伊立替康用于结直肠癌术后辅助化疗患者的护理体会

目的 探讨结直肠癌术后应用伊立替康辅助化疗的常见不良反应及护理体会.方法 回顾性分析根治术后应用伊立替康进行辅助化疗的42例结直肠癌患者的临床资料,并总结护理体会.结果 42例患者总体耐受性良好,37例患者按计划完成治疗,其余5例更改方案或停止治疗.其中发生中性粒细胞减少25例、腹泻7例、恶心呕吐12例、急性乙酰胆碱能综合征2例、肝功能损害3例、外周静脉炎2例.结论 伊立替康用于结直肠癌根治术后辅助化疗的安全性良好,通过化疗期间科学的护理干预,做好患者的心理护理及健康教育,能减轻伊立替康化疗的不良反应,保证化疗方案顺利实施.     

TOPO-1在转移性结直肠癌组织中的表达及与伊立替康化疗的相关性研究

目的　探讨拓扑异构酶1（topoisomerase1,TOPO-1）在转移性结直肠癌组织中的表达,并分析其与伊立替康（CPT-11）化疗疗效的相关性。方法 经病理活检证实为转移性结直肠癌初诊者98例,均接受FOLFIRI方案一线化疗,化疗前检测肿瘤组织TOPO-1的表达水平,分析TOPO-1表达水平与近期疗效的关系,并观察远期疗效。结果 TOPO-1 表达水平与转移性结直肠癌的临床特征无明显相关性（P＞0.05）。高表达组患者RR为52.2%（24/46）,低表达组RR为28.8%（15/52）,差异有统计学意义（P<0.05）。TOPO-1高表达组中位PFS为9.5个月（8~12个月）,低表达组为8.0个月（7~9个月）,差异有统计学意义（P=0.002）。结论 TOPO-1高表达转移性结直肠癌患者可从伊立替康化疗中获得更高的近期疗效和更长的无疾病进展生存时间,可能对伊立替康化疗更敏感。     

伊立替康二线治疗晚期结直肠癌疗效观察

背景与目的: 结直肠癌是癌症相关死亡的主要原因之一.对大多数晚期结直肠癌患者全身化疗是最佳的姑息治疗.20世纪90年代多项Ⅲ期临床研究证实拓扑异构酶Ⅰ抑制剂依立替康(开普拓,CPT-11)联合5-Fu、LV方案(FOLFIRI)治疗结直肠癌疗效显著.本研究旨在观察FOLFIRI方案二线治疗晚期结直肠癌的生存、疗效及毒副反应.方法: 60例经病理学证实的一线治疗失败后的进展期结直肠癌患者接受FOLFIRI方案化疗至少2个周期,伊立替康180 mg/m2,静脉滴注,第1天;四氢叶酸200 mg/m2,静脉滴注,第1、2天;5-FU400 mg/m2,静脉推注,第1、2天:5-FU 600 mg/m2,静脉持续滴注22 h,第1、2天,每2周重复.结果: 全组60例患者均能评价毒副反应,其中58例可评价疗效.全组无完全缓解(cR),部分缓解(PR)14例(24.14%),稳定(sD)30例(51.72%),总有效率(CR PR)2414%,疾病控制率(CR PR SD)75.86%,中位至疾病进展时间6.09个月,中位总生存期(OS)9.65个月.非血液学毒性不良反应轻微,大多为Ⅰ、Ⅱ度.只有2例患者出现Ⅲ度延迟性腹泻,1例患者出现Ⅲ度恶心呕吐. 常见的血液学毒性为粒细胞减少症.有5例患者出现Ⅲ度粒细胞减少症.没有发生粒缺性发热.结论: 伊立替康联合5-FU和叶酸二线治疗进展期结直肠癌有较高的近期疗效,不良反应可控.     

