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。     

雷替曲塞联合奥沙利铂与5-氟尿嘧啶联合顺铂方案治疗晚期胃癌的临床观察

目的 观察雷替曲塞联合奥沙利铂（L-OHP）治疗晚期胃癌的近期疗效和毒性.方法 将80例晚期胃癌患者分为两组,A组40例,给予雷替曲塞3 mg/m2,静脉滴注15分钟,d1;奥沙利铂130 mg,/m2,静脉滴注2小时,d1,3周重复1次.B组患者40例,给予5-氟尿嘧啶（5-FU）750 mg/m2,静脉滴注,d1 ～5;顺铂25 mg/m2,静脉滴注,d1 ～3,28天重复1次.结果 A、B两组患者的有效率分别为47.5％和22.5％,两组比较差异有统计学意义（P＜0.05）.不良反应主要是骨髓抑制和消化道反应.结论 与5-FU联合顺铂的方案比较,雷替曲塞联合奥沙利铂治疗晚期胃癌临床疗效较好,不良反应轻.     

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。     

雷替曲塞在晚期结直肠癌中的应用进展

以氟尿嘧啶为基础的化疗方案是结直肠癌患者的标准治疗方案,为患者带来很好的生存获益。但在耐药进展后,却往往面临无药可用的窘境。近年来,雷替曲塞的研发使用,在一定程度上缓和了这种矛盾。本文就目前雷替曲塞的作用机制及其在晚期结直肠癌临床应用中的现状做一综述。     

雷替曲塞联合伊立替康治疗转移性胃癌对血清ESM-1、IGFBP3表达的影响

目的探讨雷替曲塞联合伊立替康治疗转移性胃癌(gastric cancer,GC)对血清内皮细胞特异性分子-1(endothelial cellspecificmolecule-1,ESM-1)及胰岛素样生长因子结合蛋白3(insulin-like growth factor binding protein 3,IGFBP3)表达的影响.方法选取2015-12/2017-12入住绍兴市人民医院肿瘤内科并接受治疗的转移性GC患者55例进行研究.所有患者均采用雷替曲塞与伊立替康联合疗法:第一天,伊立替康:剂量180 mg/m~2,静脉滴注1.5h;第二天,雷替曲塞:剂量3 mg/m~2,静脉滴注1.5 h.以3 wk为一个周期,依据患者病情,最多进行6个周期.随访至2018-06-31.考察治疗后近远期疗效、治疗前后患者ESM-1和IGFBP3表达水平变化,统计治疗过程中患者发生不良反应种类及等级.结果完全缓解3例(5.45%),部分缓解10例(18.18%),稳定28例(50.91%),进展14例(25.45%),客观有效率为23.64%(13/55),疾病抑制率为74.55%(41/55).中位肿瘤进展时间为6.1 mo(95%CI:5.2-6.9 mo);中位生存时间为9.4 mo(95%CI:8.7-11.2 mo);治疗后ESM-1表达水平(0.72μg/L±0.54μg/L)显著低于治疗前(1.03μg/L±0.67μg/L)(P0.05);治疗后IGFBP3表达水平(3.27μg/L±0.45μg/mL)显著高于治疗前(2.93μg/L±0.43μg/mL)(P 0.05);患者最常见的不良反应主要有中性粒细胞减少(19/55, 34.55%)、肝功能异常(15/55, 27.27%)、贫血(18/55, 32.73%)及恶心呕吐(14/55, 25.45%).结论雷替曲塞联合伊立替康治疗转移性GC,可降低患者血清ESM-1的表达,抑制肿瘤血管的生成,并提高IGFBP3表达水平,减少癌细胞的扩散,从而有效控制病情的发展,提高患者存活期,且不良反应较少,安全性高,可为临床转移性GC患者的治疗提供前期治疗方案参考.     

伊立替康治疗结直肠癌相关胆碱能综合征89例

目的:观察和分析伊立替康治疗结直肠癌相关胆碱能综合征的发生情况.方法:应用2种FOLFIRI方案治疗转移性结直肠癌患者89例,观察和记录胆碱能综合征发生情况,并将其与患者临床资料、其他不良反应和所应用的治疗方案进行相关性分析.结果:53例(59.6%)患者发生胆碱能综合征,中位发生时间为伊立替康开始滴注后150min(30min-25h),绝大多数在用药后24h内逐渐消退,预防性应用阿托品可以有效预防胆碱能综合征发生;≥60岁老年患者胆碱能综合征明显高发(75.9%vs51.7%,P=0.029),未发现其与性别、ECOG评分等临床特征有关;出现胆碱能综合征患者迟发性腹泻有减少趋势(52.8%vs34.0%,P=0.077),未发现胆碱能综合征与其他不良反应相关;采用高剂量氟尿嘧啶治疗方案患者黏膜炎明显高发(50.0%vs27.5%,P=0.029).结论:伊立替康相关胆碱能综合征高发,应引起临床医生重视;胆碱能综合征对后续可能发生的迟发性腹泻和/或骨髓抑制无预测作用.     

