药物转运体基因多态性对伊立替康治疗结直肠癌患者所致严重不良反应的影响

目的本研究旨在探讨药物转运体（ABCB1-3435C>T和ABCC2-24C>T）基因多态性与伊立替康治疗结直肠癌患者严重不良反应（主要指3~4级迟发型腹泻和中性粒细胞减少）的关系。 方法选取郑州市中心医院结直肠癌患者91例,采集外周静脉血,通过PCR-直接测序法对ABCB1-3435C>T和ABCC2-24C>T多态性进行基因分型,记录化疗中出现的不良反应,比较不同基因型患者使用伊立替康后严重化疗毒性的发生情况。 结果在结直肠癌患者中,ABCC2-24C>T基因多态性对伊立替康所致严重的迟发性腹泻有影响（χ²=5.067,P=0.024）,对中性粒细胞减少无影响（χ²=3.107,P=0.078）,而ABCB1-3435C>T基因多态性对伊立替康所致严重的迟发性腹泻和中性粒细胞减少均无影响（分别χ²=0.237,χ²=2.139,P均>0.05）。 结论ABCC2-24C>T基因多态性可增加结直肠癌患者伊立替康所致严重不良反应的风险,使用伊立替康前,进行ABCC2-24C>T检测,可以减少伊立替康毒副作用。     

伊立替康联合卡培他滨治疗晚期结直肠癌68例临床观察

目的探索伊立替康联合卡培他滨二线治疗晚期结直肠癌的近期疗效和安全性。方法选择经FOLFOX6治疗失败的晚期结直肠癌患者68例为观察对象,采用伊立替康联合卡培他滨方案化疗(伊立替康100 mg/m2,d1、d8;卡培他滨2 000 mg/m2·d,d1~d14),每3周为1个治疗周期,患者至少接受2个周期化疗。结果 68例患者中CR 2例,PR 23例,SD 8例,PD 35例,治疗总有效率为36.8%,疾病控制率为48.5%。主要不良反应以Ⅰ~Ⅱ度为多见,其中迟发性腹泻发生率为63.2%,手足综合征发生率为33.9%,骨髓抑制发生率为75.0%,恶心、呕吐发生率为72.1%,口腔炎发生率为29.4%,肝肾功能损伤发生率为19.1%。结论伊立替康联合卡培他滨方案治疗晚期结直肠癌为有效二线治疗方案,疗效较好,且毒副反应患者可耐受。     

FOLFOX-6与FOLFILI方案治疗转移性结直肠癌的效果比较

目的 比较FOLFOX-6方案与FOLFILI方案治疗转移性结直肠癌的临床疗效及不良反应.方法 将69例转移性结直肠癌患者随机分为观察组38例和对照组31例,观察组予FOLFOX-6(奥沙利铂+亚叶酸钙+5-氟尿嘧啶)方案、对照组予FOLFILI(伊立替康+亚叶酸钙+5-氟尿嘧啶)方案化疗,14 d为一周期,2周期后观察近期疗效、不良反应,随访2a记录患者的生存期、疾病进展时间.结果 两组有效率、控制率、平均生存期、疾病进展时间均无统计学差异;观察组骨髓抑制发生率明显高于对照组,延迟性腹泻、胆碱能神经综合征发生率明显低于对照组,P均＜0.05.结论 FOLFOX-6与FOLFILI方案治疗转移性结直肠癌效果相当,均有不良反应发生,但前者以骨髓抑制为主,后者以延迟性腹泻和胆碱能神经综合征为主;临床应根据患者具体情况选用化疗方案.     

