Capecitabine/oxaliplatin as first‐line treatment for metastatic colorectal cancer: a meta‐analysis

Objective A meta‐analysis of randomized controlled trials (RCT) was carried out to determine the efficacy and safety of capecitabine plus oxaliplatin (CAPOX) or fluorouracil plus oxaliplatin (FUOX) as first‐line treatment for metastatic colorectal cancer (MCRC). Method A literature search was conducted of the Cochrane Controlled Trials Register Databases, Medline, Embase, ISI databases and Chinese Biomedical Literature Database without exclusion of material published in any language. RCTs conducted between 1998 and 2008 of CAPOX compared with FUOX regimens were considered for inclusion. Statistical analyses were carried out using RevMan software. Results Ten RCTs were included, involving 3208 patients. The meta‐analysis showed that there were no statistically significant differences in tumour response rate (RR, 0.93; 95% CI, 0.87–1.01; P = 0.09), progression‐free survival (PFS) (RR, 0.98; 95% CI, 0.94–1.01; P = 0.19), and overall survival (OS) (RR, 1.02; 95% CI, 0.97–1.07; P = 0.47) between CAPOX and FUOX regimen. However, symptoms of thrombocytopenia and hand‐foot syndrome (HFS) were increased in the CAPOX regimen (RR, 1.89; 95% CI, 1.33–2.69; P = 0.0004 and RR, 3.40; 95% CI, 2.25–5.15; P < 0.00001 respectively), while neutropenia and leucopenia occurred more frequently in the FUOX regimen (RR, 0.29; 95% CI, 0.15–0.55; P = 0.0002 and RR, 0.41; 95% CI, 0.18–0.95; P = 0.04respectively). Conclusion CAPOX was equivalent to FUOX in terms of tumour response rate, progression‐free survival (PFS), and OS in first‐line treatment for patients with MCRC, which may be considered as standard first‐line treatment in patients with MCRC.     

塞来昔布联合卡培他滨节拍化疗治疗老年患者晚期结肠癌的疗效观察

目的 探讨塞来昔布联合卡培他滨节拍化疗治疗老年患者晚期结肠癌的临床疗效。方法 回顾性研究35例老年晚期结肠癌病例,所有患者均给予口服卡培他滨500 mg,2次/d,塞来昔布200 mg,2次/d,连续服药直至病情进展,至少2月后评价疗效以及毒副反应。结果 治疗总有效率为37.1%,疾病控制率为77.1%,生活质量总改善率82.9%,中位疾病进展时间为8个月,中位生存期为14个月。所有患者均以Ⅰ、Ⅱ级毒副反应为主,主要为白细胞减少、手足综合征、恶心呕吐、腹泻、食欲减退等。结论 塞来昔布联合卡培他滨节拍化疗治疗老年晚期结肠癌具有安全、有效、毒副反应小以及患者依从性好等优点。     

节拍化疗模式下卡培他滨强化依西美坦抑制乳腺癌MCF-7细胞增殖的实验研究

目的:研究节拍化疗模式下卡培他滨联合依西美坦对乳腺癌MCF-7细胞的增殖抑制作用及信号通路机制。方法:实验分为7组,CCK-8法检测单药与联合用药组对MCF-7细胞增殖的抑制率。流式细胞仪检测分析药物作用对MCF-7细胞周期与细胞凋亡的影响。Western blot法检测各用药组MCF-7细胞p27、Bcl-2、PI3K和AKT蛋白的表达情况。结果:卡培他滨的半数抑制浓度（half maximal inhibitory concentration,IC50)为282.7 μmol/L、依西美坦IC50为103.5 μmol/L;联合用药组对MCF-7细胞增殖的抑制率高于单药组（P=0.003）;联合用药组中减小卡培他滨剂量不会显著降低细胞增殖抑制率（P=0.916）;与单药组影响细胞周期不同,联合用药会使MCF-7细胞停滞于S期或G1期;Western blot检测显示,联合用药会促进p27表达,抑制PI3K表达,促使细胞凋亡;低剂量卡培他滨会显著抑制Bcl-2表达（P=0.006）,使细胞停滞于S期。结论:小剂量卡培他滨节拍化疗联合依西美坦通过不同模式多方位影响MCF-7细胞周期及信号因子表达,显著抑制MCF-7细胞增殖。     

加味桂枝汤熏洗防治卡培他滨所致手足综合征的临床研究

[目的]观察加味桂枝汤外用熏洗以防治卡培他滨化疗所致手足综合征的临床疗效。[方法]选取卡培他滨化疗患者共35例,随机分为试验组18例和对照组17例。其中卡培他滨每日量为2500mg/m2,分两次口服,连用14d,休息7d,21d为一个周期。试验组从化疗第1天开始,使用加味桂枝汤煎剂熏洗手足,使用2个以上化疗周期,对照组从化疗第1天开始,早晚各口服维生素B6片/d及水熏洗手足,2周期后评价疗效及不良反应。[结果]试验组18例患者中3例发生Ⅰ级手足综合征,发生率为16.7%,对照组手足综合征发生率为44.4%,两者有显著性差异(P<0.05)。[结论]加味桂枝汤外用熏洗可有效防治卡培他滨化疗所致手足综合症。     