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。     

雷替曲塞联合西妥昔单抗或贝伐珠单抗治疗晚期结直肠癌临床疗效

目的 对比雷替曲塞联合西妥昔单抗或贝伐珠单抗治疗晚期结直肠癌的临床疗效。方法 80例晚期结直肠癌患者根据治疗方法的不同,采用随机数字表法分为两组各40例,甲组采用雷替曲塞联合西妥昔单抗治疗,乙组采用雷替曲塞联合贝伐珠单抗治疗,分析两组临床疗效,检测两组癌胚抗原(CEA)、鳞状细胞癌抗原(SCC),评估两组卡氏功能状态(KPS)评分,对比两组1年生存期、疾病进展时间、不良反应发生率。结果 治疗后,甲组临床总有效率稍低于乙组,差异无统计学意义(P>0.05);两组血清CEA、SCC水平较治疗前明显降低(P<0.05),而组间对比无统计学差异(P>0.05);两组KPS评分较治疗前明显升高(P<0.05),而组间对比无统计学差异(P>0.05);两组1年生存期、疾病进展时间、不良反应发生率,差异无统计学意义(P>0.05)。结论 雷替曲塞联合西妥昔单抗或贝伐珠单抗对晚期结直肠癌患者均有明显的临床疗效,且疗效相当,能减少不良反应发生,并提高患者生存质量,降低血清肿瘤标志物水平。     

雷替曲塞用于结直肠癌术中腹腔灌注化疗的近期安全性评估

目的评估雷替曲塞用于结直肠癌患者术中腹腔灌注化疗的近期安全性以及可行性。 方法回顾性分析2017年7月至2018年10月期间就诊于中国医学科学院肿瘤医院结直肠外科并进行手术治疗患者的临床资料,分为研究组和对照组,研究组40例,对照组40例,研究组在关腹后经引流管行雷替曲塞腹腔灌注化疗,对照组用蒸馏水冲洗后关腹。分析两组患者术后并发症发生率、血液学毒性、肝肾功能、胃肠道功能恢复等近期安全性的差异。 结果两组患者术后并发症发生率、血液学毒性、肝肾功能、胃肠道功能恢复时间相比较差异均无统计学意义（均P>0.05）。 结论雷替曲塞用于结直肠癌患者术中灌注化疗具有良好的安全性及耐受性,不增加术后并发症。     

Raltitrexed plus oxaliplatin in the second-line treatment of metastatic colorectal cancer

The primary endpoint of this study was to evaluate the efficacy (objective response rate; ORR) of combined chemotherapy with raltitrexed plus oxaliplatin as second-line treatment in patients with metastatic colorectal cancer (CRC). Secondary endpoints were overall survival (OS), time to progression (TTP) and toxicity (NCI-CTC criteria). The target population were patients with metastatic colorectal adenocarcinoma who progressed after first-line chemotherapy. Treatment consisted of raltitrexed 3 mg/m2 as a 15-minute intravenous (IV) infusion followed 45 minutes later by oxaliplatin 130 mg/m(2) IV as a 2-h infusion on Day 1, repeated every 3 weeks until further disease progression (PD), unacceptable toxicity or the decision of the patient. A total of 51 patients, all with WHO performance status 0-2 received a median of 6 treatment cycles (range 1-11). After 3 cycles, 8 of the 47 evaluable patients (17%) had experienced an ORR, 28 patients (59.6%) had experienced stable disease (SD) and 11 patients (23.4%) had PD. After 6 cycles, 1 of the 29 evaluable patients (3.5%) had an ORR, 13 patients (44.8%) had SD and 15 patients (51.7%) had PD. After a median follow-up of 48.9 weeks, median TTP was 18 weeks and median overall survival was 54.4 weeks. Treatment was well tolerated; grade 3 toxicities occurred in only 5/51 patients (9.8%). The most common toxicities were paraesthesia (62.7%), diarrhoea (23.5%), nausea (41.2%), vomiting (33.3%), hepatotoxicity (25.5%), and hematological toxicity (41.2%). In conclusion, the combination of oxaliplatin plus raltitrexed appears to be effective and well tolerated as second-line therapy in patients with disseminated CRC.     

