The National Cancer Institute Clinical Trials Planning Meeting for Prevention and Treatment of Chemotherapy-Induced Peripheral Neuropathy

Abstract

Although recent scientific advances have improved our understanding of basic biological mechanisms underlying chemotherapy-induced peripheral neuropathy (CIPN), few interventions are available to prevent or treat CIPN. Although some biological targets from preclinical studies show promise in nonhuman animal models, few targets have been translated to successful clinical trials. To address this problem, the National Cancer Institute’s Symptom Management and Health-Related Quality of Life Steering Committee convened a meeting of experts in the CIPN and oncology symptom management fields to participate in a Clinical Trials Planning Meeting (CTPM). Investigators presented data from preclinical and translational studies for possible CIPN interventions; these were evaluated for readiness of randomized clinical trial testing by experts, and recommendations were provided. Breakout sessions were convened to discuss and develop future studies. The CTPM experts concluded that there is compelling evidence to move forward with selected pharmacological and nonpharmacological clinical trials for the prevention and treatment of CIPN. Several key feasibility issues need to be addressed, however. These include identification of optimal outcome measures to define the CIPN phenotype, establishment of parameters that guide the evaluation of clinically meaningful effects, and adoption of approaches for inclusion of translational and biomarker and/or genetic measures. The results of the CTPM provide support for conducting clinical trials that include both pharmacological and nonpharmacological approaches, alone or in combination, with biomarkers, genetics, or other measures designed to inform underlying CIPN mechanisms. Several working groups were formed to design rigorous CIPN clinical trials, the results of which are ongoing.

Risk factors for chemotherapy‐induced peripheral neuropathy in patients receiving taxane‐ and platinum‐based chemotherapy

“…Overall CIPN incidence was lower in this study than that reported in the literature, and this has to do probably with the scales used; past studies have used quality of life scales to estimate CIPN, which often include a range of general/broader items to indicate neuropathy. Also, clinician‐based assessments, such as the NCI‐CTCAE tend to underestimate CIPN incidence (Dorsey et al, ). We have explained these reasons in more detail in the parent larger study (Molassiotis et al, ).…”

“…This may reflect sensitivity or reliability issues with the various scales measuring CIPN. As the measurement tool(s) used in future risk factor research will be related with the identification of specific risk factors, it is important to use the most reliable and valid CIPN scale (Cavaletti et al, ; Dorsey et al, ) or a combination of scales to maximize the “pick up” rates of these tools that will include both patient‐reported outcomes and objective CIPN indicators, such as with the Total Neuropathy Score clinical version (TNSc) (McCrary et al, ).…”

Overview and critical revision of clinical assessment tools in chemotherapy‐induced peripheral neurotoxicity

“…Several recommendations have recently been published concerning the assessment of CIPN in the clinical trial setting . These have highlighted the unsuitability of the NCI‐CTCAE as a trial endpoint.…”

Platinum‐induced peripheral neurotoxicity: From pathogenesis to treatment

“…Despite the widespread use of these medications, to date duloxetine, a serotonin‐norepinephrine reuptake inhibitor has been the only drug found to be associated with a significant reduction in neuropathic pain in CIPN in a randomized phase III intervention study (Table ) . The mechanism of duloxetine‐induced analgesia is due to the blocking of serotonin and norepinephrine transporters, as well as blocking of sodium channel currents and affecting the descending inhibitory pain neural networks Additional novel therapeutic strategies are currently in development …”