阿帕替尼治疗老年晚期肝癌的临床效果及安全性

目的探讨阿帕替尼治疗老年晚期肝癌的疗效及安全性。方法收集2018年1月至2018年6月49例老年晚期肝癌患者,接受阿帕替尼单药治疗。按照RECIST1.1标准进行疗效评价,NCI-CTCAE version 4.0评价药物的不良反应并随访生存情况。应用Kaplan-Meier法进行生存分析,Cox回归模型进行多因素分析。结果与治疗前相比,治疗4周后,患者病灶最大直径和及甲胎蛋白水平都降低,差异具有统计学意义(P<0.05)。治疗12周后,患者客观缓解率(CR+PR)和疾病控制率(CR+PR+SD)分别为8.16%(4/49)和77.55%(38/49)。49例老年患者的中位无进展生存期(mPFS)为7.75个月。Cox多因素分析结果表明病灶最大直径和为独立影响因素[HR:1.866,95%CI(2.470~16.916),P=0.000]。不良反应发生率为100%,以1~2级为主。结论阿帕替尼治疗老年晚期肝癌有一定疗效,且不良反应可控,可作为多线治疗失败的老年晚期肝癌患者的一种有效的治疗选择。     

甲磺酸阿帕替尼的研究现状与进展

恶性肿瘤的发生、发展与其血管生成密切相关,其中血管内皮生长因子及其受体（VEGF/VEGFR）信号通路是诱导血管新生最重要的调控途径,也是多种抗肿瘤血管生成剂的关键靶点之一。甲磺酸阿帕替尼（艾坦）是一种新型小分子的酪氨酸激酶抑制剂,高度选择性地作用于VEGFR 2,强效抑制肿瘤血管生成,从而发挥抗肿瘤作用。阿帕替尼Ⅰ、Ⅱ、Ⅲ期注册临床试验结果表明,标准化疗失败的晚期胃癌患者应用阿帕替尼生存获益,且安全性较好。目前,阿帕替尼单药或者联合其他药物治疗肺癌、肝癌、胃癌、结直肠癌和乳腺癌等多种肿瘤的基础与临床研究正在积极开展。本文系统综述与阿帕替尼相关的基础和临床研究的现状与进展,为进一步的临床应用提供参考。     

甲磺酸阿帕替尼联合中医辨证论治在晚期EGFR野生型肺腺癌中的疗效观察

目的本研究旨在进一步探讨甲磺酸阿帕替尼口服联合中医辨证论治治疗晚期EGFR野生型肺腺癌患者的有效性和安全性。方法收集2017年1月至2018年9月诊治的ⅢB-Ⅳ期EGFR野生型、肺腺癌患者,对照组(接受阿帕替尼单药治疗)患者31例,治疗组(接受阿帕替尼+中医辨证中药治疗)28例。对2组患者进行疗效、不良反应观察。结果近期客观疗效对比,治疗组ORR(14.29%)、DCR(60.71%)稍低于对照组的ORR(19.35%)及DCR(64.52%),差异无统计学意义(P0.05);生存情况对比,治疗组mPFS为3.33个月,对照组mPFS为3.0个月,组间比较无明显统计学意义(P0.05);治疗组MST为5.17个月,对照组MST为4.9个月,组间差异无明显统计学意义(P0.05);不良反应发生率对比,治疗组在高血压、蛋白尿、骨髓抑制方面发生率明显低于对照组,而蛋白尿组间差异具有统计学意义(P0.05)。结论治疗组与对照组在近期疗效及总生存方面无统计学差异;中医辨证中药治疗在一定程度上拮抗阿帕替尼导致的毒副作用,提高患者治疗耐受性,改善患者生活质量,对晚期NSCLC患者的治疗有积极影响。     

