甲磺酸阿帕替尼片治疗晚期胃癌的疗效

[目的]观察甲磺酸阿帕替尼片治疗晚期胃癌的疗效,为临床治疗提供参考.[方法]选取本院收治的经一线化疗(FOLFOX方案)方案治疗后进展的晚期胃癌患者70例,随机分为两组,对照组35例给予替吉奥治疗,观察组35例给予甲磺酸阿帕替尼片治疗,比较两组患者治疗后的临床疗效.[结果]观察组完全缓解1例,部分缓解15例,客观缓解率...     

阿帕替尼联合卡培他滨治疗晚期直肠癌的临床疗效

[目的]探讨阿帕替尼联合卡培他滨治疗晚期直肠癌的效果及安全性.[方法]在本院的就诊的70例晚期直肠癌患者,随机均分为观察组和对照组,各35例.对照组接受卡培他滨治疗,观察组接受阿帕替尼联合卡培他滨治疗.比较治疗6周期后两组患者的疗效、不良反应发生情况及生活质量,同时随访观察两组患者生存情况.[结果]治疗前两组标准体力状...     

比较吉非替尼与厄洛替尼在非小细胞肺癌中的疗效及安全性

目的 比较吉非替尼和厄洛替尼治疗非小细胞肺癌(NSCLC)的疗效和安全性.方法 回顾性分析中山大学附属第五医院44例患者的临床资料,均口服吉非替尼 250 mg,1次/d或厄洛替尼 150 mg,1次/d,直至病情进展,比较两组的疗效,无进展生存时间及不良反应.结果 吉非替尼和厄洛替尼两组患者的有效率分别为29.2%和25%(P=0.757),疾病控制率为83.3%和75%(P=0.162),无进展生存时间为7.6个月和6.2个月(P=0.995),两组差异均无统计学意义.不良反应如腹泻、皮疹等发生也相似.结论 吉非替尼和厄洛替尼治疗晚期NSCLC疗效和安全性相似.     

甲磺酸阿帕替尼在实体恶性肿瘤中的研究进展

在正常的生理条件下,新生血管的形成可以为周围组织提供能量及氧气,从而保证血流灌注。但在肿瘤患者中,血管新生出现失控,并加剧疾病进展及预后恶化。血管内皮生长因子(vascular endothelial growth factor,VEGF)及其受体(VEGFR)为诱导新生血管生成的重要调控途径。甲磺酸阿帕替尼作为国产自主研制出的抗血管生成药物,其本质为小分子的络氨酸激酶(tyrosine kinase,TK)抑制剂,其通过特异性地抑制VEGFR-2通路发挥抗血管生成作用,进而达到抗肿瘤的作用。目前国内相关指南已把其列入,特别是对于初始化疗治疗失败的晚期胃癌,其他如肺癌、乳腺癌、原发性肝细胞癌(hepatocellular carcinoma,HCC)等相关临床研究正在积极开展。     

甲磺酸阿帕替尼片联合多西他赛及顺铂治疗晚期胃癌的近远期疗效

【目的】探讨甲磺酸阿帕替尼片联合多西他赛及顺铂治疗晚期胃癌的近远期疗效。【方法】本院收治的72例晚期胃癌患者,随机分为A组(36例,采用多西他赛联合顺铂治疗)和B组(36例,采用甲磺酸阿帕替尼片联合多西他赛及顺铂治疗),比较两组患者近期抗肿瘤疗效、治疗前后肿瘤标志物水平变化、不良反应情况及1年生存率。【结果】B组临床控制率高于A组(P<0.05);两组治疗前血清癌胚抗原(CEA)、细胞角蛋白19片段抗原(CYFRA21-1)、糖类抗原199(CA199)水平比较,差异均无统计学意义(P>0.05);两组治疗后CEA、CYFRA21-1、CA199水平较治疗前均降低(P<0.05),且B组各指标水平均低于A组(P<0.05);两组高血压、蛋白尿、骨髓抑制、手足综合征发生率比较,差异无统计学意义(P>0.05);A组患者与B组患者的存活率曲线比较,差异有统计学意义(P<0.05)。【结论】对晚期胃癌患者采用甲磺酸阿帕替尼片联合多西他赛及顺铂治疗,可提高患者近期抗肿瘤疗效,降低肿瘤标志物含量,提高患者远期生存率,且安全性良好。     

