伊立替康介入治疗晚期直肠癌12例护理体会

伊立替康是一种半合成可溶性喜树碱衍生物，为DNA拓扑异构酶1抑制剂，主要用于治疗转移性直肠癌。自2000年3月以来，我们对12例晚期直肠癌患者应用此药分别行髂内动脉或肝固有动脉介入治疗，取得较好疗效。现将护理体会报告如下。     

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。     

替吉奥胶囊联合伊立替康治疗晚期结肠直肠癌的疗效观察

结肠直肠癌是威胁人类健康的常见恶性肿瘤之一,全球每年新发病例120多万,在男性中位居第3位,女性中位第2位,男女之比约为1.2∶1[1]。我国结肠直肠癌的发病率有逐年上升趋势[2],2009年已位居我国恶性肿瘤第3位,发生率为29.44/10万,死亡率为14.23/10万[3]。结肠直肠癌的主要治疗手段是根治性手术切除,但因早期无症状,临床上大部分患者就诊时已属中晚期,对于晚期结肠直肠癌患者,术后     

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。     

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。     

伊立替康联合顺铂治疗晚期食管癌27例

目的:观察伊立替康联合顺铂方案(IP)和顺铂联合氟尿嘧啶(DF)方案治疗晚期食管癌的近期疗效及毒副反应.方法:收集我科2006-07/2007-11晚期食管癌患者59例病例资料,比较在疗效和副反应间的差异.其中治疗组27例,采用IP方案,对照组32例,采用DF方案,21 d为1周期.在化疗期间均常规水化利尿,完成至少2周期化疗后进行评价疗效.结果:IP方案组与DF方案组间有效率(44.4% VS 28.1%,P<0.05)及控制率(81.5%VS 53.1%,P<0.05)差异有显著性.主要的毒副反应为恶心呕吐,IP方案组发生率为88.8%,DF方案组发生率为90.6%,无统计学差异;其次为骨髓抑制,IP方案组发生率为77.7%,DF方案组为46.8%,差异有显著性(P<0.05);再次为腹泻,IP方案组发生率为33.3%,DF方案组为9.4%,差异有显著性(P<0.05).结论:IP方案较DF方案治疗晚期食管癌增加疗效,同时也增加了血液系统毒性和腹泻的发生率,但副反应临床上患者尚可以耐受,值得推广应用.     

贝伐单抗治疗转移性结直肠癌20例近期疗效观察

将病理学证实的60例转移性结直肠癌患者随机分为两组,观察组20例予贝伐单抗（Avastin）联合伊立替康（CPT-11）、醛氢叶酸（LV）和5-氟尿嘧啶（5-Fu）,对照组40例予CPT-11联合LV和5-Fu治疗,至少化疗2个周期。观察近期疗效、不良反应和血清肿瘤标志物变化。结果观察组和对照组有效率分别为45％和35％（P〉0．05）;疾病控制率分别为80％和50％（P〈0．05）;肿瘤标志物治疗后均明显降低（P〈0．01）;两组不良反应多为Ⅰ～Ⅱ度,发生率无统计学差异（P〉0．05）。认为贝伐单抗联合伊立替康治疗转移性结直肠癌效果好,不良反应轻,值得临床借鉴。     

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...     