唐草片对伊立替康所致小鼠毒性的保护作用

目的观察治疗艾滋病中药唐草片对伊立替康引起的小鼠毒性的防治作用。方法健康昆明小鼠腹腔注射盐酸伊立替康20mg/kg,每天1次,连续6天,制备迟发型腹泻动物模型,唐草片连续灌胃给药16天。结果注射伊立替康后第7天,动物体重下降幅度最大,为11.8%。而预防性给予唐草片的小鼠,体重下降4.3%,明显小于伊立替康组(P0.05)。给予唐草片组动物白细胞数为(2.11±0.99)×10~9/L,显著高于伊立替康组(1.26±0.46)×10~9/L(P0.05)。唐草片组小鼠迟发性腹泻发生时间比伊立替康组推迟2天,腹泻发生率4.91%,低于伊立替康组腹泻发生率52.5%(P0.05)。小肠组织标本固定后进行HE染色,伊立替康组黏膜部分绒毛顶端断裂破损,上皮细胞肿胀、变性、坏死,炎性细胞大量浸润,正常腺体减少;唐草片治疗组黏膜组织基本正常,少量炎症细胞浸润。结论唐草片可以减轻伊立替康引起的肠黏膜损伤、延缓迟发型腹泻。     

伊立替康联合紫杉醇治疗复发上皮性卵巢癌的疗效观察

目的观察伊立替康联合紫杉醇治疗复发上皮性卵巢癌的疗效。方法选择30例复发的耐铂上皮性卵巢癌,采用伊立替康联合紫杉醇治疗。伊立替康80mg/m2,静脉给药,第1、8、15天,28d为1周期;紫杉醇用药剂量和方法：每疗程紫杉醇总剂量为135mg/m2,溶于500ml 0.9%氯化钠溶液或5%葡萄糖液中进行静脉滴注,2～4个周期结束后评价疗效。结果 30例均可评价疗效,完全缓解率为6.67%,部分缓解率为23.33%,总缓解率43.33%,中位肿瘤进展时间为6.8个月。不良反应主要为骨髓抑制和迟发性腹泻,无化疗毒性相关死亡病例。结论伊立替康单药是治疗复发的耐铂上皮性卵巢癌安全有效的方案。     

伊立替康联合雷替曲塞方案二线治疗晚期结直肠癌的疗效与安全性分析：一项探索性研究

目的探索伊立替康联合雷替曲塞方案二线治疗晚期结直肠癌的疗效与安全性。 方法纳入2013年6月至2016年4月于中国医科大学附属第一医院肿瘤内科晚期二线治疗结直肠癌患者13例,所有患者接受伊立替康联合雷替曲塞方案治疗,具体用药为：伊立替康：180 mg/m² d1,d8静脉滴注;雷替曲塞：3 mg/m² d1静脉滴注（15 min）;每3周。SPSS 21.0进行统计学分析,生存分析采用Kaplan-Meier及Log-rank检验法。 结果至随访终止时间（2016年12月1日）,中位随访时间10.1个月,共11例二线进展,中位疾病进展时间（TTP）为4.0个月;死亡病例共6例;疾病控制率为46.2%（SD 6例;PD 7例）;单因素分析显示：性别、年龄、BMI、原发肿块部位等对化疗疗效均无显著影响;在可评估不良反应中,主要为乏力（90%）、恶心（70%）、腹泻（60%）、肝功能损伤（37.5%）、骨髓抑制（22.2%）等,毒副反应基本可以耐受。 结论伊立替康联合雷替曲塞方案在晚期结直肠癌的二线治疗中效果肯定,且毒副反应可耐受,有望成为晚期结直肠癌的二线治疗的替代方案。     

射频消融后联合伊立替康与卡培他滨化疗在结肠癌伴肝转移治疗中的价值分析

目的观察在结肠癌伴肝转移患者中,应用射频消融联合伊立替康与卡培他滨化疗的方案的临床价值.方法回顾性分析2011-07/2016-07期间,嵊州市人民医院收治的150例结肠癌伴肝转移的临床资料,所选患者均行射频消融治疗,根据射频消融后的化疗方案不同分为两组,其中70例患者给予伊立替康联合氟尿嘧啶方案进行治疗,将其作为对照组,80例患者给予伊立替康联合卡培他滨方案进行治疗,将其作为观察组.然后将两组患者的临床疗效、不良反应等指标进行比较.结果经过治疗后,观察组患者的治疗总有效率为71.25%,高于对照组的64.28%,差异无统计学意义(P0.05);观察组患者的无进展生存时间、总生存时间分别为5.3±0.8、15.1±1.9,高于对照组的4.6±0.5、12.5±1.7,差异无统计学意义(P0.05);两组患者在脱发、肝功能损害、血小板减少的发生率上无明显差异,无统计学意义(P0.05);观察组患者的腹泻发生率为41.43%,明显高于对照组的13.75%,差异具有统计学意义(P0.05);观察组患者恶心、呕吐发生率、白细胞减少发生率及贫血发生率均低于对照组(12.5%、10.00%、16.25%vs 44.29%、38.57%、42.86%),差异有统计学意义(P0.05).结论在结肠癌伴肝转移患者中应用射频消融联合伊立替康与卡培他滨化疗的治疗方案,在保证临床疗效的同时,且具有较高的用药安全性.     

