Central Neurotoxicity of Chemotherapy

Abstract

It is undeniable that the introduction of chemotherapeutic drugs has significantly increased the survival of cancer patients. In the recent years, new drugs are being developed for cancer treatment, but the use of classical chemotherapeutic agents are still essential. Unfortunately, most treatments, including both conventional antitumor drugs and newer therapies are associated with important side effects. For this reason, characterization and treatment of the adverse effects and sequelae associated with chemotherapy is an urgent clinical need. The mechanisms of action of these drugs produce the inhibition of division of cancer cells and the induction of apoptosis or other forms of cell death. But these mechanisms are also responsible for the appearance of unwanted side effects as other types of cells could be affected. Neurons are not fast-dividing cells, but they can be affected, and chemotherapy may induce neurotoxicity. The central nervous system is protected by the blood-brain barrier and has a low rate of cellular turnover, but it is still vulnerable to antitumoral drugs. Central side effects of chemotherapy are diverse and include encephalopathy, headache, seizures, cerebellar syndromes, visual loss, myelopathy, cerebrovascular complications and confusional states. In addition, chemotherapy has been correlated with mild deficits of memory and cognition, known as chemotherapy-induced cognitive impairment, ‘chemobrain’ or ‘chemofog’. These central toxicities could be the result from direct damage to neural tissues as well as from systemic causes. This chapter will review and compile main symptoms of central neurotoxicity described in patients treated with conventional chemotherapy. To facilitate understanding, main antitumoral classes have been summarized according to their mechanism of action.