Neurologic Complications of Cancer Therapy

Although progress in cancer research is paralleled by the discovery and development of novel chemotherapeutic agents, the benefits of these agents are offset by their side-effect profiles. Of the numerous adverse effects associated with antineoplastic drugs, peripheral neuropathy is the most frequent and is often debilitating. This article reviews the treatment options--both primary and secondary--for neuropathic complications of cancer therapy. Before a potentially neurotoxic chemotherapeutic regimen is started, patients should undergo 1) a baseline neurologic history for possible coexisting risk factors for neuropathy; 2) physical evaluation; and 3) if indicated, electrophysiologic testing, including nerve conduction studies and electromyography. Patients should be followed closely for the development of neuropathic signs and symptoms. When symptoms (eg, paresthesias or pain) or deficits (eg, weakness) develop, their severity and their effect on quality of life will determine whether the neurotoxic chemotherapy should be continued at a lower dose or discontinued. Neuropathic pain should be treated aggressively with a stepwise approach. The decision to initiate therapy should be guided first by the severity of pain and second by the convenience of dosing and the side-effect profile of the medication. Specific antineuropathic pain therapy may begin with a tricyclic antidepressant (TCA), titrated to 100 to 150 mg/d, unless anticholinergic side effects appear before this dosage is reached. The TCA may be replaced by or supplemented with antiepileptic agents, such as gabapentin, which is attractive because of its rapid dose titration (maximum, 3600 mg/d) and minimal interaction with other medications. In addition to pharmacologic therapies targeting symptom management, new therapies directed at preventing the onset or progression of neurotoxicity are desperately needed.