National Cancer Institute-supported chemotherapy-induced peripheral neuropathy trials: outcomes and lessons

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is one of the most common and debilitating complications of cancer treatment. Due to a lack of effective management options for patients with CIPN, the National Cancer Institute (NCI) sponsored a series of trials aimed at both prevention and treatment. A total of 15 such studies were approved, evaluating use of various neuro-modulatory agents which have shown benefit in other neuropathic pain states. Aside from duloxetine, none of the pharmacologic methods demonstrated therapeutic benefit for patients with CIPN. Despite these disappointing results, the series of trials revealed important lessons that have informed subsequent work. Some examples of this include the use of patient-reported symptom metrics, the elimination of traditional—yet unsubstantiated—practice approaches, and the discovery of molecular genetic predictors of neuropathy. Current inquiry is being guided by the results from these large-scale trials, and as such, stands better chance of identifying durable solutions for this treatment-limiting toxicity.

Response to Crevenna and Ashbury, Vallance and Bolam, and Crevenna and Keilani regarding the effects of exercise on chemotherapy-induced peripheral neuropathy

“…Scientifically, we believe our results are significant in the broader study of CIPN and its treatment, given the dearth of promising treatment options for CIPN [8] and the lack of definitive phase III clinical trials testing the effects of exercise on CIPN where CIPN is the primary outcome. We believe this while still acknowledging that (1) our results should be interpreted with caution—as should results from all exploratory secondary analyses, (2) our observed effect sizes were relatively small, and (3) our observed CIPN symptom severity was relatively low.…”

Anti‐allodynic and anti‐inflammatory effects of 17α‐hydroxyprogesterone caproate in oxaliplatin‐induced peripheral neuropathy

“…There is currently no available therapy to effectively manage chemotherapy‐induced neuropathic pain . For symptomatic relief, evidence from clinical studies supports a moderate recommendation only for the antidepressant duloxetine . Furthermore, there are no agents recommended for use in the prevention or long lasting suppression of chemotherapy‐induced neuropathic pain .…”

Scrambler therapy efficacy and safety for neuropathic pain correlated with chemotherapy‐induced peripheral neuropathy in adolescents: A preliminary study

“…As advances in chemotherapy result in improved survival for many patients, a chief concern both during and after treatment is the presence of chemotherapy‐related neurological side effects . Chemotherapy‐induced peripheral neuropathy (CIPN), sensory and motor nerve damage or dysfunction, can produce severe neuropathic pain (NP) occurring in a “stocking‐glove” distribution and gait impairment that represent a common and serious clinical problem in many patients receiving cancer treatment .…”