肿瘤血管生成抑制剂的临床研究现状和思考

通过抑制肿瘤血管的生成治疗肿瘤是癌症研究领域的一个理论性突破，肿瘤抗血管生成疗法作为癌症治疗的新兴策略受到越来越多的关注．近年来，肿瘤血管生成抑制剂的研究发展迅猛，已由实验室阶段进入临床试验．目前已有40余种血管生成抑制剂进行了不同阶段的临床试验，但结果并不象预期的那样有效，同时还暴露出许多有待解决的问题，如血管生成抑制剂疗效的客观评价问题、临床试验的合理设计及病例选择问题、预防长期应用的毒副作用问题等．只有深入地理解血管生成抑制剂的作用机制和特性，加以改进，合理应用才能使之转化为人类征服肿瘤的利器．下面我们将侧重介绍血管生成抑制剂的临床研究现状、面临的困难和对策．     

肿瘤新生血管生成抑制剂的研究进展

肿瘤血管生成是一个多因子参与的多步骤过程 ,基本步骤包括 :肿瘤组织释放血管生成刺激因子 ;血管周围细胞外基质重塑 ,基膜降解 ;内皮细胞增殖迁移 ;新生血管成形。阻断其中任何一步 ,都将阻止肿瘤血管生成。肿瘤的血管系统已成为一个崭新的有希望的抗肿瘤治疗靶点。人们已致力于开发和研究破坏或抑制血管生成有效地阻止肿瘤生长和转移的药物 ,这类药物称为肿瘤血管生成抑制剂 (tumorangiogenesisinhibitor,TAI)。TAI具有许多优势 ,治疗发生时 ,血管形成已被启动 ,故TAI治疗具有良好的特异性 ,血管内皮细胞暴露于血流中 ,药物能直接发…     

阿帕替尼治疗晚期恶性肿瘤的临床疗效及安全性观察

目的评价阿帕替尼治疗晚期恶性肿瘤的临床疗效及安全性。方法对2015年1月至2017年4月在首都医科大学附属北京友谊医院肿瘤中心接受阿帕替尼治疗的41例晚期恶性肿瘤患者的临床资料进行回顾性分析,所有患者均口服阿帕替尼单药治疗,直至疾病进展或出现无法耐受的不良反应,观察临床疗效同时记录不良反应。根据在治疗过程中是否出现治疗相关性高血压将患者分为阿帕替尼相关高血压组(13/39)和正常血压组(26/39),比较两组患者的临床疗效(包括完全缓解率、部分缓解率、疾病稳定率、疾病进展率、客观有效率、疾病控制率、无进展生存期、生存时间)和不良反应发生情况。结果 39例可评估疗效患者的客观缓解率为5.2%,疾病控制率为66.7%;中位无疾病进展期为4.4个月,中位总生存时间为11.3个月。其中阿帕替尼相关高血压组患者的中位生存时间及中位无疾病进展期分别为23.5、6.5个月,正常血压组患者的分别为7.4、3.0个月。常见的不良反应分别为高血压31.7%,手足综合征29.3%,血小板减少14.6%,出血14.6%,白细胞减少12.2%,蛋白尿7.3%,乏力12.2%,恶心12.2%。结论阿帕替尼治疗晚期恶性肿瘤有一定的疗效,耐受性良好,阿帕替尼治疗相关性高血压有可能成为预测阿帕替尼疗效的因素之一。     

替吉奥联合顺铂在晚期胃癌的疗效观察

目的观察替吉奥联合顺铂（DDP）治疗晚期胃癌的临床疗效。方法 52例晚期胃癌患者随机分为两组,治疗组24例采用替吉奥联合顺铂治疗,对照组28例采用5-氟尿嘧啶（5-Fu）联合顺铂治疗。结果治疗组总有效率、获益率、KPS评分改善者均显著高于对照组,差异有统计学意义（P〈0.05）。结论替吉奥联合顺铂对于晚期胃癌,近期疗效较好,不良反应可耐受,值得推广及进一步研究。     

肿瘤抗血管治疗的研究进展

实体肿瘤的生成依赖于肿瘤本身新生血管的形成,肿瘤血管的再生受到众多血管刺激及抑制因子的调控。随着肿瘤血管再生理论和相应基础临床研究的快速进展,抗肿瘤血管生成治疗已成为肿瘤综合治疗中的一项重要内容。目前,已有多种血管生长抑制因子如血管抑素、肿瘤抑素等用于临床治疗研究,一些传统的抗血管生成药物也因此开辟了新的研究应用领域。现对血管生成（angiogenesis）在肿瘤发生发展中的作用、肿瘤治疗研究中的意义、抗肿瘤血管生成基因治疗研究中的进展作一综述。     

姑息性放疗联合阿帕替尼治疗晚期肺癌的近期疗效与安全性

目的 观察晚期肺癌患者接受姑息性放疗联合阿帕替尼治疗的临床近期疗效及安全性.方法 回顾性分析40例晚期肺癌患者的临床资料,按照治疗方法的不同将患者分为对照组和观察组,每组20例.对照组患者单纯接受姑息性放疗,观察组患者在此基础上联用阿帕替尼治疗.比较治疗后2组的临床近期总有效率、临床症状评分和毒副反应发生率.结果 观察...     

