tumor growth and decreased the microvessel density. Using multi-photon microscopy and electron microscopy, we found that Apa improved tumor vessel morphology by pruning distorted vessel branches and decreased the gap between endothelial cells after a 7-day treatment. Furthermore, Apa decreased vessel leakage and in creased pericyte coverage on vascular en dothelial cells, suggesting that tumor vessels were more mature and integrated. The intratumoral distribution of adriamycin (ADR) in Apa group was improved from day 7 to 10 without change in plasma drug concen tration. Tumor blood perfusion was also in creased in this window, and the expression of hypoxia induced factor 1a was downregulated, suggesting the effect of Apa on alleviating tumor hypoxic micro-e nvironme nt. In conclusi on, Apa may improve the effective perfusi on of tumor vessels and in crease the intratumoral distribution of ADR in a certain time window via normalizing tumor vessels. This normalization window (7 to 10 days of treatment) may con tribute to develop a regime n of combi ned medication in clinic use of Apa. | Kai Zhou Jing-wei Zhang Qi-zhi Wang Wen-yue Liu Jia-li Liu Lan Yao Ming-min Cai Sui-ying Ni Qing-yun Cai Guang-ji Wang Fang Zhou | 2019 | Acta Pharmacologica Sinica2019，40，4： | 10 |
| 5 | Apatinib对急性髓系白血病干祖细胞样细胞株kg1α的杀伤作用及其分子机制显示文摘目的研究新型小分子酪氨酸激酶抑制剂Apatinib对急性髓系白血病(acute myeloid leukemia,AML)干祖细胞增殖和凋亡的影响及其相关分子机制。方法 CCK8法检测不同浓度Apatinib对kg1α细胞的增殖抑制作用,Annexin V/PI法检测不同浓度Apatinib诱导kg1α细胞和原代CD34^+AML干细胞的凋亡情况,Western blot法检测Apatinib处理kg1α细胞后PI3K/AKT通路相关蛋白(AKT、Raf和PTEN)的表达变化。结果不同浓度的Apatinib(2.5,5,10,20,40μmol·L^(-1))作用48 h和72 h后对kg1α细胞均具有显著的增殖抑制作用,呈浓度和时间依赖性,与对照组相比差异均具有统计学意义(P<0.05或P<0.01)。Annexin V/PI检测细胞凋亡的结果显示,不同浓度apatinib对kg1α具有显著的诱导凋亡作用,作用48 h和72 h后的凋亡率和对照组相比差异均有统计学意义(P<0.01)。不同浓度Apatinib作用48 h后对7例原代AML干细胞均具有显著的杀伤作用,与对照组相比差异具有显著的统计学意义(P<0.01);Western blot结果显示,Apatinib处理kg1α细胞48 h后AKT/p-AKT、p-Raf表达降低,而p-PTEN表达增加。结论 Apatinib可抑制AML干祖细胞样细胞kg1α细胞的增殖,且可诱导kg1α细胞和原代CD34^+AML干祖细胞的凋亡,均呈浓度和时间依赖性,其作用机制可能是通过干扰PI3K/AKT通路实现的。 | 李志峰 邓漫漫 查洁 周勇 方志鸿 徐兵 | 2017 | 中国现代应用药学2017，34，2： | 7 |
| 6 | 阿帕替尼抑制白血病细胞株Nalm6增殖及诱导凋亡的实验研究显示文摘目的阿帕替尼(Apatinib)为新一代小分子血管内皮生长因子受体-2(vascular endothelial growth factor receptor-2,VEGFR-2)酪氨酸激酶抑制剂,对多种实体肿瘤细胞有杀伤作用。本研究探讨Apatinib对急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)细胞株Nalm6增殖抑制及诱导凋亡的作用。方法 CCK8法检测不同浓度Apatinib对Nalm6细胞的增殖抑制作用,Annexin V/PI法检测不同浓度Apatinib诱导Nalm6细胞的凋亡情况,蛋白质印迹法法检测Apatinib处理后Bcl-2、Bcl-xL和PARP蛋白的表达变化。结果 CCK-8细胞毒性实验结果显示,Apatinib对Nalm6细胞具有明显的增殖抑制作用,呈剂量及时间依赖性,作用48h后,2.5、5、10、20和40μmol/L的Apatinib对Nalm6细胞的增殖抑制率分别为(3.78±1.01)%、(13.36±1.42)%、(25.80±2.83)%、(44.40±7.74)%和(64.07±6.66)%,经多个独立样本非参数检验Kruskal-Wallis H分析,各浓度的Apatinib均能诱导Nalm6细胞凋亡,与对照组(3.61±0.91)%比较差异有统计学意义,χ~2=13.500,P=0.009;作用72h后,2.5、5、10、20和40μmol/L的Apatinib对Nalm6细胞的增殖抑制率分别为(4.57+2.38)%、(20.26+4.06)%、(39.27±1.57)%、(65.19±4.45)%和(85.54±3.37)%,经检验各浓度的Apatinib均能抑制Nalm6细胞增殖,与对照组比较差异有统计学意义,χ~2=13.500,P=0.009。48和72h的IC50分别为(24.39±0.05)和(13.18±0.08)μmol/L。凋亡实验显示,Apatinib能增加Nalm6细胞凋亡率,并呈剂量依赖性,作用48h后,对照组和10、20、30、40μmol/L Apatinib组对Nalm6细胞的凋亡率分别为(3.61±0.91)%、(5.28±1.29)%、(5.9±0.85)%、(10.18±1.48)%和(15.23±3.69)%,经检验各浓度的Apatinib均能诱导Nalm6细胞凋亡,与对照组比较差异有统计学意义,χ~2=12.433,P=0.014;作用72h后,对照组和10、20、30、40μmol/L Apatinib组对Nalm6细胞的凋亡率分别为(3.8±1.10)%、(5.33±2.08)%、(10.10±2.86)%、(12.15±1.43)%和(25.61±3.63)%,经检验各浓度的Apatinib均能诱导Nalm6细胞凋亡,与对照组比较差异有统计学意义,χ~2=12.233,P=0.016。蛋白质印迹法结果显示,Apatinib作用Nalm6细胞24、48h后均能下调Bcl-2和Bcl-xl的表达,切割PARP蛋白。结论 Apatinib能抑制Nalm6细胞增殖,并诱导其凋亡,其机制可能与下调Bcl-2和Bcl-xl有关。 | 王焱 邓漫漫 查洁 周勇 贺伶俐 邓素琪 张蕾丝 徐兵 | 2017 | 中华肿瘤防治杂志2017，24，4： | 7 |
