Chemotherapy‐induced neuropathy

Abstract

Neurotoxic side effects of cancer therapy are second in frequency to hematological toxicity. Unlike hematological side effects that can be treated with hematopoietic growth factors, neuropathies cannot be treated and protective treatment strategies have not been effective. For the neurologist, the diagnosis of a toxic neuropathy is primarily based on the case history, the clinical and electrophysiological findings, and knowledge of the pattern of neuropathy associated with specific agents. In most cases, toxic neuropathies are length-dependent, sensory, or sensorimotor neuropathies often associated with pain. The platinum compounds are unique in producing a sensory ganglionopathy. Neurotoxicity is usually dependent on cumulative dose. Severity of neuropathy increases with duration of treatment and progression stops once drug treatment is completed. The platinum compounds are an exception where sensory loss may progress for several months after cessation of treatment ("coasting"). As more effective multiple drug combinations are used, patients will be treated with several neurotoxic drugs. Synergistic neurotoxicity has not been extensively investigated. Pre-existent neuropathy may influence the development of a toxic neuropathy. Underlying inherited or inflammatory neuropathies may predispose patients to developing very severe toxic neuropathies. Other factors such as focal radiotherapy or intrathecal administration may enhance neurotoxicity. The neurologist managing the cancer patient who develops neuropathy must answer a series of important questions as follows: (1) Are the symptoms due to peripheral neuropathy? (2) Is the neuropathy due to the underlying disease or the treatment? (3) Should treatment be modified or stopped because of the neuropathy? (4) What is the best supportive care in terms of pain management or physical therapy for each patient? Prevention of toxic neuropathies is most important. In patients with neuropathy, restorative approaches have not been well established. Symptomatic and other management are necessary to maintain and improve quality of life.

Animal Models of Chemotherapy-Evoked Painful Peripheral Neuropathies

“…Finally, proprioception loss may result in pseudoathetosis or ataxia with several functional impairment. 1,7,8 These symptoms may be disabling, adversely affecting activities of daily living and thereby quality of life, even after several months or years after treatment discontinuation. 3 The recovery from symptoms is often incomplete and a long period of regeneration is sometimes required to restore function.…”

“…It appears that onset and severity depends on a variety of factors, including concomitant medical conditions such as diabetes, alcoholism, and paraneoplasic sensory neuropathy. 1,6 Typically, the clinical presentation reflects an axonal peripheral neuropathy with glove-and-stocking distribution sensory loss, combined with features suggestive of nerve hyperexcitability, including paresthesia, dysesthesia, and pain. Pain is a prominent and important side effect for many patients.…”

I-387, a Novel Antimitotic Indole, Displays a Potent In vitro and In vivo Antitumor Activity with Less Neurotoxicity

“…The expression of MDR proteins, such as P-gp and MRPs, and mutations of the target protein are known to result in drug resistance. In addition, peripheral neurotoxicity is considered to be a major side effect in the clinical application of antimitotic agents because they bind to β-tubulin, which is the primary component of the axonal microtubules (22).…”

Overview of symptoms, pathogenesis, diagnosis, treatment, and prognosis of various acquired polyneuropathies

“…Motor symptoms are generally less manifest than sensory ones. However, the symptoms can completely resolve in most cases after stopping medications, although they can be only partially reversible or permanent in some cases [23].…”