Interventions for preventing neuropathy caused by cisplatin and related compounds

 

Abstract

Background

Cisplatin and several related antineoplastic agents used to treat many types of solid tumors are neurotoxic, and most patients completing a full course of cisplatin chemotherapy develop a clinically detectable sensory neuropathy. Effective neuroprotective therapies have been sought.

Objectives

To examine the efficacy of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related agents.

Search methods

We searched the Cochrane Neuromuscular Disease Group Specialized Register (25 August 2010), the Cochrane Central Register of Controlled Trials (Issue 3, 2010 in The Cochrane Library), MEDLINE (January 1966 to August 2010), EMBASE (January 1980 to August 2010), LILACS (January 1982 to August 2010), CINAHL (January 1982 to August 2010) for randomized trials designed to evaluate neuroprotective agents used to prevent or limit neurotoxicity of cisplatin and related agents among human patients.

Selection criteria

Quasi-randomized or randomized controlled trials whose participants received cisplatin (or related compounds) chemotherapy with or without a potential chemoprotectant (acetylcysteine, amifostine, ACTH, BNP7787, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxcarbazepine, or vitamin E) and were evaluated zero to six months after completing chemotherapy using quantitative sensory testing (primary) or other measures including nerve conduction studies or neurological impairment rating using validated scales (secondary).

Data collection and analysis

We identified 16 randomized trials involving five possible chemoprotective agents in the initial 2006 review. Each study was reviewed by two authors who extracted the data and reached consensus. The 2010 update identified 11 additional randomized trials consisting of nine possible chemoprotective agents, including three treatments (acetylcysteine, calcium and magnesium, and oxcarbazepine) not among those described in the 2006 review. The included trials in the updated review involved eight unrelated treatments and included many disparate measures of neuropathy, resulting in insufficient data for any one measure to combine the results in most instances.

Main results

One of four eligible amifostine trials (541 total participants in all four trials) used quantitative sensory testing and demonstrated a favorable outcome in terms of amifostine neuroprotection, but the vibration perception threshold result was based on data from only 14 participants receiving amifostine who completed the post-treatment evaluation and should be regarded with caution. Of the six eligible glutathione trials (354 participants), one used quantitative sensory testing but reported only qualitative analyses. Four eligible Org 2766 trials (311 participants) employed quantitative sensory testing reported disparate results; meta-analyses of three trials using comparable measures showed no significant vibration perception threshold neuroprotection. The remaining trial reported only descriptive analyses. The single eligible trials involving acetylcysteine (14 participants), diethyldithiocarbamate (195 participants), calcium and magnesium (33 participants), and oxcarbazepine (32 participants) and the two eligible trials involving vitamin E (57 participants) did not perform quantitative sensory testing. In all, data from 1,537 participants were included.

Authors' conclusions

At present, the data are insufficient to conclude that any of the purported chemoprotective agents (acetylcysteine, amifostine, calcium and magnesium, diethyldithiocarbamate, glutathione, Org 2766, oxycarbazepine, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.

 

Plain language summary

Interventions for preventing neuropathy caused by cisplatin and other tumor inhibiting platinum drugs

Cisplatin and other related platinum drugs used to treat solid tumors are toxic to the nervous system. Most people who complete a full course of cisplatin chemotherapy develop a sensory neuropathy. Symptoms can include tingling in the extremities and numbness. The neuropathy may only partially recover or not recover at all. To try to reduce the toxicity of platinum drugs, neuroprotective therapies have been sought. These include acetylcysteine, acetyl-L-carnitine, amifostine, calcium and magnesium, growth factors, glutathione, Org 2766, oxcarbazepine, and vitamin E. The initial review identified 16 randomized controlled trials of five different potential neuroprotective therapies. The 2010 update identified an additional 5 randomized controlled trials, which described three potential chemoprotective therapies not included in the 2006 review. Although the trials included a total of 1,537 participants, meta-analysis was possible for only a small number of measures in very few trials. The data from the trials were insufficient to conclude that any of the neuroprotective agents tested prevent or limit the neurotoxicity of platinum drugs.