伊立替康联合国产替吉奥胶囊治疗转移性结直肠癌的临床研究

目的:观察伊立替康联合国产替吉奥胶囊作为一线方案治疗转移性结直肠癌的临床疗效和安全性。方法:24例既往未化疗的转移性结直肠癌患者,应用伊立替康联合国产替吉奥胶囊化疗,伊立替康(180mg/m2)第1天,国产替吉奥胶囊口服剂量(60mg/m2,2次/日),连续14天,21天为1周期,连用2周期以上评价疗效。结果:24例疗效均可评价,其中CR 0例,PR 15例,SD 3例,PD 6例,RR 62.5%,DCR 75.0%,15例缓解的病例,中位缓解时间为1.8个月,中位疾病进展时间为5.6个月,中位无进展生存期为13个月。不良反应主要为Ⅰ-Ⅱ级,表现为白细胞减少、血小板减少、疲乏、恶心、呕吐等。结论:伊立替康联合国产替吉奥胶囊治疗转移性结直肠癌疗效确切、耐受性好、易于实施,值得临床进一步推行。     

雷替曲塞联合伊立替康与FOLFIRI方案二线治疗晚期结直肠癌的近期疗效

目的:观察雷替曲塞联合伊立替康方案治疗晚期结直肠癌的近期疗效和安全性。方法:经病理组织学或细胞学确诊的 44例晚期结直肠癌患者随机分为对照组（22例)和实验组（22例)。对照组,伊立替康180mg/m2静滴90min d1,亚叶酸钙400mg/m2静滴d1,5-氟尿嘧啶400mg/m2静推d1,2000mg/m2静滴46h d1。实验组,伊立替康180mg/m2静滴90min d1,雷替曲塞3mg/m2静滴15min d1,21天为1周期,2周期后评价疗效。结果:对照组PR 3例、SD 5例、PD 14例,实验组PR 4例、SD 6例、PD 12例,两组均无CR病例。两组有效率(RR)分别为13.6%和18.2％,疾病控制率(DCR)分别为36.4％和45.5%（P>0.05)。对照组乏力、周围神经毒性、黏膜炎和脉管炎发生率分别为72.7%、31.8%、36.4%和27.3%(P<0.05),实验组血红蛋白减少发生率为59.1%(P<0.05)。结论:雷替曲塞联合伊立替康方案与FOLFIRI方案的近期疗效相当,但不良反应更轻,可以作为晚期结直肠癌的有效姑息治疗方案。     

伊立替康联合氟尿嘧啶/亚叶酸钙二线治疗转移性结直肠癌

背景与目的：晚期和（或）转移性结直肠癌是癌症死亡的第二位主要原因。以前治疗晚期大肠癌的标准方案是氟尿嘧啶（5-FU）联合亚叶酸钙（LV），其有效率可达23％左右。20世纪90年代，几个三期临床研究证实了拓扑异构酶Ⅰ抑制剂伊立替康（开普拓，CPT-11）联合FU-LV（FOLFIRI）方案治疗结直肠癌疗效显著。本研究的目的是观察伊立替康联合5-FU和LV组成的二线化疗方案，治疗一线化疗失败后的中国人群中转移性结直肠癌的远期生存情况、临床疗效及安全性。方法：入组患者为转移性结直肠癌经5-FU，LV以及奥沙利铂等药物一线化疗失败后的患者24例，行CPT-11联合5-FU／LV的持续静脉滴注的两周治疗方案，患者至少接受6个疗程以上。按照WHO实体瘤近期客观疗效评定标准进行评价。结果：全组24例均可评价疗效及毒副反应。完全缓解（CR）为0（0／24），部分缓解（PR）5例（5／24），有效率达20％；稳定（SD）17例（17／24），进展（PD）2例（2／24）。中位疾病进展时间6．6个月（6—24个月），中位生存期10．7个月。不良反应主要是恶心呕吐，厌食，白细胞减少，脱发，延迟性腹泻，多为Ⅰ／Ⅱ度。Ⅲ／Ⅳ度不良反应10例，其中腹泻合并白细胞伴发热5例。结论：伊立替康联合5-FU和LV为治疗晚期转移性结直肠癌有效的二线方案，不良反应能控制，可供临床安全使用。     

