阿帕替尼联合化疗用于一线及以上化疗失败后晚期胃癌的临床疗效

目的:观察阿帕替尼联合化疗用于一线及以上化疗失败后晚期胃癌的临床疗效及生存分析。方法:按照制定的患者纳入和排除标准收集自2016 年3 月至2017 年4 月郑州大学第一附属医院肿瘤内科72 例胃癌晚期患者,随机分为单纯化疗组、阿帕替尼单药组、阿帕替尼联合化疗组,分析比较三组患者的临床疗效及预后影响因素分析。结果:单纯化疗组、阿帕替尼单药组、阿帕替尼联合化疗组的疾病控制率（DCR）分别为48.3%、61.1%和72.0%（P>0.05）,客观缓解率（ORR）分别为13.8%、16.7%和28.0%（P>0.05）。3~4 级不良反应发生率分别为17.1%、16.8%和24.0%（P>0.05）。以单纯化疗组为对照,其他两组患者中位无进展生存期（mPFS）分别为93、117（P>0.05）、160 d（P=0.001）。经单因素和多因素COX分析发现,有无腹水（P=0.041）、TNM分期（P=0.036）及治疗方案（P=0.001）是mPFS的独立影响因素。结论:阿帕替尼联合化疗用于一线及以上化疗失败的晚期胃癌的缓解率较高,不良反应可控,安全性较好,有可观的生存获益。     

HER2阳性胃癌的治疗研究进展

抗人表皮生长因子受体2（human epidermal growth factor receptor 2,HER2）的靶向治疗显著延长了HER2阳性晚期胃癌患者的生存期,抑制HER2通路已成为HER2阳性晚期胃癌一线治疗的基础策略。ToGA研究中的曲妥珠单抗联合5-Fu/卡培他滨及顺铂的化疗方案是HER2阳性晚期胃癌一线化疗的标准方案。后ToGA时代,曲妥珠单抗联合其它的多个化疗方案不仅在晚期胃癌的二线治疗和转化性治疗中有突出的疗效,而且在局部进展期胃癌的新辅助治疗中有望发挥更大的作用。目前胃癌抗HER2治疗的研究方向是开发新的抗HER2药物,以及与其它信号通路的靶向药物联合。动态的基因检测有助于明确抗HER2治疗耐药的分子生物学机制,目前的临床研究在克服耐药性方面已取得进展。本文就HER2阳性晚期胃癌治疗方面的最新进展及今后的研究方向进行综述,以期指导临床实践。      

Overall survival benefits for irinotecan‐containing regimens as first‐line treatment for advanced gastric cancer: An updated meta‐analysis of ten randomized controlled trials

The standard treatment for patients with advanced gastric cancer (AGC) is still debated, and the available data on the benefit of irinotecan‐containing regimen as first‐line treatment for those patients are controversial. We performed a systematic review and meta‐analysis of randomized controlled trials to determine the survival benefits of irinotecan‐containing regimens in this setting. A total of 1,837 patients from ten trials were included in the analysis. Our results showed that irinotecan‐containing regimens significantly improved overall survival [OS: hazard ratio (HR) 0.86, 95% CI = 0.78–0.94, p = 0.002] and progression‐free survival [HR = 0.82, 95% CI = 0.69–0.97, p = 0.026); however, the improvement of time to failure (HR = 0.90; 95% CI = 0.77–1.04, p = 0.15), 1‐year survival rate [1‐year SR: relative risk (RR) 1.10, 95% CI = 0.97–1.24, p = 0.13] and overall response rate (RR = 1.16, 95% CI = 0.91–1.49, p = 0.24] were nonsignificant. Equivalent frequencies of toxicities were found between the two groups excluding more Grade 3 or 4 fatigue (p = 0.001) in irinotecan‐containing regimens. This updated meta‐analysis provided strong evidence for a survival benefit of irinotecan‐containing regimen as first‐line treatment for AGC. A clear advantage of irinotecan‐containing over nonirinotecan‐containing regimen had not been established. These results should help to inform decisions about patient management and design of future trials.     

胃癌分子靶向治疗的研究进展

目前晚期胃癌的治疗方式是以全身化疗为主的综合治疗。尽管化疗能够延长肿瘤患者的生存期,但副作用较明显,近年来,随着对胃癌的各种相关分子的信号转导通路的逐渐认识,在分子水平抑制肿瘤生长的治疗方式越来越受到人们关注,众多靶向药物应运而生,如曲妥珠单抗、阿帕替尼、Claudin18.2等,各种靶向药物为晚期胃癌的治疗提供了良好的前景。     

