S-1与卡培他滨或氟尿嘧啶治疗晚期结直肠癌的疗效对比Meta分析

目的 利用现有文献资料,对S-1与卡培他滨或氟尿嘧啶治疗晚期结直肠癌的治疗数据进行对比荟萃分析,以此论证S-1替代卡培他滨或氟尿嘧啶的可行性。方法 在PubMed、Cochrane Library、Embase、CNKI数据库中检索已发表的文献,在临床试验中心（https://www.clinicaltrials.gov/）中搜寻符合要求的对照试验。资料的提取和质量评价是依据Cochrane Handbook 5.1.0,并使用RevMan 5.3软件对相关病例对照研究进行Meta分析。结果 来自11项随机对照研究的3 462名患者的数据纳入分析。与卡培他滨或氟尿嘧啶方案相比,S-1治疗组的OS得到改善,但PFS、DCR、ORR并不具有统计学意义。在不良反应中,S-1组的腹泻、肾功能不全和手足综合征的发生率较对照组低。但在合理的对比剂量下S-1组血小板降低的发生率高于对照组。结论 晚期结直肠癌的治疗中,S-1替换常规化疗方案中的卡培他滨或氟尿嘧啶有一定的疗效优势。     

晚期乳腺癌替吉奥与卡培他滨治疗疗效及安全性对比研究

目的 氟尿嘧啶前体药物单药治疗晚期乳腺癌患者,对于改善生活质量有优势.但卡培他滨手足综合征发生率高,替吉奥胶囊在中国乳腺癌患者中的有效性及安全性仍有待进一步研究证实.本研究比较两种氟尿嘧啶前体药物,替吉奥单药对照卡培他滨单药二/三线治疗晚期乳腺癌患者的疗效及安全性.方法 安徽医科大学第一附属医院肿瘤内科2012-01-01-2015-06-30收治的既往一线或二线治疗失败的转移性乳腺癌患者63例,随机分为替吉奥治疗组(32例)和卡培他滨治疗组(31例),按照患者体表面积(body surface area,BSA)设置给药剂量.替吉奥组40～60 mg(BSA＜1.25m2,40 mg;1.25～1.5m2,50 mg;＞1.5 m2,60mg),于早晚饭后口服.连续口服28d,休息14d,每6周为1个周期;卡培他滨组:2 500 mg/(m2·d),分2次服用,连续口服14 d,休息7d,每3周为1个周期.两组均每6周进行疗效评价,每周期评价安全性,主要研究终点为无进展生存期(progression-free survival,PFS).所有数据均采用SPSS19.0软件进行分析.结果 中位随访12.0个月,替吉奥组中位PFS为5.5个月(95％CI:4.7～6.3),卡培他滨组中位PFS为4.0个月(95％CI:2.4～5.6),两组差异无统计学意义,P=0.638.替吉奥组客观反应率(objective reaction,ORR)为31.3％(10/32),疾病控制率(disease control rate,DCR)为65.6％(21/32);卡培他滨组ORR为32.3％(10/31),DCR为67.7％(21/31).两组比较差异均无统计学意义,均P＞0.05.两组总体不良反应发生率相当,多为1～2度可耐受,替吉奥组高胆红素血症发生率更高(40.6％ vs 6.4％,P=0.006),卡培他滨组手足综合征发生率更高(45.2％vs 9.4％,P=0.004),差异有统计学意义.结论 替吉奥及卡培他滨单药二/三线治疗晚期乳腺癌疗效相当,毒性谱稍有不同,但均可耐受.替吉奥化疗期间推荐检测血清胆红素水平,尤其是合并肝转移患者.其手足综合征发生率下降,对于改善患者生活质量更有优势,值得临床进一步探索.     