伊立替康与4-氨基吡啶联合应用对人结直肠癌细胞增殖作用的影响

目的 研究肿瘤化学治疗药物伊立替康(CPT-11)对人结直肠癌细胞株HT-29细胞的作用及对钾离子通道阻断剂4-氨基吡啶(4-AP)的影响,并探讨其抗HT-29细胞的可能机制.方法 CPT-11、4-AP以及两药联合应用对HT-29细胞增殖及细胞侵袭力的影响分别用MTT比色法和Transwell法检测.用流式细胞术膜联蛋白V-异硫氰酸荧光素碘化丙啶双染法检测上述两种药物对HT-29细胞凋亡的影响.用膜片钳方法 检测ATP敏感性钾电流(IKATP)的电流变化.结果 1.0～64.0μg/ml CPT-11可呈剂量依赖性和时间依赖性地抑制HT-29细胞增殖,而1.0 mmol/L的4-AP可使CPT-11的作用增强.16.0 μg/ml CPT-11和1.0 mmol/L 4-AP单独应用均可明显诱导HT-29凋亡、抑制HT-29细胞侵袭力,而两药联合应用能明显增加上述诱导凋亡和抑制侵袭力的作用.不同浓度CPT-11可剂量依赖性地降低细胞膜IKATP水平,呈剂量依赖负相关性.结论 CPT-11抑制人结直肠癌HT-29细胞增殖和侵袭力、诱导细胞凋亡等作用可被4-AP协同增强,可能机制与CPT-11抑制ATP敏感性钾通道开放有关.     

伊立替康治疗复发及难治性神经母细胞瘤疗效观察

目的探讨伊立替康对复发及难治性神经母细胞瘤（NB）患者的安全性、疗效及生存质量的影响。方法 7例3～22岁复发及难治性NB患者接受伊立替康治疗,40～50 mg/m2,静滴60 min,1次/d,连续治疗5 d;每3周为一周期。应用影像学等评估疗效,并评价血液学和非血液学毒性反应,应用体能评分和面部表情评分进行生存质量评估。结果 7例患者平均每例接受了3个疗程的伊立替康治疗,3例患者疾病稳定,平均疾病进展时间为2个月,临床获益率为42.9%（3/7）。最常见的3～4度毒性反应是骨髓抑制,未见到严重腹泻等非血液学毒性反应。患者生存质量都得到了不同程度的提高。结论伊立替康单药可以通过减轻疼痛等方式提高NB患者的生存质量。     

Current place of high-dose irinotecan chemotherapy in patients with metastatic colorectal cancer

Introduction  Irinotecan has an important place in the treatment of metastatic colorectal cancer. It was initially administered as monotherapy, but is now generally used in combination with 5-fluorouracil or targeted therapies (cetuximab or bevacizumab), with various doses. Methods  We here review the main studies assessing irinotecan doses escalation, and discuss the potent advantages of this escalation. Results  Several studies have demonstrated a dose–intensity relationship for irinotecan, and high doses (up to 600 mg/m² as monotherapy, 260 mg/m² in combination therapy) have been used with satisfactory safety and higher objective response rates. It is possible that, in practice, some patients receive insufficient doses of irinotecan. Dose escalation could be considered in carefully selected patients: young patients with a good performance status and normal liver function. This approach could be useful in patients with liver metastases, which may become resectable in the case of a major tumour response. It is wise to perform UGT1A1 genotyping prior to dose escalation to detect patients at high risk of toxicity (genotype 7/7). The role of another laboratory parameter, which needs to be evaluated is the KRAS status of the tumour. A KRAS mutation confers resistance to cetuximab, which reduces treatment options, especially in first-line. However, in the CRYSTAL trial comparing FOLFIRI to FOLFIRI-cetuximab as first-line therapy, the presence of a KRAS mutation did not appear to influence the efficacy of FOLFIRI. The value of irinotecan dose escalation needs to be determined in this setting. Conclusion  Irinotecan dose escalation is potentially of interest in highly selected patients, but this concept is only based on phase I or II trials and must be validated by a randomized trial. Its value regarding other regimens such as FOLFIRINOX or combinations with targeted therapies also needs to be determined.     

