Intervention Review
Interventions for preventing neuropathy caused by cisplatin and related compounds
Editorial Group: Cochrane Neuromuscular Disease Group
Published Online: 16 FEB 2011
Assessed as up-to-date: 24 AUG 2010
DOI: 10.1002/14651858.CD005228.pub3
Copyright © 2011 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd.
Database Title
Additional Information
How to Cite
Albers JW, Chaudhry V, Cavaletti G, Donehower RC. Interventions for preventing neuropathy caused by cisplatin and related compounds. Cochrane Database of Systematic Reviews 2011, Issue 2. Art. No.: CD005228. DOI: 10.1002/14651858.CD005228.pub3.
Publication History
- Publication Status: New search for studies and content updated (no change to conclusions)
- Published Online: 16 FEB 2011
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.