替吉奥联合卡培他滨治疗晚期转移性胰腺癌的疗效观察

目的探讨替吉奥联合卡培他滨治疗晚期转移性胰腺癌的临床疗效。方法选取2013年1月至2016年1月间山东省临朐县人民医院收治的50例晚期胰腺癌患者,按照治疗方式不同分为观察组与对照组,每组25例。观察组采用替吉奥联合卡培他滨治疗,对照组采用卡培他滨治疗,观察两组患者治疗效果及安全性。结果观察组患者治疗有效率和疾病控制率分别为48.0%和80.0%,对照组患者分别为20.0%和40.0%,差异均有统计学意义(均P<0.05)。两组患者6个月生存率分别为67.9%和60.5%,1年生存率分别为31.3%和26.5%,中位生存时间分别为9.2个月和8.1个月,差异均无统计学意义(均P>0.05)。观察组患者粒细胞减少率和恶心呕吐发生率分别为36.0%和32.0%,均高于对照组患者的12.0%和8.0%,差异均有统计学意义(均P<0.05);两组患者腹泻、贫血、肝功能损伤和周围神经病变等不良反应发生率的比较,差异均无统计学意义(均P>0.05)。结论替吉奥联合卡培他滨治疗晚期转移性胰腺癌短期疗效较优,有延长生存时间趋势,不良反应可耐受、安全性较高,值得临床推广。     

伊立替康联合卡培他滨二线治疗晚期结直肠癌

目的:观察伊立替康(开普拓,CPT-11)联合卡培他滨(希罗达)治疗一线化疗失败的晚期结直肠癌的疗效及安全性。方法:72例晚期结直肠癌患者,均为经氟脲嘧啶(5-FU)、亚叶酸钙(LV)以及奥沙利铂等药物一线化疗失败者,行CPT-11联合卡培他滨方案治疗,CPT-11180mg/m2,静脉滴注90min,第1天;卡培他滨1250mg/m2,2次/天,第1～14天口服,休息7天,21天为1个疗程,每例患者至少接受4个疗程。按照WHO实体瘤近期客观疗效评定标准进行评价。结果:72例均可评价疗效及不良反应。完全缓解(CR)为0,部分缓解(PR)16例,有效率(RR)22.2%(16/72),稳定(SD)44例,进展(PD)12例。中位疾病进展时间7.6个月(6～28个月),中位生存期12.8个月。不良反应主要为恶心、呕吐、厌食、白细胞减少、脱发和延迟性腹泻,多为Ⅰ～Ⅱ度。结论:伊立替康联合卡培他滨二线治疗晚期结直肠癌,用药方便、疗效肯定,不良反应低,可广泛用于临床。     

伊立替康联合卡培他滨治疗晚期结直肠癌的临床观察

目的观察伊立替康联合卡培他滨治疗晚期结直肠癌的疗效和安全性。方法回顾性分析62例复发或转移性结直肠癌患者,接受伊立替康联合卡培他滨治疗：伊立替康125mg／m^2 d1、d8、d15静脉滴注90min;卡培他滨（希罗达）2500mg/m^2,分早晚2次,第1—14天,每28天重复。治疗至少2个周期,按照WHO标准进行疗效和不良反应评价,并观察至疾病进展时间及总生存期。结果62例患者中,可评价疗效的有59例。其中一线治疗28例,RR42．8％,DCR71．4％,TTP 8．6个月,MST18．8个月;二线治疗31例,RR32．3％,DCR61．2％,TTP 7．2个月,MST13．2个月。不良反应主要为恶心与呕吐、迟发性腹泻、粒细胞减少,多为Ⅰ-Ⅱ度,且一线和二线治疗的不良反应无统计学差异。结论伊立替康联合卡培他滨治疗晚期结直肠癌疗效高,不良反应可耐受,值得扩大样本进一步观察。     

伊立替康联合卡培他滨治疗晚期结直肠癌的临床观察

目的：观察伊立替康（CPT-11）联合卡培他滨（Capecitabine,希罗达）治疗晚期结直肠癌的疗效及毒性反应。方法：从2004年2月-2006年5月对晚期结直肠癌采用CPT-11联合卡培他滨方案化疗。入组患者均经病理组织学证实,且有可测量病灶。具体方案为：CPT-11250mg／m^2 iv,d1;希罗达1250mg／m^2 po,bid,d1-d14。21天为1个周期,化疗2个周期后评价疗效及毒性反应。结果：可评价疗效者60例,其中完全缓解（CR）4例,部分缓解（PR）22例,有效率（RR）为43．3％,稳定（SD）28例（46．7％）,进展（PD）6例（10．0％）。临床受益率为83．3％,疼痛缓解率83．3％。肿瘤中位进展时间7．2个月,中位生存期13．8个月。主要毒副反应为迟发性腹泻和中性粒细胞减少,未出现治疗相关性死亡。结论：CPT-11联合卡培他滨方案治疗晚期结直肠癌患者有较好疗效,毒副反应可以接受。     