卡培他滨片联合奥沙利铂注射剂治疗晚期结肠癌患者的临床研究

目的观察卡培他滨片联合奥沙利铂注射剂治疗晚期结肠癌患者的临床疗效及安全性。方法将97例晚期结肠癌患者随机分为对照组49例和试验组48例。对照组给予130 mg·m^-2奥沙利铂,静脉滴注,于2~3 h内滴完,第1天;试验组在对照组治疗的基础上,给予1 250 mg·m^-2卡培他滨,bid,口服,第1~14天。2组患者均治疗6个疗程,每个疗程21 d。比较2组患者的临床疗效,血清癌基因ras产物P21蛋白(rasP21)和环氧化酶-2(COX-2)的水平,以及药物不良反应的发生情况。方法治疗后,试验组和对照组的总有效率分别为60.42%(29例/48例)和36.73%(18例/49例),差异有统计学意义(P<0.05)。治疗后,试验组和对照组的rasP21分别为(10.03±2.11)和(19.90±3.02)ng·mL^-1,COX-2分别为(3.11±1.10)和(6.70±2.01)ng·mL^-1,差异均有统计学意义(均P<0.05)。2组患者的药物不良反应均以恶心呕吐、白细胞减少、血小板减少、手足综合征、神经毒性和皮炎为主。试验组和对照组的总药物不良反应发生率分别为66.67%(32例/48例)和73.47%(36例/49例),差异无统计学意义(P>0.05)。结论卡培他滨片联合奥沙利铂注射剂治疗晚期结肠癌患者的临床疗效确切,其能明显降低血清rasP21和COX-2水平,且不增加药物不良反应的发生率。     

口服与注射长春瑞滨联合卡培他滨治疗蒽环类，紫杉类耐药性晚期乳腺癌的比较研究

目的 探讨口服长春瑞滨联合卡培他滨治疗葸环类、紫杉类耐药的转移性乳腺癌的疗效及不良反应。方法 80例确诊葸环类、紫杉类耐药的转移性乳腺癌患者随机分为两组。口服长春瑞滨联合希罗达组（试验组）：40例患者口服江苏豪森酒石酸长春瑞滨软胶囊45．50mg／（m^2-d），第1、8、15天服用，口服卡培他滨1650mg／（m^2·d），连服1—14d，每3周为1个周期，连用4个周期。注射长春瑞滨联合希罗达组（对照组）：40例患者，长春瑞滨（江苏豪森）25mg／（m^2·d）第1、8天静脉滴注，口服卡培他滨1650mg／（m^2·d），连服1-14d，每3周为1个周期，连用4个周期。治疗结束2周后评价疗效。结果 入组患者80例均可评价疗效，试验组有效率为42．5％，1年生存率为45．0％，中位进展时间4．7月，中位生存时间11．0月；对照组有效率为37．5％，1年生存率为42．5％，中位进展时间4．6月，中位生存时间10．6月；两组比较差异无统计学意义（P〉0．05）。在毒副反应方面，Ⅲ／IV便秘、局部静脉炎、HB下降、WBC下降、ANC下降、总Ⅲ／IV反应率两组比较。差异均有统计学意义（P〈0．05）。结论 口服长春瑞滨联合卡培他滨治疗葸环类、紫杉类耐药的转移性乳腺癌与静脉剂型疗效一致，并且在毒副反应上，口服长春瑞滨明显较静脉剂型轻，并且应用方便。     

奥沙利铂联合卡培他滨对实验性胃癌大鼠胃癌组织中肿瘤相关因子表达的影响及其协同抗肿瘤作用

目的：探讨奥沙利铂联合卡培他滨对实验性胃癌大鼠胃癌组织中肿瘤相关因子表达和血清炎症因子水平的影响,阐明其抗肿瘤作用的可能机制。方法：60只Wistar大鼠随机分为对照组、模型组、奥沙利铂组、卡培他滨组和奥沙利铂联合卡培他滨组（联合组）,每组12只。采用BGC823胃癌细胞株复制实验性胃癌模型,实验大鼠按分组要求分别给予奥沙利铂（20 mg·kg^-1）和（或）卡培他滨（400 mg·kg^-1）,对照组和模型组大鼠给予等体积生理盐水,连续给药8周。测定大鼠肿瘤平均质量,TUNEL染色检测胃癌细胞的凋亡情况,Western blotting法检测大鼠胃癌组织中P53、信号转导与激活因子3（STAT3）和血管内皮生长因子（VEGF）蛋白表达水平,酶联免疫吸附法（ELISA）测定大鼠血清中白细胞介素6（IL-6）、白细胞介素10（IL-10）和肿瘤坏死因子α（TNF-α）水平。结果：与对照组比较,模型组大鼠胃癌组织中P53、STAT3和VEGF蛋白表达水平及血清中IL-6、IL-10和TNF-α水平明显升高（P<0.05）;与模型组比较,奥沙利铂组、卡培他滨组和联合组大鼠肿瘤平均质量及胃癌组织中P53、STAT3和VEGF蛋白表达水平均明显降低（P<0.05）,胃癌组织中细胞凋亡指数（AI）明显升高（P<0.05）,血清中IL-6、IL-10和TNF-α水平明显降低（P<0.05）;联合组大鼠肿瘤平均质量和胃癌组织中P53、STAT3和VEGF蛋白表达水平及血清中IL-6、IL-10和TNF-α水平明显低于奥沙利铂组和卡培他滨组（P<0.05）。结论：奥沙利铂和卡培他滨能够通过降低大鼠胃癌组织中肿瘤相关因子蛋白表达水平和血清中IL-6、IL-10和TNF-α水平达到抗肿瘤作用,二者联合应用的抗肿瘤作用明显优于单用奥沙利铂或卡培他滨。     