| 7 | Apatinib对卵巢癌细胞A2780增殖及紫杉醇敏感性的影响显示文摘目的:研究阿帕替尼(apatinib)对卵巢癌细胞A2780增殖及紫杉醇敏感性的影响,并探讨其相关机制。方法:CCK-8法检测apatinib对A2780细胞增殖的影响,克隆形成实验检测apatinib对A2780细胞增殖能力的作用,流式细胞术检测apatinib对A2780细胞凋亡和细胞周期分布的影响,Western blot法检测apatinib靶蛋白。结果:与对照组比较,apatinib明显抑制卵巢癌A2780细胞的增殖及克隆形成(P<0.01)。Apatinib作用24h后,A2780细胞凋亡率明显增加(P<0.01),呈浓度依赖性的细胞周期阻滞。Apatinib诱导A2780细胞中CDK2表达下降和p21表达上升。小剂量apatinib显著提高A2780细胞对紫杉醇的敏感性。结论:Apatinib可显著抑制卵巢癌细胞的增殖并增强其对紫杉醇的敏感性。 | 李婧 刘秋利 陈玲 唐美 邱海峰 王元 | 2018 | 现代妇产科进展2018，27，5： | 6 |
| 8 | The ACTIVE study protocol:apatinib or placebo plus gefitinib as first-line treatment for patients with EGFR-mutant advanced non-small cell lung cancer(CTONG1706)显示文摘Background:Gefitinib,as the first epidermal growth factor receptor tyrosine kinase inhibitors(EGFR-TKI)approved for the treatment of advanced non-small cell lung cancer(NSCLC),has been proved to significantly improve the progression-free survival(PFS)in the first-line setting but suffers from resistance 7-10 months after treatment initia-tion.Apatinib(YN968D1),a potent vascular endothelial growth factor receptor(VEGFR)2-TKI,specifically binds to VEGFR2 and leads to anti-angiogenetic and anti-neoplastic effect.Concurrent inhibition of VEGFR and EGFR path-ways represents a rational approach to improve treatment responses and delay the onset of treatment resistance in EGFR-mutant NSCLC.This ACTIVE study aims to assess the combination of apatinib and gefitinib as a new treatment approach for EGFR-mutant NSCLC as a first-line setting.Methods:This multicenter,randomized,double-blind,placebo-controlled phase III study(NCT02824458)has been designed to assess the efficacy and safety of apatinib or placebo combined with gefitinib as a first-line treatment for patients with EGFR-mutant advanced NSCLC.A total of 310 patients with EGFR-mutation(19del or 21L858R),pathological stage IIIB to IV non-squamous NSCLC were to be enrolled.The primary endpoint is investigator assessment of PFS,and the secondary endpoints include independent radiological central(IRC)-confirmed PFS,overall survival(OS),objective response rate(ORR),disease control rate(DCR),time to progressive disease(TTPD),duration of response(DoR),quality of life(QoL)and safety.The patients are randomized in a 1:1 ratio to receive gefitinib(250 mg,p.o.q.d.)plus apatinib(500 mg,p.o.q.d.)or gefitinib plus placebo,given until disease progression or intolerable adverse events.Exploratory biomarker analysis will be performed.This study is being conducted across China and comprises of 30 participating centers.Enrollment commenced in August 2017 and finished in December 2018,most of the patients are in the follow-up period.Anticipated outcomes and significance:The present study will be the first to evaluate the efficacy and safety profile of the combination of apatinib plus gefitinib as a first-line therapy for patients with EGFR-positive advanced non-squamous NSCLC.Importantly,this trial will provide comprehensive evidence on the treatment of EGFR-TKIs combined with antiangiogenic therapy. | Zhonghan Zhang Fan Luo Yang Zhang Yuxiang Ma Shaodong Hong Yunpeng Yang Wenfeng Fang Yan Huang Li Zhang Hongyun Zhao | 2019 | Cancer Communications2019，39，1： | 5 |