卡培他滨治疗转移性结直肠癌的初步疗效观察

结直肠癌在欧洲癌症死因的第二位[1],在我国正呈逐渐上升的趋势.转移性结直肠癌的治疗较为困难,平均生存期6～9个月[2],5年以上生存不到5%.     

卡培他滨联合奥沙利铂对比氟尿嘧啶联合奥沙利铂治疗结直肠癌疗效与安全性的Meta分析

[目的]分析卡培他滨联合奥沙利铂方案对比氟尿嘧啶(5-Fu)联合奥沙利铂方案(FOLFOX)治疗结直肠癌的疗效与安全性.[方法]在Pubmed、EMBase数据库、万方数据库、中国知网、Cochrane图书馆上进行检索,时间2005年1月至2015年12月,对符合纳入标准的随机对照试验进行质量评价、数据提取,并应用Revman 5.3进行meta分析.[结果]共纳入6个随机对照试验,共2463例患者,卡培他滨组与氟尿嘧啶组完全缓解率(CR)(OR=0.90,95％CI:0.39 ～2.10,P=0.81)、部分缓解率(PR) (OR=0.81,95％CI:0.65～1.00,P=0.84)差异均无统计学意义.卡培他滨组在中位无进展生存期(mPFS) (HR=1,95％CI:0.97～1.15,P=0.21)、中位总生存期(mOS) (HR=1,95％CI:0.98～1.18,P=0.14)方面表现出与5-Fu组相似结果.在安全性方面,卡培组有较高的手足综合征发生风险,而口腔黏膜炎、中性粒细胞减少方面较5-Fu组发生率低,差异均有统计学意义(P＜0.01),其他毒副反应两组差异不明显.[结论]卡培他滨联合奥沙利铂治疗结直肠癌疗效与5-Fu组相近,且毒副反应可接受及处理.     

5-氟尿嘧啶或卡培他滨联合奥沙利铂治疗转移性结直肠癌有效性及安全性的Meta分析

目的比较5-氟尿嘧啶（5-Fu）或卡培他滨联合奥沙利铂治疗转移性结直肠癌的临床疗效和安全性。方法以转移性结直肠癌、奥沙利铂、5-Fu、卡培他滨为检索词,查阅2011年6月前发表的有关5-Fu或卡培他滨联合奥沙利铂治疗转移性结直肠癌的随机对照研究。由2名作者各自独立对入选文献中试验设计、研究对象的特征、研究结果等内容按照预先制订的数据表进行摘录。采用RevMan4．2软件进行统计分析。结果按照筛选标准,共有6篇文献入选,全部研究共计2189例转移性结直肠癌患者。两组患者基本特征均衡可比。临床疗效方面,有效率合并相对危险度（RR）为0．92[95％CI（0．82,1．02）,P=0．121,中位无疾病进展生存时间、中位生存时间合并加权均数差（WMD）分别为-0．19[95％CI（-0．73,0．35）,P=0．49],-1．91[95％CI（-2．53,0．16）,P：0．08],综合分析结果两组间均无优劣。Ⅲ～Ⅳ级毒副作用的比较中,中性粒细胞减少的综合分析显示卡培他滨组的发生率显著低于5-Fu组,合并RR为0．24[95％a（0．11,0．55）,P=0．0007],而手足症状发生率高于5-Fu组,合并RR为2．83[95％a（1．66,4．82）,19=0．0001]。结论5-Fu或卡培他滨联合奥沙利铂治疗转移性结直肠癌疗效无优劣。在Ⅲ～Ⅳ级毒性方面中性粒细胞减少在5-Fu组更易发生,卡培他滨组主要以手足症状为主。     

