Advances in the Management of Oxaliplatin-Induced Neuropathy: Focus on Glutamine and Using Pharmacogenomics to Predict the Effectiveness of Opioid Drugs

Oxaliplatin神經毒性治療方面的進展：聚焦在麩醯胺酸以及利用基因體多型性來預測鴉片類藥物Oxaliplatin疼痛性神經病變之療效

王緯書(Wei-Shu Wang)

《台灣癌症醫學雜誌》 1卷3期 (2014/12) Pp. 175-185

https://doi.org/10.6323/JCRP.2014.1.3.01

摘要

神經毒性是oxaliplatin治療期間最常見的副作用。根據不同的臨床研究報告，oxaliplatin所引起的嚴重神經毒性的機率約為12%至18%。依症狀之不同，oxaliplatin神經毒性可分為兩類。第一類是相當特殊、急性的、暫時性的週邊神經過度敏感現象，通常在給藥後幾個小時內就會發生。第二類與cisplatin引起的神經毒性類似，係發生於肢端末稍的感覺神經病變。這類型的神經毒性會持續數個月，導致神經功能明顯失常，並有可能會影響後續的治療。目前已有幾種策略用來預防或治療oxaliplatin引起的神經毒性，包括「打打停停」（stop-and-go）策略、鈣及鎂離子的輸注、抗癲癇藥物、glutathione、xaliproden、非類固醇消炎藥、麩醯胺酸、以及鴉片類藥物等。於本文中，作者聚焦於oxaliplatin導致週邊神經病變的機轉、麩醯胺酸用於oxaliplatin神經毒性的療效、基因體多型性所導致鴉片類藥物於oxaliplatin疼痛性神經病變療效的差異，以及可否利用神經傳導速率檢查來客觀評估oxaliplatin所引起的神經毒性。

關鍵字

神經毒性 ； 麩醯胺酸 ； 基因體多型性 ； 鴉片類藥物

並列摘要

One form of neurotoxicity is the principal and dose-limiting toxicity of oxaliplatin. It has been observed that the incidence of oxaliplatin-induced severe neurotoxicity has varied from 12% to 18% in different clinical trials. Oxaliplatin-induced neuropathy can be divided into two distinct syndromes. The first is a unique syndrome of acute, transient peripheral nerve hyperexcitability occurring shortly after the infusion of oxaliplatin. The second one is a peripheral sensory neuropathy occurring mainly in the distal extremities with symptoms similar to those caused by cisplatin. It may last for several months, and results in a severe disturbance of neurologic function, and has a significant impact on oxaliplatin treatment. Various strategies have been proposed to prevent or treat oxaliplatin-induced neurotoxicity, including the stop-and-go concept, calcium and magnesium infusions, antiepileptic drugs, glutathione, xaliproden, NSAIDs, glutamine, and opioid drugs. In this article, the authors focus on the mechanisms of peripheral neuropathy induced by oxaliplatin, the role of glutamine in the management of oxaliplatin-neuropathy, genomic polymorphisms involved in an altered susceptibility to opioid drugs in managing oxaliplatin-induced neuropathic pain, and the use of nerve conduction velocity studies in objectively assessing oxaliplatin-induced neuropathy.

並列關鍵字

oxaliplatin ； neuropathy ； glutamine ； genomic polymorphism ； opioid drugs