Chemotherapy-induced peripheral neuropathy: where are we now?

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major challenge, with increasing impact as oncological treatments, using potentially neurotoxic chemotherapy, improve cancer cure and survival. Acute CIPN occurs during chemotherapy, sometimes requiring dose reduction or cessation, impacting on survival. Around 30% of patients will still have CIPN a year, or more, after finishing chemotherapy. Accurate assessment is essential to improve knowledge around prevalence and incidence of CIPN. Consensus is needed to standardize assessment and diagnosis, with use of well-validated tools, such as the EORTC-CIPN 20. Detailed phenotyping of the clinical syndrome moves toward a precision medicine approach, to individualize treatment. Understanding significant risk factors and pre-existing vulnerability may be used to improve strategies for CIPN prevention, or to use targeted treatment for established CIPN. No preventive therapies have shown significant clinical efficacy, although there are promising novel agents such as histone deacetylase 6 (HDAC6) inhibitors, currently in early phase clinical trials for cancer treatment. Drug repurposing, eg, metformin, may offer an alternative therapeutic avenue. Established treatment for painful CIPN is limited. Following recommendations for general neuropathic pain is logical, but evidence for agents such as gabapentinoids and amitriptyline is weak. The only agent currently recommended by the American Society of Clinical Oncology is duloxetine. Mechanisms are complex with changes in ion channels (sodium, potassium, and calcium), transient receptor potential channels, mitochondrial dysfunction, and immune cell interactions. Improved understanding is essential to advance CIPN management. On a positive note, there are many potential sites for modulation, with novel analgesic approaches.

Figure 1

Clinical features of CIPN.

Figure 2

Important components for an ideal CIPN assessment tool.

Figure 3

Schematic overview of mechanisms underlying chemotherapy-induced peripheral neuropathy and mechanism-based disease interventions. CCL2 indicates C-C motif chemokine 2; CX3CL1, C-X3-C motif chemokine ligand 1; HDAC6, histone deacetylase 6; IL-10, interleukin 10; IENF, intraepidermal nerve fiber; RNS, reactive nitrogen species; ROS, reactive oxygen species; SNRIs, serotonin-norepinephrine reuptake inhibitors. From: Beyond symptomatic relief for chemotherapy-induced peripheral neuropathy: Targeting the source, Ma et al. Cancer, Volume: 124, Issue: 11, Pages: 2289-2298, First published: 20 February 2018, DOI: (10.1002/cncr.31248).