阿帕替尼与替吉奥二线治疗晚期胃癌患者的临床疗效比较

目的 探究阿帕替尼与替吉奥二线治疗晚期胃癌患者的临床疗效.方法 选取经化学药物治疗失败的晚期胃癌患者118例,依据治疗方案的不同将患者分为靶向组及对照组,各59例,其中,靶向组患者口服阿帕替尼进行治疗,对照组患者口服替吉奥进行治疗;观察比较两组患者治疗前及治疗过程中白细胞计数(WBC)、血小板计数(PLT)、不良反应情况及疗效.结果 治疗前两组患者的WBC及PLT比较,差异无统计学意义(P﹥0.05);治疗过程中靶向组患者腹泻、皮疹及口腔炎的发生率低于对照组,高血压及手足综合征的发生率高于对照组,差异有统计学意义(P﹤0.05);治疗后两组患者的WBC及PLT水平均降低,且对照组患者降低更为显著(P﹤0.05);靶向组患者的疗效优于对照组,差异有统计学意义(P﹤0.05).结论 靶向药物阿帕替尼相对于替吉奥对二线治疗晚期胃癌患者具有疗效显著、不良反应轻微等优势;治疗过程中靶向组出现较多的血压升高患者,经对症治疗后症状得到缓解.     

阿帕替尼治疗晚期化疗耐药胃癌的临床体会

目的:探讨阿帕替尼治疗晚期化疗耐药的胃癌疗效及临床特点。方法:报道阿帕替尼治疗晚期化疗耐药的2例胃癌的临床疗效、不良反应及影像学变化并结合文献讨论。结果:第一例患者服药后的总生存期又延长了7个月。第二例患者的无进展生存期达6个月,仍在继续服药中。两例患者治疗后病灶均出现液化,影像学上表现为CT值下降。治疗期间均出现手足综合征和腹泻的不良反应。结论:阿帕替尼治疗晚期化疗耐药的胃癌可以获得较好的疗效。阿帕替尼的疗效与手足综合征和腹泻的不良反应等可能有相关性。分子靶向药物的疗效评价标准不能仅局限于RECIST,需要进一步完善。     

Apatinib plus S-1 for previously treated,advanced gastric or gastro-oesophageal junction adenocarcinoma: a phase 2, single-arm,prospective study

BackgroundThe current management of advanced gastric or gastro-oesophageal junction adenocarcinoma remains unsatisfactory. We investigated the efficacy and safety of the combination therapy of apatinib and S-1, considering the potential advantage of home-based treatment without hospital admission, in patients with platinum-refractory gastric or gastro-oesophageal junction adenocarcinoma.MethodsIn this open-label, single-arm, phase 2 trial, in each 21-day cycle, eligible patients received apatinib at an initial dose of 500 mg once daily continuously and S-1 at a dose of 40–60 mg twice daily on days 1–14 until the trail was discontinued disease progression, development of intolerable toxicity, or withdrawal of consent. The primary endpoints were progression-free survival. The secondary endpoints were objective response rates, disease control rates, and safety, and overall survival. This study was registered at ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT04338438","term_id":"NCT04338438"}}NCT04338438.ResultsBetween April 2015 and May 2019, we included 37 patients with advanced gastric or gastro-oesophageal junction adenocarcinoma refractory to first-line platinum-containing therapy. At the data cutoff, the 6-month progression-free survival was 31.5%, the median progression-free survival and overall survival were 4.2 (95% CI: 3.50–4.90) months and 8.2 (95% CI: 4.69–11.71) months, respectively. Of 37 eligible patients, 8 (21.6%) patients reached objective responses, 31 (83.8%) patients reached disease control. Grade 3 or 4 adverse events occurred in 8 (21.6%) patients, including hand-foot syndrome, hypertension, and diarrhea, etc.ConclusionsThe combination of Apatinib and S-1 showed promising efficacy and manageable toxicity as a home-based, second-line therapy in patients with advanced gastric or gastro-oesophageal junction adenocarcinoma, especially for the elder patients with poor performance status.Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT04338438","term_id":"NCT04338438"}}NCT04338438.     

同步放化疗对不能手术局部晚期胃癌的疗效

目的:观察同步放化疗对不能手术的局部胃癌晚期（Ⅱ-Ⅲc）患者的近期疗效。方法:将55例不能手术的局部晚期胃癌患者随机分为2组,28例进行同步放化疗治疗,先行XELOX方案化疗1周期,于2周期化疗第2天同时进行适形放疗,并按化疗周期进行3、4周期XELOX方案治疗。27例患者进行4周期XELOX方案化疗。结果:无进展生存期（PFS）:同步放化疗组为7.11个月,化疗组为5.13个月 (P＜0.05);一年生存率同步放化疗组60%高于化疗组51%,两者比较,无统计学意义(P＞0.05);肿瘤客观缓解率（ORR）同步放化疗组67.8%,化疗组40.7%（P＜0.05）;患者卡氏评分两组治疗前后均无统计学意义(P＞0.05)。结论:同步放化疗可以提高不能手术局部晚期胃癌患者近期疗效。     

