氨磷汀对顺铂肾毒性损害的保护作用

顺铂(DDP)是临床常用的化疗药物之一,其抗瘤谱广,广泛用于治疗肺癌、食管癌、大肠癌、睾丸和头颈部恶性肿瘤等,但明显的肾毒性在一定程度上限制了其临床应用。氨磷汀是美国FDA按一类新药优先批准上市的第1个泛细胞保护剂,即广谱的选择性细胞     

氨磷汀对草酸铂和氟脲嘧啶脱氧核苷肾毒性的保护作用

氨磷汀 (Amifostine)是美国FDA批准上市的第一个泛细胞保护剂。其作用机理是它是一种有机硫代磷酸化合物 ,正常组织对其摄取迅速而代谢缓慢 ,肿瘤组织则有缓慢摄取 ,结果正常组织因有高浓度氨磷汀而起到清除因化放疗产生的氧自由基作用 ,但不影响放化疗的抗肿瘤作用。国外研究证明[1～ 4 ] :氨磷汀对化疗药物所引起的肾毒性、骨髓毒性保护作用尤为明显 ,并对耳毒性、粘膜毒性、心脏毒性和放疗引起的口腔干燥综合症也有防护作用。我们利用上述优点对一名晚期肺癌患者进行治疗。患者黄×× ,男 ,76岁 ,7年前因确诊为右肺腺癌 ,进行根治性手…     

神经节苷脂对奥沙利铂所致周围神经毒性的预防作用

目的 探讨神经节苷脂对奥沙利铂所致周围神经毒性的预防作用.方法 入组86例接受含奥沙利铂方案化疗的晚期胃癌患者,随机均分为2组,每组43例,观察组43例在接受含奥沙利铂方案化疗的同时给予神经节苷脂,而对照组仅接受含奥沙利铂方案化疗,完成4周期化疗后,比较观察2组患者周围神经毒性发生情况,并用肌电图诱发电位仪检测腓总神经感觉神经传导速度(SNCV)和运动神经传导速度(MNCV).结果 观察组周围神经毒性发生率为23.26%(10/43),低于对照组的51.16%(22/43),差异有统计学意义(χ2=7.167,P=0.007).观察组腓总神经SNCV和MNCV分别为(45.23±5.41)m·s-1、(44.17±4.29)m·s-1,明显快于对照组的(35.27±5.17)m·s-1、(37.90±4.05)m·s-1,差异均有统计学意义(t=8.728,P<0.001;t=6.969,P<0.001).结论 神经节苷脂能够预防奥沙利铂所致的周围神经毒性,有利于化疗的顺利进行.     

氨磷汀对顺铂肾毒性损伤的保护作用及其机制的研究

目的 观察顺铂的肾毒性损伤部位、形式与肾功能检查结果的相关性,以了解细胞凋亡的发生机制和氨磷汀的保护机制是否与肾组织Fas和FasL表达改变有关。方法 随机将大鼠分成3组,即对照组（生理盐水）、顺铂组（6mg／kg）和氨磷汀组（顺铂6mg／kg＋氨磷汀200mg／kg）,取其血清标本和肾组织,分别做血清BUN、Cr检测和肾组织病理学检查,并用原位缺口末端标记法（TUNEL）做肾组织凋亡细胞检测、Fas和FasL免疫组化染色,再用图像分析软件对其做阳性细胞计数和染色总灰度值测定。结果 顺铂组动物血清BUN、Cr值均明显高于对照组和氨磷汀保护组,3d时,差异已有统计学意义（P〈0．05）;5d时,两者差异分别为P〈0．01和P〈0．05;10d时,恢复正常。顺铂组肾小管上皮细胞坏死和凋亡均很严重,其凋亡细胞计数明显高于对照组和氨磷汀组（P值均〈0．01）,肾组织Fas和FasL表达的总灰度值,明显高于对照组和氨磷汀组（P值均〈0．01）。结论 氨磷汀对顺铂的肾毒性损伤有保护作用,其机制可能与抑制肾组织Fas和FasL的表达有关。     

消化道肿瘤患者应用奥沙利铂引起周围神经毒性的护理进展

奥沙利铂(L-HOP、草酸铂、奥铂、艾克博康、艾恒)是第3代铂类广谱化疗药物,其疗效好,胃肠、血液、肾、耳毒性较顺铂低,对消化道肿瘤有显著疗效,已成为消化道辅助化疗的标准方案和复发转移性大肠癌的一线化疗方案[1]。周际昌[2]报告,奥沙利铂神经毒性发生率为82%。周围神经毒性在临床治疗中广泛存在,严重的神经毒性反应可以影响患     

