奥曲肽治疗化疗相关性腹泻的临床观察

目的：观察奥曲肽治疗严重化疗相关性腹泻的疗效。方法：2006年11月-2009年12月我院收治的患者32例,均在化疗过程中出现Ⅱ至Ⅳ级腹泻,应用醋酸奥曲肽治疗,应用方法为醋酸奥曲肽0．1mg,皮下注射,每8小时1次,或25ug／h,持续泵入,每天8h-12h,观察腹泻的治疗效果。结果：醋酸奥曲肽治疗32例化疗相关性腹泻患者总有效率为90．6％,治疗后患者KPS评分明显改善,未见明显不良反应。结论：醋酸奥曲肽治疗严重化疗相关性腹泻有效、安全,可改善患者的生存质量。     

奥曲肽治疗严重化疗相关性腹泻的疗效观察

目的:化疗是控制癌症发展,延长患者生命的重要治疗方法,但化疗相关腹泻是很多化疗方案的不良反应,常带给癌症患者痛苦且导致营养不良及体液、蛋白质和电解质的减少,严重可致化疗过程中断,严重影响化疗进程,并且增加住院费用,加重患者心理负担,降低肿瘤的治疗效果,其发病机制尚不清楚,目前无统一的治疗方案,本文探讨醋酸奥曲肽治疗严重化疗相关性腹泻的疗效.方法:将2006年1月～2008年6月本科严重化疗相关性腹泻患者62例,随机分为治疗组和对照组,治疗组采用醋酸奥曲肽注射液(力尔宁,Li Er Ning Injection,简称LEN)0.15～0.2mg+0.9%氯化钠注射液50mL内,8h静脉持续泵入或静脉滴注,对照组给予思密达治疗.观察患者治疗前后的KPS评分和腹泻的治疗效果并进行统计学分析.结果:治疗组腹泻治愈总有效率93.7%,时照组为40%,P＜0.05.治疗前治疗组与对照组KPS评分无显著性差异;治疗组治疗后KPS评分较治疗前明显增高,有显著性差异;治疗后治疗组KPS评分明显高于对照组;对照组治疗前后则无显著性差异.结论:利尔宁(醋酸奥曲肽注射液)为吉林一心制药有限公司的产品.在本研究中证实醋酸奥曲肽注射液8h持续静脉泵入或静脉滴注可以治疗严重的化疗相关性腹泻(CID),可减轻患者痛苦,保证化疗顺利进行.醋酸奥曲肽对严重化疗相关性腹泻疗效好,不良反应少,改善患者的生存质量,值得在临床中进一步推广.     

奥曲肽治疗放疗所致急性腹泻的疗效观察

目的:观察奥曲肽治疗放疗相关性腹泻的疗效。方法:2011年8月-2014年9月我院收治在放疗过程中出现Ⅱ-Ⅳ级腹泻的患者67例,Ⅱ-Ⅲ级患者应用奥曲肽100μg皮下注射,每天3次,Ⅳ级患者给予奥曲肽25μg/h,持续泵入,每天8-12h,观察腹泻的治疗效果。结果:奥曲肽治疗67例放疗相关性腹泻的治愈率为85.07%,治疗后患者Karnofsky 体力状态（KPS）评分明显提高,未见明显不良反应。结论:奥曲肽治疗放疗相关性腹泻,尤其对Ⅱ-Ⅲ级腹泻有较好的疗效,安全可靠,有效改善患者生存治疗,保障放疗顺利进行。     

醋酸奥曲肽治疗化疗相关性腹泻疗效观察

目的探讨醋酸奥曲肽治疗化疗相关性腹泻的疗效。方法选择发生化疗相关性腹泻的肿瘤患者31例,给予醋酸奥曲肽100μg肌肉注射,3次／日治疗,记录患者一般状况、腹泻次数及用药反应。结果治疗总有效率为87．09％（27／31）,其中24例（77．42％）在3天之内症状完全控制,4例6天后腹泻仍未控制,判断为无效。结论醋酸奥曲肽抑制肠蠕动及肠液分泌,是治疗化疗相关性腹泻的有效措施。     