Impacts of fluorouracil‐metabolizing enzymes on the outcomes of patients treated with S‐1 alone or S‐1 plus cisplatin for first‐line treatment of advanced gastric cancer

A phase III trial of S‐1 plus cisplatin (SP) versus S‐1 alone, for first‐line treatment of advanced gastric cancer (SPIRITS trial), has shown that overall survival was better in patients treated with SP than with S‐1 alone. In the present retrospective biomarker study, we aimed to develop a methodology to identify the patients with advanced gastric cancer who would respond better to S‐1 alone than SP. We studied 120 patients who received S‐1 alone or SP for first‐line chemotherapy for advanced gastric cancer, and quantitatively evaluated mRNA levels of thymidylate synthase (TS), thymidine phosphorylase (TP), orotate phosphoribosyltransferase (OPRT), dihydropyrimidine dehydrogenase, vascular endothelial growth factor‐A, and epidermal growth factor receptor in paraffin‐embedded specimens of primary tumors. Multivariate survival analysis in patients who received S‐1 monotherapy (66 patients) demonstrated that low TP expression (hazard ratio: 2.55 (95% CI: (1.33 to 4.89)), low TS (2.71 (1.36 to 5.37)), and high OPRT (0.33 (0.13 to 0.86)) were significant predictors of long overall survival. In patients with lower expression of both TP and TS (n = 23) than their cutoff values, the S‐1 alone group (n = 15) had longer overall survival than the SP group (n = 8; median overall survival, 18.2 months vs. 9.4 months), whereas the frequency of overall adverse events in the S‐1 alone group tended to be lower than that in SP group. Our results suggest that these biomarkers are useful for selection of patients with advanced gastric cancer in whom treatment with S‐1 alone will yield survival benefit.     

进展期胃癌的分子靶向治疗进展

胃癌是目前世界上危害人类健康的主要疾病之一,不能手术切除的进展期胃癌预后较差,寻求手术以外途径治疗胃癌的转移、复发具有重要意义。分子靶向治疗具有分子特异性和选择性,能高效并选择性地抑制或杀伤肿瘤细胞,同时减少对人体正常组织的损伤,是目前肿瘤治疗领域发展的新方向。随着胃癌分子病理学的研究深入,针对进展期胃癌的分子靶向治疗的药物研发成功并开始走向临床。本文综合近年来较有影响力的临床试验,阐述靶向药物在进展期胃癌中的地位,其中,贝伐单抗、西妥昔单抗联合氟尿嘧啶、铂类、紫杉类药物均表现出较好的疗效和安全性。ＴｏＧＡ试验确立了曲妥珠单抗在治疗进展期胃癌上的地位,但靶向治疗药物在进展期胃癌治疗中广泛应用有赖于更多的临床试验证据支持。     

胃癌综合治疗

胃癌临床上虽有多种治疗方法可供选择,但其术后复发率、死亡率都较高。目前,外科手术仍然是胃癌治疗的主要手段,并在胃癌根治性手术的规范化取得共识。化学治疗、放射治疗主要用于术后辅助治疗、预防复发及晚期胃癌的治疗;热疗、靶向治疗、免疫治疗是目前研究的热点。     

局部进展期胃癌的综合治疗

局部进展期胃癌由于局部区域复发率高,影响治疗的疗效.胃癌根治术后的辅助性放化疗可进一步提高疗效,对于接受D2手术的患者,术后同步放化疗仍可能提高生存率.无论术前放疗还是术前化疗都可以提高局部进展期胃癌的切除率,降低局部复发率,并延长生存期,是目前局部进展期胃癌的研究方向.     

阿帕替尼治疗晚期胃癌的临床疗效观察

目的:探讨阿帕替尼治疗晚期胃癌患者的临床疗效和安全性。方法:回顾性分析我院2016年1月至2017年2月接受阿帕替尼治疗的28例化疗失败的胃癌患者,给予阿帕替尼500 mg/d,直至患者出现疾病进展或不可耐受的不良反应,分析其疗效和安全性。结果:阿帕替尼治疗晚期胃癌的有效率（RR）为10.7%,疾病控制率（DCR）为42.8%,中位无进展生存时间（PFS）为3.6个月,中位总生存时间（OS）为5个月,患者耐受性良好,常见的不良反应为高血压、手足综合征和蛋白尿。结论:阿帕替尼治疗二线或以上化疗失败的晚期胃癌具有良好的疗效和安全性。     

Challenges in first line chemotherapy and targeted therapy in advanced gastric cancer

Chemotherapy prolongs survival in advanced gastric cancer (AGC). The challenges involved in this procedure are providing a framework to aid in determining the best single or combined chemotherapy protocols for targeted agents in front-line therapy for patients in a clinical setting. A review of Phase II-III studies published or referenced in major oncology congress publications from 1970 to 2013 was performed. Cisplatin and fluoropyrimidine remain the reference regimen. Fluoropyrimidine combined with oxaliplatin or irinotecan may also be employed in special situations. There are no comparative studies of the same regimens with or without anthacyclines; thus, the effectiveness of anthacyclines remains under debate. The introduction of trastuzumab in the front-line therapy of HER2-positive patients and ramucirumab in refractory patients ushered in an age of targeted therapy for this disease.     

