(275) Somatosensory Predictors of Response to Pregabalin in Painful Chemotherapy-Induced Peripheral Neuropathy (CIPN): A Randomized, Placebo-Controlled, Crossover Study

Abstract

Painful chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating and treatment-resistant sequela of many chemotherapeutic medications. Ligands of α2δ subunits of voltage-gated Ca2+ channels, such as pregabalin, have shown efficacy in reducing mechanical hypersensitivity in animal models of neuropathic pain. In addition, some data suggested that pregabalin may be more efficacious in relieving neuropathic pain in subjects with increased hypersensitivity to pinprick. We hypothesized that mechanical hypersensitivity, as quantified by decreased mechanical pain threshold (MPT) at the dorsal feet, would be predictive of a greater reduction in average daily pain in response to pregabalin versus placebo. In a prospective, randomized, double-blinded study, 26 patients with painful CIPN from oxaliplatin, docetaxel, or paclitaxel received 28-day treatment with pregabalin (titrated to maximum dose 600mg a day) and placebo in cross-over design. Twenty-three participants completed both arms and were eligible for efficacy analysis. There was no significant difference between pregabalin and placebo in reducing average daily pain (22.5% vs 10.7%, p = 0.23) or worst pain (29.2% vs 16.0%, p = 0.13) from baseline. Post-hoc analysis of patients with CIPN caused by oxaliplatin only (n = 18) demonstrated a larger reduction in worst pain with pregabalin than with placebo (35.4% vs 14.6%, p = 0.04). MPT was not significantly correlated with reduction in average pain (p = 0.20) or worst pain (p = 0.19) in response to pregabalin. In summary, baseline mechanical pain threshold tested on dorsal feet did not meaningfully predict the analgesic response to pregabalin in painful CIPN. This work was supported by the ASPIRE grant program by Pfizer, Inc.