A Systematic Review and Meta-Analysis of the Effectiveness of Neuroprotectants for Paclitaxel-Induced Peripheral Neuropathy

Abstract

BackgroundPaclitaxel-induced peripheral neuropathy (PIPN) is a disabling side effect of paclitaxel with few effective preventive strategies. We aim to determine the efficacy of pharmacological and non-pharmacological neuroprotective interventions in preventing PIPN incidence.MethodsBiomedical literature databases were searched from years 2000 to 2021 for trials comparing neuroprotective interventions and control. Meta-analysis was performed using the random-effects model. The primary outcome was the incidence of PIPN.ResultsOf 24 relevant controlled trials, 14 were eligible for meta-analysis. Pooled results from seven non-pharmacological trials were associated with a statistically significant 48% relative reduction of PIPN risk with low heterogeneity. Conversely, pooled results from six pharmacological trials were associated with a significant 20% relative reduction of PIPN risk with moderate heterogeneity. Both pharmacological and non-pharmacological approaches appear effective in reducing PIPN incidence in the treatment arm compared to control (pooled RR < 1).ConclusionCurrent evidence suggests that both interventions may reduce PIPN risk. Non-pharmacological interventions appear more effective than pharmacological interventions.

Current and Emerging Pharmacotherapeutic Interventions for the Treatment of Peripheral Nerve Disorders

“…However, the translatability of these findings between species and to humans have been equivocal and contentious, further complicating the bench-to-bedside process [ 180 , 181 ]. Instead of focusing on current non-pharmacotherapeutic and therapeutic approaches that have had limited success, such as exercise, conventional analgesics, dietary supplements and drug repositioning efforts, which have been recently reviewed [ 182 , 183 , 184 , 185 , 186 ], the following Section 4.3 will explore two novel, emerging pharmacotherapeutics that have been of particular interest in recent years, in relation to CIPN prevention and treatment, with insights from both preclinical and clinical studies.…”

Non-Pharmacological Self-Management Strategies for Chemotherapy-Induced Peripheral Neuropathy in People with Advanced Cancer: A Systematic Review and Meta-Analysis

“…In the most recent 2020 clinical practice guidelines for CIPN developed by the American Society of Clinical Oncology (ASCO) [12] and the European Society for Medical Oncology (ESMO) [13], no recommendations were made for preventing CIPN, and the use of duloxetine was the only treatment described as having some evidence to support its use for reducing neuropathic pain. Despite limited supporting evidence, other pharmacological treatments used in practice include anticonvulsants (e.g., gabapentin/pregabalin), tricyclic antidepressants (e.g., amitriptyline), opioids (e.g., oxycodone), as well as topical lidocaine [4,[13][14][15]. Pharmacological interventions target neuropathic pain, which is just one of a cluster of symptoms associated with CIPN [6].…”

“…Pharmacological interventions target neuropathic pain, which is just one of a cluster of symptoms associated with CIPN [6]. In addition to lack of efficacy and narrow scope of use, pharmaceutical therapies used for CIPN are associated with unfavorable side effects, such as nausea, dizziness, and drowsiness, and include problematic outcomes of polypharmacy interactions with other medications commonly prescribed in advanced cancer due to multimorbidity [4,14]. These toxicities lead to prolonged infusion times, chemotherapy dose reductions, and treatment cessation, which has negative impacts on treatment efficacy and reduces the quality of life [12].…”

“…These toxicities lead to prolonged infusion times, chemotherapy dose reductions, and treatment cessation, which has negative impacts on treatment efficacy and reduces the quality of life [12]. Unsurprisingly, non-pharmacological self-management interventions are of growing interest in assisting in the prevention and management of CIPN [14,16].…”

“…Non-pharmacological interventions are generally not first-line therapies for CIPN; however, there is emerging evidence to support their early use [13,16]. A recent systematic review of 24 controlled trials determined non-pharmacological interventions to be more effective than pharmacological treatments in managing Paclitaxel-induced peripheral neuropathy symptoms in people diagnosed with any cancer or stage [14]. Specifically, beneficial effects on CIPN symptoms were described for Chinese herbal medicine, acupuncture, exercise, vitamin E and Omega-3 polyunsaturated fatty acid (PUFA) supplementation, massage, and foot baths [16].…”