卡培他滨治疗老年晚期结直肠癌的临床探讨

目的:观察卡培他滨(希罗达)对老年晚期结、直肠癌的作用.方法:采用前瞻性随机对照研究方法,将沈阳军区总医院肿瘤科和辽宁省肿瘤医院内一科收治的老年晚期结、直肠癌61例随机分为两组,治疗组30例,应用卡培他滨加艾迪注射液治疗;对照组31例,单用艾迪注射液治疗.两周期结束后对客观疗效和不良反应进行评价.结果:治疗组可评价指标25例,有效率(CR PR)36.0%;对照组可评价指标24例,有效率(CR PR)16.7%,P＜0.05,差异有显著性.治疗组出现Ⅰ0以上腹泻5例,Ⅰ0～Ⅱ0恶心、呕吐3例,Ⅰ0骨髓抑制2例,Ⅰ0～Ⅱ0手足综合征4例,对症处理后症状均可消失,无1例因药物不良反应而中止治疗.对照组出现Ⅰ0以上胃肠道反应2例,未出现明显腹泻、手足综合征及骨髓抑制.两组均未发生与治疗相关性死亡.结论:卡培他滨做为新一代5-FU的口服靶向性药物,主要通过肿瘤组织中较高活性的TP酶激活而完整地被胃肠粘膜吸收,在肿瘤组织内部释放5-FU而进-步达到抗肿瘤作用.由于其疗效较好、靶向性强、不良反应轻微,是老年晚期结、直肠癌患者的首选化疗药物,特别适合不宜化疗和既往应用5-FU治疗无效的患者.     

Toxicity associated with capecitabine plus oxaliplatin in colorectal cancer before and after an institutional policy of capecitabine dose reduction

Background:

Capecitabine plus oxaliplatin (CAPOX) is an established treatment option in colorectal cancer, but can be associated with severe toxicities.

Methods:

Following reporting of severe diarrhoea and dehydration with capecitabine 2000 mg m^–2 per day plus oxaliplatin every 3 weeks (CAPOX 2000) in 2006, we instituted a policy change to reduce capecitabine dose to 1700 mg m^–2 per day (CAPOX 1700). We undertook a retrospective analysis comparing toxicities encountered before and after this dose change.

Results:

Of the 400 patients treated, no significant differences were seen between the CAPOX 2000 and CAPOX 1700 in grades 3 and 4 diarrhoea (21% vs 19% P=0.80), stomatitis (0% vs 1% P=0.50) or grades 2–4 hand foot syndrome (16% vs 11% P=0.18). Grades 3 and 4 neutropenia (9.5% vs 3.5% P=0.03) and all grades hyperbilirubinaemia (60% vs 40% P<0.0001) were significantly reduced with CAPOX 1700. Rates of hospitalisation due to toxicities were not different between two groups (13% vs 11% P=0.53).

Conclusions:

No clinically or statistically significant differences in gastrointestinal toxicities or hospitalisation rate were seen after reducing our routine capecitabine dose from CAPOX 2000 to CAPOX 1700.     

