Chemotherapy-induced peripheral neuropathy: pathogenesis and emerging therapies

Peripheral neuropathy is a major dose-limiting side effect of many chemotherapeutic agents. The type and degree of neuropathy depend on the chemotherapy drug, dose-intensity, and cumulative dose. Disabling peripheral neuropathy has a significant negative impact on quality of life. Accordingly, a reliable assessment of chemotherapy-induced peripheral neurotoxicity is necessary, especially if potential neuroprotective agents are to be investigated. Chemoprotectants are agents that have been developed to ameliorate the toxicity associated with cytotoxic drugs. They aim to provide site-specific protection for normal tissues, without compromising antitumor efficacy. Several chemoprotectant compounds have been studied in recent clinical trials. These trials must include sufficient dose-limiting events for study and assessment of both toxicity and antitumor effect. A future avenue of investigation includes the identification of patients at higher risk for the development of peripheral neuropathy based on their genotype. Identification of these higher-risk patients may enable us to devise prevention strategies prior to the onset of this potentially debilitating complication.