氨磷汀对顺铂致肾功能异常患者再化疗的肾脏保护作用

目的观察氨磷汀对顺铂（DDP）致肾功能异常患者再化疗的肾脏保护作用。方法对19例因DDP化疗致肾功能异常患者,再次应用含DDP方案化疗,静脉用DDP前30min加用氨磷汀250mg/m^2,治疗前及治疗后不同时间分别测定血尿素氮、血肌酐值,观察肾功能的变化情况。结果19例患者,有效4例,稳定12例,进展3例,总有效率达84.2%。结论DDP化疗后肾功能轻度异常患者,再次采用含DDP方案化疗时,加用氨磷汀可以防止肾功能的进一步损害。     

氨磷汀预防消化道肿瘤草酸铂化疗引起的神经毒性

背景与目的:草酸铂广泛用于消化道肿瘤的化疗,突出的神经毒性限制了剂量和疗效的提高.本研究旨在评价氨磷汀对草酸铂神经毒性的防治效果.方法:92例FOLFOX 4方案化疗的结直肠癌、胃癌患者,随机进人氨磷汀组(草酸铂前静脉注射氨磷汀500 mg/m2,n=46)或对照组(草酸铂前静脉注射还原性谷胱甘肽1500 mg/m2,n=46).每化疗2周期详细评价神经毒性.结果:氨磷汀组Ⅰ～Ⅱ度和Ⅲ～Ⅳ度神经毒性发生率与对照组相比,分别为10.9%:73.9%(P＜0.001)和2.2%:19.6%(P=0.007),均显著降低.氨汀组因化疗毒性的方案改变明显少于对照组(4.3%:23.9%,P=0.007).化疗近期有效率氨磷汀组与对照组差异无显著性(44.4%:38.5%,P=0.659).结论:氨磷汀对含草酸铂方案化疗的神经毒性有明显防治作用.不降低化疗疗效.     

还原型谷胱甘肽用于预防和降低奥沙利铂周围神经毒性的研究

目的:观察还原型谷胱甘肽(GSH)预防和降低奥沙利铂周围神经毒性的作用.方法:将78例肠癌术后和胃癌术后准备进行FOLFOX4或mFOLFOX6方案化疗的患者,随机分为GSH组40例和对照组38例.GSH组在奥沙利铂化疗每周期同时给予GSH 1.8 g/d,1次/d,加入生理盐水100 mL,共3 d(化疗前1 d、当日和第2天).对照组在化疗每周期同时给予生理盐水100 mL,共3 d(化疗前1 d、当日和第2天).在治疗前、化疗4个周期后、化疗8个周期后及化疗12个周期后分别记录临床感觉神经系统检查结果,并记录奥沙利铂周围神经毒性级别.有神经毒性症状的患者随访1年,每3个月复查1次临床感觉神经系统检查.结果:在治疗前、化疗4个周期、化疗8个周期后GSH组与对照组的周围神经毒性发生率差异无统计学意义,P>0.05.完成12个周期化疗后GSH组3级周围神经毒性发生率为15%,4级周围神经毒性发生率为0,对照组3级周围神经毒性发生率为39.5%,4级周围神经毒性发生率为5.3%,3～4级神经毒性两组间差异有统计学意义,P<0.05.随访1年后,GSH组>2级神经毒性发生率为0,1级神经毒性发生率为7.5%(3例);对照组>2级神经毒性发生率为0,1级神经毒性发生率为23.7%(9例).两组差异有统计学意义,P<0.05.结论:化疗时使用GSH可以预防和减少奥沙利铂所致周围神经毒性.     

氨磷汀对行化疗的肿瘤患者的保护作用

目的探讨氨磷汀对进行化疗的肿瘤患者的保护作用。方法对60例恶性肿瘤患者,采取随机双盲法分为治疗组、对照组各30例。对照组只作常规化疗,治疗组在化疗前30 min加予氨磷汀500 mg/m2静脉点滴,同时评估2组患者化疗的毒副作用。结果治疗组化疗后出现的骨髓抑制明显低于对照组,差异有统计学意义（P〈0.01）;2组肝脏、肾脏毒性差异无统计学意义（P〉0.05）。结论氨磷汀可以降低化疗引起的骨髓抑制的发生率,对化疗患者具有保护作用。     

Assessment of amifostine as protection from chemotherapy-induced toxicities after conventional-dose and high-dose chemotherapy in patients with germ cell tumor