雷替曲塞联合伊立替康2周方案对比FOLFIRI方案二线治疗晚期结直肠癌的疗效观察

目的 观察雷替曲塞联合伊立替康2周方案治疗转移性结直肠癌的有效性和安全性。方法 经病理组织学或细胞学确诊的50例晚期转移性结直肠癌患者分为试验组（n=25）和对照组（n=25）。试验组方案： 雷替曲塞 2.5mg／m² 静滴,d₁;伊立替康（CPT-11） 180mg／m² 静滴,d₁。对照组方案：CPT-11 180mg／m² 静滴90min,d₁;亚叶酸钙 400mg／m² 静滴,d₁;5-FU 400mg／m² 静滴,d₁;5-FU 2400mg／m² 持续静滴46～48 h,d₁、d₂。两方案均2周为1周期,每周期评价毒副反应,每3个周期评价疗效,直至疾病进展或毒性不能耐受,最多治疗12个周期。结果 试验组获CR 1例,PR 4例,SD 18例,PD 2例;对照组获PR 2例,SD 19例,PD 4例。两组有效率（RR）分别为20％和8％,疾病控制率（DCR）分别为92％和84％,差异均无统计学意义（P＞0.05）。试验组1、2级转氨酶升高的发生率为24％,高于对照组的4％（P＜0.05）;对照组1、2级中性粒细胞减少、口腔黏膜炎的发生率均高于试验组（48％ vs. 20％,32％ vs. 8％,P＜0.05）。结论 雷替曲塞联合伊立替康2周方案与FOLFIRI方案的近期疗效相当,但毒副反应更轻,可以作为转移性结直肠癌的有效姑息治疗方案。     

结直肠癌组织中HSP90α蛋白表达与伊立替康敏感性的关系分析

目的:检测结直肠癌组织热休克蛋白90α(HSP90α)的表达,并分析其与伊立替康敏感性的关系.方法:对98例结直肠癌手术后复发或转移采用伊立替康化疗患者的资料进行回顾分析,均对手术切除组织采用免疫组化法检测癌组织和癌旁组织HSP90α蛋白表达.对比癌组织和癌旁组织HSP90α蛋白阳性表达率;对比化疗敏感和耐药患者癌组织...     

伊立替康联合替加氟持续静脉滴注治疗晚期结直肠癌的临床观察

目的 观察国产伊立替康(Irinotecan)联合替加氟(Tegafur)持续静脉滴注治疗晚期结直肠癌的有效性及安全性.方法 全组共53例,方案具体用法为:国产伊立替康150 mg/m2～180 mg/m静脉滴注d1,替加氟2000mg/m2持续静脉滴注48 h,亚叶酸钙注射液200 mg/m静脉滴注d1、d2.2周重...     