微波消融联合肝动脉栓塞术治疗结直肠癌术后肝转移的疗效及对肝功能变化的影响

目的对比分析单独肝动脉化疗栓塞术(transcatheter arterial chemoembolization,TACE)治疗与TACE联合微波消融术(microwave ablation,MWA)治疗结直肠癌肝转移患者的疗效及预后影响.方法收集2013-01/2015-01在我院治疗的84例原发性结直肠癌患者的临床资料进行回顾性分析,患者依据不同治疗方案分为TACE联合MWA组(n=40)、单独TACE组(n=44).比较两组患者的治疗效果及不良反应发生情况,比较两组患者的肝功能变化、生活质量及生存情况.结果治疗后1 mo,TACE联合MWA组和单独TACE组的治疗有效率、疾病控制率分别为77.5%、85.0%和38.6%、56.8%;TACE联合MWA组的治疗有效率、疾病控制率均显著高于单独TACE组(χ~2=5.441,P0.05).治疗1周后,两组患者的血清总胆红素、A LT及白蛋白水平比较均无显著差异(t=3.662,2.816,2.578,P0.05).治疗期间,两组患者恶心、呕吐、血小板减少、白细胞减少、血红蛋白减少、黏膜炎、胆碱能综合征及迟发性腹泻等不良反应发生情况比较均无显著差异(χ~2=1.056,0.784,1.022,2.103,0.668,P0.05).治疗6 mo后,TACE联合MWA组患者的生理状况、情感状况、功能状况、家庭及社会状况、生活质量总评分均显著高于单独TACE组患者(t=5.139,6.052,4.331,4.508,4.417,P0.05).TA C E联合M WA组患者治疗后半年、1年的生存率与单独TACE组患者比较无显著差异(χ~2=0.216,1.492,P0.05),但治疗后2年、3年的生存率均显著高于单独TACE组患者(χ~2=3.894,4.017,P0.05).结论微波消融联合肝动脉栓塞术治疗结直肠癌肝转移患者疗效显著,且相比于单独的肝动脉化疗栓塞术能够进一步提高患者的生活质量、延长生存时间,同时不会增加不良反应发生情况.     

雷替曲塞联合伊立替康治疗晚期结直肠癌的临床观察

目的分析雷替曲塞联合伊立替康治疗晚期结直肠癌的疗效及安全性。 方法纳入中国医学科学院肿瘤医院内科2015年1月至2018年12月收治的34例既往一线或二线使用含氟尿嘧啶类化疗方案失败的晚期结直肠癌患者,接受雷替曲塞联合伊立替康方案治疗,主要观察终点为客观有效率（ORR）,次要观察终点包括疾病无进展生存时间（PFS）、总生存时间（OS）、疾病控制率（DCR）和安全性。 结果34例患者病理确诊均为结直肠腺癌。近期疗效中观察到部分缓解（PR）为6例,疾病稳定（SD）为25例,疾病进展（PD）为3例,客观有效率（ORR）为17.6%（6/34）,疾病控制率（DCR）为91.2%（31/34）。其中,二线患者ORR为21.7%（5/23）,DCR为91.3%（21/23）;三线患者ORR为9.1%（1/11）,DCR为90.9%（10/11）。34位患者全部追踪至疾病进展,疾病无进展中位生存时间（mPFS）为180天（95% CI：157.2~202.8）,截止2020年2月27日末次随访未观察到中位总生存时间（mOS）,平均OS（389.0±51.1）天。其中,接受二线治疗患者的mPFS为193天,平均OS（412.0±61.5）天。接受三线治疗患者的mPFS为150天,mOS为311天。治疗后肿瘤标志物CEA与CA19-9水平均有降低,其中CA19-9治疗前后平均水平为（169.8±48.0）U/mL和（143.8±57.7）U/mL（t=0.700,P=0.655）。CEA治疗前平均水平为（255.0±40.6）ng/mL,治疗后为（104.2±32.4）ng/mL,下降趋势经比较差异具有统计学意义（t=1.759,P=0.001）。安全性方面,常见不良反应包括恶心呕吐、腹泻、白细胞及中性粒细胞减少、血红蛋白降低和转氨酶升高等,多为Ⅰ~Ⅱ级,Ⅲ级不良反应有中性粒细胞减少（2/34）、白细胞减少（1/34）和转氨酶升高（1/34）,无Ⅳ级不良反应及化疗相关死亡事件发生。 结论雷替曲塞联合伊立替康治疗晚期结直肠癌疗效确切,安全性良好。其中二线治疗ORR与国内外既往研究相似,但不良反应更低,值得临床进一步推广应用。     