Perioperative ECX chemotherapy in older adults with gastroesophageal adenocarcinoma

Introduction

Perioperative epirubicin, cisplatin and 5-FU or capecitabine (ECF/X) chemotherapy is recognised as a standard of care for patients with resectable gastroesophageal adenocarcinoma; however, there is limited evidence regarding its use in older patients. The aims of this study were to assess the effectiveness and tolerability of perioperative ECX chemotherapy in patients aged ≥70?years-old (group 1) compared with a younger population (group 2), and to assess differences in the histology of these groups.

Oral drugs in the treatment of metastatic colorectal cancer

Introduction: Intravenous administration of fluoropyrimidine-based chemotherapy has been the cornerstone of treatment in metastatic colorectal cancer (mCRC) for decades. The availability of oral capecitabine has improved the tolerability in monotherapy schedules, and has simplified combination schedules. Since then, other oral drugs have proven efficacy in this setting.

Areas covered: We review the available evidence and most recent data concerning oral drugs with proven efficacy in mCRC, including capecitabine, S-1, trifluridine-tipiracil (TAS-102) and regorafenib.

Expert opinion: The use of capecitabine is widely implemented in the care of mCRC. However, with recent data supporting its prolonged use, the relatively high incidence of hand-foot syndrome (HFS) may impair quality of life. In Asian populations, S-1 is associated with equivalent efficacy but lower incidence of HFS compared to capecitabine. Further studies evaluating the effects of S-1 in Western populations are needed. Both regorafenib and TAS-102 improve the overall survival of patients in whom all other treatment options have failed. Since only a subset of patients appears to benefit, future studies to identify predictive biomarkers are needed.     

卡培他滨联合阿司匹林对SGC-7901细胞增殖的体外抑制作用

目的探讨卡培他滨联合阿司匹林对SGC-7901细胞增殖和凋亡的体外抑制作用及其作用机制。方法体外培养SGC-7901细胞,MTT法检测卡培他滨1.0μmol/L与阿司匹林0.5、1.0、3.0 mmol/L单用和联用对SGC-7901细胞体外增殖的抑制作用;倒置相差显微镜观察卡培他滨1.0μmol/L与阿司匹林3.0 mmol/L单独及联合用药对SGC-7901细胞形态的影响;PI/Annexin V-FITC双染色流式细胞术分析卡培他滨1.0μmol/L与阿司匹林3.0 mmol/L单独及联合用药诱导SGC-7901的细胞凋亡率;Western blotting分析卡培他滨1.0 mmol/L与阿司匹林3.0 mmol/L单独及联合用药对COX-2、VEGF表达的影响。结果卡培他滨与阿司匹林对SGC-7901细胞均有生长抑制作用,且联合组的抑制率高于卡培他滨组和阿司匹林组,两组间比较差异具有统计学意义(P0.05)。用药处理24 h后,在显微镜下可观察到SGC-7901细胞发生细胞凋亡的形态学改变,联合组相对于卡培他滨、阿司匹林单独用药组的变化更明显。PI/Annexin V双染分析表明,卡培他滨1.0μmol/L+阿司匹林3.0 mmol/L联合组的细胞凋亡率明显高于阿司匹林3.0 mmol/L组或卡培他滨1.0μmol/L组。阿司匹林3.0 mmol/L、卡培他滨1μmol/L以及卡培他滨1.0μmol/L+阿司匹林3.0 mmol/L联合组电泳可以检测出环氧合酶-2(COX-2)、血管内皮生长因子(VEGF)的特异蛋白条带。阿司匹林单用时,COX-2表达量受到抑制(P0.01),蛋白表达下调,而VEGF表达无明显抑制;卡培他滨单用时,VEGF表达量受到抑制(P0.01),蛋白表达下调,而COX-2表达无明显抑制;卡培他滨联合阿司匹林处理时,SGC-7901细胞的COX-2、VEGF表达量均受到抑制(P0.01),同时下调COX-2及VEGF蛋白表达。结论卡培他滨联合阿司匹林能够明显抑制胃癌SGC-7901细胞的增殖,并促进其凋亡,其作用机制与COX-2、VEGF蛋白表达的调控有关。