阿帕替尼治疗胃癌及其他肿瘤的研究现状

转移性胃癌是一类生存期很短的致死性恶性肿瘤,目前有许多针对晚期胃癌靶向治疗的研究,但结果并不理想,仅仅有少数靶向药物可以改善胃癌预后,如曲妥珠单抗和雷莫芦单抗。血管内皮生长因子(vascular endothelial growth factors,VEGF)与肿瘤发生发展密切相关,晚期胃癌患者中VEGF水平呈高表达,因此靶向VEGF被认为是胃癌治疗的新方向。在与血管生成相关的靶向药物中,阿帕替尼是一种靶向血管内皮生长因子受体2(vascular endothelial growth factors receptor, VEGFR2)的口服小分子受体酪氨酸激酶抑制剂,其口服生物利用度好并对胃癌有效。最新研究结果显示阿帕替尼作为三线方案可以改善胃癌患者生存结局,因此阿帕替尼很可能成为晚期胃癌治疗的关键药物。本文对阿帕替尼抗肿瘤机制、药代动力学、有效性及安全性、相关临床试验及最新研究进展简以综述。     

阿帕替尼联合放疗治疗非小细胞肺癌的临床研究

目的探讨阿帕替尼联合放疗治疗非小细胞肺癌(NSCLC)的临床疗效及安全性。方法依据随机数字表法将60例NSCLC患者分为观察组和对照组,每组30例,观察组患者采用阿帕替尼联合放疗,对照组患者仅采用放疗。比较两组患者的近期疗效、治疗前后的血清血管内皮生长因子(VEGF)和缺氧诱导因子-1α(HIF-1α)水平、生活质量及不良反应发生情况。结果观察组患者的总有效率为83.3%(25/30),高于对照组的56.7%(17/30),差异有统计学意义(P﹤0.05)。治疗后,两组患者的血清VEGF、HIF-1α水平均低于本组治疗前,且观察组患者的血清VEGF、HIF-1α水平均低于对照组,差异均有统计学意义(P﹤0.05)。治疗后,两组患者的卡氏功能状态(KPS)评分和生活质量评分均高于本组治疗前,且观察组患者的KPS评分和生活质量评分均高于对照组,差异均有统计学意义(P﹤0.05)。观察组患者的不良反应总发生率为33.3%(10/30),明显低于对照组的83.3%(25/30),差异有统计学意义(P﹤0.01)。结论阿帕替尼联合放疗治疗NSCLC具有协同作用,通过下调VEGF、HIF-1α的表达改善肿瘤微环境的乏氧状态,增强放疗敏感性,提高近期疗效,改善患者生活质量,且安全性较好,二者联合有望成为一种新的治疗策略。     

阿帕替尼治疗多线治疗失败后晚期乳腺癌的疗效及预后临床研究

目的 观察甲磺酸阿帕替尼单药治疗多线治疗失败的晚期乳腺癌的疗效及安全性.方法 将30例经三线及以上治疗失败后接受甲磺酸阿帕替尼治疗的晚期乳腺癌患者作为治疗组,22例经三线及以上治疗失败后接受最佳支持治疗的晚期乳腺癌患者作为对照组,比较两组患者的疗效、不良反应及预后.结果 治疗组患者总有效率及疾病控制率分别为36.7％(...     

卡瑞利珠单抗联合白蛋白紫杉醇二线治疗晚期胃癌的疗效及安全性

目的:评估卡瑞利珠单抗联合白蛋白紫杉醇(以下简称白紫)对比阿帕替尼联合白紫二线治疗晚期胃癌的疗效与不良反应,进一步探讨胃癌后线免疫治疗的获益人群。方法:随机选择2019年06月至2021年05月我院局部进展/远处转移胃癌一线应用L-OHP+卡培他滨/替吉奥,或者FOLFOX方案治疗进展后的112例患者分为两组,研究组55例予卡瑞利珠单抗联合白紫,对照组57例予白紫联合阿帕替尼二线治疗,观察客观缓解率(objective response rate, ORR)、疾病控制率(disease control rate, DCR)、无进展生存期(progression-free survival, PFS)、生存时间(overall survival, OS)和不良反应。采用Kaplan-Meier及COX回归分析进行生存分析。结果:平均随访12.8个月,研究组和对照组的ORR为45.5%、26.3%,DCR为76.4%、57.9%(P<0.05);mPFS为5.6个月、4.4个月(P<0.05),mOS为13.1个月、11.6个月(P<0.05)。ECOG PS评分=0、E...     