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。     

UGT1A1基因多态性与伊立替康为主方案治疗晚期结直肠癌的毒性和疗效的相关性分析

目的 探讨中国汉族人结直肠癌患者尿苷二磷酸葡糖苷酸转移酶1A1（UGT1A1）基因多态性分布,评价UGT1A1基因多态性与伊立替康（CPT-11）为主方案治疗晚期结直肠癌的毒性和疗效的关系。方法 以CPT-11为主的FOLFIRI方案（CPT-11 180mg／m²）和IFL方案（CPT-11 125mg／m²）治疗晚期结直肠癌,检测患者的UGT1A1*28和UGT1A1*6基因型,分析UGT1A1基因多态性及其与化疗毒性、疗效和预后的相关性。结果 共纳入192例患者,189例行UGT1A1*28和UGT1A1*6基因型检测,野生型占37.6％,1个位点变异型占43.9％,2个位点突变异型占18.5％。183例可评价毒副反应,3～4级中性粒细胞减少的发生率为26.6％（51／183）;3～4级迟发性腹泻的发生率为15.1％（29／183）。2个位点变异的患者3～4级迟发性腹泻发生率显著高于野生型患者（26.5％vs.9.0％,P=0.021）。UGT1A1*28野生型、杂合突变型、纯合突变型的2～4级迟发性腹泻的发生率分别为29.6％、37.5％和88.9％,差异具有统计学意义（P=0.02）。UGT1A1*28纯合突变者4级中性粒细胞减少的发生率为33.3％,高于UGT1A1*28野生型的9.6％,但差异无统计学意义（P=0.07）。Logistic多因素分析显示UGT1A1*28和UGT1A1*6基因型是2～4级迟发性腹泻的影响因素。CPT-11剂量高者的3～4级中性粒细胞减少（OR=5.666,95%CI：2.088～15.377,P=0.001）和2～4级迟发性腹泻（OR=4.481,95%CI：1.568～12.807,P=0.005）发生率也显著升高。158例可评价疗效,获CR 3例、PR 30例、SD 91例、PD 34例,总有效率为20.9％。2个位点变异患者的有效率为33.3％,高于野生型的15.3％,但差异无统计学意义（P=0.063）。治疗时间在6周以下者疾病进展的风险显著增加（OR=6.106,95％CI：1.680～22.197,P=0.006）。Cox多因素分析显示,ECOG评分、治疗时间及治疗方案是影响患者预后的独立因素,而UGT1A1基因多态性与预后无关。结论 UGT1A1*28和UGT1A1*6基因型2个位点变异的患者应用CPT.11为主方案化疗的不良反应发生率较高,但疗效较好,由不良反应导致的治疗时间缩短可能会影响其获得更好的疗效。     

Weekly irinotecan in patients with metastatic colorectal cancer failing 5-fluorouracil-based chemotherapy: efficacy and prognostic factors

AIMS AND BACKGROUND: We evaluated the efficacy and tolerability of weekly irinotecan as a second-line treatment in patients with colorectal cancer failing 5-fluorouracil-based chemotherapy and searched for predictive and prognostic factors. METHODS: A total of 36 patients were included. Median age was 53 years (range, 33-72). One treatment cycle consisted of irinotecan, 100 mg/m2 weekly, for 4 weeks followed by a 2-week rest. Gender, age, primary site, number of metastatic sites, histologic subtype, differentiation, pretreatment CEA, CA 19-9 and lactate dehydrogenase levels and marker response to treatment were investigated as predictive factors for response to treatment and as prognostic factors in the overall survival and time to progression of the patients. RESULTS: A total of 120 cycles (median, 3 cycles) was delivered. An overall 14% objective response rate (1 complete and 4 partial responses) was achieved. The median response duration was 4 months (range, 2-7). Another 36% of the patients had stable disease for a median duration of 4 months (range, 2-8). Median time-to-disease progression was 4 months and overall median survival was 12 months (95% confidence interval, 9-15). Pretreatment serum CA 19-9 level and marker response to two courses of treatment were found to be clinically significant in time to progression and overall survival. Younger age (< or = 45 years) was a poor prognostic factor associated with a shorter time to progression. The major toxicity was grade 3-4 diarrhea, which occurred in 28% of the patients, and treatment was discontinued in 3 (8%) patients due to toxicity. Other hematological and non-hematological toxicities were mild and manageable. CONCLUSIONS: We concluded that weekly irinotecan at the dose of 100 mg/m2 is an effective and tolerable treatment option, with a 50% disease control rate, for patients with colorectal cancer failing previous 5-fluorouracil-based chemotherapy.     

Single-agent irinotecan as second-line weekly chemotherapy in elderly patients with advanced colorectal cancer

