阿帕替尼治疗晚期及术后复发肺肉瘤样癌的疗效分析

目的探索阿帕替尼治疗晚期及术后复发肺肉瘤样癌的疗效。方法收集2016年6月至2019年8月Ⅲ~Ⅳ期及术后复发的肺肉瘤样癌患者21例,口服阿帕替尼(250~425 mg/d)治疗,30 d为1个疗程,观察并分析疗效及评价安全性。结果21例患者中,完全缓解(CR)为0,部分缓解(PR)为14.3%(3例),稳定(SD)为33.3%(7例),疾病进展(PD)为52.4%(11例);客观反应率(ORR)为13.3%(3例),疾病控制率(DCR)为47.6%(10例)。中位总生存期(mOS)为4.6个月,中位无进展生存期(mPFS)为1.0个月。病灶≥6 cm(或≥5 cm)较<6 cm(或<5 cm)平均OS明显缩短,差异有统计学意义(P<0.05);术后分期Ⅰ~Ⅱ期较Ⅲ~Ⅳ期平均OS明显延长(P<0.05)。位于中央的病灶较周围的病灶平均OS明显缩短,差异有统计学意义(P<0.01)。性别、年龄(>60岁,≤60岁)、吸烟史(是/否)对疗效影响差异无统计学意义。常见不良反应包括高血压38.1%(8例)、蛋白尿23.8%(5例)、手足综合征28.6%(6例)、腹泻28.6(6例)、骨髓抑制38.1%(8例)。结论阿帕替尼治疗晚期及术后复发肺肉瘤样癌具有一定疗效,不良反应可控,病灶大小、位置及分期可能是疗效的独立影响因素。     

阿帕替尼对Her2阴性晚期胃癌患者的治疗效果及毒副作用分析

目的:探究Her2阴性晚期胃癌患者采用阿帕替尼进行治疗的疗效及毒副作用。方法:按照不同治疗方法将本院就诊的Her2阴性晚期胃癌患者分为阿帕替尼组(AP组)和替吉奥组(TI组),各46例,分析比较两组患者的临床疗效、生活质量、毒副作用及远期疗效。结果:治疗后,AP组11例、TI组6例患者出现部分缓解,AP组患者RR、DCR数值明显比TI组高(P<0.05);AP组患者生活质量明显优于TI组(P<0.05)。AP组和TI组患者均出现血小板减少、蛋白尿、肝功能异常等不良反应,但未出现Ⅳ级毒副作用,其中AP组患者高血压、血小板减少的发病率分别为63.52%、76.73%,TI组患者发病率分别为62.45%、78.11%, AP组出现毒副作用的患者人数与TI组比较无明显差异(P>0.05)。随访3年结果显示,AP组患者3年生存率为10.86%,TI组患者为0,AP组患者总生存率明显高于TI组(P<0.05)。结论:阿帕替尼对Her2阴性晚期胃癌患者的临床疗效及远期治疗效果较佳,虽然治疗后也会出现一定的毒副作用,但与替吉奥治疗后出现的毒副作用相近,且患者身体承受程度较佳。阿...     

阿帕替尼和替吉奥对结肠癌治疗效果的系统评价和Meta分析

目的通过系统评价和Meta分析探讨阿帕替尼与替吉奥对比治疗结肠癌的有效性和安全性。方法以"阿帕替尼""替吉奥""结肠癌""等为中文关键词,以"Apatinib""Tegafur""Colon cancer"等为英文关键词,检索PubMed,Cochrane Library,Embase,Web of Science,中国知网、中国生物医学文献服务系统、维普数据库、万方数据知识服务平台,时间限制在从建库到2020年12月。评价阿帕替尼和替吉奥对结肠癌的总体疗效,结肠癌进展和无进展生存期的差异。研究采用RevMan 5.3软件进行Meta分析。结果Meta分析结果显示,阿帕替尼与替吉奥对结肠癌的疗效相比,部分缓解+稳定的差异没有统计学意义(RR=1.10,95%CI,0.71~1.71,P=0.640),在结肠癌进展方面的差异没有统计学意义(RR=0.51,95%CI:0.28~1.32,P=0.205),在无进展生存期方面阿帕替尼组大于替吉奥组,差异具有统计学意义(SMD=0.90,95%CI;0.42~1.37,P<0.0001)。结论相较于替吉奥,阿帕替尼用于治疗结肠癌患者能明显延长无进展生存期,总体生存效益有所提高。     

First-line treatment of apatinib in elderly patient of advanced gastric carcinoma: A case report of NGS-driven targeted therapy

