Neurologic complications of cancer therapy

Abstract

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.

Spinal Changes of a Newly Isolated Neuropeptide Endomorphin-2 Concomitant with Vincristine-Induced Allodynia

“…To our knowledge, there are no analgesic drugs that could be labeled both safe and effective in treating CNP [20], [34]–[38]. To identify such therapeutic strategies, it is necessary and crucial to elucidate the molecular mechanisms resulting in CNP following chemotherapy.…”

The Maintenance of Cisplatin- and Paclitaxel-Induced Mechanical and Cold Allodynia is Suppressed by Cannabinoid CB2 Receptor Activation and Independent of CXCR4 Signaling in Models of Chemotherapy-Induced Peripheral Neuropathy

“…Sensory abnormalities (such as tingling, numbness) as well as shooting and burning pain due to chemotherapy can impair the quality of life in patients [2]. To date, no medication has been recognized to effectively and safely cure chemotherapy-induced neuropathy [6,9,10]. …”

Chemotherapy-evoked neuropathic pain: Abnormal spontaneous discharge in A-fiber and C-fiber primary afferent neurons and its suppression by acetyl-l-carnitine

“…Neurotoxicity is the dose-limiting side-effect for chemotherapeutics in the taxane and vinca alkaloid classes, and in many cases the nerve damage is accompanied by a chronic painful peripheral neuropathy (Uhm and Yung, 1999;Verstappen et al, 2003;Dougherty et al, 2004;Cata et al, 2006b). There are no validated means for the prevention or treatment of the pain syndrome and its cause is not understood.…”