| 9 | Apatinib as an alternative therapy for advanced hepatocellular carcinoma显示文摘Angiogenesis plays an important role in the occurrence and development of tumors.Registered tyrosine kinase inhibitors targeting vascular endothelial growth factor reduce angiogenesis.Apatinib,a tyrosine kinase inhibitor,can specifically inhibit vascular endothelial growth factor receptor 2,showing encouraging anti-tumor effects in a variety of tumors including advanced hepatocellular carcinoma(HCC).This article intends to review the clinical research and application prospects of apatinib in the field of HCC. | Xi-Hao Zhang Man-Qing Cao Xiu-Xiu Li Ti Zhang | 2020 | World Journal of Hepatology2020，12，10： | 4 |
| 10 | Multicenter phaseⅡstudy of apatinib single or combination therapy in HER2-negative breast cancer involving chest wall metastasis显示文摘Objective:Breast cancer(BC)with chest wall metastasis(CWM)usually shows rich neovascularization.This trial explored the clinical effect of apatinib on human epidermal growth factor receptor 2(HER2)-negative advanced BC involving CWM.Methods:This trial involved four centers in China and was conducted from September 2016 to March 2020.Patients received apatinib 500 mg/d[either alone or with endocrine therapy if hormone receptor-positive(HR+)]until disease progression or unacceptable toxicity.Progression-free survival(PFS)was the primary endpoint.Results:We evaluated 26 patients for efficacy.The median PFS(mPFS)and median overall survival(mOS)were4.9[range:2.0-28.5;95%confidence interval(95%CI):2.1-8.3]months and 18(range:3-55;95%CI:12.9-23.1)months,respectively.The objective response rate(ORR)was 42.3%(11/26),and the disease-control rate was76.9%(20/26).In the subgroup analysis,HR+patients compared with HR-negative patients had significantly improved mPFS of 7.0(95%CI:2.2-11.8)months vs.2.3(95%CI:1.2-3.4)months,respectively(P=0.001);and mPFS in patients without or with chest wall radiotherapy was 6.4(95%CI:1.6-19.5)months vs.3.0(95%CI:1.3-4.6)months,respectively(P=0.041).In the multivariate analysis,HR+status was the only independent predictive factor for favorable PFS(P=0.014).Conclusions:Apatinib was highly effective for BC patients with CWM,especially when combined with endocrine therapy.PFS improved significantly in patients with HR+status who did not receive chest wall radiotherapy.However,adverse events were serious and should be carefully monitored from the beginning of apatinib treatment. | Huiping Li Cuizhi Geng Hongmei Zhao Hanfang Jiang Guohong Song Jiayang Zhang Yaxin Liu Xinyu Gui Jing Wang Kun Li Zhongsheng Tong Fangyuan Zhao Junlan Yang Guoliang Chen Qianyu Liu Xu Liang | 2021 | Chinese Journal of Cancer Research2021，33，2： | 4 |
| 11 | Phase Ⅱ study of apatinib in combination with oral vinorelbine in heavily pretreated HER2-negative metastatic breast cancer and clinical implications of monitoring ctDNA显示文摘Objective:Apatinib is an oral TKI targeting VEGFR-2.Single-agent apatinib treatment has been shown to produce an objective response in patients with pretreated m BC.Oral vinorelbine also holds promise as a treatment of choice in patients with m BC.This study aimed to investigate the efficacy and safety of the oral vinorelbine-apatinib combination in patients with pretreated m BC.In addition,we detected gene variants in ct DNA to explore the therapeutic implications.Methods:This study enrolled patients with HER2-negative m BC who were pretreated with anthracycline/taxanes.Patients were treated with apatinib at 500 mg/425 mg daily plus