非比麸治疗结直肠癌肠造口术后患者19例

目的:观察非比麸颗粒对结直肠癌肠造口术后患者的疗效及其安全性.方法:选取2010-01/2011-07在我科住院的结直肠癌行肠造口术后患者19例,连续口服非比麸颗粒治疗1wk,采用自身前后对照方法观察服药前后大便频率、大便性状、造口周围皮肤及医患双方满意度情况,并进行量化评分比较.结果:非比麸颗粒能明显改善结直肠癌肠造口术后大便频率、大便性状及造口周围皮肤刺激[(1.09±0.78)分vs(2.03±0.63)分,(4.32±0.49)分vs(6.01±0.66)分,(0.44±0.21)分vs(1.57±0.57)分,均P<0.05],服药期间未发现明显不良反应.结论:非比麸颗粒可以改善肠造口术后大便频率、大便性状及造口周围皮肤刺激,安全有效,满意度高.     

c-src activating mutation analysis in Chinese patients with colorectal cancer

AIM: To investigate the occurrence of cellular src (c-src) activating mutation at codon 531 in colorectal cancer patients from Chinese mainland. METHODS: Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay followed by sequencing and single-strand conformation polymorphism analysis were carried out to screen 110 samples of primary colorectal cancer and 20 colorectal liver metastases. RESULTS: Only one sample showed PCR-RFLP-positive results and carried somatic codon 531 mutations. No additional mutation of c-src exon 12 was found. CONCLUSION: c-srccodon 531 mutation in colorectal cancer is not the cause of c-srcactivation.     

A phase I study of combination therapy with S-1 and irinotecan (CPT-11) in patients with advanced colorectal cancer

Purpose  The aim of this study was to determine the maximum tolerated dose, recommended dose and dose-limiting toxicities of irinotecan (CPT-11) plus S-1 in advanced colorectal cancer. Methods  S-1 was administered orally at 80 mg/m² per day for 14 consecutive days followed by a 2-week rest. CPT-11 was given intravenously on days 1 and 15 of each course, at an initial dose of 80 mg/m² per day, stepping up to 100, 120 or 150 mg/m² per day. Courses were repeated every 4 weeks, unless disease progression or severe toxicities were observed. Results  A total of 21 patients were entered in this study. The maximum tolerated dose of CPT-11 was considered to be 150 mg/m², because 2 of 3 patients developed dose-limiting toxicities such as leukopenia, neutropenia, diarrhea and anorexia. The recommend dose of CPT-11 was set at 120 mg/m². Tumor response rate was 42.8% and median progression-free survival time was 10 months (95% confidential interval, 6.0–14.0 months). Conclusion  A combination of S-1 and CPT-11 showed a good safety profile and can be recommended for further phase II studies in patients with colorectal cancer.     

FOLFOX/FOLFIRI pharmacogenetics:The call for a personalized approach in colorectal cancer therapy

While 5-fluorouracil used as single agent in patients with metastatic colorectal cancer has an objective response rate around 20%,the administration of combinations of irinotecan with 5-fluorouracil/folinic acid or oxaliplatin with 5-fluorouracil/folinic acid results in significantly increased response rates and improved survival.However,the side effects of systemic therapy such as myelotoxicity,neurotoxicity or gastrointestinal toxicity may lead to life-threatening complications and have a major impact on the quality of life of the patients.Therefore,biomarkers that would be instrumental in the choice of optimal type,combination and dose of drugs for an individual patient are urgently needed.The efficacy and toxicity of anticancer drugs in tumor cells is determined by the effective concentration in tumor cells,healthy tissues and by the presence and quantity of the drug targets.Enzymes active in drug metabolism and transport represent important determinants of the therapeutic outcome.The aim of this review was to summarize published data on associations of gene and protein expression,and genetic variability of putative biomarkers with response to therapy of colorectal cancer to 5-fluorouracil/leucovorin/oxaliplatin and 5-fluorouracil/leukovorin/irinotecan regimens.Gaps in the knowledge identified by this review may aid the design of future research and clinical trials.     

