Chemotherapy-Induced Peripheral Neuropathy in Cancer Survivors

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most challenging and complex complications of cancer chemotherapy. Peripheral neuropathy is a disturbance of function or pathological change in a nerve or nerves,[1] and CIPN generally is diffuse and bilateral, resulting from systemic toxicity to nerves. Several classes of chemotherapeutic drugs cause peripheral neuropathy, including the plant alkaloids (vincristine and vinblastine(Drug information on vinblastine)), taxanes (paclitaxel and docetaxel [Taxotere]), platinum-based compounds (cisplatin, carboplatin(Drug information on carboplatin), and oxaliplatin(Drug information on oxaliplatin) [Eloxatin]), and other drugs, such as thalidomide(Drug information on thalidomide).

The incidence and severity of CIPN vary considerably for each peripherally neurotoxic agent when administered alone or in combination, but for vincristine, cisplatin(Drug information on cisplatin), oxaliplatin, and paclitaxel(Drug information on paclitaxel), estimates for the occurrence of CIPN are as high as 70% to 90%.[2–6] As many as 60% of patients receiving docetaxel(Drug information on docetaxel) and 40% of those treated with carboplatin develop CIPN.[3,7] The development of both short- and long-term CIPN is highly dependent on factors such as age, single dose intensity, cumulative dose, duration of therapy, combinations of neurotoxic agents, coexisting neuropathies (for example, diabetic neuropathy), genetic susceptibility, and alcohol(Drug information on alcohol) abuse.[8–14]

Exact mechanisms for CIPN are not clearly understood; however, studies indicate that it is related to axonal damage of peripheral nerves, causing dysfunctional effects in primary afferent fibers that give rise to abnormal impulse transmission, nerve hyperexcitability, spontaneous or ectopic discharge from nerves, and pain.[15–18] Neurotoxic effects of chemotherapy target the neuronal cell body, the axonal transport system, the myelin sheath, and glial support structures of peripheral nerves.[19]

The onset, severity, characteristics, and duration of clinical manifestations of CIPN are highly variable. Typically, CIPN is characterized by a glove-and-stocking distribution in the hands and feet with sensory loss or hypersensitivity, and in some cases motor and autonomic dysfunction. Symptoms include paresthesia (an abnormal sensation such as numbness or tingling, spontaneous or evoked, and not unpleasant), dysesthesia (an unpleasant abnormal sensation, spontaneous or evoked), allodynia (pain from stimuli that are not typically painful, such as touch), hyperalgesia (exaggerated pain in response to stimuli that are typically painful), hypoalgesia (diminished pain response to a typically painful stimulus), or pain that is burning, shooting, or electric-shock–like.[1]