Background:We assessed the efficacy of amifostine for protectionfrom chemotherapy-induced toxicities in patients treated withconventional-dose paclitaxel, ifosfamide, cisplatin (TIP) and high-dosecarboplatin, etoposide and thiotepa (CET) followed by peripheral bloodprogenitor cell (PBPC) rescue. Patients and methods:In a prospective single-center study 40patients with relapsed or refractory germ-cell tumors (GCT) were treated with3 cycles of conventional-dose TIP followed by one cycle of high-dose CET.Patients were randomized either to receive one fixed dose of 500 mg amifostineper day of conventional-dose TIP and two fixed doses of 500 mg per dayamifostine during high-dose CET (group A,n = 20) or noamifostine (group B, n= 20). Prior to the first cycle of TIP, onecourse of 175 mg/m² paclitaxel and 5 g/m² ifosfamide(TI) followed by granulocyte-colony stimulating factor (G-CSF) at 10µg/kg/day were given for PBPC mobilization. Results:Toxicities and response to conventional-dose TIP andhigh-dose CET could be evaluated in 40 patients (100%) and 32 of 40patients (80%), respectively. Peripheral neurotoxicity (i.e.paresthesia or sensorymotor impairment), hearing impairment, hematologictoxicity, nephrotoxicity, nausea, myalgia, skin- and liver-toxicity did notdiffer siginificantly between the two patient groups. Likewise, the responserates to TIP and high-dose CET were comparable in patients withor without amifostine. After a median follow-up of 18 months, 8 of 20(40%) patients of group A and 6 of 20 (30%) patients of groupB are without relapse. Conclusion:Repeated low doses of 500 mg amifostine additional toconventional-dose TIP or high-dose CET showed no unequivocal advantage inprotection from treatment-related toxicities. Furthermore, no significantdifferences in response rates or survival could be observed in this smallnumber of patients.     

A randomized trial of amifostine in patients with high-dose VIC chemotherapy plus autologous blood stem cell transplantation

This pilot study evaluates the degree of side effects during high-dose chemotherapy (HD-VIC) plus autologous bone marrow transplant (HDCT) and its possible prevention by the cytoprotective thiol-derivate amifostine. Additionally, the in-patient medical costs of both treatment arms were compared. 40 patients with solid tumours were randomized to receive HD-VIC chemotherapy with or without amifostine (910 mg/m(2)at day 1-3) given as a short infusion prior to carboplatin and ifosfamide. Patients were stratified according to pretreatment. HDCT consisted of an 18 h infusion of carboplatin (500 mg/m(2/)d over 18 h), ifosfamide (4 g/m(2)/d over 4 h) and etoposide (500 mg/m(2)/d) all given for 3 consecutive days. All patients received prophylactic application of G-CSF (5 microg kg(-1)subcutaneously) to ameliorate neutropenia after treatment. Patients were monitored for nephrotoxicity, gastrointestinal side effects, haematopoietic recovery, as well as frequency of fever and infections. The median fall of the glomerular filtration rate (GFR) was 10% from baseline in the amifostine group (105 to 95 ml min(-1)) and 37% in the control patient group (107 to 67 ml min(-1)) (P< 0.01). Amifostine-treated patients revealed a less pronounced increase in albumin and low molecular weight protein urinary excretion. Stomatitis grade III/IV occurred in 25% without versus 0% of patients with amifostine (P = 0.01). Acute nausea/vomiting was frequently observed immediately during or after the application of amifostine despite intensive antiemetic prophylaxis consisting of 5-HT3-receptor antagonists/dexamethasone/trifluorpromazine. However, delayed emesis occurred more often in the control patients. Engraftment of neutrophil (> 500 microl(-1))and thrombocytes (> 25 000 microl(-1))were observed at days 9 versus 10 and 10 versus 12, respectively, both slightly in favour of the amifostine arm. In addition, a lower number of days with fever and a shortened duration of hospital stay were observed in the amifostine arm. The reduction of acute toxicity observed in the amifostine arm resulted in 30% savings in costs for supportive care (Euro 4396 versus Euro 3153 per patient). Taking into account the drug costs of amifostine, calculation of in-patient treatment costs from the start of chemotherapy to discharge revealed additional costs of Euro 540 per patient in the amifostine arm. This randomized pilot study indicates that both organ and haematotoxicity of HD-VIC chemotherapy can be ameliorated by the use of amifostine. Additionally, a nearly complete preservation of GFR was observed in amifostine-treated patients which may be advantageous if repetitive cycles of HDCT are planned. Larger randomized trials evaluating amifostine cytoprotection during high-dose chemotherapy are warranted.     