奥曲肽联合碘油经肝动脉灌注治疗不可切除肝癌疗效观察

目的:观察奥曲肽联合碘油经肝动脉灌注治疗不可切除肝癌的临床疗效.方法:分组比较奥曲肽联合化疗栓塞(实验组20例)与单纯化疗栓塞(对照组20例)对症状改善、肿瘤退缩及血生化指标的影响.结果:实验组与对照组在治疗前后近期癌灶疗效和症状体征疗效上有统计学意义.奥曲肽对患者肝肾功能、造血系统及胃肠道系统无明显影响.结论:与常规TACE术相比,以奥曲肽作为灌注药物,对肝癌病人进行TACE术能一定程度上提高疗效和安全性,并能提高患者的生存质量.     

奥曲肽对伊立替康化疗后迟发性腹泻小鼠肠黏膜损伤的治疗作用

目的:观察和探索奥曲肽对伊立替康化疗后迟发性腹泻小鼠肠黏膜损伤的治疗作用。方法:健康昆明小鼠30只,随机分成3组:A组:CPT-11致小鼠腹泻奥曲肽治疗组;B组:CPT-11致小鼠腹泻对照组;C组:腹腔注射等量生理盐水作为空白对照。观察迟发性腹泻发生情况,实验开始后第9天将小鼠处死,取小肠及结肠组织。光镜下根据Chiu标准对肠黏膜损伤程度进行分级。结果:与对照组相比,治疗组小鼠伊立替康引起的迟发性腹泻症状明显减轻,肠黏膜损伤程度亦减轻(P<0.05)。结论:奥曲肽可以对伊立替康引起的迟发性腹泻起到一定程度的治疗作用。     

奥曲肽对伊立替康化疗后迟发性腹泻小鼠肠黏膜损伤的预防作用

目的:观察奥曲肽对伊立替康化疗引起的迟发性腹泻小鼠肠黏膜损伤的预防作用.方法:健康昆明小鼠20只,随即分成对照组,伊立替康组,奥曲肽组,伊立替康及奥曲肽预防组.观察迟发型腹泻发生情况,实验开始后第8天将小鼠处死,取小肠及结肠组织.光镜下根据Chiu标准对肠黏膜损伤程度进行分级.结果:与伊立替康组比较,伊立替康及奥曲肽预防组小鼠腹泻发生率和肠黏膜损伤程度显著降低.结论:奥曲肽可以对伊立替康引起的迟发型腹泻起到一定程度的预防作用.     

奥曲肽联合碘油经肝动脉灌注治疗不可切除肝癌疗效观察

目的：观察奥曲肽联合碘油经肝动脉灌注治疗不可切除肝癌的临床疗效。方法：分组比较奥曲肽联合化疗栓塞（实验组20例）与单纯化疗栓塞（对照组20例）对症状改善、肿瘤退缩及血生化指标的影响。结果：实验组与对照组在治疗前后近期癌灶疗效和症状体征疗效上有统计学意义。奥曲肽对患者肝肾功能、造血系统及胃肠道系统无明显影响。结论：与常规TACE术相比,以奥曲肽作为灌注药物,对肝癌病人进行TA—CE术能一定程度上提高疗效和安全性,并能提高患者的生存质量。     

善宁治疗严重化疗相关性腹泻的疗效观察

目的 探讨善宁治疗常规治疗无效的严重化疗相关性腹泻的疗效.方法 2004年以来常规治疗无效的化疗相关性腹泻13例,善宁0.3 mg/d,观察腹泻次数等.结果 13例患者,善宁治疗后腹泻24 h内停止7例(53.8%),24～48 h内停止5例(38.5%),48～72 h内停止1例(7.7%).结论 善宁能抑制肠液分泌,对严重化疗相关性腹泻疗效好,不良反应少,临床需进一步观察总结.     