oral vinorelbine 60 mg/m2 on days 1,8,and 15 of every cycle(3 weeks).The primary endpoint was PFS.The secondary endpoints were ORR,CBR,OS,and safety.Patients eligible for ct DNA detection were evaluated before and during treatment.Results:Forty patients were enrolled.The median PFS was 5.2 months(95%CI,3.4–7.0 months),and the median OS was 17.4 months(95%CI,8.0–27.0 months).The ORR was 17.1%(6/35),and the CBR was 45.7%(16/35).The most common AEs included gastrointestinal reaction,myelosuppression,and hypertension.In 20 patients,ct DNA was detected at baseline and during treatment.A significant difference was found in PFS for undetected vs.detected baseline ct DNA(13.9 months vs.3.6 months,P=0.018).Conclusions:All-oral therapy with apatinib plus vinorelbine displayed objective efficacy in patients with heavily pretreated HER2-negative m BC,with acceptable and manageable toxicity profiles.Patients with no gene variant detected and lower variant allele frequencies in ct DNA at baseline showed longer PFS. | Anjie Zhu Peng Yuan Nanlin Hu Mingzhou Li Wenmiao Wang Xue Wang Jian Yue Jiayu Wang Yang Luo Fei Ma Pin Zhang Qing Li Binghe Xu Shanbo Cao Giuseppe Lippi Yoichi Naito Mohammed A.Osman Gustavo N.Marta Gianluca Franceschini Armando Orlandi | 2021 | Cancer Biology & Medicine2021，18，3： | 4 |
| 12 | A retrospective analysis of the safety and efficacy of apatinib in treating advanced metastatic colorectal cancer显示文摘Objective Colorectal cancer(CRC) is a heterogeneous disease in which both epigenetic alterations and gene mutations transform normal cells into cancer cells. Apart from a variety of standard treatments, there are few options available to improve a CRC patient's overall survival(OS) and quality of a life. The objective of the present retrospective study was to analyze the response and toxicity associated with apatinib in patients with metastatic CRC(m CRC).Method Data on the use of apatinib as salvage therapy were collected from patients diagnosed with m CRC, Eastern Cooperative Oncology Group(ECOG) performance status ≤ 3, from the Luhe Hospital. A total of 17 patients with stage IV unresectable m CRC, who received at least one cycle of apatinib, between October 2015 and February 2017, were involved in this study. Our primary endpoints were the overall response rate(ORR) and disease control rate(DCR), and the secondary objectives were progression-free survival(PFS), OS and safety.Result Seventeen patients with a median age of 62 years(34–83 years) were enrolled. Twelve patients were male, and the location of the primary tumor was in the colon and the rectum in 9 and 8 patients, respectively. Liver metastasis was observed in 9 patients and lung metastasis in 5. The ECOG performance status was 0 to 2 in 13 patients. The ORR at the first evaluation was 17.6 %(3/17). The DCR was 82.4%(14/17). The median PFS was 3.0 months(95% confidence interval(CI): 1.924–4.076 months) and the median OS was 5.4 months(95% CI: 3.383–7.417 months). Grade 1–2 adverse events included hypertension(52.9%), fatigue(64.7%), anorexia(29.4%), hoarseness(23.5%), proteinuria(23.5%), and development of rashes(17.6%). Grade 3 adverse events included thrombocytopenia(5.9%) and proteinuria(5.9%). There were no Grade 4 adverse events in our analysis.Conclusions Apatinib was found to be both safe and effective in the treatment of advanced m CRC, and its associated toxicities were acceptable and manageable. However, further studies are required to validate these findings. | Li Wang Juan Lu Yi Liu Yunfei Gao Man Kong Jiandong Yang Bin Kong Xuebing Li Xifen Huang Wenzhong Pei | 2017 | Oncology and Translational Medicine2017，3，5： | 4 |
