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Phase 1/2 study of concurrent chemoradiotherapy with weekly irinotecan hydrochloride for advanced/recurrence uterine cancer:A multi-institutional study of Kansai Clinical Oncology Group 被引量:1
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作者 Satoshi Takeuchi Haruo Kuroboshi +8 位作者 Taisuke Mori Kimihiko Ito Eiji Kondo Tsutomu Tabata Yoshio Itani Ryuji Kawaguchi Kyosuke Takeuchi Toshinori Soejima Ryohei Sasaki 《Chinese Journal of Cancer Research》 SCIE CAS CSCD 2020年第2期218-227,共10页
Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using iri... Objective:Concurrent chemoradiotherapy using cisplatin was thought to be standard treatment for squamous cell carcinoma of cervix,but it had not been effective for adenocarcinoma.Concurrent chemoradiotherapy using irinotecan hydrochloride(CPT-11)had been effective for colorectal cancer,thus,we chose CPT-11 as a candidate for gynecologic adenocarcinoma.To evaluate the maximum tolerated dose(MTD)of weekly CPT-11 with external pelvic radiotherapy,a phase 1/2 study was conducted according to modified Fibonacci method.Methods:Eligible patients were advanced uterine cancer with measurable diseases[performance score(PS):0-2].Study period was from August 1 st,2002 to December 31 st,2008.The starting dose level(DL)of CPT-11 was 30 mg/m2(DL1)given weekly for 4 weeks.Subsequently,dose escalation was scheduled in 10 mg/m2 increments to 60 mg/m^2(DL4).The fixed radiotherapy consisted of whole pelvic 1.8 Gy/d,once a day in weekday for five weeks and it amounted to 45 Gy(25 fractions)in total.Results:Seventeen patients were enrolled.As for toxicities,one(1/17:5.9%)grade(G)4 neutropenia lasting 7 days had been seen in DL4.G2 diarrhea was identified in 35.3%(6/17)of the patients,and 11.8%(2/17)G3 diarrhea was observed in DL3 and DL4.Thus,the MTD of CPT-11 was defined as dose of 60 mg/m^2.The recommended dose was decided as 50 mg/m^2.The response rate was 88.2%[9 complete response(CR),3 partial response(PR),3 stable disease(SD),2 not evaluable(NE)].Disease control rate at 1 month after treatment completion was 100%but distant metastases were found in 24%(4/17)in longer outcome.Conclusions:MTD was 60 mg/m^2 and recommended dose was set as 50 mg/m2.This concurrent chemoradiation using weekly CPT-11 was feasible at 50 mg/m^2,and it might be effective even in adenocarcinoma of the uterus. 展开更多
关键词 Concurrent chemoradiotherapy(CCRT) irinotecan hydrochloride(cpt-11) cervical adenocarcinoma endometrial cancer
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OK-432增强CPT-11抗肿瘤活性的实验研究 被引量:3
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作者 王湘辉 藤本敏博 +2 位作者 张滨 磨伊正义 柴福录 《中国肿瘤临床》 CAS CSCD 北大核心 2001年第12期930-933,共4页
目的:探讨OK-432增强CPT-11抗肿瘤活性的机制。方法:将荷B16黑色素瘤的C57BL/6小鼠随机分为对照组、CPT-11治疗组、联合治疗组,于接种后第3天腹腔分别注射生理盐水、CPT-11、CPT-11加OK-432。观察肿瘤生长体积;测定各组脾细胞分泌的IL-2... 目的:探讨OK-432增强CPT-11抗肿瘤活性的机制。方法:将荷B16黑色素瘤的C57BL/6小鼠随机分为对照组、CPT-11治疗组、联合治疗组,于接种后第3天腹腔分别注射生理盐水、CPT-11、CPT-11加OK-432。观察肿瘤生长体积;测定各组脾细胞分泌的IL-2、IL-4、IL-6、IL-10、IL-12、IFN-γ,并在体外观察了SN-38对OK-432刺激这些细胞因子分泌的影响。结果:OK-432显著增强CPT-11对B16黑色素瘤生长的抑制(P<0.05);CPT-11在体内显著抑制小鼠脾细胞IL-12和IFN-γ的分泌,与OK-432联合使用显著增加小鼠脾细胞IL-2、IL-6、IL-12和IFN-γ的分泌(P<0.05);在体外SN-38对OK-432刺激的IL-6、IL-12分泌无显著影响(P>0.05)。结论:OK-432在体内可通过刺激IL-12和Th1细胞因子的分泌,增强CPT-11的抗肿瘤活性。 展开更多
关键词 细胞因子 OK-432 irinotecan 黑色素瘤 cpt-11 抗癌药 免疫治疗