Gastric carcinoma (GC) is a common gastrointestinal malignancy with high incidence and mortality worldwide, and most patients are diagnosed in the late stages of disease. Palliative chemotherapy provides a survival benefit for patients with inoperable advanced GC. However, elderly patients who are unable to tolerate chemotherapy had worse prognosis due to lack of effective treatment. Herein we reported a Chinese elderly GC patient using next generation sequencing (NGS)-based tumor DNA analysis. Valuable gene variants of vascular endothelial growth factor (VEGF) A gene amplification were detected. Additionally, a novel NOTCH1-BPHL fusion has been identified. He received antiangiogenic drug apatinib and showed both good clinical and radiographic response, but eventually died of non-cancer related cause, with progression free survival time (PFS) and overall survival time (OS) up to 9.53 months. This was the first GC case with apatinib usage as first-line treatment under the guidance of NGS gene profiling.     

阿帕替尼致高血压、肾病综合征1例

1例72岁男性高血压患者,既往血压控制良好。因诊断晚期肺鳞癌,于2018年5月4日开始院外口服阿帕替尼片(250 mg,qd)治疗。6 d后出现血压升高,2018年6月14日为进一步检查及治疗入院。入院后查血压:167/97 mm Hg,血清白蛋白23.9 g·L-1,肌酐143.6μmol·L-1,尿素7.11 mmol·L-1,血脂正常,24小时尿蛋白检测:11.86 g。考虑阿帕替尼可能导致高血压、肾病综合征,给予停药、降压、降蛋白尿等对症治疗,患者血压恢复正常;1个月后复查:血清白蛋白30.9 g·L-1,肌酐106.6μmol·L-1;24小时尿蛋白检测:3.65 g。     

Clinical study of apatinib plus temozolomide for the treatment of recurrent high-grade gliomas

ObjectivesRecurrent high-grade glioma, a malignant tumor of the brain or spinal cord associated with poor prognosis with a median survival of <6 months. Recurrent high-grade glioma does not have standard treatment even if some strategies have some effect in recurrent gliomas. Apatinib, as a tyrosine kinase inhibitor shown to be effective in treating the lung and gastric cancer. The present study investigated the efficacy and safety of apatinib in combination with dose-dense regimens of temozolomide for treating recurrent glioma.Patients and methodsEighteen patients with recurrent high-grade glioma were enrolled and treated with apatinib (500 mg/day) and TMZ (50 mg/m²/day). Patients who achieved partial response or stable disease continued treatment. Administration of drug was terminated for patients with progressive disease, who could not tolerate toxicity, and who required discontinuation due to other medical conditions.ResultsFrom the 18 cases, only 17 were included in the evaluation of the curative effect of the drug and in that four showed partial responses, ten had stable disease, remaining three exhibited progressive disease. The disease control rate was 82.3% (14/17). Progression-free and overall survival was found to be 4 months and 9.1 months, respectively. Three patients became transiently capable of self-care (Karnofsky performance status >70). Cognition and quality of life improved after treatment and from the safety perspective, three most common adverse reactions included epilepsy (24.1%), hypertension (20.7%), and fatigue (17.2%).ConclusionApatinib and TMZ may represent an alternative treatment option for patients with recurrent high-gradeglioma, especially those with a low Karnofsky performance status. However, studies using a larger sample size are required to confirm these findings.     

Apatinib induces apoptosis of breast cancer cells by redistribution of Fas into lipid rafts

Apatinib, an oral anti-angiogenic agent, has been shown to have anti-cancer effects for several cancer cell types. However, little is known about the direct anti-tumor activity of apatinib for breast cancer cells. Herein, the direct effect of apatinib on breast cancer cells and its mechanism of action were assessed. Cell viability was measured with a Cell Counting Kit-8. Cell apoptosis was assessed by flow cytometry. The expression of caspase-8 and the cleavage of poly ADP ribose polymerase were assessed by Western blotting analysis. Lipid rafts and Fas distribution were determined by immunofluorescence microscopy. Apatinib suppressed breast cancer cell proliferation in a dose-dependent manner. Furthermore, apatinib enhanced the aggregation of lipid rafts and the redistribution of Fas into lipid rafts. Pretreatment with methyl-β-cyclodextrin, a cholesterol-sequestering agent, significantlyreversed Fas redistribution and apatinib-induced apoptosis.In conclusion, these results demonstrated that apatinib induced apoptosis of breast cancer cells partially through recruitment of Fas into lipid rafts.     