| 13 | Effective combined therapy for pulmonary epithelioid hemangioendothelioma: A case report显示文摘BACKGROUND Pulmonary epithelioid hemangioendothelioma(P-EHE)is a rare disease.Thus far,consensus on a standard treatment for P-EHE has not been established given its low incidence worldwide.Apatinib combined with chemotherapy with doxorubicin/cyclophosphamide has been used as an effective combination treatment for human malignancies.However,the efficacy of this combination has not been reported in P-EHE cases.CASE SUMMARY We present the case of a 64-year-old woman with chest tightness,cough,and chest pain.Computed tomography showed multiple unresectable pulmonary nodules.She had been misdiagnosed with lung carcinoma and underwent gefitinib treatment at a hospital.Subsequently,the patient underwent a cardiothoracic surgery for further disease investigation.CD31,CD34,and Vimentin expression were detected in the resected nodule specimens by immunohistochemical analyses,and pathological analyses confirmed the diagnosis of P-EHE.Following this,four cycles of apatinib combined with chemotherapy with doxorubicin/cyclophosphamide were initiated.The patient demonstrated stabilization of multiple bilateral nodules and showed a dramatic improvement in the clinical presentation after combination treatment.The patient could not tolerate the side effects of chemotherapy.Therefore,she then continued apatinib monotherapy,which is ongoing to date.The patient was stable at the last follow-up after 24 mo.CONCLUSION Apatinib combined with chemotherapy with doxorubicin/cyclophosphamide may be an effective therapeutic option for P-EHE treatment. | Xiu-Qin Zhang Heng Chen Shu Song Yan Qin Li-Ming Cai Fang Zhang | 2020 | World Journal of Clinical Cases2020，8，10： | 3 |
| 14 | Transarterial Chemoembolization Combined with Apatinib for Treatment of Advanced Hepatocellular Carcinoma:Analysis of Survival and Prognostic Factors显示文摘Objective Apatinib is a novel inhibitor of vascular endothelial growth factor receptor-2.The goal of this study was to evaluate overall survival(OS)after a combination of transarterial chemoembolization(TACE)and apatinib in patients with advanced hepatocellular carcinoma(HCC)and to identify the factors affecting patient survival.Methods Fifty-one patients with advanced HCC who received TACE in combination with apatinib in our hospital from June 2015 to May 2017 were enrolled.The OS and progression-free survival(PFS)were calculated using the Kaplan-Meier method.The log-rank test and Cox regression model were used to determine the factors affecting OS.Results The median OS and PFS of the patients were 15 months and 10 months,respectively.The 1-,2-,and 3-year survival rates were 64.7%,23.5%,and 1.8%,respectively.Univariate survival analysis showed that patients with Child-Pugh A(P=0.006),reduction rate of proper hepatic artery(P=0.016),hand-foot syndrome(P=0.005),secondary hypertension(P=0.050),and without ascites(P=0.010)had a better OS.Multivariate analysis showed that hand-foot syndrome(P=0.014),secondary hypertension(P=0.017),and reduction rate of proper hepatic artery(P=0.025)were independent predictors of better OS.Conclusion TACE combined with apatinib is a promising treatment for advanced HCC.Hand-foot syndrome,secondary hypertension,and the reduction rate of proper hepatic artery were associated with a better OS. | Zi-yi LIU Xue-feng KAN Li-jie ZHANG Joyman MAKAMURE Qing LI Dan ZHAO Guo-feng ZHOU Gan-sheng FENG Chuan-sheng ZHENG Bin LIANG | 2022 | Current Medical Science2022，42，5： | 1 |
