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Review
. 2021 Apr 16;22(8):4112.
doi: 10.3390/ijms22084112.

Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment

Silvia Triarico  1 , Alberto Romano  1 , Giorgio Attinà  1 , Michele Antonio Capozza  1 , Palma Maurizi  1 , Stefano Mastrangelo  1 , Antonio Ruggiero  1
Affiliations
Review

Vincristine-Induced Peripheral Neuropathy (VIPN) in Pediatric Tumors: Mechanisms, Risk Factors, Strategies of Prevention and Treatment

Silvia Triarico et al. Int J Mol Sci. .

Abstract

Vincristine-induced peripheral neurotoxicity (VIPN) is a very common side effect of vincristine chemotherapy among pediatric patients with cancer. Neuropathy may be sensory, motor and/or autonomic, with consequent reduction, delay or discontinuation of vincristine-chemotherapy, but also pain, disability, reduced quality of life of patients and an increase in medical costs. Vincristine acts out its antineoplastic function by altering the normal assembly and disassembly of microtubules, with their consequent mitosis block and death. Vincristine leads to VIPN through a complex mechanism of damage, which occurs not only on the microtubules, but also on the endothelium and the mitochondria of nerve cells. Furthermore, both patient-related risk factors (age, race, ethnicity and genetic polymorphisms) and treatment-related risk factors (dose, time of infusion and drug-drug interactions) are involved in the pathogenesis of VIPN. There is a lack of consensus about the prophylaxis and treatment of VIPN among pediatric oncologic patients, despite several molecules (such as gabapentin, pyridoxine and pyridostigmine, glutamic acid and glutamine) having been already investigated in clinical trials. This review describes the molecular mechanisms of VIPN and analyzes the risk factors and the principal drugs adopted for the prophylaxis and treatment of VIPN in pediatric patients with cancer.

Keywords: chemotherapy-induced peripheral neuropathy; molecular mechanisms; pediatric cancer; prevention; risk factors; treatment; vincristine.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The first part of the figure shows the interaction between vincristine and the tubulin dimers. The second part shows the vincristine concentration-dependent action: the arrest of polymerization at low dose and amplification of depolymerization at a high dose.
Figure 2
Figure 2
VIPN pathogenesis, which involves mitochondria, endothelium and microtubules of nerve cells.
See this image and copyright information in PMC

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