伊立替康辅助FOLFOX化疗方案对结直肠癌患者血清肿瘤标志物及miR-200a、miR-190含量的影响

背景目前对于结直肠癌的治疗方式仍以手术为主,术后采用化疗、靶向药物治疗等药物辅助,其中靶向药受到遗传基因和价格因素的制约,化疗药物仍是治疗首选.同时已被更多的研究所证实,联合用药可以从更多途径抑制癌细胞的生长,其疗效优于单一化疗药物.目的探讨伊立替康辅助FOLFOX化疗方案在结直肠癌(colorectal cancer, CRC)中应用价值.方法选取2017-03/2019-02我院CRC患者92例,依据简单随机数字表法分为研究组(n=46)与对照组(n=46).靶向治疗基础上对照组采取FOLFOX方案,研究组在对照组基础上采取伊立替康.统计2组肿瘤控制率、血清肿瘤标志物、miR-200a、miR-190表达情况、血清转化生长因子-α(TGF-α)、胰岛素样生长因子Ⅱ(IGF-Ⅱ)水平、毒副反应发生率,随访12 mo,统计2组生存率.结果研究组肿瘤控制率(71.74%)与对照组(65.22%)间无显著差异(P0.05);治疗后研究组血清CEA、CA125、CA199、CA72-4、TGF-α、IGF-Ⅱ水平低于对照组(P 0.05);治疗后研究组血清miR-200a、miR-190表达高于对照组(P0.05); 2组均未发生Ⅳ度毒副反应,且研究组的毒副反应发生率与对照组相比无明显差异(P0.05);研究组治疗后6 mo、9 mo、12 mo生存率(95.56%、88.89%、80.00%)与对照组(91.11%、75.56%、64.44%)间无显著差异(P0.05).结论联合采取FOLFOX化疗方案及伊立替康治疗CRC,可降低血清肿瘤标志物、TGF-α、IGF-Ⅱ含量,调节miR-200a、miR-190表达,且不会增加毒副反应发生风险.     

奥沙利铂联合氟尿嘧啶和亚叶酸钙方案治疗70岁及以上转移性结直肠癌的疗效和安全性

目的 对比观察奥沙利铂联合氟尿嘧啶和亚叶酸钙方案(FOLFOX4)治疗70岁及以上转移性结直肠癌患者与70岁以下患者的不良反应和疗效.方法 61例转移性结直肠癌患者,其中≥70岁组28例,＜70岁组33例,两组患者均接受FOLFOX4方案化疗,14 d为1个周期,治疗期间观察不良反应,3个周期后评价疗效.结果 61例患者均可评价不良反应及疗效.主要不良反应为骨髓抑制、胃肠道反应及神经毒性,≥70岁组腹泻的发生率高于＜70岁组,但主要为1～2度不良反应.≥70岁组白细胞和中性粒细胞下降的发生率高于＜70岁组(92.8%比78.8%和39.3%比36.3%),但差异无统计学意义.≥70岁组神经系统毒性发生率为46.5%,＜70岁组为36.4%,均为1～2度,两组间差异无统计学意义.≥70岁组患者近期有效率为25%,疾病控制率为71.4%,中位疾病进展时间(TTP)为6个月,＜70岁组患者近期有效率24.2%,疾病控制率84.8%,中位TTP 7个月,两组有效率和疾病控制率差异无统计学意义,而＜70岁组患者的中位TTP比≥70岁组略长.结论FOLFOX4方案同样适用于≥70岁转移性结直肠癌患者,其耐受性较好且疗效肯定.

