Neurotoxicity of chemotherapy

Publisher Summary Neurological side effects are a common complication following chemotherapy and can adversely affect clinical management of the cancer patient. Cancer patients during chemotherapy report problems with memory retrieval, learning, and concentration, which may persist after treatment has finished or never fully resolve. Peripheral neuropathies are the most common neurological complications in patients receiving chemotherapy, especially with regimens containing taxanes, platinum, and vinca alkaloids. Acute encephalopathy is another common problem in oncology patients; however, encephalopathy because of cytotoxic drug exposure is generally self-limiting and recovers spontaneously. Leukoencephalopathy may follow on from acute encephalopathy, but may also be the first indication of neurotoxicity several months to years after administration of cytotoxic drugs. Neurotoxicity is a frequent and dose-limiting side effect of chemotherapy, and apart from dose reduction or discontinuing the drugs implicated in the development of neurotoxicity, there is very little in the way of specific pharmacological management to reverse their side effects. Search for new anticancer agents has switched away from classical cytotoxics that kill cancer cells by inducing DNA damage to agents that modify growth signaling pathways, and the two main types of agents are the -mabs, which are monoclonal antibodies that target either cell surface receptors or circulating ligand, and the -ibs, which are small drug molecules that target intracellular stages of signaling pathways. These drugs have a much gentler side effect profile compared with cytotoxic agents and very little in the way of neurotoxicity has been reported in the literature to date.