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Phase Ⅱ study of protracted irinotecan infusion and a low-dose cisplatin for metastatic gastric cancer 被引量:7
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作者 Hiroshi Imamura Masataka Ikeda +8 位作者 Hiroshi Furukawa Toshimasa Tsujinaka Kazumasa Fujitani Kenji Kobayashi Hiroyuki Narahara Michio Kato Haruhiko Imamoto Arimichi Takabayashi Hideaki Tsukuma 《World Journal of Gastroenterology》 SCIE CAS CSCD 2006年第40期6522-6526,共5页
AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase Ⅱ trial to decrease its toxic-ity. METHODS: The eligibility criteria were: (1) histologi-cally proven measurable gastric cancer; (2)... AIM: To test protracted irinotecan infusion plus a low-dose cisplatin in this Phase Ⅱ trial to decrease its toxic-ity. METHODS: The eligibility criteria were: (1) histologi-cally proven measurable gastric cancer; (2) performance status of 0 or 1; (3) no prior chemotherapy or comple-tion of prior therapy at least 4 wk before enrollment; (4) adequate function of major organs; (5) no other active malignancy; and (6) written informed consent. The regi-men consisted of irinotecan (60 mg/m2) on d 1 and 15 by 24-h infusion and cisplatin (10 mg/m2) on d 1, 2, 3, 15, 16, and 17. Treatment was repeated every 4 wk. RESULTS: Thirty-one patients were registered between April 2000 and January 2001. The response rate for all 31 patients, 20 patients without prior chemotherapy, and 11 patients with prior chemotherapy was 52% (16/31), 60% (12/20), and 36% (4/11), respectively. The median survival time was 378 d. The median number of courses given to all patients was 2. Grade 4 neutropenia oc-curred in 11 (35%) patients, while grade 3 to 4 diarrhea or nausea occurred in 1 (3%) and 3 (10%) patients, respectively. Fatigue was minimal as grade 1 fatigue was found only in 3 (10%) patients. Other adverse events were mild and no treatment-related deaths occurred.CONCLUSION: This regimen showed a high level of ac-tivity and acceptable toxicity in patients with metastatic gastric cancer. 展开更多
关键词 Gastric cancer cpt-11 CDDP Protracted irinotecan Chemotherapy
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Temporary Dysarthria Induced by Irinotecan-Case Report of This Rare Adverse Event
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作者 Mayndra Mychelle Landgrat] Cinthia Leite Frizzera Borges Bognar +7 位作者 Raquel Bezerra Guerra Andrea Morais Borges Fernando Silva Picont Gislaine Femandes Silva Pamela Carvalho Muniz Pedro Nazareth Aguiar Junior Gilberto de Lima Lopes Junior Michelle Samora de Almeida 《Journal of Pharmacy and Pharmacology》 2017年第9期636-641,共6页
This report describes the case of a patient with dysarthria during the administration of the third cycle of Folfu'i for the treatment of metastatic colon cancer. After a thorough neurological examination and neuroima... This report describes the case of a patient with dysarthria during the administration of the third cycle of Folfu'i for the treatment of metastatic colon cancer. After a thorough neurological examination and neuroimaging, structural causes were excluded and thus the dysarthria was attributed to the irinotecan infusion. A slowing down of the infusion rate to 180 min during the 15 subsequent cycles led to the cessation of the