Abstract：

Objective To observe the safety and efficacy of FOLFOX4 regiment in elderly versus young patients with advanced colorectal cancer. Methods There were 61 patients enrolled in this study, with 28 elderly patients aged 70 years and over, 33 young patients aged less than 70 years.They suffered from advanced/recurrent colorectal cancer and received FOLFOX4 regiment (Oxaliplatin +CF+5-FU). Every 14 days were as a cycle, and the therapeutic safety and efficacy were evaluated after three cycles. Adverse events and response to treatment were compared between the elderly and young patients. Results The main adverse effects were myelosuppression, gastrointestinal disturbance and neurotoxicity. The incidence rate of diarrhea was significantly higher in elderly patients than in young patients, but the most of diarrhea were at grade Ⅰ - Ⅱ. The incidence rates of leucocyte decrease and neutrophil decrease were higher in elderly patients than in young patients (92. 8% vs. 78. 8%, 39.3% vs. 36.3%), but there were no statistically significant differences between them. The incidence rate of neurotoxicity was 46.5% in elderly patients and 36.4% in young patients (P＞0. 05). The recent efficacy rate was 25%, disease control rate was 71.4% and median time-to-progression (TTP) was 6 months in elderly patients and 24.2%, 84.8% and 7 months in young patients (all P＞0.05). Conclusions FOLFOX4 regiment is well-tolerated and effective in both young and elderly patients.     

DPYD、ABCB1、GSTP1、ERCC1基因多态性与晚期结肠癌临床特征、不良反应、预后的关系

目的检测晚期肠癌患者药物基因多态性,分析其与临床特征、以奥沙利铂或氟尿嘧啶为主化疗方案不良反应和预后的关系。 方法收集2016年3月至2018年5月在中国解放军总医院肿瘤内科住院治疗的108例晚期结肠癌患者的外周血,以Life平台检测对DPYD、ABCB1、GSTP1、ERCC1基因进行单核苷酸多态性（SNP）分型,比较不同基因型与患者KRAS状态、肿瘤部位（左右）、不良反应和中位无进展生存时间（PFS）的差异。 结果纳入晚期肠癌患者108例,DPYD 4个位点（rs3918290、rs55886062、rs67376798、rs2297595）均为野生型,ERCC1（rs11615）GG纯合型基因52例（48.1%）,AG杂合型基因50例（46.3%）,AA野生型基因6例（5.6%）。GSTP1（rs1695）AG杂合型突变36例（33.3%）,AA野生型66例（66.1%）,GG纯和突变型6例（5.6%）。ABCB1（rs1045642）AG杂合型基因58例（53.7%）,GG纯合型基因42例（38.9%）,AA野生型8例（7.4%）。肿瘤位于左右半结肠与ERCC1基因分布频率有关（χ²=4.802,P=0.028）,与GSTP1,ABCB1基因分布频率无关。KRAS突变患者ABCB1杂合突变率42.9%,未见突变患者为72.7%,两者差异具有统计学意义（χ²=3.939,P=0.047）。GSTP1 AG型和GG型较AA型易产生2~3级全身不良反应高（77.8% vs. 45.5%,χ²=5.193;P=0.023）。ABCB1 GG型和AA型患者发生3~4级不良反应率为32.9%,对比AG型患者发生不良反应率为62.1%,差异具有统计学意义（χ²=4.862,P=0.027）。中位疾病进展时间PFS与ABCB1和GSTP1基因多态性无关,与不同ERCC1基因型有关,ERRC1杂合型突变（AG型）患者较纯和型（GG型＋AA型）具有较短PFS（5.6 m vs. 8.0 m,P=0.029）。 结论检测基因多态性具有临床价值,对晚期肠癌化疗的不良反应、预后及为患者调整化疗方案具有有效的指导作用。     

