Neurotoxicity of antineoplastic drugs: Mechanisms, susceptibility, and neuroprotective strategies

This review summarizes the adverse effects on the central and/or peripheral nervous systems that may occur in response to antineoplastic drugs. In particular, we describe the neurotoxic side effects of the most commonly used drugs, such as platinum compounds, doxorubicin, ifosfamide, 5-fluorouracil, vinca alkaloids, taxanes, methotrexate, bortezomib and thalidomide. Neurotoxicity may result from direct action of compounds on the nervous system or from metabolic alterations produced indirectly by these drugs, and either the central nervous system or the peripheral nervous system, or both, may be affected. The incidence and severity of neurotoxicity are principally related to the dose, to the duration of treatment, and to the dose intensity, though other factors, such as age, concurrent pathologies, and genetic predisposition may enhance the occurrence of side effects. To avoid or reduce the onset and severity of these neurotoxic effects, the use of neuroprotective compounds and/or strategies may be helpful, thereby enhancing the therapeutic effectiveness of antineoplastic drug.