AIMS AND BACKGROUND: Irinotecan is a standard option for relapsed/refractory advanced colorectal cancer. Although in a recently reported, randomized trial it was found that a regimen of irinotecan once every 3 weeks was associated with a lower incidence of severe diarrhea than with weekly treatment with similar efficacy, there is no evidence in the literature that suggests the optimal dosing strategy for the drug, along with treatment efficacy and safety, following 5-fluorouracil/oxaliplatin-based chemotherapy in elderly patients. A phase II study has reported significantly reduced toxicity when irinotecan was administered once a week for 2 weeks, followed by a week rest. PATIENTS AND METHODS: From January 2004 to April 2005, we analyzed, retrospectively, our data on single-agent irinotecan as a second-line chemotherapy in elderly patients (> or =70 years) with advanced colorectal cancer. Twenty-three patients were evaluated. CPT-11 (80 mg/m2) was given as a 60-min intravenous infusion in repeated 21-day courses comprising weekly treatment for 2 consecutive weeks followed by a 1-week rest. Tumor measurements were obtained after every third course of therapy. Toxicity was assessed weekly using the National Cancer Institute Common Toxicity Criteria, version 2. RESULTS: The median number of treatment courses received per patient was 4 (range, 1-8). All patients were assessable for toxicity and 21 for response. The most frequently observed severe toxicities were diarrhea (grade 3, 13%) and neutropenia (grade 3, 30.4%; grade 4, 8.6%). Only 1 case of neutropenic fever occurred. Other hematological and non-hematological toxicities were mild and manageable. Objective partial responses were observed in 3 patients (13%). An additional 10 patients (43%) had stable disease as their best response. To date, 12 patients have progressed with a median time-to-progression of 4.3 months and a median survival of 8.3 months. CONCLUSIONS: A weekly irinotecan administration can induce tumor control in elderly patients with advanced colorectal cancer that has progressed during or shortly after 5-fluorouracil/oxaliplatin-based chemotherapy. However, a careful monitoring of hematological toxicity and special instructions to prevent and manage diarrhea are mandatory in this setting of patients.     

伊立替康联合5氟尿嘧啶或卡培他滨治疗消化系统肿瘤的回顾性分析

目的探讨伊立替康联合氟尿嘧啶类药物在晚期结直肠癌、胃癌治疗中的疗效和不良反应。方法 28例消化系统肿瘤患者采用伊立替康为主联合化疗方案治疗。伊立替康用药剂量为69 mg/m2～200 mg/m2,中位周剂量强度为80 mg/m2。治疗周期1～22个不等,平均治疗周期数为4.5个,观察指标,进行疗效评价。结果初步观察结果显示,以伊立替康为主的联合化疗方案在贲门癌、胃癌、结直肠癌的有效率为54.5%。发生急性胆碱能综合症3例(11.7%),5例(17.9%)患者发生Ⅰ度腹泻,4例(14.3%)发生Ⅱ度腹泻,经易蒙停干扰后继续治疗;2例(7.1%)发生出现Ⅲ度腹泻。结论以伊立替康为主的联合化疗方案在贲门癌、胃癌、结直肠癌有效,腹泻与治疗剂量强度密切相关,急性胆碱能综合征通过延长输注时间得以缓解。     

Current evidence of irinotecan combination chemotherapy with TS-1 in patients with advanced colorectal cancer

A combination of irinotecan (CPT-11) with continuous intravenous infusions of (infusional) 5-fluorouracil (5-FU) and Leucovorin (LV) is one of the standard treatments for advanced colorectal cancer patients. However, recent concerns about safety and convenience have prompted the development of new oral fluoropyrimidine derivatives and improved regimens. TS-1, the oral fluoropyrimidine widely used in the treatment for gastric cancer, was approved for advanced colorectal cancer. Recently, several phase I/II studies assessed the efficacy and safety of combined treatment with TS-1 plus CPT-11 in patients with advanced colorectal cancer. These results showed that TS-1 plus CPT-11 was very effective. Toxicity was generally mild and manageable on an outpatient basis. Current evidence showed that a combination of CPT-11 plus TS-1 was more convenient and easier to administer than a combination of CPT-11 plus infusional 5-FU and LV. It is essential to prove that the combination of TS-1 plus CPT-11 can replace the combination of infusional 5-FU and LV plus CPT-11 without negatively affecting efficacy and toxicity.     