奥曲肽持续皮下泵入治疗恶性肠梗阻的临床观察

目的　观察奥曲肽持续皮下泵入给药在恶性肠梗阻姑息性治疗中的作用。方法　收集２００７年３月至２００９年４月收治的２６例恶性肠梗阻患者进行回顾分析。分为奥曲肽组１１例和对照组１５例,比较两组患者在治疗前后肠梗阻相关症状变化、肛门恢复排气排便时间、胃肠减压引流液量、鼻胃管留置时间、拔管率和肠梗阻近期疗效。结果　奥曲肽组肠梗阻相关症状改善率为８１.８％（９／１１）,明显优于对照组４６.７％（７／１５）。奥曲肽组患者恢复排气排便所需平均时间为３.２天,明显优于对照组５８天。奥曲肽组鼻胃管留置时间为（５±１.２）天,拔管率为５４.５％,均明显优于对照组（１０±２.３）天和２０.０％。奥曲肽组肠梗阻的近期疗效好转率为７２.７％,优于对照组２６.７％。结论　奥曲肽持续皮下泵入给药配合常规治疗,能够显著改善晚期恶性肠梗阻患者,尤其是终末期患者的生活质量,为恶性肠梗阻的治疗提供了一种新的治疗思路和方法。     

A multicenter, randomized trial of long-acting octreotide for the optimum prevention of chemotherapy-induced diarrhea: results of the STOP trial

Diarrhea is a well-recognized side effect of chemotherapy and can result in chemotherapy delay and/or dose reduction, potentially reducing the therapeutic benefit of treatment. Octreotide has been shown to be effective in controlling chemotherapy-induced diarrhea (CID). In this open-label, randomized, multicenter study, designed to asses the effects of two dose levels of octreotide long-acting release (LAR), patients with active or prior CID and scheduled for chemotherapy were randomized to receive up to six doses of either 30 or 40 mg of octreotide LAR. The primary endpoint was the proportion of patients experiencing severe diarrhea during the trial. Secondary endpoints included the proportion of patients requiring IV fluids due to diarrhea, unscheduled visits to healthcare professionals due to diarrhea, and changes in primary therapy, as well as treatment satisfaction and quality of life. In total, 147 patients were randomized and received at least 1 dose; 124 patients were efficacy-evaluable. Baseline characters were balanced in the 30-mg and 40-mg groups with the exception of gender. Fewer patients in the 40-mg group compared with those in the 30-mg group experienced severe diarrhea (61.7% vs 48.4%; P = 0.14), required IV fluid (31.7% vs 18.8%; P = 0.10), and had diarrhea-related unscheduled healthcare visits (41.7% vs. 28.1 %; P = 0.11); however, these differences were not statistically significant. No significant differences were observed between the treatment groups in either measured quality of life or treatment satisfaction. Adverse events were balanced between the two groups. No specific recommendations can be made from this trial regarding the use of 30 mg versus 40 mg of octreotide LAR for CID.     

Octreotide LAR resolves severe chemotherapy-induced diarrhoea (CID) and allows continuation of full-dose therapy

Severe diarrhoea after chemotherapy is a dose-limiting toxicity of first-line chemotherapeutic agents approved for the treatment of colorectal cancer including 5-fluorouracil + leucovorin (5-FU/LV) and irinotecan (CPT-11). This report explores the potential of the long-acting version of the somatostatin analogue octreotide, for secondary prophylaxis in patients suffering from chemotherapy-induced diarrhoea (CID). A case series of three patients in a general community setting with colorectal cancer and severe refractory diarrhoea after fluoropyrimidine or irinotecan therapy resulting in suspension of chemotherapy, hospitalization, and/or refusal of further treatment. After the failure of initial aggressive antidiarrhoeal therapy with loperamide and/or diphenoxylate-atropine, patients were treated with octreotide LAR (30 mg q28d). The ability of octreotide LAR to resolve diarrhoea, prevent further episodes of grade 3 or 4 gastrointestinal toxicity and prevent costly hospitalizations. Octreotide LAR 30 mg q28d speed resolution of diarrhoea and was able prevent further episodes during subsequent cycles of chemotherapy. One patient who initially refused chemotherapy because of CID was able to complete his treatment. All patients reported improvement in quality of life following resolution of diarrhoea with octreotide LAR and no further hospitalizations because of CID were necessary.     

