Abstract
Oxaliplatin (OXA) is a platinum compound primarily used in the treatment of gastrointestinal cancer. OXA-induced peripheral neurotoxicity (OXAIPN) is the major non-hematological dose-limiting toxicity of OXA-based chemotherapy and includes acute transient neurotoxic effects that appear soon after OXA infusion, and chronic non-length dependent sensory neuronopathy symmetrically affecting both upper and lower limbs in a stocking-and-glove distribution. No effective strategy has been established to reverse or treat OXAIPN. Thus, it is necessary to early predict the occurrence of OXAIPN during treatment and possibly modify the OXA-based regimen in patients at high risk as an early diagnosis and intervention may slow down neuropathy progression. However, identifying which patients are more likely to develop OXAIPN is clinically challenging. Several objective and measurable early biomarkers for OXAIPN prediction have been described in recent years, becoming useful for informing clinical decisions about treatment. The purpose of this review is to critically review data on currently available or promising predictors of OXAIPN. Neurological monitoring, according to predictive factors for increased risk of OXAIPN, would allow clinicians to personalize treatment, by monitoring at-risk patients more closely and guide clinicians towards better counseling of patients about neurotoxicity effects of OXA.
Highlights
Our group identified that the burden of acute symptoms measured when patients have completed half of the planned OXA-based treatment was independently associated with nearly double risk of developing severe chronic OXA-induced peripheral neurotoxicity (OXAIPN) in a prospective multicenter study including 200 CRC
The majority of published studies assessed individual OXAIPN susceptibilities on single nucleotide polymorphisms (SNPs), which are mainly associated with gene variations in detoxification enzymes; DNA repair; drug transport; metabolism; neuronal receptors and ion channels (Figure 3)
Some ofand these studies are of interest; tellingly, by they have provided inconof significant methodological limitations, including small sample sizes; retrospective study sistent findings and failed, in principle, to be replicated by other independent groups bedesign; of a post hoc limitations, analysis of oncology-based of different, not cause ofimplementation significant methodological including smalldatabases sample sizes; retrospecpre-planned size; lack of a pre-study of hypothesis based on the role of the databases investigated tive study design; implementation a post hoc analysis ofknown oncology-based of targets in the nervous system; inappropriate outcomebased measures forknown neurological different, not peripheral pre-planned size; lack of a pre-study hypothesis on the role of impairment and differences to DNA origin, extraction andinappropriate genotyping [96]
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. OXAIPN development cannot be accurately predicted in a gastrointestinal cancer patient patient before OXA treatment initiation and the common common inter-individual inter-individual variability in severity severity of OXAIPN ofof a uniform insult is a is major challenge in clinical practice. Prediction of development and progression of OXAIPN and adecision timely decision to the OXA the dosing patients at high risk is clinically important. OXAIPN, and in adjusting dose more to balance the riskthe of neurotoxicity against antineoplastic efficacy
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