Chemotherapy-induced peripheral neurotoxicity

T of solid and hematological malignancies is still largely based on systemic chemotherapy, alone or in combination with surgery and or radiation treatment. In parallel with the improvement in anti-cancer therapy, the management of several among its most serious side effects became easier. However, other chemotherapy-related toxicities emerged as major clinical problems, sometimes requiring anticancer treatment modification or even withdrawal. Among them damage of the peripheral nervous system is particularly frequent and potentially severe after the administration of several widely-used compounds such as platinum-drugs, antitubulins, immunomodulatory drugs and proteasome inhibitors. In view of a scenario showing higher efficacy of anti-cancer therapy leading to a high number of cancer-survivors, the relevance of long-lasting or permanent side effects has also become increasingly important, being chemotherapy-induced peripheral neurotoxicity (CIPN) one of the most severe for its impact on treated subjects’ quality of life. Moreover, CIPN is associated with a remarkable increase in direct and indirect health-related cost in cancer patients. The most common entry sites into peripheral nervous system used by anticancer drugs are dorsal root ganglia and this might explain why sensory impairment is the most common clinical feature of CIPN. However, variable association with motor or autonomic damage is typical of the different drugs types. Moreover, neuropathic pain may be a common symptom, particularly with some of these compounds which are particularly toxic on small nerve fibers as it can be reproduced in relevant animal models.