| 15 | Programmed death ligand-1 regulates angiogenesis and metastasis by participating in the c-JUN/VEGFR2 signaling axis in ovarian cancer显示文摘Background:Although programmed cell death-ligand 1(PD-L1)plays a wellknown function in immune checkpoint response by interacting with programmed cell death-1(PD-1),the cell-intrinsic role of PD-L1 in tumors is still unclear.Here,we explored the molecular regulatory mechanism of PD-L1 in the progression and metastasis of ovarian cancer.Methods:Immunohistochemistry of benign tissues and ovarian cancer samples was performed,followed by migration,invasion,and angiogenesis assays in PDL1-knockdown ovarian cancer cells.Immunoprecipitation,mass spectrometry,and chromatin immunoprecipitation were conducted along with zebrafish and mouse experiments to explore the specific functions and mechanisms of PD-L1 in ovarian cancer.Results:Our results showed that PD-L1 induced angiogenesis,which further promoted cell migration and invasion in vitro and in vivo of ovarian cancer.Mechanistically,PD-L1 was identified to directly interact with vascular endothelial growth factor receptor-2(VEGFR2)and then activated the FAK/AKT pathway,which further induced angiogenesis and tumor progression,leading to poor prognosis of ovarian cancer patients.Meanwhile,PD-L1 was found to be regulated by the oncogenic transcription factor c-JUN at the transcriptional level,which enhanced the expression of PD-L1 in ovarian cancer.Furthermore,we demonstrated that PD-L1 inhibitor durvalumab,combined with the antiangiogenic drug,apatinib,could enhance the effect of anti-angiogenesis and the inhibition of cell migration and invasion.Conclusion:Our results demonstrated that PD-L1 promoted the angiogenesis and metastasis of ovarian cancer by participating in the c-JUN/VEGFR2 signaling axis,suggesting that the combination of PD-L1 inhibitor and antiangiogenic drugs may be considered as a potential therapeutic approach for ovarian cancer patients. | Yufei Yang Lingfang Xia Yong Wu Hongyu Zhou Xin Chen Haoran Li Midie Xu Zihao Qi Ziliang Wang Huizhen Sun Xi Cheng | 2021 | Cancer Communications2021，41，6： | 1 |
| 16 | Traditional Chinese Medicine for Treatment of Apatinib-induced Hand and Foot Skin Reaction:A case report显示文摘Squamous cell carcinoma arising at maxillary sinus is a rare neoplasm, characterized by aggressive growth pattern and glooming prognosis. A 78-year-old woman presented with left maxillary sinus carcinoma. The patient received four courses of chemotherapy after surgery in our center. Eight months after treatment, the patient experienced local progress, severe gastrointestinal reactions and asthenia. Then apatinib was used as third-line treatment. Good curative effect was achieved with 250 mg apatinib per day, while adverse reaction such as hand and foot skin reaction affected the quality of her life. Traditional Chinese medicine exhibits good results and no obvious side effects in relieving hand and foot skin reaction. Traditional Chinese medicine is Chinese treasure, it remains challenging, and further investigations are needed. | Shan-Qi Guo Xiao-Jiao Gao Xiao-Jiang Li Ying-Jie Jia | 2019 | TMR Cancer2019，2，2： | 1 |