Clinical predictors of colorectal polyps and carcinoma in a low prevalence region： Results of a colonoscopy based study

AIM： To estimate the prevalence of colorectal cancer （CRC） in patients with long lasting colonic symptoms undergoing total colonoscopy; and to establish clinical features predicting its occurrence. METHODS： This prospective study was carried out in Imam Hospital, Tabriz University of medical sciences, Iran. Continuous patients with long lasting lower gastrointestinal tract symptoms who had the criteria of a colonoscopy were included. The endoscopist visualized the caecum documented by a photo and/or a specimen from terminal ileum. RESULTS： Four hundred and eighty consecutive symptomatic patients [mean age （SD）： 42.73 （16.21）] were included. The prevalence of colorectal neoplasia was 15.3% （34 subjects） and 37.7% （181 subjects） had a completely normal colon. Adenomatous polyps were detected in 56 （11.7%） patients, in 12.3% of men and 10.9% of women. The mean age of the patients with a polyp was significantly higher than the others （49.53 ± 14.16 vs 41.85 ± 16.26, P = 0.001）. Most of the adenomatous polyps were left sided and tubular; only 22.5% of polyps were more than 10 mm. Cancer was detected in 16 （3.6%） of our study population, which was mostly right sided （57.2%）. The mean age of patients with cancer was significantly higher than the others （60.25 ± 8.26 vs 42.13 ± 16.08, P 〈 0.005） and higher than patients with polyps [60.25 （8.26） vs 49.53 （1.91） （P 〈 0.0005）]. None of the symptoms （diarrhea, abdominal pain, rectal bleeding, constipation, altering diarrhea and constipation, history of cancer, known irritable bowel disease, history of polyp and fissure or family history of cancer） were predictors for cancer or polyps, but the age of the patient and unexplainedanemia independently predicted cancer. CONCLUSION： Less advanced patterns and smaller sizes of adenomas in Iran is compatible with other data from Asia and the Middle East, but in contrast to western countries. Prevalence of colonic neoplasia in our community seems to be lower th     

Systemic treatment of patients who have colorectal cancer and inflammatory bowel disease

Colorectal cancer is the most common malignant complication in patients who have IBD. The disease is difficult to diagnose because there is an overlap in symptoms in patients who have colon cancer and those who have IBD. Much has been learned about the incidence of colorectal cancer in patients who have IBD and its correlation with disease activity, duration, and anatomic location; however, almost no data are available regarding specific therapeutic considerations during adjuvant or palliative chemotherapy for these patients with respect to their underlying disease. Patients who have IBD who develop colorectal cancer are at higher risk for developing severe diarrhea during chemotherapy that may be due to the toxic effects of cytotoxic drugs or a flare of the IBD. Continuous infusional 5-FU alone, in combination with leucovorin, or in combination with oxaliplatin (FOLFOX) seems to be tolerated best. Bolus infusions of 5-FU (Roswell Park or Mayo regimens) and combination therapy of irinotecan with 5-FU should be avoided because of severe diarrhea and the possibility of sepsis. When diarrhea develops or worsens, empiric aminosalicylates may be given. Although it is theoretically possible that anti-EGFR therapies could affect IBD activity adversely, clinical experience with cetuximab in patients who have colorectal cancer has not shown any significant gastrointestinal side effects. Therefore, it seems reasonable to use it in patients who have colorectal cancer and IBD. The administration of bevacizumab has been associated with rare episodes of intestinal perforation; it should be used with great care in patients who have IBD. More studies and an integrative, multidisciplinary approach from oncologists and gastroenterologists are needed to provide optimal care for patients who have IBD during chemotherapy for colorectal cancer     

Randomized trial comparing weekly bolus 5-fluorouracil plus leucovorin versus monthly 5-day 5-fluorouracil plus leucovorin in metastatic colorectal cancer