进展期胃癌综合治疗的现状和进展

本文主要综述进展期胃癌的手术治疗、化学治疗及放射治疗的现状和进展。对于Ⅱ／Ⅲ期的胃癌主要是以D2手术根治为主，并辅以术中的热疗。对于完整的术前分期检查，使得Ⅲa／Ⅳ期的患者予以新辅助化疗后再行手术，这部分手术再切除，可提高胃癌患者的生存率，亦能改善生活质量：术后的辅助治疗，在原有的氟尿嘧啶、多柔比星（阿霉素）、顺铂治疗方案的基础上，氟尿嘧啶与奥沙利铂（乐沙定）、氟尿嘧啶、顺铂与紫杉醇组合及顺铂加CPT-11组成的方案有效率均有不同程度的提高：术后的放化疗结合也在研究探讨之中。     

晚期胃癌化疗进展

随着细胞毒药物和分子靶点药物的研发,晚期胃癌患者姑息化疗取得一定进展。患者中位生存期可接近1年。本文主要介绍新药多西紫杉醇、紫杉醇、奥沙利铂、伊立替康、卡培他滨、S1及靶向药物在晚期胃癌治疗中的作用以及局部晚期胃癌的化疗策略,尤其重点介绍Ⅲ期临床试验研究结果。提出一些新联合方案,如含多西他赛的DCF方案、含奥沙利铂的EOX和FLO方案、含卡培他滨的EOX和顺铂＋希罗达方案、含伊立替康的ILF方案、含S1的S1＋DDP方案,可以作为一线治疗晚期胃癌的新的参考方案。而靶向药物在晚期胃癌治疗中结论尚不明确,其有效性、安全性和最终收益有待进一步的研究;新辅助化疗可作为局部晚期胃癌治疗的选择。     

阿帕替尼治疗晚期胃癌临床观察

目的 目前仅仅有少数靶向药物可以改善晚期胃癌患者的预后,研究显示甲磺酸阿帕替尼作为三线方案可以改善胃癌患者生存质量.本研究对晚期胃癌使用甲磺酸阿帕替尼的临床疗效和安全性进行分析.方法 回顾性分析2015-01-30-2016-10-01安徽省肿瘤治疗中心收治的30例化疗失败、有可测量病灶晚期胃癌患者临床资料,其中安徽省立医院肿瘤科16例,安徽省心脑血管医院肿瘤科9例和安徽省肿瘤医院肿瘤内科5例.所有患者予以甲磺酸阿帕替尼单药500mg,1次/d,口服28 d为1个周期至疾病进展,观察临床疗效和不良反应.采用Cox比例风险回归模型进行生存分析.结果 全部患者均可评价疗效.其中完全缓解占0(0/30),部分缓解占10.0％(3/30),疾病稳定占46.7％(14/30),疾病进展占43.3％(13/30).缓解率为10.0％,疾病控制率为56.7％(17/30),中位无进展生存时间为3.84个月,中位生存时间为4.95个月,甲磺酸阿帕替尼主要不良反应包括高血压、蛋白尿、手足综合征和腹泻.Cox比例风险回归模型进行生存分析显示,随着治疗时机线数的增加(HR=5.029,95％CI为1.519～16.653,P=0.008)、体质量减少(HR=22.095,95％CI为3.624～134.700,P=0.001)疾病进展的风险增加.有手足综合征者死亡风险较低(HR=0.331,95％CI为0.153～0.714,P=0.005),而体质量减轻者的死亡风险较高(HR=6.549,95％CI为1.079～39.744,P=0.041).结论 甲磺酸阿帕替尼治疗化疗失败的晚期胃癌仍有较好的疾病控制及生存获益,不良反应可控制.出现手足综合征的患者早期使用可能具有生存优势.     

甲磺酸阿帕替尼治疗晚期胃癌的疗效及安全性分析

目的:观察甲磺酸阿帕替尼治疗晚期胃癌的临床疗效和毒副反应.方法:回顾性分析2016年01月至2018年01月在我院接受二线或以上的单纯化疗或甲磺酸阿帕替尼单独治疗的晚期胃癌患者,单纯化疗组56例作为对照组,甲磺酸阿帕替尼组34例.收集两组患者的一般临床资料,分析其临床近期疗效、无进展生存期和毒副反应.结果:对照组和甲磺...