依维莫司初治罕见晚期血管肉瘤的临床疗效及安全性分析

目的:探讨mTOR抑制剂依维莫司治疗晚期血管肉瘤的临床疗效及安全性。方法:收集2013年11月至2018年9月采用依维莫司初治的5例晚期血管肉瘤患者的临床资料,观察并分析疗效与不良反应情况。结果:4例晚期血管肉瘤患者经依维莫司治疗数天后症状缓解,病灶缩小;1例阿帕替尼耐药的晚期血管肉瘤患者对依维莫司无反应,病情进展。依维莫司治疗不良反应主要为口腔溃疡,其中2例患者2级、3例患者1级。结论:依维莫司初治晚期血管肉瘤起效快,疗效较好,不良反应可控,值得进一步研究。     

胃镜定位联合腹腔镜治疗胃间质瘤的 有效性及安全性评估

目的 研究胃镜定位联合腹腔镜治疗胃间质瘤的有效性及安全性评。方法 将2009年8月~2013年12月，该院收治的胃间质瘤患者90例纳入研究对象，采用数字表法随机分为观察组（胃镜定位联合腹腔镜治疗）和对照组（仅进行腹腔镜手术），比较两组患者的手术情况、术后恢复情况及应激反应程度。结果 观察组患者的肿瘤定位时间(17.2±2.1)min、手术时间(40.3±6.2)min、术后肛门排气时间(1.3±0.2)d、流质饮食时间(2.5±0.4)d、卧床时间(3.8±0.5)d以及住院总时间(7.9±0.9)d明显短于对照组；术中出血量(36.2±5.2)mL、术后肾上腺素(94.7±10.4)ng/mL、去甲肾上腺素水平(123.3±14.2)ng/mL、HAMA评分(17.3±2.5)、HAMD评分(16.8±2.3)以及中转开腹(2.22%)明显低于对照组(P <0.05)。结论 胃镜定位联合腹腔镜治疗有助于缩短手术时间、减小手术创伤、促进术后恢复并缓解应激反应，是治疗胃间质瘤安全、有效的手术方法。     

Pharmacokinetics and safety of capmatinib with food in patients with MET-dysregulated advanced solid tumors

PurposeIn the Phase II GEOMETRY mono-1 study, the potent and selective mesenchymal-epithelial transition (MET) inhibitor capmatinib exhibited considerable efficacy in MET exon 14 skipping (METex14)–mutated metastatic non–small cell lung cancer at a dose of 400 mg BID. The current recommended dose is 400 mg BID in tablet formulation, with or without food. This article reports the pharmacokinetic (PK) profile, safety, and tolerability of capmatinib 300 and 400 mg BID given with food in MET-dysregulated advanced solid tumors.MethodsThis multicenter, open-label, Phase I study enrolled adult patients with MET-dysregulated advanced solid tumors. In the dose escalation phase, capmatinib tablets were orally administered at a dose of 300 mg BID with food; if tolerated, the dose escalation cohort of 400 mg BID was to be opened to enrollment. In the expansion phase, patients were to be enrolled at the higher of the tolerated doses. Tablets were taken within 30 minutes of an unrestricted meal type, except on cycle 1 day 1 (C1D1) and cycle 1 day 7 (C1D7), when they were given with a high-fat meal. The primary objectives were to determine the higher of the tolerated study doses and assess PK variables, with a secondary objective of safety.FindingsOverall, 35 patients (300 mg BID, n = 8; 400 mg BID, n = 27) with MET-dysregulated advanced solid tumors were enrolled; all patients had received prior antineoplastic therapy, and the most common primary site was lung (45.7%). Among PK-evaluable patients, the median T_max for capmatinib after administration with a high-fat meal (on C1D1/C1D7) was 4.0 to 5.6 hours across doses. At steady state (C1D7), capmatinib accumulation was low across dose levels (geometric mean of accumulation ratios, 1.29–1.69), with an increase in exposure (AUC_tau and C_max) from 300 to 400 mg BID. There were no occurrences of dose-limiting toxicity. All patients experienced at least 1 adverse event, and treatment-related adverse events occurred in 28 patients (80%; 300 mg BID, n = 6; 400 mg BID, n = 22), the most frequent of which were fatigue (37.1%) and nausea (34.3%).ImplicationsCapmatinib tablet formulation at a dose of up to 400 mg BID with food is well tolerated in patients with MET-dysregulated advanced solid tumors, with safety observations consistent with the existing profile under fasted conditions. These findings support the capmatinib dosing recommendation of 400 mg BID with or without food. ClinicalTrials.gov identifier: NCT02925104.     

