Epithelial growth factor receptor (EGFR)-inhibition for relief of neuropathic pain—A case series

BackgroundNeuropathic pain remains a significant challenge with unsatisfactory therapeutic options. Its pathogenesis may involve the neuropathic triad of neuronal, glial and immune cells. Communication between these cells is possibly perpetuated by mitogen-activated protein kinase (MAPK)-signaling. For several years, we successfully treated a rectal cancer patient with the epithelial growth factor receptor (EGFR)-inhibitor cetuximab, for debilitating neuropathic pain due to progressive malignant invasion of the sacral plexus. Here, we report the effect of treatment with various EGFR-inhibitors in five additional patients with severe and long-standing, therapy-resistant neuropathic pain.MethodsAll patients had well-documented neuropathic pain syndromes with the following etiologies: inflammatory polyneuropathy, complex regional pain syndrome type 1, radiculopathy after failed back surgery, malignant invasion of the sacral plexus by bladder cancer, and phantom limb pain. All patients were given intravenous (extracellular) EGFR-inhibitors (cetuximab, panitumumab) initially, and switched to oral (intracellular) agents (gefitinib, erlotinib) after an analgesic effect was obtained.ResultsFour of the five patients responded, all within 24 h of intravenous administration, with a mean decrease in worst pain from 9 to 1 on a 10-point scale. All four EGFR-inhibitors were effective. The clinical courses, including patient-reported pain relief, are prospectively documented with 78–219 days follow-up for those who responded to treatment. Toxicities were transient and manageable.Conclusions/implicationsEGFR-inhibition resulted in dramatic relief of neuropathic pain. A plausible biological explanation involves the interruption of MAPK-signaling. The role of EGFR-inhibition as a target for the treatment of neuropathic pain appears promising and warrants investigation.

► Serendipitous observation of epithelial growth factor receptor (EGFR) inhibition causing dramatic relief of neuropathic pain.
► This effect was confirmed by EGFR-inhibition in five further patients with severe neuropathic pain.
► Treatment with EGFR-inhibitors resulted in rapid, dramatic and durable pain relief.
► Four of five patients responded and four of four drugs used were effective.
► A class effect of EGFR-inhibition is suggested on neuropathic pain.