Interventions for preventing neuropathy caused by cisplatin and related compounds.
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 among human patients.


METHODS
We searched the 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) 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 neuroprotectant (amifostine, diethyldithiocarbamate, glutathione, Org 2766, 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. Each study was reviewed by two authors who extracted the data and reached consensus. The included trials involved five 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
The one of five eligible amifostine trials (541 participants) using quantitative sensory testing demonstrated a favorable outcome in terms of amifostine neuroprotection, but the subclinical result was based on 14 participants receiving amifostine. Of the five eligible glutathione trials (327 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 one eligible diethyldithiocarbamate trial (214 participants) and the one eligible vitamin E trial (27 participants) did not perform quantitative sensory testing.


CONCLUSIONS
At present, the data are insufficient to conclude if any of the purported neuroprotective agents (amifostine, diethyldithiocarbamate, glutathione, Org 2766, or Vitamin E) prevent or limit the neurotoxicity of platin drugs among human patients.
Albers
J
J
University of Michigan, Department of Neurology, 1C325/0032 University Hospital, 1500 E. Medical Center Drive, Box 0316, Ann Arbor, MI 48109-0032, USA. jwalbers@umich.edu
Chaudhry
V
V
Cavaletti
G
G
Donehower
R
R
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives / Q000627:therapeutic use; D004999:Amifostine / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000009:adverse effects*; D002945:Cisplatin / Q000009:adverse effects* / Q000031:analogs & derivatives; D004050:Ditiocarb / Q000627:therapeutic use; D005978:Glutathione / Q000627:therapeutic use; 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*; D016032:Randomized Controlled Trials as Topic; D014810:Vitamin E / Q000627:therapeutic use
D000970:Antineoplastic Agents; D018696:Neuroprotective Agents; D010446:Peptide Fragments; D014810:Vitamin E; C013765:Org 2766; D000324:Adrenocorticotropic Hormone; D004050:Ditiocarb; D005978:Glutathione; D004999:Amifostine; D002945:Cisplatin