BACKGROUND/AIMS: The purpose of this study was to compare the efficacy and toxicity profiles of weekly intravenous (i.v.) bolus injection of 5-fluorouracil plus low-dose leucovorin with the Mayo Clinics' monthly 5-day schedule of 5-fluorouracil and leucovorin in the treatment of metastatic colorectal cancer. METHODOLOGY: A total of 96 patients with previously untreated metastatic colorectal cancer were randomized to receive either a weekly i.v. bolus injection of 5-fluorouracil 400 mg/m2 plus leucovorin 20 mg/m2 (weekly arm), or i.v. bolus injection of 5-fluorouracil 425 mg/m2 plus leucovorin 20 mg/m2 for 5 consecutive days every 4 or 5 weeks (monthly arm). Therapy was continued until disease progression or unacceptable toxicity appeared. In the presence of disease progression, the study regimen was stopped and second-line treatment was instituted after the patient was discontinued from this study. RESULTS: There was no significant difference of response rates between both regimens. The response rate were 14.3% in the weekly arm (2 CR and 5 PR, 95% CI: 2.6-25.2%) and 10.6% in the monthly arm (1 CR and 4 PR; 95% CI: 6.5-32.3%), respectively (P = 0.8957). The survival times were also similar between the two (P = 0.4207, log-rank test). The median survival were 15.8 months in the monthly arm and 18.4 months in the weekly arm. Hematologic toxicity was minimal in both arms. However, the monthly arm produced a higher toxicity in severe (grade 3-4) diarrhea (14.9% vs. 2%; P = 0.029) and stomatitis (8.5% vs. 0; P = 0.054). CONCLUSIONS: Weekly bolus injection of 5-fluorouracil and low-dose leucovorin achieved a similar response rate and survival as compared with the Mayo Clinics' monthly 5-day schedule, but severe toxicity was less commonly seen using the weekly regimen. As current chemotherapeutic treatment for metastatic colorectal cancer is largely palliative rather than curative, the weekly bolus regimen may be a more favorable approach in managing metastatic colorectal cancer.     

冠状动脉慢性闭塞患者采用不同抗凝方案的围术期心肌损伤情况及不良事件分析

目的 回顾性观察冠状动脉慢性闭塞（chronic total occlusion，CTO）患者行经皮冠状动脉介入治疗（percutaneous coronary intervention, PCI）时，不同抗凝方案围术期心肌损伤及不良事件的差异。方法 选取2016年6月-2017年6月就诊于北京安贞医院确诊为CTO患者396例，根据术中抗凝方案分为比伐芦定组（54例）、普通肝素组（168例）和普通肝素+血小板糖蛋白IIb/IIIa受体抑制剂（Glycoprotein IIb/IIIa Receptor Inhibitor,GPI)组（174例），观察比较三组患者的临床基线、术中相关指标以及围术期心肌损伤和不良事件发生情况。结果 三组患者间心肌梗死病史、糖尿病病史、CABG病史、替格瑞洛、血尿酸、手术时间存在统计学差异（P＜0.05），其余临床基线资料及手术相关指标差异均无统计学意义（P＞0.05）。三组患者的围术期心肌损伤发生率差异有统计学意义（44.4% vs. 73.8% vs. 58%，P＜0.001），支架内血栓（7.4% vs. 0% vs. 1.1%，P＝0.002）、心包填塞发生率（3.7% vs. 1.2% vs. 0%，P＝0.029）的差异也有统计学意义。结论 CTO患者行PCI治疗的临床实践中，比伐芦定可以降低围术期心肌损伤发生率，但增加了支架内血栓和心包填塞的发生率。     

Tolerability profiles of rofecoxib (Vioxx) and Arthrotec. A comparison of six weeks treatment in patients with osteoarthritis

