Amifostine配合含铂方案化疗前应用的临床观察与护理

Amifostine（又称阿米福汀、氨磷汀）目前作为一种备受关注的全新的抗癌辅助药，能选择性保护正常器官化疗、放疗的毒性攻击，而不保护肿瘤细胞，不影响化疗药的抗肿瘤效果，并可明显减少化疗相关肝、肾功能损害的发生，减轻化疗药物所造成的骨髓、心脏、耳及神经系统的毒性，是一种安全的细胞保护剂。但是，应用过程中也会出现一些不良反应，如恶心、呕吐、一过性血压降低、头晕、乏力，个别患者有嗜睡，因此，对于护理要求较高。我科自2006年10月-2007年6月应用Amifostine配合含铂方案化疗前使用14例，现将临床观察及护理体会介绍如下。

Amifostine:一种广谱细胞保护剂与恶性血液病

Amifostine作为一种化疗正常细胞广谱保护剂具有内在促干细胞增殖作用,可提高白血病大剂量化疗效果,增强自体干细胞移植体外净化作用,改善骨髓异常增生综合征无效造血,在恶性血液病患者的应用具有广阔前景。

Cytoprotective effects of amifostine,ascorbic acid and N-acetylcysteine against methotrexate-induced hepatotoxicity in rats

AIM:To investigate the potential role of oxidative stress and the possible therapeutic effects of N-acetyl cysteine(NAC),amifostine(AMF)and ascorbic acid(ASC)in methotrexate(MTX)-induced hepatotoxicity.METHODS:An MTX-induced hepatotoxicity model was established in 44 male Sprague Dawley rats by administration of a single intraperitoneal injection of20 mg/kg MTX.Eleven of the rats were left untreated(Model group;n=11),and the remaining rats were treated with a 7-d course of 50 mg/kg per day NAC (MTX+NAC group;n=11),50 mg/kg per single dose AMF(MTX+AMF group;n=11),or 10 mg/kg per day ASC(MTX+ASC group;n=11).Eleven rats that received no MTX and no treatments served as the negative control group.Structural and functional changes related to MTX-and the various treatments were assessed by histopathological analysis of liver tissues and biochemical assays of malondialdehyde(MDA),superoxide dismutase(SOD),catalase,glutathione(GSH)and xanthine oxidase activities and of serum levels of aspartate aminotransferase,alanine aminotransferase,alkaline phosphatase and total bilirubin.RESULTS:Exposure to MTX caused structural and functional hepatotoxicity,as evidenced by significantly worse histopathological scores[median(range)injury score:control group:1(0-3)vs 7(6-9),P=0.001]and significantly higher MDA activity[409(352-466)nmol/g vs 455.5(419-516)nmol/g,P<0.05].The extent of MTX-induced perturbation of both parameters was reduced by all three cytoprotective agents,but only the reduction in hepatotoxicity scores reached statistical significance[4(3-6)for NAC,4.5(3-5)for AMF and 6(5-6)for ASC;P=0.001,P=0.001 and P<0.005vs model group respectively].Exposure to MTX also caused a significant reduction in the activities of GSH and SOD antioxidants in liver tissues[control group:3.02(2.85-3.43)μmol/g and 71.78(61.88-97.81)U/g vs model group:2.52(2.07-3.34)μmol/g and 61.46(58.27-67.75)U/g,P<0.05];however,only the NAC treatment provided significant increases in these antioxidant enzyme activities[3.22(2.54-3.62)μmol/g and 69.22(61.13-100.88)U/g,P<0.05 and P<0.01vs model group respectively].CONCLUSION:MTX-induced structural and functional damage to hepatic tissues in rats may involve oxidative stress,and cytoprotective agents(NAC>AMF>ASC)may alleviate MTX hepatotoxicity.

Effectiveness and safety of different amifostine regimens：Preliminary results of a phase Ⅱ multicenter randomized controlled trial

Objective：The radioprotective effects of amifostine remain uncertain in patients with nasopharyngeal carcinoma（NPC）,and adverse effects and cost limit generalization of its classical everyday regimen.This phase II multicenter randomized controlled trial aimed to explore whether amifostine could ameliorate the toxicities of NPC patients in the era of intensity-modulated radiotherapy（IMRT）,and to compare different regimens of amifostine on effectiveness and safety.Methods：Patients with stage I–IVB NPC were involved prospectively from January 1st,2013.All patients received radical treatment based on IMRT.After a randomization stratified by their stage,these patients were allocated into 3 groups：the group treated without amifostine,the group treated with the everyday regimen of amifostine,and the group treated with the every-other-day regimen.The 3 groups of patients were compared on radiotherapy-related acute toxicities,treatment effects of NPC,and amifostine-related complications.This trial was registered on the clinicaltrials.gov（ID：NCT01762514）.Results：Until August 31st,2017,totally 187 patients completed experimental intervention.Only amifostine of everyday regimen appeared to reduce the patient proportion of mucositis（79.1%vs.96.8%,P=0.002）.Hypocalcemia was less common in patients treated without amifostine than in those treated with amifostine（22.6%vs.53.4%vs.41.8%,P=0.002）.Neither complete remission rates nor the survivals were affected by amifostine.Conclusions：Amifostine of everyday regimen could reduce mucositis in NPC patients who received IMRT,though it also had the possibility to cause more hypocalcemia.