细胞免疫参数对结直肠癌的评估价值

目的:评估结直肠癌患者抗肿瘤免疫状态.方法:应用流式细胞术检测100例未转移结直肠癌患者、100例伴有转移结直肠癌患者和100例健康志愿者外周血CD4+、CD8+、NK、B、CD4+CD25HighCD127lowTreg、Th/Treg值,采用单因素方差分析进行比较,分析差异.结果:转移性结直肠癌患者组分别与正常对照组和非转移性结直肠癌患者组相比,CD4+CD25HighCD127lowTreg细胞升高(7.72%±2.20%vs6.08%±1.47%,5.91%±1.55%,均P<0.05),CD4+T细胞降低(34.04%±8.71%vs37.83%±7.62%,37.68%±8.89%,均P<0.05),Th/Treg值降低(4.70±1.72vs6.47±2.54,6.81±4.09,均P<0.05).结直肠癌患者与正常对照组CD8+T细胞、NK细胞、B细胞三组两两相比,均无统计学意义.结论:转移性结直肠癌患者免疫功能紊乱,主要表现为CD4+T细胞、Th/Treg值降低,CD4+CD25HighCD127lowTreg细胞升高.     

Irinotecan therapy and molecular targets in colorectal cancer： A systemic review

Irinotecan is the second line chemotherapy for advanced stage colorectal cancer （CRC） after failure of first line chemotherapy with oxaliplatin and 5-fluorouracil. The aim of this review is to analyse the data on irinotecan as second line chemotherapy for advanced CRC and the potential roles of the molecular markers, p53 and vascular endothelial growth factor （VEGF） in the management of advanced CRC. Thus, the English literature from 1980 to 2008 concerning irinotecan, p53, VEGF and CRC was reviewed. On review, Phase Ⅱ and Ⅲ clinical trials showed that irinotecan improves pain-free survival, quality of life, 1-year survival, progression-free survival and overall survival in advanced CRC. p53 and VEGF were expressed in CRC and had a predictive power of aggressive clinical behaviour in CRC. Irinotecan sensitizes p53 wild type, mutant and null cells to Fas- mediated cell apoptosis in CRC cells. Wild type p53 cells were more sensitive to irinotecan than mutated p53. Irinotecan has an anti-VEGF effect inhibiting endothelial cell proliferation, increasing apoptosis and reducing microvascular density which is only limited by irinotecan toxicity levels. To conclude, irinotecan improves the patient＇s quality of life and the survival rates of patients with advanced CRC. p53 and VEGF status of the patients＇ tumour is likely to affect the responsiveness of CRC to irinotecan. It is recommended that studies of the expression of these molecular markers in relation to chemoresponsiveness of irinotecan should be carried out for better management of patients with advanced CRC.     

Clinical and molecular analysis of hereditary non-polyposis colorectal cancer in Chinese colorectal cancer patients

AIM:To analyze the frequency of hereditary non-polyposis colorectal cancer(HNPCC)in Chinese colorectal cancer(CRC)patients,and to discuss the value of microsatellite instability(MSI)and/or immunohistochemistry(IHC)for MSH2/MLH1 protein analysis as pre-screening tests in China.METHODS:The Amsterdam criteriaⅠandⅡ(clinical diagnosis)and/or germline hMLH1/hMSH2 mutations(genetic diagnosis)were used to classify HNPCC families.Genetic tests,including microsatellite instability,immunohistochemistry for MSH2/MLH1 proteins and hMSH2/hMLH1 genes,were performed in each proband.RESULTS:From July 2000 to June 2004,1988 patients with colorectal cancer were analysed and 114 CRC patients(5.7%)from 48 families were categorized as having HNPCC,including 76 from 26 families diagnosed clinically and 38 from the other 22 families diagnosed genetically.The sensitivity and specificity of high MSI and IHC for predicting mutations were 100% and 54%,and 79% and 77%,respectively.CONCLUSION:The frequency of HNPCC is approximately 10% among all Chinese CRC cases.The MSI and IHC detections for hMSH2/hMLH1 proteins are reliable pre-screening tests for hMLH1/hMSH2 germline mutations in families suspected of having HNPCC.