卡培他滨与氟尿嘧啶/亚叶酸钙联合奥沙利铂治疗晚期胃癌的随机对照临床研究

背景与目的：目前对进展期及转移性胃癌还没有标准的化疗方案,而且缺乏有效率高、毒副反应小、安全的化疗方案.毒副反应是晚期胃癌化疗的限制性因素,影响患者的生活质量.本研究观察及比较两种常用化疗方案卡培他滨联合奥沙利铂方案（XELOX）与氟尿嘧啶/亚叶酸钙联合奥沙利铂方案（FOLFOX4）治疗晚期胃癌的临床疗效及毒副反应,以期取得在较佳疗效保证的同时,毒副反应小,耐受性更好的效果.方法：48例晚期胃癌患者随机分成两组,XELOX组与FOLFOX4组.XELOX组25例,用卡培他滨联合奥沙利铂方案化疗,卡培他滨1000 mg/m^2,口服,2次/日,第1～14天;奥沙利铂130 mg/m^2,静脉点滴,第l天;2l d为1个周期.FOLFOX4组23例,用氟尿嘧啶/亚叶酸钙联合奥沙利铂方案化疗,奥沙利铂85 mg/m^2,静脉点滴,第1天;亚叶酸钙200 mg/m^2,静滴2 h后予氟尿嘧啶400 mg/m^2,推注,后续600 mg/m^2持续静滴22 h,第1、2天;每2周重复,4周为1周期.两组均治疗2周期以上.按wH0标准评价客观疗效和毒副反应.结果：入组48例均可评价疗效,XELOX组有效率56.0%,中位TTP 5.8个月,MST 10个月,FOLFOX4组有效率47.8%,中位TTP 5.7个月,MST 9.8个月.两组近期有效率差异无显著性.毒副反应比较,手足综合征以：XELOX组显著（P＜0.05）,Ⅲ/Ⅳ级恶心呕吐发生率以FOLFOX4.组显著（P＜0.05）,其余毒副反应除腹泻外发生率以FOIFOX4组稍高,但差异无显著性.结论：XELOX方案与FOLFOX4方案治疗晚期胃癌疗效确切,毒副反应能耐受.两组近期疗效相似,毒副反应以XELOX组更易耐受,尤其对一般情况欠佳及老年的患者耐受性好.     

结直肠癌组织AEG-1/MTDH表达Meta分析

目的 星形胶质细胞瘤上调基因1 (Astrocyte elevated gene-1,AEG-1)具有调控细胞转化、抑制凋亡和促进侵袭转移等多种生物学功能,其编码的蛋白质又叫异黏蛋白(Metadherin,MTDH),但是国内外研究者对AEG-1/MTDH与结肠癌及其病理特征和预后关系尚存争议,本研究应用Meta分析方法研究AEG-1/MTDH在人结直肠癌组织中表达的临床意义.方法 检索CNKI、维普、万方和PubMed数据库,收集2001-01-2015-07的国内外专业期刊公开发表的文献、学位论文及学术会议的相关文献,根据结直肠癌标本的临床分期、病理分级、淋巴结转移和预后以及AEG-1/MT-DH蛋白的检测和评价结果,采用NOS量表作为纳入标准筛选文献.应用RevMan 5.3软件对各研究原始数据进行统计处理,计算合并OR、RR及95％CI,同时绘制Meta分析森林图和漏斗图.并应用StataSE 12.0软件进行敏感性分析.结果 共有11篇文献纳入系统评价,对原始数据AEG-1/MTDH蛋白阳性表达率进行Meta分析,结果显示,结直肠癌组AEG-1/MTDH表达高于正常对照组,OR=13.55,95％CI为6.06～30.30,P＜0.01;Ⅲ+Ⅳ期低于Ⅰ+Ⅱ期,OR=3.66,95％CI为2.55～5.24,P＜0.01;高、中分化组低于低分化组,OR=1.44,95％CI为1.11～1.85,P＜0.01;淋巴结转移组高于无淋巴结转移组,OR=3.32,95％CI为2.44～4.52,P＜0.01;AEG-1/MTDH为结直肠癌患者独立预后因素,RR=1.57,95％CI为1.08～2.29,P=0.02.结论 AEG-1/MTDH蛋白表达升高可能在结直肠癌的发生和发展中起重要作用,检测AEG-1/MTDH蛋白对指导结直肠的临床诊治有重要参考意义.     

A phase II Study of the global dose and schedule of capecitabine in Japanese patients with metastatic colorectal cancer

