The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects.
The sulfhydryl containing compounds WR-2721 and glutathione as radio- and chemoprotective agents. A review, indications for use and prospects.
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DOI：
10.1038/sj.bjc.6690404
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发表时间：
1999-05
影响因子：
8.8
通讯作者：
de Vries, EGE
中科院分区：
文献类型：
--
作者：
Hospers, GAP;Eisenhauer, EA;de Vries, EGE
恶性肿瘤的放疗和化疗常伴有明显的毒性反应。降低毒性的一种方法是与化学保护剂的伴随治疗。本文综述了两种巯基化合物，即最近在许多国家注册用于人体的化合物WR-2721（amifostine）和天然存在的化合物谷胱甘肽（GSH）。GSH未注册为化学保护剂。WR-2721是一种氨基硫醇前药，必须通过膜结合碱性磷酸酶转化为活性化合物WR-1065。WR-1065和GSH都作为天然存在的硫醇。当静脉内施用这些化合物时，没有发现对肿瘤的保护作用。甚至有体外证据表明，在用WR-2721预处理后，以及在用卡铂和紫杉醇治疗后的体内，马磷酰胺的抗肿瘤作用增加。随机临床研究表明，WR-2721和GSH可降低顺铂诱导的肾毒性，WR-2721可降低放疗诱导的毒性。与WR-2721相关的副作用是恶心、呕吐和低血压，GSH没有副作用。WR-2721和GSH作为化学保护剂的确切作用尚不完全清楚。未来的研究应检查这些药物对粘膜炎，心脏毒性，神经和耳毒性，继发性肿瘤的发展及其对生活质量的影响的保护作用。© 1999癌症研究运动
Radio- and chemotherapy for the treatment of malignancies are often associated with significant toxicity. One approach to reduce the toxicity is the concomitant treatment with chemoprotective agents. This article reviews two sulfhydryl compounds, namely the agent WR-2721 (amifostine), a compound recently registered for use in human in many countries, and the natural occurring compound glutathione (GSH). GSH is not registered as a chemoprotective agent. WR-2721 is an aminothiol prodrug and has to be converted to the active compound WR-1065 by membrane-bound alkaline phosphatase. WR-1065 and GSH both act as naturally occurring thiols. No protective effect on the tumour has been found when these compounds are administered intravenously. There is even in vitro evidence for an increased anti-tumour effect with mafosfamide after pretreatment with WR-2721, and in vivo after treatment with carboplatin and paclitaxel. Randomized clinical studies have shown that WR-2721 and GSH decrease cisplatin-induced nephrotoxicity and that WR-2721 reduces radiation radiotherapy-induced toxicity. Side-effects associated with WR-2721 are nausea, vomiting and hypotension, GSH has no side-effects. An exact role of WR-2721 and GSH as chemoprotectors is not yet completely clear. Future studies should examine the protective effect of these drugs on mucositis, cardiac toxicity, neuro- and ototoxicity, the development of secondary neoplasms and their effect on quality of life. © 1999 Cancer Research Campaign
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影响因子：
158.5
作者：
Alberts, DS;Liu, PY;Hoskins, WJ
通讯作者：
Hoskins, WJ
影响因子：
8.8
作者：
BETTICHER, DC;ANDERSON, H;THATCHER, N
通讯作者：
THATCHER, N
影响因子：
8.8
作者：
DEWIT, R;STOTER, G;SYLVESTER, R
通讯作者：
SYLVESTER, R
影响因子：
3
作者：
DIRE, F;BOHM, S;ZUNINO, F
通讯作者：
ZUNINO, F
DOI：
10.1111/j.1365-2362.1991.tb01366.x
发表时间：
1991-02-01
影响因子：
5.5
作者：
AEBI, S;ASSERETO, R;LAUTERBURG, BH
通讯作者：
LAUTERBURG, BH