episodes of dysarthria. In 2016, it was estimated there will be 134,490 new cases of colorectal cancer with a five-year survival rate of 21% among patients with metastatic disease. As Irinotecan is often part of the therapeutic regimen in such cases, both in the first and second-line setting, there is a need to report rare adverse outcomes in order to fmd out ways to better manage of these events. The mechanism by which Irinotecan causes dysarthria is unknown and further research in this area is warranted. 展开更多
关键词 COLON cancer irinotecan DYSARTHRIA ADVERSE event toxicity cpt- 11.
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盐酸伊立替康脂质体制备的影响因素考察 被引量:2
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作者 杨建坤 刘宏伟 +3 位作者 张俭俭 谢瑞娟 刘慧光 曹德英 《中国新药杂志》 CAS CSCD 北大核心 2007年第23期1962-1964,共3页
目的:对盐酸伊立替康的脂质体制备方法进行考察。方法:在预实验的基础上初步确定盐酸伊立替康脂质体的制备方法和处方,然后通过单因素考察初步确定影响脂质体制备的因素。结果:硫酸铵梯度法制备的盐酸伊立替康脂质体包封率较高(75.40%)... 目的:对盐酸伊立替康的脂质体制备方法进行考察。方法:在预实验的基础上初步确定盐酸伊立替康脂质体的制备方法和处方,然后通过单因素考察初步确定影响脂质体制备的因素。结果:硫酸铵梯度法制备的盐酸伊立替康脂质体包封率较高(75.40%),且能保持药物活性。结论:采用硫酸铵梯度法制备脂质体给药系统,制备工艺简单,重现性好,质量稳定,是一种很有前途的靶向给药系统。 展开更多
关键词 盐酸伊立替康 脂质体 硫酸铵梯度法 包封率
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反相离子对高效液相色谱法检查盐酸伊立替康(CPT-11)有关物质
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作者 乔善宝 季旼 +1 位作者 象丽丽 陈东英 《药物分析杂志》 CAS CSCD 北大核心 2013年第3期439-442,共4页
目的:采用反相离子对高效液相色谱法优化盐酸伊立替康中有关物质的检查方法。方法:采用C18色谱柱(150 mm×4.6 mm,5μm),以甲醇-20 mmol·L-1磷酸氢二钠溶液(含7.7 mmol·L-1辛烷磺酸钠)(50∶50)为流动相进行等度洗脱,检测... 目的:采用反相离子对高效液相色谱法优化盐酸伊立替康中有关物质的检查方法。方法:采用C18色谱柱(150 mm×4.6 mm,5μm),以甲醇-20 mmol·L-1磷酸氢二钠溶液(含7.7 mmol·L-1辛烷磺酸钠)(50∶50)为流动相进行等度洗脱,检测波长为255 nm,柱温40℃。结果:经优化的反相离子对色谱法明显改善了盐酸伊立替康和各有关物质的保留行为及分离情况,色谱运行总时间不超过10 min。进一步通过强制降解试验验证了该色谱方法的专属性。结论:本方法简单快速,有利于满足伊立替康有关物质检查的质量控制要求。 展开更多
关键词 高效液相色谱 离子对 盐酸伊立替康 杂质分析 强制降解 质量控制 喜树碱衍生物
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葛根芩连汤三氯甲烷提取物缓解伊立替康所致肠毒性的作用机制分析 被引量:5
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作者 吴亿晗 成颜芬 +6 位作者 王迪 杨晓琴 钟雪梅 林洁 傅超美 章津铭 胡一晨 《中国实验方剂学杂志》 CAS CSCD 北大核心 2021年第16期16-23,共8页
目的:基于经典名方葛根芩连汤"解表清里、主协热下利"的功效,制备葛根芩连汤三氯甲烷提取物用于缓解伊立替康所致的肠毒性,为经典名方葛根芩连汤的开发与应用提供实验依据。方法:60只小鼠随机分为正常组、模型组、洛哌丁胺组... 目的:基于经典名方葛根芩连汤"解表清里、主协热下利"的功效,制备葛根芩连汤三氯甲烷提取物用于缓解伊立替康所致的肠毒性,为经典名方葛根芩连汤的开发与应用提供实验依据。方法:60只小鼠随机分为正常组、模型组、洛哌丁胺组(阳性药盐酸洛哌丁胺胶囊,0.4 mg·kg^(-1))和葛根芩连汤三氯甲烷提取物高、低剂量组(2.3,1.16 g·kg^(-1))。采用盐酸伊立替康(CPT-11,剂量55 mg·kg^(-1))连续4 d腹腔注射制备小鼠迟发性腹泻模型,正常组注射等体积生理盐水;分别在第5天灌胃给予相应药物,正常组和模型组给予相应体积蒸馏水,连续给药5 d。观察各组小鼠的一般情况,计算腹泻指数。运用苏木素-伊红(HE)染色观察小鼠结肠组织病理变化,按试剂盒说明书检测结肠组织中肿瘤坏死因子-α(TNF-α),白细胞介素-1β(IL-1β),环氧合酶-2(COX-2),细胞间黏附分子-1(ICAM-1),谷胱甘肽过氧化物酶(GSH-Px),超氧化物歧化酶(SOD),丙二醛(MDA),一氧化氮(NO)的含量。同时,采用蛋白免疫印迹法(Western blot)检测各组小鼠结肠组织的Kelch样环氧氯丙烷相关蛋白1(Keap1),核转录因子E2相关因子2(Nrf2),紧密连接蛋白-1(ZO-1),血红素氧合酶-1(HO-1),紧密连接蛋白(Occludin)表达情况。结果:与正常组比较,模型组经腹腔注射CPT-11造模后小鼠体质量显著降低(P<0.01),腹泻指数显著升高(P<0.01),结肠组织中TNF-α,IL-1β,COX-2,ICAM-1,MDA,NO含量显著升高(P<0.01),GSH-Px,SOD显著降低(P<0.01);HE染色显示,模型组小鼠结肠可见大量炎性细胞,结肠黏膜可见缺损、肿胀、出血及炎性渗出;结肠组织Keap1,Nrf2,ZO-1,HO-1与Occludin蛋白表达水平均显著降低(P<0.01)。与模型组比较,洛哌丁胺组和葛根芩连汤三氯甲烷提取物高、低剂量组可缓解小鼠体质量降低,且腹泻指数明显下降;TNF-α,IL-1β,COX-2,ICAM-1,MDA,NO水平降低,GSH-Px和SOD含量显著上升;HE染色显示,葛根芩连汤三氯甲烷提取物高、低剂量组细胞紧密排列,胞核清晰;结肠组织屏障功能相关蛋白Keap1,Nrf2,HO-1,Occludin,ZO-1表达升高。结论:葛根芩连汤三氯甲烷提取物可能通过调节炎症及氧化应激来增强肠道屏障功能,进而缓解CPT-11所致迟发性腹泻,可为中药缓解化疗药物的毒副作用提供参考,并且为经典名方的开发提供依据。 展开更多
关键词 葛根芩连汤 盐酸伊立替康(cpt-11) 肠毒性 氧化应激 炎症 迟发性腹泻 洛哌丁胺 肿瘤
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