Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Feb 24:8:86.
doi: 10.3389/fphar.2017.00086. eCollection 2017.

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

Nicolas Kerckhove  1 , Aurore Collin  2 , Sakahlé Condé  3 , Carine Chaleteix  4 , Denis Pezet  5 , David Balayssac  1
Affiliations
Review

Long-Term Effects, Pathophysiological Mechanisms, and Risk Factors of Chemotherapy-Induced Peripheral Neuropathies: A Comprehensive Literature Review

Nicolas Kerckhove et al. Front Pharmacol. .

Abstract

Neurotoxic anticancer drugs, such as platinum-based anticancer drugs, taxanes, vinca alkaloids, and proteasome/angiogenesis inhibitors are responsible for chemotherapy-induced peripheral neuropathy (CIPN). The health consequences of CIPN remain worrying as it is associated with several comorbidities and affects a specific population of patients already impacted by cancer, a strong driver for declines in older adults. The purpose of this review is to present a comprehensive overview of the long-term effects of CIPN in cancer patients and survivors. Pathophysiological mechanisms and risk factors are also presented. Neurotoxic mechanisms leading to CIPNs are not yet fully understood but involve neuronopathy and/or axonopathy, mainly associated with DNA damage, oxidative stress, mitochondria toxicity, and ion channel remodeling in the neurons of the peripheral nervous system. Classical symptoms of CIPNs are peripheral neuropathy with a "stocking and glove" distribution characterized by sensory loss, paresthesia, dysesthesia and numbness, sometimes associated with neuropathic pain in the most serious cases. Several risk factors can promote CIPN as a function of the anticancer drug considered, such as cumulative dose, treatment duration, history of neuropathy, combination of therapies and genetic polymorphisms. CIPNs are frequent in cancer patients with an overall incidence of approximately 38% (possibly up to 90% of patients treated with oxaliplatin). Finally, the long-term reversibility of these CIPNs remain questionable, notably in the case of platinum-based anticancer drugs and taxanes, for which CIPN may last several years after the end of anticancer chemotherapies. These long-term effects are associated with comorbidities such as depression, insomnia, falls and decreases of health-related quality of life in cancer patients and survivors. However, it is noteworthy that these long-term effects remain poorly studied, and only limited data are available such as in the case of bortezomib and thalidomide-induced peripheral neuropathy.

Keywords: anticancer drugs; chemotherapy-induced peripheral neuropathy; long-term effects; pathophysiological mechanisms; risk factors.

PubMed Disclaimer

Figures

FIGURE 1
FIGURE 1
Mechanisms of chemotherapy-induced peripheral neuropathy. Pathophysiological alterations triggered by platinum, taxanes, vinca-alkaloids, and bortezomib/thalidomide in the peripheral nervous system, dorsal root ganglia and spinal cord. 5-HT, 5-hydroxytryptamine; ATF-3, cyclic AMP-dependent transcription factor 3; EM2, endomorphin-2; HCN, potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel; Il-1β, interleukin-1β; Il-10, interleukin-10; Il-4, interleukin-4; KCNQ, potassium channel, subfamily Q; MAPK, mitogen-activated protein kinase; MYD88, myeloid differentiation primary response gene 88; Nav1.9, voltage-gated sodium channel member 1.9; NMDA, N-methyl-D-aspartate; NF-κB, nuclear factor-kappa B; OCT2, solute carrier family 22 member 2 (organic cation transporter); ROS, reactive oxygen species; SOD, superoxide dismutase; TLR4, toll-like receptor 4; TNF, tumor necrosis factor; TRAAK, TWIK-related arachidonic acid activated K+ channel; TREK1, TWIK1-related K+ channel 1; TRIF, TIR-domain-containing adapter-inducing interferon-β; TRPA1, transient receptor potential cation channel, subfamily A, member 1; TRPM8, transient receptor potential cation channel subfamily M member 8; TRPV1, transient receptor potential vanilloid 1.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Abd-Elsayed A. A., Ikeda R., Jia Z., Ling J., Zuo X., Li M., et al. (2015). KCNQ channels in nociceptive cold-sensing trigeminal ganglion neurons as therapeutic targets for treating orofacial cold hyperalgesia. Mol. Pain 11:45 10.1186/s12990-015-0048-8 - DOI - PMC - PubMed
    1. Altaf R., Lund Brixen A., Kristensen B., Nielsen S. E. (2014). Incidence of cold-induced peripheral neuropathy and dose modification of adjuvant oxaliplatin-based chemotherapy for patients with colorectal cancer. Oncology 87 167–172. 10.1159/000362668 - DOI - PubMed
    1. Amos L. A., Löwe J. (1999). How Taxol stabilises microtubule structure. Chem. Biol. 6 R65–R69. 10.1016/s1074-5521(99)89002-4 - DOI - PubMed
    1. André T., Boni C., Navarro M., Tabernero J., Hickish T., Topham C., et al. (2009). Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J. Clin. Oncol. 27 3109–3116. 10.1200/JCO.2008.20.6771 - DOI - PubMed
    1. Arastu-Kapur S., Anderl J. L., Kraus M., Parlati F., Shenk K. D., Lee S. J., et al. (2011). Nonproteasomal targets of the proteasome inhibitors bortezomib and carfilzomib: a link to clinical adverse events. Clin. Cancer Res. 17 2734–2743. 10.1158/1078-0432.CCR-10-1950 - DOI - PubMed