BACKGROUND: Although the standard 3-week capecitabine regimen (1250 mg/m(2) twice daily for 2 weeks followed by a 1-week rest) has shown superior activity and improved safety over bolus 5-fluorouracil/leucovorin in two large randomized phase III trials in Europe and in the United States, only a 4-week regimen of capecitabine (828 mg/m(2) twice daily for 3 weeks) has been studied in Japan. Therefore, we performed a phase II study to investigate the 3-week regimen of capecitabine in Japanese patients with metastatic colorectal cancer (MCRC). METHODS: Previously untreated patients with MCRC received oral capecitabine 1250 mg/m(2) twice daily for 2 weeks. Treatment was repeated every 3 weeks. Blood and urine samples were collected for pharmacokinetic analysis. RESULTS: Sixty patients were enrolled. The overall response rate was 35% [95% confidence interval (CI), 23-48%], and 52% of patients had stable disease. The median time to progression was 5.5 months (95% CI, 4.2-6.7 months). The median overall survival was 20.2 months (95% CI, 16.6-27.8 months). The most frequently occurring adverse drug reaction was hand-foot syndrome (all-grade 73%; grade 3 13%). Diarrhea, anorexia, nausea and stomatitis were each seen in 37% of patients. The pharmacokinetic profiles of capecitabine and its metabolites were similar to those reported in Caucasian patients. CONCLUSIONS: The 3-week regimen of capecitabine was effective and well tolerated in Japanese patients with MCRC as well, and could be used as the basic regimen for future combination therapies.     

卡培他滨和雷替曲塞分别联合贝伐珠单抗治疗晚期结直肠癌的疗效及安全性比较

目的:探讨卡培他滨和雷替曲塞分别联合贝伐珠单抗对晚期结直肠癌患者疗效及安全性的影响。方法:回顾性分析我院2014年1月至2018年12月收治的晚期结直肠癌患者共147例临床资料,其中采用卡培他滨联合贝伐珠单抗治疗77例设为对照组,采用雷替曲塞联合贝伐珠单抗治疗70例设为观察组;比较两组近期疗效、随访生存情况及不良反应发生情况。结果:两组ORR和DCR比较差异无显著性（P＞0.05）;两组中位PFS和OS比较差异无显著性（P＞0.05）;观察组I-II级恶心呕吐、周围神经毒性及手足综合征发生率均显著低于对照组（P＜0.05）;同时观察组III-IV级手足综合征发生率显著低于对照组（P＜0.05）。结论:相较于卡培他滨,雷替曲塞联合贝伐珠单抗治疗晚期结直肠癌可获得相近疾病控制和生存获益,同时还有助于减轻药物不良反应,提高治疗耐受性。     

Phase II study of capecitabine and mitomycin C as first-line treatment in patients with advanced colorectal cancer

This study was designed to assess the safety and efficacy of capecitabine and mitomycin C (MMC) in previously untreated patients with advanced colorectal cancer (CRC). Patients received capecitabine 2500 mg m(2) day 1, orally divided in two doses of 1250 mg m(-2) in the morning and evening for 14 days every 21 days and MMC 7 mg m(-2) (maximum total dose 14 mg) as an intravenous bolus every 6 weeks for a total of four courses. The median age was 70 years (range 24-85) and the majority of patients (86.9%) were of performance status 1/2. The most common metastatic site was liver. In all, 84 patients were assessable for response. The overall response rate was 38% (95% CI: 27.7-49.3) and a further 33.3% of patients achieved stable disease over 12 weeks. There was good symptom resolution ranging from 64 to 86%. Grade 3/4 toxicity was as follows: hand-foot syndrome 19.7%; diarrhoea 10%; neutropenia 2.4%; infection 2.3%. Capecitabine and MMC have shown encouraging activity with a favourable toxicity profile, a convenient administration schedule, and could be considered for patients deemed unsuitable for oxaliplatin and irinotecan combinations.     

伊立替康联合卡培他滨二线治疗38例晚期结直肠癌的临床观察

目的：观察伊立替康联合卡培他滨二线治疗晚期结直肠癌的疗效及不良反应。方法：38例晚期结直肠癌患者予以伊立替康200mg／m^2,第1天,口服卡培他滨1000mg／m^2一日两次,联用14天,每21天重复,至少治疗2周期。结果：本组患者有效率7．9％（3／38）,疾病控制率55．3％（21／38）,其中部分缓解（PR）3例,稳定（SD）18例,进展（PD）17例。中位进展时间（TTP）及中位总生存期分别为4月和11月,临床疗效是影响TTP及OS的主要预后因素。3度以上不良反应主要为中性粒细胞减少（18．4％）及腹泻（10．5％）。结论：伊立替康联合卡培他滨二线治疗晚期结直肠癌具有良好的疗效与耐受性。     

Higher capecitabine AUC in elderly patients with advanced colorectal cancer (SWOGS0030)

Background:

The aging process is accompanied by physiological changes including reduced glomerular filtration and hepatic function, as well as changes in gastric secretions. To investigate what effect would aging have on the disposition of capecitabine and its metabolites, the pharmacokinetics between patients ⩾70 years and <60 years were compared in SWOG0030.