化学保护剂阿米福汀在晚期胃癌病人中的应用

目的研究化疗保护剂阿米福汀(amifostine)对晚期胃癌化疗病人的应用价值。方法采用自身对照，对比单纯化疗组与阿米福汀 静脉化疗组的毒副反应。结果阿米福汀 静脉化疗组消化道反应有所增加，总体毒副反应较单纯化疗组明显减少，但无统计学差异(P=0．225)。结论阿米福汀作为高效、安全的化疗保护剂，值得在大剂量化疗以及既往化疗出现明显毒副反应的患者中应用。     

A randomized trial of amifostine as a cytoprotective agent in patients receiving chemotherapy for small cell lung cancer

A randomized trial was conducted to determine whether administration of Amifostine with chemotherapy for small cell lung cancer could decrease the toxicity. 84 patients with small cell lung cancer of favourable prognosis (limited disease, performance status 0-1; limited disease with performance status 2 but normal sodium and alkaline phosphatase, or extensive disease with performance status 0-1, normal sodium and alkaline phosphatase) received treatment with Ifosfamide 3 g/m(2)intravenously, Carboplatin (Glomerular filtration rate + 25) x6 mg intravenously, Etoposide 50 mg orally, twice daily, for 7 days, every 3 weeks. Patients were randomized to receive amifostine 740 mg/m(2)immediately prior to the intravenous drugs (n = 42) or to receive chemotherapy alone (n = 42). The two groups were similar with respect to baseline prognostic factors. There was no significant difference in the occurrence of grade III or IV neutropenia or thrombocytopenia between the two groups, nor in the response rate or overall survival, for which the median was 11 months in the chemotherapy only group and 14 months in the group treated with amifostine. This study has not shown a protective effect from the use of amifostine with this regimen and there does not appear to be any effect upon the efficacy of treatment.     

Phase III multicenter randomized trial of amifostine as cytoprotectant in first-line chemotherapy in ovarian cancer patients.

BACKGROUND: A phase III multicenter randomized trial has been designed in order to address whether amifostine (WR-2721, Ethyol), an organic thiophosphate cytoprotector, can protect ovarian cancer patients from toxicity induced by carboplatin-paclitaxel chemotherapy. PATIENTS AND METHODS: Patients were randomly assigned to receive carboplatin [area under the curve (AUC) 5 mg.min/ml] and paclitaxel (175 mg/m(2)) with (arm A) or without (arm B) amifostine (910 mg/m(2)) every 21 days for six cycles. RESULTS: One-hundred and eighty-seven patients were accrued: 93 patients in arm A and 94 patients in arm B. There was no difference in terms of erythrocytopenia between the two arms; grade 3-4 thrombocytopenia was higher in arm A (3.3% versus 0.6%; P = 0.0010). There was no significant reduction of grade 3-4 leukopenia in arm A (11.8% versus 13.8%). The incidence of grade 3-4 neutropenia was lower in arm A (31.3% versus 37.9%; P = 0.03), as was the incidence of severe mucositis (4.7% versus 15.4% in arm A versus arm B, respectively; P <0.0001). Finally, amifostine appears to be protective against neurotoxicity (grade 3-4 neurotoxicity 3.7% versus 7.2%; P = 0.02). With a median follow-up of 24 months (range 2-41), time to progression was similar between the two groups. CONCLUSIONS: We showed that amifostine can exert some protection from the cumulative toxicity associated with this regimen. The results need to be confirmed in other randomized trials with this combination.     

氨磷汀对老年恶性肿瘤患者化疗中骨髓的保护作用

目的:研究广谱的细胞保护剂氨磷汀在老年恶性肿瘤患者化疗中骨髓的保护作用。方法:采用随机、开放、对照的原则,选择20例实体肿瘤患者,化疗50例次,分两组,观察组化疗前应用氨磷汀,对照组不用,比较两组间化疗后血细胞的变化情况。结果:观察组与对照组比较,化疗后血液毒性明显减轻,统计学处理有显著性差异。结论:氨磷汀对化疗患者的骨髓有一定的保护作用,特别是对老年恶性肿瘤化疗患者的应用是安全和有效的。     

氨磷汀对血液恶性肿瘤化疗患者肝脏保护作用的临床观察

目的:观察氨磷汀对血液恶性肿瘤化疗患者肝脏保护作用及药物的安全性。方法:将18例血液恶性肿瘤患者合并病毒性肝炎或既往化疗肝脏不能耐受者,分为对照组(单纯化疗)和治疗组(化疗加阿米福汀),作自身前后对照研究,化疗前后监测肝功能,同时观察药物不良反应。结果:化疗相关肝功能损害对照组出现18例,治疗组出现3例(P<0.01)。结论:氨磷汀能明显减少化疗相关的肝功能损害,且不良反应少见。     