| 17 | Patients with Metastatic Colorectal Cancer after Failure of Second-Line Treatment May Benefit from Low-Dose Apatinib and S-1 Combined with Jianpi Bushen Jiedu Decoction显示文摘Objective: To evaluate the effect and safety of low-dose of apatinib and S-1 combined with Jianpi Bushen Jiedu Decoction(JBJD) in patients with metastatic colorectal cancer(mCRC) who have failed second or above lines treatment, in order to provide more treatment option for mCRC patients by integrated medicine. Methods: Thirteen patients were selected from a single-arm, open-label clinical study from April 2019 to September 2020. The patients were treated with low-dose apatinib(250 mg, once a day) and S-1(20 mg, twice a day) combined with JBJD for at least one cycle and were followed up to August 2021. The primary endpoint was disease progression-free survival(PFS). Disease control rate(DCR), objective response rate(ORR), and overall survival(OS) of patients were observed as the secondary endpoints. Adverse events were recorded as well. Results: The average age of the 13 patients was 56.5±13.0 years and 76.9% were male. The median PFS and median OS were 4.6 and 8.3 months, respectively. The ORR was 7.7%(1/13) while the DCR was 61.5%(8/13). The common adverse events were hypertension, proteinuria, elevated transaminase, and thrombocytopenia. One patient experienced thrombocytopenia of grade 3. Conclusions: Patients with mCRC after failure of the second or above lines of treatment may potentially benefit from the treatment of low-dose apatinib and S-1 combined with JBJD because of its similar effect as the standard dose of target therapy and relatively better safety.(Registration No. ChiCTR1900022673) | CHEN Yue XU Yu-ying JIANG Hai-jun WANG Lei ZHAI Jia-wei ZHANG Tong YANG Yu-fei | 2022 | Chinese Journal of Integrative Medicine2022，28，10： | 1 |
| 18 | Clinical effects of apatinib mesylate for treatment of multiple brain micrometastases:Two case reports显示文摘BACKGROUND Apatinib is a small-molecule multitargeted tyrosine kinase inhibitor.Apatinib has demonstrated encouraging antitumor activities.This study aimed to observe the efficacy and safety of apatinib for the treatment of multiple brain micrometastases.CASE SUMMARY We report two patients with multiple brain micrometastases after failure of second-line treatment.Both patients had extracerebral metastases.When the patients took 250 mg/d apatinib orally,the intracerebral lesions disappeared.The extracerebral lesions were partially alleviated.Both patients had a progressionfree survival of more than 12 mo and were still stable.The safety was good.The main adverse events(AEs)were mild hypertension and proteinuria,which could be controlled.CONCLUSION Apatinib has clear efficacy and good tolerance in patients with multiple brain micrometastases after failure of second-line treatment. | Jun-Hui Guo Yuan-Yuan Wang Jiang-Wei Zhang Pei-Min Liu Yan-Jun Hao Hai-Rui Duan | 2020 | World Journal of Clinical Cases2020，8，7： | 0 |