Bevacizumab plus infusional 5-fluorouracil, leucovorin and irinotecan for advanced colorectal cancer that progressed after oxaliplatin and irinotecan chemotherapy： A pilot study

AIM： To evaluate the combination of bevacizumab with infusional 5-fluorouracil （5-FU）, leucovorin （LV） and irinotecan （FOLFIRI） in patients with advanced colorectal cancer （CRC） pretreated with combination regimens including irinotecan and oxaliplatin. METHODS： Fourteen patients （median age 56 years） with advanced CRC, all having progressed after oxaliplatin- and irinotecan-based combination chemotherapy, were enrolled in this study. Patients were treated with 2 h infusion of irinotecan 150 mg/m2 on d 1, plus bevacizumab 5 mg/kg iv infusion for 90 min on d 2, and iv injection of LV 20 mg/m2 followed by a bolus of 5-FU 400 mg/m2 and then 22 h continuous infusion of 600 mg/m2 given on two consecutive days every 14 d. RESULTS： The median number of cycles of chemotherapy was six （range 3-12）. The response rate was 28.5%, one patient had a complete response, and three patients had a partial response. Eight patients had stable disease. The median time to progression was 3.9 mo （95% CI 2.0-8.7）, and the median overall survival was 10.9 mo （95% CI 9.6-12.1）. Grade 3/4 neutropenia occurred in five patients, and two of these developed neutropenic fever. Grade 3 hematuria and hematochezia occurred in one. Grade 2 proteinuria occurred in two patients. However, hypertension, bowel perforation or thromboembolic events did not occur in a total of 90 cycles. CONCLUSION： Bevacizumab with FOLFIRI is well tolerated and a feasible treatment in patients with heavily treated advanced CRC.     

Effect of mucin production on survival in colorectal cancer： A case-control study

AIM： TO investigate the impact of mucin production on prognosis in colorectal cancer, in terms of overall survival （OS） and time to disease progression （TTP） in patients with mucinous compared to those with nonmucinous colorectal cancer （NMCRC）, matched for age, gender, and tumor stage. METHODS： Thirty five patients with mucinous colorectal cancer （MCRC） were matched for age, gender, and tumor stage with 35 controls having NMCRC. OS and TTP were compared among 4 groups divided according to mucin content： group A （50%-75% mucin）, group B （75%-100% mucin）, group C or controls （〈 50% mucin）. Group D consisted of all patients with tumors having 〈 75% mucin （controls and groups A together）. RESULTS： Median survival in MCRC and NMCRC groups was 46.2 and 112.9 mo, respectively （P = 0.26）. OS in groups A and B was 70.1 and 32.8 mo （P = 0.46）, and in groups B and D was 32.8 and 70.1 mo, respectively （P = 0.143）. TTP in MCRC and NMCRC was 50.17 and 44.77 too, respectively （P = 0.795）. TTP in groups A, B, and D was 70.1, 24.8, and 65.5 too, respectively. Twenty-eight percent of patients with MCRC had poorly differentiated adenocarcinoma versus 8.6% in NMCRC patients （P = 0.028）. CONCLUSION： MCRC is associated with a non-significant decrease in median survival and TTP, particularly when mucin content is 〉 75% of tumor volume. However, it tends to be more poorly differentiated. A larger study matching for stage and grade is needed.     

体重指数与结直肠癌预后的相关性研究

目的探讨体重指数(body mass index,BMI)与结直肠癌患者临床病理特征和预后的关系。 方法回顾性分析2005年7月至2011年6月解放军总医院收治的107例结直肠癌患者的临床和随访资料。将患者分为正常体重组(BMI<23.0kg/m²)、超重组(23.0 kg/m²≤BMI<27.5 kg/m²)和肥胖组(BMI≥27.5 kg/m²),比较三组临床病理因素,并分析BMI与5年生存率的关系。 结果正常体重组37例(34.6%),超重组54例(50.5%),肥胖组16例(14.9%)。中位生存时间为37个月,1、3、5年的总生存率分别为95.3%、81.9%、74.0%。单因素生存分析显示,肿瘤位置、浸润程度、淋巴结转移和临床分期对5年生存率有影响(均P<0.05)。BMI与肿瘤浸润程度有关(P＝0.039),对5年生存率无显著影响,但随着BMI增加,5年生存率呈上升趋势(69.2% vs 72.0% vs 93.8%,P＝0.239)。多因素生存分析显示,肿瘤位置和临床分期是本组患者预后的独立危险因素(均P<0.05),BMI非独立危险因素(P＝0.343)。 结论BMI对结直肠癌患者的预后无显著影响。     

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.     