黄芪注射液联合弥可保防治奥沙利铂化疗所致神经毒性的效果

目的:探讨黄芪注射液联合弥可保在奥沙利铂化疗所致神经毒性中的防治效果。方法:选取2013年10月至2016年10月我院收治的胃癌或结直肠癌患者58例做为研究对象。将患者随机分为两组,患者均接受奥沙利铂化疗,每2周1次,共化疗4周期。化疗第1天起,研究组给予黄芪注射液联合弥可保治疗,对照组仅给予弥可保治疗,直至化疗结束。观察两组周围神经传导功能、Karnofsky（KPS）评分、神经毒性发生率及严重程度。结果:治疗前两组运动神经传导速度（motor nerve conduction velocity,MCV）、感觉神经传导速度(sensory nerve conduttion velocity,SCV)比较无统计学意义（P＞0.05）;治疗后两组MCV均增加（P＜0.05）,研究组MCV显著优于对照组（P＜0.05）。两组SCV治疗后与治疗前对比,组间对比,差异均不具有统计学意义（P＞0.05）。研究组各治疗周期的KPS评分均高于对照组（P＜0.05）。两组患者神经毒性发生率及严重程度比较,差异不具有统计学意义（Z=-1.127,P＞0.05）。结论:黄芪注射液联合弥可保对奥沙利铂化疗所致神经毒性的防治效果理想,可显著改善神经传导功能及患者健康状况,降低神经毒性发生率及严重程度。     

A Phase II trial of subcutaneous amifostine and radiation therapy in patients with head-and-neck cancer

PURPOSE: Intravenous amifostine 200 mg/m2 reduces xerostomia in head-and-neck cancer patients. This Phase II study evaluated subcutaneous (s.c.) amifostine in a similar patient population. PATIENTS AND METHODS: Patients received amifostine 500 mg, administered as two 250-mg s.c. injections 60 min before once-daily radiation for head-and-neck cancer (50-70 Gy in 5-7 weeks). The primary endpoint was the incidence of > or =Grade 2 acute xerostomia. RESULTS: Fifty-four patients received s.c. amifostine and radiotherapy. The incidence of > or =Grade 2 acute xerostomia was 56% (95% CI, 43-69%) and the incidence of > or =Grade 2 late xerostomia at 1 year was 45% (95% CI, 29-61%). The incidence of acute xerostomia was lower than reported previously with no amifostine in a controlled study; rates of acute xerostomia were similar between s.c. and i.v. amifostine in the two studies. The rate of late xerostomia with s.c. amifostine was intermediate between rates for i.v. amifostine and no amifostine, and not statistically significantly different from either historical control. Grades 1-2 nausea and emesis were the most common amifostine-related adverse events. Grade 3 amifostine-related adverse events reported by >1 patient included: dehydration (11%); rash (6%); and weight decrease, mucositis, dyspnea, and allergic reaction (each 4%). Seven patients (13%) had serious cutaneous adverse events outside the injection site. One-year rates of locoregional control, progression-free survival, and overall survival were 78%, 75%, and 85%, respectively. CONCLUSIONS: Subcutaneous amifostine provides a well-tolerated yet simpler alternative to i.v. amifostine for reducing acute xerostomia in head-and-neck cancer patients.     

静滴左卡尼汀预防化疗药物神经毒性的临床观察

目的：评价左卡尼汀对化疗药物神经毒性的防治效果.方法：42例肿瘤患者,随机进入左卡尼汀组（化疗药物给药前静脉注射左卡尼汀1500mg/m2,n=21）或对照组（化疗药物给药前静脉注射还原性谷胱甘肽1500mg/m2,n =21）.化疗第2、4、6周期详细评价外周感觉神经毒性分级、肿瘤相关性疲劳分级和体力状况评分以及行神经电生理检查.结果：左卡尼汀组Ⅲ-Ⅳ度神经毒性发生率与对照组相比,为9.5％∶55％（P=0.001）,肿瘤相关性疲劳分级3-4级患者发生率显著降低,（57.1％∶90％,P=0.017）.化疗近期有效率左卡尼汀组与对照组差异无显著性（33.3％∶40％,P =0.760）.结论：左卡尼汀对化疗药物引起的神经毒性有明显防治作用,不降低化疗疗效.