title: 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.
  
  
  OBJECTIVE
  To examine the efficacy of purported chemoprotective agents to prevent or limit the neurotoxicity of cisplatin and related agents.
  
  
  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.
  
  
  METHODS
  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).
  
  
  METHODS
  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.
  
  
  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.
  
  
  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.
authors.affiliation: Department of Neurology, University of Michigan, 1C325/0032 University Hospital, 1500 E. Medical Center Drive, Box 0316, Ann Arbor, USA, MI 48109-0032.
authors.forename: James W
authors.initials: JW
authors.lastname: Albers
authors.forename: Vinay
authors.initials: V
authors.lastname: Chaudhry
authors.forename: Guido
authors.initials: G
authors.lastname: Cavaletti
authors.forename: Ross C
authors.initials: RC
authors.lastname: Donehower
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects* / Q000031:analogs & derivatives; D006801:Humans; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D010446:Peptide Fragments / Q000627:therapeutic use; D010523:Peripheral Nervous System Diseases / Q000139:chemically induced / Q000517:prevention & control*
chemical_list: D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D002945:Cisplatin