Survival after oxaliplatin therapy of irinotecan-pretreated advanced colorectal cancer patients

BACKGROUND/AIMS: The activity of oxaliplatin (OHP) and irinotecan (CPT) alone or in combination with 5-fluorouracil (5-FU) in advanced colorectal cancer is comparable, but there are limited data on the effectiveness of oxaliplatin in patients pretreated by irinotecan. METHODOLOGY: We have analyzed retrospectively the survival of 77 consecutive advanced colorectal cancer patients treated with OHP after previous CPT therapy. Multivariate analysis was performed by Cox regression method, with the results expressed as hazard ratio (HR). RESULTS: The median survival from the start of OHP therapy was 10.7 months (1-year survival 43%). The median survival was not reached in 10 patients treated by hepatic arterial infusion of OHP (>10.6 months). The median survival from the diagnosis of advanced/metastatic disease was 34.3 months. On multivariate analysis, hemoglobin <125g/L (HR=2.42), neutrophils <5200 per microL (HR=0.36), duration of advanced/metastatic disease <21 months (HR=2.40) and interval from last CPT administration <3 months (HR=0.27) were statistically significant (p<0.05) independent predictors of survival from the start of OHP treatment, but only hemoglobin (HR=2.07), neutrophils (HR=0.32) and CEA <100microg/L (HR=0.44) were independent predictors of survival from the last CPT. There were 4 treatment-induced deaths after combination of OHP and raltitrexed (TOMOX). CONCLUSIONS: More than 40% of patients pretreated by irinotecan survived 1 year after start of OHP therapy. The therapy was similarly effective as a second or higher line of treatment. Hemoglobin levels and neutrophil count were independent factors associated with survival. The number of toxic deaths observed after TOMOX is alarming.     

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。     

Favorable toxicity profile of raltitrexed in elderly patients treated for colorectal cancer: a case series

BACKGROUND: Age-related physiological changes may lead to an increased toxicity of chemotherapy in the elderly, thus making tumor treatment difficult in this increasing subset of patients. OBJECTIVE: Since many trials claimed a favorable therapeutic index with raltitrexed, the aim of our preliminary study was to evaluate the anticancer activity and the toxic profile of this drug in the elderly. METHODS: Thirteen elderly patients with colorectal cancer, aged 75-90 years, were enrolled in a monochemotherapy treatment with raltitrexed. Due to their advanced age, the drug was administered with a 33% reduction of the dose. RESULTS: One partial response, four disease stabilizations, and two disease progressions were observed in 7 patients with advanced colorectal cancer. The patients with response or disease stabilisation had a satisfactory time to progression. Four out of 6 patients treated in the adjuvant setting for Dukes' C colorectal cancer remain disease free at observation periods of 15+ to 29+ months. Toxicity was virtually absent in all patients. CONCLUSIONS: The activity of monochemotherapy with raltitrexed appears to be appealing, above all because it is observed in the absence of toxicity. Though recent reports suggest some concern about severe complications of treatment with raltitrexed, administration of reduced doses of this drug seems to be a putative therapy for those patients who, because of their age, are highly susceptible to the adverse effects of chemotherapy.     

Sirolimus, bevacizumab, 5-Fluorouracil and irinotecan for advanced colorectal cancer： A pilot study

AIM： To evaluate the efficacy and the safety of combined 5-Fluorouracil, irinotecan, bevacizumab and sirolimus in refractory advanced colorectal carcinoma. METHODS： We initiated a regimen with at day 1 an injection （iv） of bevacizumab at 5 mg/kg, followed by 180 mg/m^2 irinotecan, followed by Leucovorin 400 mg/m^2, followed by a 5-Fluorouracil bolus 400 mg/m^2 and a 46-h infusion 2400 mg/m^2. Sirolimus was given orally as continuous administration of 2 mg twice a day every days. This treatment was repeated every 14 d. RESULTS： A total of 12 patients were enrolled. All patients presented with metastatic disease that had failed at least three lines of chemotherapy that contained oxaliplatin, irinotecan and bevacizumab. Cetuximab failure was also observed in all K-Ras wildtype patients. The median number of cycles was 8.5 （range 2-20） and clinical benefit was observed in eight patients. The median time to progression was 5 mo and the median survival was 8 too. Grade 3 neutropenia developed in four patients, and grade 3 diarrhea and stomatitis in two.CONCLUSION： The combination regimen of 5-Fluorouracil,irinotecan, bevacizumab and sirolimus in advanced colorectal carcinoma after failure of dassical be.absent is feasible and promising. Further evaluation of this combination is required.