Therapeutic Agents for Oxaliplatin-Induced Peripheral Neuropathy; Experimental and Clinical Evidence

Abstract

Oxaliplatin is an essential drug in the chemotherapy of colorectal, gastric, and pancreatic cancers, but it frequently causes peripheral neuropathy as a dose-limiting factor. So far, animal models of oxaliplatin-induced peripheral neuropathy have been established. The mechanisms of development of neuropathy induced by oxaliplatin have been elucidated, and many drugs and agents have been proven to have neuroprotective effects in basic studies. In addition, some of these drugs have been validated in clinical studies for their inhibitory effects on neuropathy. In this review, we summarize the basic and clinical evidence for the therapeutic effects of oxaliplatin. In basic research, there are many reports of neuropathy inhibitors that target oxidative stress, inflammatory response, sodium channel, transient receptor potential (TRP) channel, glutamate nervous system, and monoamine nervous system. Alternatively, very few drugs have clearly demonstrated the efficacy for oxaliplatin-induced peripheral neuropathy in clinical trials. It is important to activate translational research in order to translate basic research into clinical research.

Antioxidant and Neuroprotective Effect of a Grape Pomace Extract on Oxaliplatin-Induced Peripheral Neuropathy in Rats: Biochemical, Behavioral and Histopathological Evaluation

“…Besides, mechanical allodynia has been reported in numerous rodent models of platinum induced chronic neuropathy. For a review see Kawashiri et al (2021) [ 13 ]…”

“…The first type, is an acute neurosensory toxicity present in 90% of patients immediately or shortly after infusion, mainly characterized by dysesthesia and/or paresthesia of the distal extremities enhanced by exposure to cold [ 12 ]. Although this type of neuropathy is always reversible, long-term administration of oxaliplatin is associated with a chronic cumulative peripheral neuropathy (PN), seen as superficial and deep sensory loss, sensory ataxia, functional impairment, proprioceptive loss and decreased tendon reflexes [ 12 , 13 , 14 ]. It may last for several months after the end of oxaliplatin treatment and usually symptoms that emerge are so intense it results in discontinuation of the treatment [ 14 , 15 , 16 ].…”

Preclinical and Clinical Evidence of Therapeutic Agents for Paclitaxel-Induced Peripheral Neuropathy

“…In particular, many inhibitors of neuropathy targeting oxidative stress, inflammatory response, ion channels, TRP channels, cannabinoid receptor, and monoamine nervous system have been identified as candidates for inhibiting PIPN in animal research. In particular, more reports of inhibitors targeting peripheral and central inflammatory responses, TRP channels, and cannabinoid receptors were noted compared with pre-clinical research reports on oxaliplatin-induced peripheral neuropathy [130]. Targeting these may be useful in the search for PIPN-specific therapeutics.…”

Prevention of Oxaliplatin-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

“…Platinum-related mechanisms include direct platinum-induced DNA damage in dorsal root ganglion, mitochondrial dysfunction, oxidative stress, and increased neuronal apoptosis (10,83). On the other hand, oxaliplatinspecific mechanisms and targeted neuroprotective interventions have been examined in various pre-clinical studies, as summarized in a recent systematic review by Kawashiri et al (84). Unfortunately, success in animal-based models has not consistently translated into clinical effectiveness.…”