Neuroprotectant drugs in cisplatin neurotoxicity.
Cisplatin (CDDP) is one among the most effective and widely used anticancer drugs. Its use is, however, often limited by its peripheral neurotoxicity, which may be severely disabling and sometimes not reversible. To prevent or reduce CDDP peripheral neurotoxicity several "neuroprotective" drugs have been proposed. This goal is of extreme importance in the treatment of cancer patients, especially in view of the better results obtained by anticancer chemotherapy in terms of longer disease-free survival which has made even more crucial than in the past the point of the quality of life of the long-surviving patients. The data of pre-clinical and clinical studies with neuroprotectant agents are often conflicting, in some cases because of inadequate methods of evaluation and/or study design used to examine their effectiveness. The aims of this review will be 1) to discuss and describe the most appropriate methods of evaluation of CDDP and neuro-protectant drugs in experimental in vitro and in vivo pre-clinical studies 2) to evaluate critically the results of the clinical trials reported so far with the combined treatment and 3) to explore the possible future strategies to achieve neuroprotection during high-dose CDDP treatment in humans.
Cavaletti
G
G
Clinica Neurologica, Istituto di Scienze Biomediche S. Gerardo, Università di Milano, Italy.
Cascinu
S
S
Venturino
P
P
Tedeschi
M
M
Tredici
G
G
D000324:Adrenocorticotropic Hormone / Q000031:analogs & derivatives; D000818:Animals; D000970:Antineoplastic Agents / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002945:Cisplatin / Q000009:adverse effects* / Q000037:antagonists & inhibitors; D002986:Clinical Trials as Topic; D006801:Humans; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000494:pharmacology; D009420:Nervous System / Q000187:drug effects*; D013438:Sulfhydryl Compounds / Q000494:pharmacology
D000970:Antineoplastic Agents; D002121:Calcium Channel Blockers; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; D013438:Sulfhydryl Compounds; D000324:Adrenocorticotropic Hormone; D002945:Cisplatin