Methods:

Twenty-nine unresectable colorectal cancer patients were stratified to either ⩾70 or <60 years of age, where the disposition of capecitabine and its metabolites were compared.

Results:

Notable increase in capecitabine area under the curve (AUC) was accompanied by reduction in capecitabine clearance in ⩾70 years patients (P<0.05). No difference in 5''-deoxy-5-fluorocytidine, 5''-deoxy-5-fluorouridine (DFUR), and 5-fluorouracil (5FU) AUCs between the two age groups, suggesting that carboxylesterase and cytidine deaminase (CDA) activity was similar between the two age groups. These results suggest that metabolic enzymes involved in converting capecitabine metabolites are not altered by age. An elevation in capecitabine Cmax and reduction in clearance was seen in females, where capecitabine AUC was 40.3% higher in women. Elevation of DFUR Cmax (45%) and AUC (46%) (P<0.05) was also noted, suggesting that CDA activity may be higher in females.

Conclusion:

Increases in capecitabine Cmax and AUC was observed in patients ⩾70 years when compared with younger patients who were >60 years.     

A meta-analysis of two randomised trials of early chemotherapy in asymptomatic metastatic colorectal cancer

This report constitutes a prospectively planned meta-analysis combining two almost identical trials undertaken in Australasia and Canada to study the effect of starting chemotherapy immediately in asymptomatic patients with metastatic colorectal cancer. Patients (n=168) were randomised to receive either immediate or delayed treatment (at onset of predefined symptoms). Australasian patients received either weekly 5-fluorouracil and leucovorin (500 and 20 mg m(-2), respectively) (n=59) or the daily x 5 Mayo Clinic schedule (425 and 20 mg m(-2), respectively) (n=42). Canadian patients were treated with the Mayo schedule (n=67). Otherwise, the two studies were almost identical in design and each used the European Organisation for the Research and Treatment of Cancer (EORTC) QLQ-C30 instrument for measuring quality of life (QoL). Treatment was continued until 6 months had elapsed or disease progression occurred. Low accrual led to trial suspension before the predetermined sample size for either study was reached. Median survival was not significantly better with immediate treatment (median 13.0 vs 11.0 months; hazard ratio, 1.15; 95% confidence interval (CI) 0.79-1.72; P=0.49). There was no statistically significant difference in progression-free survival (time from randomisation until first evidence of progression after chemotherapy, 10.2 vs 10.8 months; hazard ratio, 1.08; 95% CI 0.71-1.64; P=0.73). There was no difference in overall QoL or its individual domains between the two treatment strategies at baseline or at any subsequent time point. Early treatment of asymptomatic patients with metastatic colorectal cancer did not provide a survival benefit or improved QoL compared to withholding treatment until symptoms occurred.     

氟尿嘧啶为基础的化疗方案FOLFOX或FOLFIRI在结直肠癌治疗中的心脏毒性

目的:评价持续滴注氟尿嘧啶为基础的FOLFOX或FOLFIRI联合方案在结直肠癌化疗中心脏毒性的发生情况和临床表现。方法:对接受至少一周期以上FOLFOX或FOLFIRI方案化疗的结直肠癌患者,观察和记录氟尿嘧啶相关的心脏毒性。结果:82例患者进入本研究,10例（12.2%）患者出现了心脏事件,1例心力衰竭,1例室性心动过速,1例心肌梗死,其余7例出现心绞痛;所有患者经停药或舌下含服硝酸甘油等处理后好转。结论:持续滴注氟尿嘧啶为基础的FOLFOX或FOLFIRI结直肠癌化疗方案有一定的心脏毒性,对一些致死性的心脏毒性应高度重视。