紫杉醇、奥沙利铂联合氟尿嘧啶方案与S1＋奥沙利铂方案在治疗进展期胃癌中的疗效对比研究

目的比较紫杉醇、奥沙利铂联合氟尿嘧啶方案与S1十奥沙利铂方案在治疗晚期胃癌中的临床疗效和安全性。方法选取60例经组织或细胞病理学证实的晚期胃癌患者,随机分为紫杉醇、奥沙利铂联合氟尿嘧啶组（TOF组）和s1十奥沙利铂组（S0x组）,每组30例。TOF组治疗方案为：紫杉醇135mg/m2,第1天,使用前按照说明书要求进行预处理;氟尿嘧啶500rng／m2,化疗泵持续静脉滴注,第1～5天;奥沙利铂100mg／m2,静脉滴注2h,第1天。SOX组治疗方案为：替吉奥胶囊根据体表面积给药,体表面积〈1．25m2,40mg,2次／d;体表面积125～1．50m2,50mg,2次／d;体表面积〉1．50m2,60mg,2次／d,早晚餐后口服,第1～14天;停药7d;奥沙利铂130mg／m2静脉滴注,第1天,21d为一个周期。2个周期后评价疗效并记录毒副作用。结果TOF组客观缓解率为43．3％,疾病控制率为60％,中位无进展生存（PFS）时间为6．5个月;S0x组客观缓解率为36．7％,疾病控制率为56．7％,中位无进展生存（PFS）时间为5．8个月。2组客观缓解率和疾病控制率比较差异无统计学意义。TOF组最常见的不良反应是骨髓抑制、恶心呕吐、口腔黏膜炎,SOX组主要为骨髓抑制。TOF组的不良反应发生率较SOX组更高。结论两种方案治疗进展期胃癌均有成效,紫杉醇、奥沙利铂联合氟尿嘧啶方案不良反应更大,但患者均可耐受。     

VAC/IE方案一线姑息治疗晚期成人横纹肌肉瘤的疗效及安全性分析

目的:探讨VAC/IE方案治疗晚期成人横纹肌肉瘤(RMS)的疗效及安全性。方法:选择2010年1月至2018年12月在复旦大学附属中山医院肿瘤内科接受VAC/IE方案一线姑息治疗的成人RMS患者16例,中位发病年龄31岁,分析其疗效及不良反应。结果:平均随访时间13个月。16例患者VAC/IE方案的总体有效率(ORR)达37.5%(6例)、疾病控制率达68.8%(11例),中位无进展生存时间为5.8个月,中位总生存时间为15个月。所有患者共化疗93个周期,其中,3级以上化疗不良反应主要包括中性粒细胞下降(34/93,36.6%)、恶心呕吐(27/93,29.0%)。结论:成人RMS是一种罕见的高度恶性肿瘤,总体预后差。对于晚期患者,在预防性升白细胞及止吐治疗基础上,采用VAC与IE方案交替姑息治疗有效可行。     

Efficacy and safety of endoscopic submucosal dissection for tumors of the esophagogastric junction

BACKGROUND AND STUDY AIMS: The esophagogastric junction (EGJ) has been considered a difficult location for endoscopic treatment of tumors, due to its narrow lumen and sharp angle. Endoscopic submucosal dissection (ESD) is a method of endoscopic resection, capable of removing large tumors in an en bloc fashion. The aim of this study was to evaluate the efficacy and safety of ESD for EGJ tumors. PATIENTS AND METHODS: For 30 lesions of EGJ tumors treated by ESD, the size of the lesions and resected specimens, the en bloc resection rate, complications, and local recurrence were assessed. RESULTS: The average maximum diameters of the lesions and resected specimens were 22.4 mm and 40.6 mm respectively. The complete en bloc resection (R0) rate was 97% (29/30). Histological evaluation of the resected specimens revealed five cases of angiolymphatic invasion and five cases of submucosal invasion deeper than 500 microm. Perforation occurred in one case but was safely managed by rotatable clips and administration of antibiotics for 3 days. Local recurrence was not observed in any patient during follow-up (mean 14.6 months, range 6-31 months). CONCLUSIONS: ESD can be safely performed for EGJ tumors, with a high en bloc resection rate. For lesions with no apparent submucosal invasion findings, ESD is a curative and diagnostic treatment option that may be considered before open surgery.     