Octreotide in the treatment of severe chemotherapy-induced diarrhea

Background:Chemotherapy-induced diarrhea (CID) is a common sideeffect of a number of chemotherapeutic agents. Conventional therapy for severeCID with opioids or loperamide is moderately effective. A prospective trialwas conducted using octreotide acetate for treatment of severe CID refractoryto loperamide. Patients and methods:Thirty-two patients with grade 2 and 3 CIDrefractory to loperamide were treated with octreotide at a dosage of 100µg subcutaneously 3 ×/day for three days followed by 50µg 3 ×/day for three days. Previous chemotherapy consistedof regimens containing fluorouracil, leucovorin, CPT-11, cyclophosphamide,methotrexate and cisplatin. Primary tumors were colorectal(n = 23), gastric (n = 3), and othercancers (n = 6). Results:Complete resolution of diarrhea was obtainedin 30 of 32 patients (94%); 5 within 24 hours, 14 within48 hours, and 11 within 72 hours of treatment. Nineteenpatients were treated as outpatients. Thirteen were hospitalized for amedian of three days. Response was unaffected by age, gender, performancestatus, previous chemotherapy or primary tumor site. No side effects relatedto octreotide were observed. Conclusions:Octreotide 100 µg subcutaneously3 ×/day for three days is an effective, safe treatment for CIDgiven primarily or as a second-line therapy after loperamide failure.     

Chemotherapy-induced diarrhea: pathophysiology, frequency and guideline-based management

Diarrhea is one of the main drawbacks for cancer patients. Possible etiologies could be radiotherapy, chemotherapeutic agents, decreased physical performance, graft versus host disease and infections. Chemotherapy-induced diarrhea (CID) is a common problem, especially in patients with advanced cancer. The incidence of CID has been reported to be as high as 50-80% of treated patients (≥30% CTC grade 3-5), especially with 5-fluorouracil bolus or some combination therapies of irinotecan and fluoropyrimidines (IFL, XELIRI). Regardless of the molecular targeted approach of tyrosine kinase inhibitors and antibodies, diarrhea is a common side effect in up to 60% of patients with up to 10% having severe diarrhea. Furthermore, the underlying pathophysiology is still under investigation. Despite the number of clinical trials evaluating therapeutic or prophylactic measures in CID, there are just three drugs recommended in current guidelines: loperamide, deodorized tincture of opium and octreotide. Newer strategies and more effective agents are being developed to reduce the morbidity and mortality associated with CID. Recent research focusing on the prophylactic use of antibiotics, budesonide, probiotics or activated charcoal still have to define the role of these drugs in the routine clinical setting. Whereas therapeutic management and clinical work-up of patients presenting with diarrhea after chemotherapy are rather well defined, prediction and prevention of CID is an evolving field. Current research focuses on establishing predictive factors for CID like uridine diphosphate glucuronosyltransferase-1A1 polymorphisms for irinotecan or dihydropyrimidine-dehydrogenase insufficiency for fluoropyrimidines.     

外源性FHIT基因对奥曲肽诱导胃癌细胞MGC-803凋亡的影响

目的:探讨外源性脆性组氨酸三联体(fragile histidine triad, FHIT)基因对奥曲肽(octreotide)诱导胃癌细胞凋亡的影响,并探讨其作用机制.方法:采用脂质体法将带有FHIT基因的表达载体pRcCMV-FHIT和空载体pRcCMV分别转入FHIT表达缺失的人类胃癌细胞系MGC-803中.Western 印迹法检测转染细胞中FHIT蛋白的表达.使用不同浓度的奥曲肽(10~(-10)、10~(-9)、10~(-8) 、10~(-7)和10~(-6)mol/L)分别处理各组细胞24、48 和72 h, MTT法检测分析细胞增殖情况,FCM法检测细胞凋亡. Western印迹法检测奥曲肽作用细胞前后,细胞中bcl-2和bax的表达.结果:转染FHIT基因后,胃癌细胞系MGC-803中检测到FHIT蛋白的表达.奥曲肽(10~(-8) mol/L)处理细胞48 h后,转染FHIT基因组细胞的凋亡率为(26.777±1.702)%,与转染空载体组的(13.800±0.511)%和空白细胞组的(12.634±0.479)%相比,凋亡率明显增高(F=245.789,P<0.05,).转染FHIT基因组细胞经奥曲肽处理后bcl-2蛋白表达量减少,bax蛋白表达量增加.结论:外源性FHIT基因表达与奥曲肽可协同促进胃癌细胞MGC-803凋亡,其机制可能与bcl-2家族中的凋亡相关蛋白改变有关.     

