Relief of neuropathic pain through epidermal growth factor receptor inhibition: a randomized proof-of-concept trial

Christian Kersten*, Marte G. Cameron, Andrew G. Bailey, Marie T. Fallon, Barry J. Laird, Vicki Paterson, Rory Mitchell, Sue M. Fleetwood-Walker, Fergus Daly, Svein Mjaland

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

6 Citations (Scopus)

Abstract

Objective. Case reports and a case series have described relief of neuropathic pain (NP) after treatment with epidermal growth factor receptor inhibitors (EGFR-Is). These observations are supported by preclinical findings. The aim of this trial was to explore a potential clinical signal supporting the therapeutic efficacy of EGFR-Is in NP. Methods. In a proof-of-concept trial using a randomized, double-blind, placebo-controlled design, 14 patients with severe, chronic, therapy-resistant NP due to compressed peripheral nerves or complex regional pain syndrome were randomized to receive a single infusion of the EGFR-I cetuximab and placebo in crossover design, followed by a single open-label cetuximab infusion. Results. The mean reduction in daily average pain scores three to seven days after single-blinded cetuximab infusion was 1.73 points (90% confidence interval [CI] = 0.80 to 2.66), conferring a 1.22-point greater reduction than placebo (90% CI = -0.10 to 2.54). Exploratory analyses suggested that pain reduction might be greater in the 14 days after treatment with blinded cetuximab than after placebo. The proportion of patients who reported >= 50% reduction in average pain three to seven days after cetuximab was 36% (14% after placebo), and comparison of overall pain reduction suggests a trend in favor of cetuximab. Skin rash (grade 1-2) was the most frequent side effect (12/14, 86%). Conclusions. This small proof-of-concept evaluation of an EGFR-I against NP did not provide statistical evidence of efficacy. However, substantial reductions in pain were reported, and confidence intervals do not rule out a clinically meaningful treatment effect. Evaluation of EGFR-I against NP therefore warrants further investigation.

Original languageEnglish
Pages (from-to)2495-2505
Number of pages11
JournalPain medicine
Volume20
Issue number12
Early online date20 May 2019
DOIs
Publication statusPublished - Dec 2019

Keywords

  • Neuropathic Pain
  • Compressed Nerve
  • Failed back surgery syndrome
  • Complex Regional Pain Syndrome
  • Epidermal Growth Factor Receptor
  • Cetuximab
  • Clinical importance
  • Cancer
  • Management
  • Outcomes
  • Placebo
  • Burden

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