阿帕替尼治疗EGFR野生型晚期非小细胞肺癌的疗效及安全性

目的:探索阿帕替尼治疗表皮生长因子受体(epidermal growthfactor receptor,EGFR)野生型晚期非小细胞肺癌(non-small cell lung cancer,NSCLC)的疗效及安全性.方法:回顾性纳入62例本中心符合纳入标准的、接受阿帕替尼单药治疗晚期NSCLC患者,分析其疗效及不良...     

Apatinib induces 3‐hydroxybutyric acid production in the liver of mice by peroxisome proliferator‐activated receptor α activation to aid its antitumor effect

Apatinib, an antiangiogenic agent, shows efficient antitumor activity in a broad range of malignancies. Considering tumor is a type of metabolic disease, we investigated the metabolomics changes in serum and tumor after apatinib treatment and the molecular mechanism of characteristic changes associated with its antitumor efficacy. Molecules in serum and tumor tissue were extracted and analyzed by a gas chromatography‐mass spectrometry metabolic platform. Apatinib significantly inhibited e tumor growth and alleviated metabolic rearrangement in both serum and tumor of A549 xenograft mice. Among these endogenous metabolites, 3‐hydroxybutyric acid (3‐HB) was significantly increased in serum, tumor and liver after apatinib treatment. Interestingly, giving exogenous 3‐HB also inhibited tumor growth. Gene expression, dual luciferase reporter gene assay and molecular docking analysis all indicated that apatinib could induce 3‐HB production through the dependent activation of peroxisome proliferator‐activated receptor α (PPARα) and promotion of fatty acid utilization in the liver. Therefore, increased content of 3‐HB induced by PPARα activation in the liver partially contributed to the antitumor effect of apatinib. It may provide clues to another potential mechanism underlying the antitumor effect of apatinib besides its antiangiogenic effect through inhibiting vascular endothelial growth factor receptor 2.     

The safety and efficacy of TACE combined with apatinib on patients with advanced hepatocellular carcinoma: a retrospective study

As a novel vascular endothelial growth factor receptor-2 tyrosine kinase inhibitor (VEGFR2-TKI), apatinib has a certain anti-tumor effect for a variety of solid tumors. The present study evaluates its efficacy and safety in advanced hepatocellular carcinoma (HCC). In this study, 47 patients with advanced HCC were included. TACE monotherapy group included 22 patients that responded to TACE, while the group that received TACE and apatinib included 25 patients that progressed on TACE and were able to receive apatinib off label. Median overall survival (OS) was significantly improved in the apatinib plus TACE group compared with the TACE group. Similarly, apatinib in combination with TACE significantly prolonged median progression-free survival (PFS) compared with TACE monotherapy. Furthermore, there was a significant difference between combination therapy and monotherapy in both Barcelona clinic liver cancer (BCLC) B and BCLC C group. The combination therapy had a dramatic effect on OS and PFS for patients at both BCLC B and BCLC C level. The most common clinically adverse events of apatinib plus TACE group were fatigue, weight loss, hypertension, hand-foot syndrome and anorexia, which were manageable and tolerable. The efficacy analysis showed that there was no significant association of survival benefit with age, gender, Eastern Cooperative Oncology Group (ECOG) performance status, hypertension and hand-foot syndrome. Patients with macrovascular invasion and extrahepatic invasion showed worse survival benefits. In conclusion, apatinib combined with TACE revealed certain survival benefits for HCC patients who experienced progression following TACE, which can provide a promising strategy for HCC treatment.