奥曲肽联合阿司匹林增强对肝癌细胞生长的抑制作用

背景与目的:奥曲肽和阿司匹林均能抑制肝癌细胞生长,但两种非细胞毒性药物的抗肿瘤机制不同。从多环节发挥抗癌作用的角度考虑,联合治疗可使多种药物获得协同作用,产生最大的抑瘤效应,减少用药量,降低不良反应。本文旨在探讨奥曲肽联合阿司匹林对人肝癌细胞生长的作用。方法:采用3H-胸腺嘧啶核苷掺入法观察单独或联合应用奥曲肽和阿司匹林对体外培养人肝癌细胞株SMMC-7721生长的影响,根据中效原理判断两者之间相互作用的关系。建立人肝癌裸鼠原位移植瘤模型,观察奥曲肽和阿司匹林单独或联合作用对体内肝癌生长的影响。结果:奥曲肽与阿司匹林在体外联合作用能显著抑制SMMC-7721生长,其合用浓度与3H-胸腺嘧啶核苷掺入量呈显著负相关,r=-0.9594,P<0.01。奥曲肽与阿司匹林的大多数效应范围尤其是高水平效应时合用指数小于1,具有明显的协同作用。奥曲肽联合阿司匹林能显著抑制人肝癌裸鼠原位移植瘤的生长,抑瘤率高达89.47%,较单用阿司匹林组(69.92%)明显升高,且联合组肿瘤内的纤维组织增生较对照组明显增多。在各组裸鼠的体内实验中未见明显不良反应。结论:奥曲肽联合阿司匹林不仅显著增加单用其中一种药物对人肝癌细胞株生长的抑制作用,也明显提高对裸鼠肝癌原位移植瘤的抑瘤率,提示两者联合应用对抑制肝癌     

Octreotide treatment of patients with hepatocellular carcinoma - a retrospective single centre controlled study

Background

Studies of treatment with octreotide of patients with hepatocellular carcinoma (HCC) gave conflicting results. We analyzed retrospectively the survival of our patients treated with octreotide monotherapy and compared it to stage-matched patients who received either TACE, multimodal therapy or palliative care.

Methods

95 patients seen at the department of Gastroenterology and Hepatology, Medical University of Vienna with HCC in BCLC stage A or B, who received either TACE, multimodal therapy, long-acting octreotide or palliative care were reviewed for this retrospective study.

Results

Survival rates of patients with BCLC stage B and any "active" treatment (long-acting octreotide, TACE or multimodal therapy) were significantly higher (22.4, 22.0, 35.5 months) compared to patients who received palliative care only (2.9 months). Survival rates of patients with BCLC stage A and "active" treatment (31.4, 37.3, 40.2 months) compared to patients who received only palliative care (15.1 months) did not show statistically significant differences. Octreotide monotherapy showed a similar outcome compared to patients who received TACE or multimodal therapy.

Conclusion

Survival under octreotide treatment was not different compared to TACE or multimodal therapy and might be a therapeutic option for patients with HCC.     

奥曲肽辅助治疗肝癌破裂出血31例观察

目的探讨肝癌合并破裂出血患者应用奥曲肽辅助治疗的临床意义。方法肝癌合并破裂出血患者一经确诊除给予快速输液、应用止血剂、抗休克等常规治疗外，同时给予奥曲肽0．1mg i．v，然后再给予0．5～1．0mg，静脉滴注维持24h。次日根据病情继续滴注或改为0．1 mgi．h q6h，连续应用3～5d。结果本组31例，非手术治疗11例，手术探查20例。1例为全肝癌破裂并大量血性腹水，连续应用奥曲肽等保守治疗12d，发生多器官功能障碍综合症死亡，其余病例病情稳定后顺利出院。结论肝癌合并破裂出血患者应用奥曲肽，能降低门静脉压力，缓解并存的门静脉高压，为尽快渡过急性出血期、稳定病情、进一步采取手术治疗和各种非手术治疗赢得了时间。