阿帕替尼治疗晚期乳腺癌20例

目的 研究阿帕替尼治疗晚期乳腺癌的临床疗效及预后。方法 2015年5月至2017年6月皖北煤电集团总医院及宿州市立医院经病理学确诊的44例乳腺癌病人中20例口服阿帕替尼,24例行姑息对症支持治疗,比较两组总生存期、无进展生存期、疗效及对口服阿帕替尼不良反应的观察。结果 阿帕替尼组病人的中位总生存期(14个月)及中位无进展生存期(11个月)均长于姑息治疗组(6个月,4个月),两组差异有统计学意义(Kaplan-Meier法,P<0.05);阿帕替尼组病人的疾病控制率(85%)远高于姑息治疗组(46%),两组差异有统计学意义(χ² =14.204,P=0.003);口服阿帕替尼治疗中,不良反应多为1[KG-*3]～2级,治疗过程中无因为不能耐受不良反应而停止阿帕替尼靶向治疗。结论 阿帕替尼治疗一线、二线及三线治疗失败的晚期乳腺癌有较好的临床疗效及生存获益,不良反应可控制,值得临床上广泛应用。     

胃恶性肿瘤患者阿帕替尼的治疗药物监测研究

目的：探讨在胃恶性肿瘤患者中开展阿帕替尼治疗药物监测的情况,为临床安全合理用药提供参考。方法：采用LC-MS/MS测定2021年1月～2023年3月期间我院胃恶性肿瘤患者体内阿帕替尼的暴露水平,分析药物浓度与不良反应,疗效及不同联合用药种类之间的关系,考察性别、年龄、联合用药及肝肾功能等因素对稳态谷浓度的影响。结果：阿帕替尼回归直线方程为Y=0.065 12X+0.027 45,r²=0.998 7,血清样本在1.00～500μg·L^-1内具有良好的线性,定量下限为1.00μg·L^-1。50例患者中,血清药物谷浓度范围为10.39～364.74μg·L^-1,未发现疾病状况及不良反应与药物稳态谷浓度存在显著关联。与单抗类药物联用的阿帕替尼患者血药浓度显著高于紫杉醇组(P<0.05),其他各组之间差异无统计学意义(P>0.05)。肾小球滤过率(eGFR)是影响稳态谷浓度的重要因素。结论：在阿帕替尼治疗过程中,利用稳态谷浓度进行治疗药物监测的意义有限。阿帕替尼治疗期间需要密切关注肾功能的监测,...     

Apatinib Monotherapy or Combination Therapy for Non-Small Cell Lung Cancer Patients With Brain Metastases

Apatinib, an oral small molecular receptor tyrosine kinase inhibitor (TKI) developed first in China, exerts antiangiogenic and antineoplastic function through selectively binding and inhibiting vascular endothelial growth factor receptor 2 (VEGFR-2). In this study, we aimed to explore the efficacy and safety profile of apatinib monotherapy, or combined with chemotherapy or endothelial growth factor receptor (EGFR)-TKI in heavily pretreated non-small cell lung cancer (NSCLC) patients with brain metastases. We performed a retrospective analysis for relapsed NSCLC patients with brain metastases from our institute, who received apatinib (250 mg or 500 mg p.o. qd) monotherapy, or combination with EGFR-TKI or chemotherapy as second or more line systemic therapy until disease progression or unacceptable toxicity occurred. The objective response rate (ORR), disease control rate (DCR), median progression-free survival (mPFS), median overall survival (mOS), and safety were analyzed. A total of 26 eligible patients were included: 24 patients diagnosed with adenocarcinoma, 2 with squamous carcinoma, and 14 patients harboring EGFR sensitizing mutations. The mPFS and mOS were 4.93 (range, 0.27−32.91; 95% CI 3.64−6.22) and 14.70 (range, 0.27−32.91; 95% CI 0.27−43.60) months for the whole group. The ORR and DCR were 7.7% (2/26) and 69.2% (18/26) for the entire lesions, and 7.7% (2/26) and 79.6% (20/26) for brain metastases, respectively. Compared with patients who received apatinib monotherapy, patients who received apatinib combination treatment had more favorable mPFS (11.77 vs. 2.27 months, p<0.05) and mOS (24.03 vs. 6.07 months, p<0.05). Treatment-related toxicities were tolerable including grade 1/2 hypertension, hand-and-foot syndrome, fatigue, nausea, liver dysfunction, myelosuppression, skin rash, and palpitation. In conclusion, apatinib exhibited high activity and good tolerance for NSCLC patients with brain metastasis, and it might become a potential choice for metastatic brain tumors in NSCLC patients.