TEM1表达与胃癌患者新辅助化疗疗效相关性研究

  目的  检测胃癌组织中P53、人表皮生长因子受体2（HER-2）、肿瘤内皮标记物1（TEM1）的表达情况,结合新辅助化疗后临床疗效进行相关性分析,探讨其作为新辅助化疗疗效生物学标志物的可能性。  方法  选取2015年5月至2017年5月于兰州大学第一医院就诊以氟尿嘧啶为基础行新辅助化疗的63例胃癌患者,对新辅助化疗前的胃癌标本行免疫组织化学法检测P53、HER- 2、TEM1的表达情况,通过影像学评估新辅助化疗疗效,分析各肿瘤指标与新辅助化疗疗效之间的关系。  结果  63例进展期胃癌患者新辅助化疗后总有效率为69.8%,其中完全缓解（complete response,CR）2例,部分缓解（partial response,PR）7例,疾病稳定（stable disease,SD）35例,疾病进展（progressive disease,PD）19例;单因素分析结果显示TEM1阳性、T分期较高的患者新辅助化疗疗效较差（均P < 0.05）;病变部位、分化程度、病灶大小、P53（P=0.488）阳性及HER-2（P=0.106）阳性表达与胃癌新辅助化疗疗效无相关。多因素分析结果显示TEM1阳性、T分期高可能是进展期胃癌患者新辅助化疗疗效差的预测因素。  结论  TEM1作为肿瘤基质的标志物,其阳性表达可能成为预测胃癌新辅助化疗疗效差的重要分子生物学指标。      

First-line chemotherapy with irinotecan plus capecitabine for advanced colorectal cancer

OBJECTIVE: The aim of this study was to evaluate efficacy and safety of the combination chemotherapy with irinotecan plus capecitabine in patients with advanced colorectal adenocarcinoma. METHODS: Patients with histologically proven advanced colorectal adenocarcinoma received a first-line chemotherapy with irinotecan 240 mg/m2 on day 1 and capecitabine 2,000 mg/m2/day as an intermittent regimen of 2 weeks of treatment followed by a 1-week rest. Treatment was repeated every 3 weeks. RESULTS: Thirty-nine patients were registered, and 36 were assessable for responses. Sixteen objective responses (44%) were observed with a median response duration of 6.9 months. Stable disease was documented in 14 cases (39%). The median time to progression was 6.7 months. The median overall survival was not reached at the time of analysis, and the 1-year survival rate was 67%. Two patients died: 1 due to sepsis not complicating myelosuppression, and 1 patient, known as a hepatitis B virus carrier prior to chemotherapy, died of hepatic failure, the cause of which was not clinically verified. Frequently encountered therapy-related events were leukopenia and gastrointestinal side effects including diarrhea. Severe hand-and-foot syndrome was observed in only 1 patient. CONCLUSIONS: The combination chemotherapy of irinotecan and capecitabine is an active and tolerable regimen for advanced colorectal adenocarcinoma, but the observed deaths suggest a future randomized trial that requires a cautious patient selection.     

Sensitivity to previous irinotecan treatment does not predict the efficacy of combination chemotherapy with cetuximab plus irinotecan for wild-type KRAS metastatic colorectal cancer

The aim of this study was to evaluate the association of sensitivity to previous irinotecan-based chemotherapy with efficacy of cetuximab plus irinotecan therapy in metastatic colorectal cancer (MCRC) patients with wild-type KRAS. We analysed a pooled data set consisting of data from 87 MCRC patients from two previous phase II studies (n = 60) and a group given off-protocol treatment (n = 27) following irinotecan-, oxaliplatin-, and fluoropyrimidine-based chemotherapy. Overall objective response rate to cetuximab plus irinotecan was 28.7%, median progression-free survival (PFS) was 5.3 months, and median overall survival was 12.2 months. Objective response rate did not significantly differ between patients with a favourable response to previous irinotecan (n = 23), stable disease (n = 38), or progressive disease (n = 26), with observed rates of 29.2%, 31.6%, and 23.1%, respectively. Additionally, the non-parametric Spearman rank correlation coefficients (ρ) between the PFS of previous irinotecan-based chemotherapy and that of cetuximab plus irinotecan were quite low (ρ = 0.067 and 0.057 in patients with previous irinotecan as first- and second-line therapies, respectively). Although exploratory nature and small sample size may be limitations of this study, these findings indicate that the efficacy of irinotecan plus cetuximab in MCRC patients with wild-type KRAS did not differ by previous sensitivity to irinotecan.