OBJECTIVE: To compare the incidence of selected spontaneously reported adverse events (AEs) in patients with osteoarthritis (OA) treated with rofecoxib (VIOXX, 12.5 mg qd) or Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid). METHODS: Double-blind, parallel-group, 6-week study of patients aged > or = 40 years with a clinical diagnosis of OA treated with rofecoxib or Arthrotec. Primary endpoint: self-reported diarrhea; secondary endpoints: abdominal pain, discontinuations due to AEs, GI AEs and NSAID-type GI AEs (ie., acid reflux, dyspepsia, epigastric discomfort, heartburn, nausea, vomiting). RESULTS: Among 483 patients (80.3% females, mean age 62.1), the rofecoxib group vs the Arthrotec group respectively reported diarrhea 6.2% vs 16.2% (p<0.001); drug-related diarrhea 3.7% vs 16.2% (p<0.001); one or more clinical AEs 52.9% vs 73.0% (p<0.001); GI AEs 28.9% vs 48.5% (p<0.001); NSAID-type GI AEs 18.6% vs 29.9% (p=0.004); discontinuations due to abdominal pain 0.4% vs 3.7% (p<0.05); and discontinuations due to any AE 4.1% vs 9.1% (p=0.029). No significant differences were observed in efficacy. CONCLUSION: Rofecoxib 12.5 mg qd has improved GI tolerability and similar efficacy compared to Arthrotec (diclofenac 50 mg/misoprostol 200 mcg bid).     

Oral fluoropyrimidine versus intravenous 5‐fluorouracil for the treatment of advanced gastric and colorectal cancer: Meta‐analysis

Background and Aim

5‐Fluorouracil (5‐Fu) is one of the most commonly prescribed antineoplastic agents against gastric and colorectal cancers. Continuous infusion would be the optimal way of its administration, however, may usually cause thrombosis, infection, and prolonged hospital stay. Oral fluoropyrimidines would be an attractive alternative, but their efficiency and toxicities for the treatment of gastric and colorectal cancer are still obscure as compared with infusion 5‐Fu.

Methods

Literature retrieval, trials selection and assessment, data collection, and statistic analysis were performed according to the Cochrane Handbook. The outcome measures were tumor response rate, progression‐free survival, overall survival, and adverse effects.

Results

Twenty‐nine randomized controlled trials, comprising totally 15 154 patients, were included. Meta‐analysis showed similar overall outcome in terms of response rate (1.01; 95% confidence interval [CI], 0.92–1.12), progression‐free survival (hazard ratio 1.00; 95%CI, 0.94–1.06), and overall survival (hazard ratio 0.96; 95%CI, 0.92–1.01) between oral fluoropyrimidine‐based and intravenous 5‐Fu‐based regimens in gastric and colorectal cancer patients. The risk of grade 3/4 neutropenia, thrombocytopenia, and stomatitis was more prominent in intravenous 5‐Fu‐based regimens; while more frequent grade 3/4 hand‐foot syndrome, diarrhea, and anorexia were detected in oral fluoropyrimidine‐based regimens.

Conclusions

Oral‐fluoropyrimidines showed equivalent response and similar survival outcomes, but different toxicity profiles, as compared with intravenous 5‐Fu. Thus, it would be a more convenient and adjustable alternative in treatment of advanced gastric and colorectal cancer.     

Compassionate use programme of irinotecan in colorectal cancer patients in The Netherlands

BACKGROUND: Irinotecan is an effective treatment for metastatic colorectal cancer. However, its use may be associated with troublesome adverse effects such as delayed diarrhoea, acute cholinergic syndrome and neutropenic infection. The manufacturer decided to release irinotecan for compassionate use in The Netherlands prior to its regulatory approval (June 1998) and first introduction for second-line treatment of metastatic colorectal cancer. In view of the drug's adverse effect profile this was done in a carefully controlled manner. METHODS: Irinotecan was made available to patients with colorectal cancer with elaborate precautions. Treating physicians requesting irinotecan for compassionate use received a protocol, providing recommendations for the proper use and the prevention/management of potentially troublesome adverse events. Limited demographic, toxicity and efficacy data were collected. RESULTS: Between June 1997 and September 1998, 112 patients were registered for this programme, 103 of whom actually received irinotecan. The percentage of patients experiencing grade 3-4 adverse effects was relatively low: delayed diarrhoea in 17%, nausea and vomiting 17%, acute cholinergic syndrome 6%, febrile neutropenia 4% and neutropenic infection 2%. Five partial tumour responses and a high proportion of patients with 'no change' were noted. CONCLUSIONS: The carefully controlled release of irinotecan for compassionate use with a very detailed protocol for guidance and advice on safety precautions seems to have contributed to the relatively safe use of the drug outside the setting of a formal clinical trial.