| 19 | Individualized treatment for gastric cancer with rib metastasis: Acase report显示文摘BACKGROUND Gastric cancer (GC) with bone metastasis is rare, and rib metastasis is even lesscommon. The clinical prognosis of GC with bone metastasis is poor given the lackof an effective treatment.CASE SUMMARY A 70 year old man was referred to Shaoxing People’s Hospital with left chest painand slight dyspnea. Chest computed tomography (CT) revealed a metastaticlesion in the left 3rd rib. Esophagogastroduodenoscopy revealed several ulcers inthe angle and antrum of the stomach, and tumor biomarkers including CEA andCA-199 were clearly increased. In addition, lymph node metastasis in the lessercurvature of the stomach was identified by positron emission tomography/CTscanning. Further pathological examination confirmed metastatic adenocarcinomain the rib and medium-low differentiated adenocarcinoma in the gastric space.The patient had GC with rib metastasis, and was clinically staged as T3NxM1 (IVB).Based on multidisciplinary team opinions, the patient received five courses ofchemotherapy (CAPOX plus aptinib), and then underwent rib resection andlaparoscopic radical distal gastrectomy. The patient started four courses ofchemotherapy after surgery, and then capecitabine and aptinib were administeredorally for 3 mo. Follow-up was performed on an outpatient basis usingabdominal/chest CT and tumor biomarkers. The patient exhibited an overallsurvival greater than 2 years, and the disease-free survival was approximately 18mo. His adverse events were tolerable.CONCLUSION The incidence of GC with rib metastases is extremely low, and patients can obtainmore benefits from individualized treatment formulated by multidisciplinaryteam. Chemotherapy plus surgery might represent an alternative option for GCwith rib metastasis. | Yu Zhang Zhen-Xing Zhang Zeng-Xin Lu Fang Liu Geng-Yuan Hu Feng Tao Min-Feng Ye | 2020 | World Journal of Gastrointestinal Surgery2020，12，12： | 0 |
| 20 | Efficacy and adverse reactions of apatinib as secondline or later-line treatment in advanced lung cancer显示文摘Objective The objective was to investigate the prognostic factors of advanced lung cancer treated with apatinib by log-rank regression analysis.Methods Sixty patients with advanced stage lung cancer confirmed at The First People’s Hospital of Nanning between January 2018 and December 2018 who had received a second-line treatment or a treatment above this level were included.All patients were treated with 425 mg/d apatinib orally for a 28-day course of treatment.Log-rank regression analysis of remission rates,disease control rates,adverse events,and prognostic factors in all patients was performed.Results After treatment,the total remission rate was 6.7%,and the disease control rate was 61.7%(37/60).Progression-free survival was 3.2±0.1 months,and overall survival was 5.3±0.5 months.The overall incidence of grade 3-4 adverse reactions was 15.0%(9/60),and these adverse reactions were significantly relieved by reducing the drug dose or suspending drug use.Differentiation degree,Eastern Cooperative Oncology Group(ECOG)score,and adverse reactions were all important and independent risk factors affecting the prognosis of patients(P<0.05).Conclusion Apatinib treatment could effectively inhibit the progress of the disease for patients with advanced lung cancer and prolong their survival with relatively mild toxicity and side effects,which is beneficial to patient tolerance.Moreover,the degree of differentiation,ECOG score,and adverse reactions could affect the prognosis of patients. | Tao Ren Yan Wu | 2021 | Oncology and Translational Medicine2021，7，4： | 0 |
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