新辅助化疗两种方式治疗局部晚期宫颈癌疗效及安全性比较

目的对比研究静脉化疗和介入性动脉化疗结合手术2种方式治疗局部晚期官颈癌的疗效。方法按照初始时接受治疗方法的不同，将140例局部晚期（Ⅰb2～Ⅱb期）宫颈癌患者分为实验组（介入性子宫动脉化疗＋手术）和对照组（静脉化疗＋手术）2组，各70例。观察治疗后患者的近期总有效率、治疗前后肿瘤直径变化情况、根治手术率、3年和5年生存率（OS）及无进展生存率（PFS）、并发症、病理危险因素（子宫宫旁浸润率、淋巴结转移率）发生情况。结果2组患者近期总体有效率均较高，但差异无统计学意义；实验组治疗后瘤体直径变小比对照组的更明显，其获得根治性手术机会比对照组高，相应的淋巴结转移率、子宫宫旁浸润率低于对照组；2组的3年期的生存率、无进展生存率无差异，但5年期生存率、无进展生存率实验组比对照组高。结论动脉介入途径新辅助化疗治疗局部晚期宫颈癌手术切净率、5年生存率均优于静脉化疗，是一种安全有效的治疗手段。     

Efficacy and safety of short duration radiotherapy combined with chemotherapy for advanced rectal cancer

BACKGROUNDRadiotherapy or chemoradiotherapy is widely used for the treatment of rectal cancer preoperatively. Although the combination of radiotherapy and chemotherapy as an established preoperative neoadjuvant therapy shows high efficacy in the treatment of rectal cancer, some patients experience a response of poor tolerance and outcomes due to the long duration radiotherapy. The study compared short duration radiotherapy plus chemotherapy vs long duration radiotherapy plus chemotherapy for rectal cancer to determine whether short duration radiation treatment should be considered to diminish complications, reduce risk of recurrence and improve survival in patients with rectal cancer. AIMTo evaluate the efficacy and safety of short duration radiotherapy combined with chemotherapy for the treatment of advanced rectal cancer.METHODSOne hundred patients with stage IIIB or higher severe rectal cancer were selected as the study subjects at The First Affiliated Hospital of Hebei North University between December 2018 and December 2019. The patients were assigned to different groups based on the treatment regimens. Fifty patients who received preoperative short durations of radiotherapy plus chemotherapy were enrolled in an observation group and fifty patients who received conventional radiotherapy and chemotherapy were enrolled in a control group. Colonoscopic biopsy was performed for all patients with pathological diagnosis of rectal cancer. The expression of tumor-related factors such as RUNX3 and Ki-67 was quantitatively analyzed using immunohistochemistry in the tissues of the patients before and after treatment. Moreover, the duration of procedure, the amount of bleeding during the operation, the anus-conserving rate, the incidence of postoperative complications (wound infection, anastomotic leakage, postoperative intestinal obstruction, etc.) and postoperative pathology were compared between the two groups. The overall survival rate, recurrence rate and distant metastasis rate were also compared through postoperative reexamination and regular follow-up. RESULTSThere was no significant difference in the positive expression rate of RUNX3 and Ki-67 between the two groups before the treatment (P > 0.05). Compared with the pretreatment value, the positive rate of RUNX3 was increased and the positive rate of Ki-67 was decreased in both groups after the treatment (all P < 0.05). The incidence of leukopenia, thrombocytopenia, neutropenia and diarrhea were higher in the observation group than in the control group (all P < 0.05). There was no significant difference in the incidence of anemia, fatigue, neurotoxicity and nausea and vomiting between the two groups (all P > 0.05). No significant difference was observed in the duration of procedure, intraoperative bleeding, the anus-conserving rate and the incidence of postoperative complications between the two groups (P > 0.05). After 1 year of follow-up, the 1-yr survival rate was 80.0% in the observation group and 68.0% in the control group, the recurrence rate was 8.0% in the observation group and 10.0% in the control group, the distant metastasis rate was 6.0% in the observation group and 8.0% in the control group difference (all P < 0.05). CONCLUSIONShort duration radiotherapy combined with chemotherapy can improve the cure rate, prolong the survival time and reduce the incidence of complications in patients with advanced rectal cancer.