Amifostine对环磷酰胺衍生物所致正常造血祖/干细胞毒性的保护作用

为了估价Amifostine(WR-2721)对正常造血干细胞的保护作用,我们用不同剂量的环磷酰胺衍生物(4-HC,ASTA-Z)对13例正常造血干细胞进行了体外处理,并测定其PCM-CFU-GM,5R-CFU-GM和LTO-IC的LD_(95),发现在处理前经过WR-2721孵育的13例中10例LD_(95)明显增加(P<0.05),显示了明确的保护效果,而在9例白血病祖细胞组中,这种保护效果却没有被发现。相反,经过WR-2721孵育9例白血病祖细胞对化疗的敏感性都有不同程度的增加。

Inhaled amifostine for the prevention of radiation-induced lung injury

Objective:To alleviate radiation-induced lung injury and prevent the related pneumonitis and pulmonary fibrosis by inhaled amifostine(AMI).Methods:15 Gy 60Coγ-ray irradiation was performed on the thoracic area of rats once to establish the radiation injury model.AMI was intraperitoneally(i.p.)injected or intratracheally(i.t.)administered to the rats 30 min preirradiation.The protective effects of the two AMI administration manners were compared in the aspects of hematopoietic system,lung edema,and histopathological examination,and the mechanisms were explored.Results:Compared to i.p.AMI,i.t.AMI remarkably alleviated radiation-induced lung injury and prevented consequent pneumonitis or pulmonary fibrosis.Specifically,i.t.AMI notably protected white blood cells and platelets,reduced the lung wet/dry weight ratio,and decreased collagen volume fractions compared to the model group(P<0.05),while i.p.AMI showed no significant difference with the model group(P>0.05).The high therapeutic efficiency of i.t.AMI was related to its high antioxidation and anti-inflammation effects with downregulation of pro-inflammatory cytokines,the enhanced superoxide dismutase activity,the low levels of malondialdehyde and total proteins.Conclusion:Inhaled AMI is a promising medicine for preventing radiation-induced lung injury,including pneumonitis and pulmonary fibrosis.

Acupoint Sticking at Shenque(CV 8) with Ginger-prepared Ban Xia(Rhizoma Pinelliae) for Nausea and Vomiting Induced by Amifostine

Objective: To observe the treatment effect of acupoint sticking at Shenque(CV 8) with ginger-prepared Ban Xia(Rhizoma Pinelliae) on nausea and vomiting induced by Amifostine for myelodysplastic syndromes(MDS). Methods: Totally 124 eligible subjects intervened by Amifostine were randomized into 2 groups by the visiting order, an observation group and a control group, 62 in each group. The control group was intervened by conventional treatment, while the observation group was by acupoint sticking at Shenque(CV 8) with ginger-prepared Ban Xia(Rhizoma Pinelliae)in addition to the same conventional treatment. The occurrence rate of nausea and vomiting in the two groups were observed. Results: After intervention, the occurrence rate of nausea and vomiting in the observation group was significantly lower than that in the control group(P<0.01). Conclusion: Acupoint sticking at Shenque(CV 8) with ginger-prepared Ban Xia(Rhizoma Pinelliae) can produce a content effect on nausea and vomiting induced by Amifostine for MDS.

Prevention of pelvic radiation disease

Pelvic cancers are among the most frequently diagnosed cancers worldwide. Treatment of patients requires a multidisciplinary approach that frequently includes radiotherapy. Gastrointestinal(GI) radiation-induced toxicity is a major complication and the transient or long-term problems, ranging from mild to very severe, arising in non-cancerous tissues resulting from radiation treatment to a tumor of pelvic origin, are actually called as pelvic radiation disease. The incidence of pelvic radiation disease changes according to the radiation technique, the length of follow up, the assessmentmethod, the type and stage of cancer and several other variables. Notably, even with the most recent radiation techniques, i.e., intensity-modulated radiotherapy, the incidence of radiation-induced GI side effects is overall reduced but still not negligible. In addition, radiation-induced GI side effects can develop even after several decades; therefore, the improvement of patient life expectancy will unavoidably increase the risk of developing radiation-induced complications. Once developed, the management of pelvic radiation disease may be challenging. Therefore, the prevention of radiation-induced toxicity represents a reasonable way to avoid a dramatic drop of the quality of life of these patients. In the current manuscript we provide an updated and practical review on the best available evidences in the field of the prevention of pelvic radiation disease.