Amelioration of oxaliplatin neurotoxicity by drugs in humans and experimental animals: A minireview of recent literature

The broad spectrum anti-neoplastic drug oxaliplatin is a third-generation platinum compound that inhibits DNA synthesis, mainly by causing intrastrandal cross-links in DNA. The drug is particularly useful alone and in combination with flurouracil and leucovorin in colorectal cancer, but it is also used for other cancers such as those of the ovary, lung, breast and liver, as well as non-Hodgkin's lymphoma. The drug is known to cause neurological, gastrointestinal and haematological toxicities. Neurotoxicity occurs in most of the treated patients and is considered to be a serious limitation for the use of the drug. The mechanism of the neurotoxicity is not known with certainty but may involve prolongation of sodium channels opening. Strategies to ameliorate oxaliplatin neurotoxicity include the use of several 'neuroprotective' drugs. This MiniReview attempts to list and comment on the action and use of some of these agents, which include carbamazepine, gabapentin, calcium and magnesium salts, reduced glutathione, N-acetylcysteine and a few others. None of these drugs have been proven to be effective in large, controlled, clinical trials.