 

摘要

背景

預防因cisplatin和相關化合物引起的神經病變的治療方式

被用來治療很多種實體腫瘤的Cisplatin和數個相關的抗腫瘤藥物是有神經毒性的,而且大多數接受完整療程的cisplatin化學治療的病人發展出臨床可以查覺的感覺神經病變.有效的神經保護療法已經被尋找了.

目標

為了檢查傳說中可以預防或限制cisplatin和相關物質對人類的神經毒性的化學保護劑的效果.

搜尋策略

我們收尋了Cochrane Neuromuscular Disease Group Register (January 2005), the Cochrane Central Register of Controlled Trials (The Cochrane Library, Issue 1 2005), MEDLINE (from January 1966 to March 2005), EMBASE (from January 1980 to March 2005), LILACS (from January 1982 to March 2005), CINAHL (from January 1982 to March 2005)的隨機試驗,所有為了評估可以預防或限制cisplatin和相關物質對人類產生神經毒性的神經保護劑之效果.

選擇標準

受試者為接受cisplatin(或相關化合物)的化學治療,有或沒有加上潛在的神經保護劑(amifostine, diethyldithiocarbamate, glutathione, Org 2766, or vitamin E)的半隨機或隨機對照組試驗，在完成化學治療0到6個月後被評估,評估方式為量化的感覺測試(初級)和其它測量方式包括神經傳導研究或使用有效的評分評量神經受損程度.

資料收集與分析

我們找到了和5個可能的化學保護劑有關的16個隨機試驗.每一個研究被兩個作者回顧,擷取資料和達成共識.被包括的試驗涉及5個不相關的治療和包含許多不同測量神經病變的方法,導致在大多數情況下沒有任何一種方式可以合併這些結果產生足夠的資料.

主要結論

在5個合格的amifostine試驗中的一個(541個受試者),使用定量的感覺測試顯示amifostine在神經保護上有較好的結果,但是這個次臨床的結果是依據14個接受amifostine的受試者.在5個合格的glutathione試驗中的一個(327個受試者),使用的是定量的感覺測試但是只報告了定性的分析.4個合格的Org 2766 trials (311個受試者)使用定量的感覺測試,報告了不同的結果;3個使用比較方法的試驗的綜合分析顯示沒有顯著的震動感覺閥值的神經保護作用.剩下的試驗報告了只有描述性的分析.1個合格的diethyldithiocarbamate試驗(214個受試者)和1個合格的vitamin E 試驗(27個受試者)沒有進行定量的感覺測試.

作者結論

目前,資料不足以下結論証明任何推測具有神經保護之藥劑(amifostine, diethyldithiocarbamate, glutathione, Org 2766, or Vitamin E)可以預防或限制鉑金類的藥物對人類的神經毒性.

翻譯人

本摘要由新光醫院李建欣翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

預防因cisplatin和其它腫瘤抑制的鉑金類藥物所引起的神經病變的治療方式. Cisplatin和其它被用來治療實質腫瘤相關的鉑金類藥物對神經系統是有毒的.大多數接受完整療程的cisplatin化學治療的病人發展出感覺神經病變.症狀包括肢體的刺痛和麻木.這種神經病變可以是只有部分恢復或完全沒有恢復.嘗試尋找神經保護劑來減少鉑金類藥物的毒性.這些包括 amifostine, growth factors, glutathione, Org 2766, acetylLcarnitine, and vitamin E.這個回顧找到16個隨機對照組試驗,具有5個不同的有潛在可能的神經神經保護療法.雖然這些試驗包括了共1420的受試者,綜合分析只可能於一些很少的試驗中的少數統計方式.從這些試驗中的資料不足以下結論證明任何試驗的神經保護劑可以預防或限制鉑金類的藥物對人類的神經毒性.更多的研究是需要的.