Document resource
Background/Objectives Chemotherapy-induced peripheral neuropathy (CIPN) can result in early chemotherapy cessation and chronic, disabling neuropathic symptoms. Duloxetine has previously demonstrated efficacy for symptom relief, however evidence is limited to painful CIPN, which is a phenotype experienced by less than half of all CIPN patients. Furthermore, previous studies have not explored neurophysiological mechanisms underlying symptom relief associated with duloxetine. This trial assessed whether duloxetine reduces overall neuropathic symptom burden in patients with CIPN and its impact on neurophysiological parameters.Methods A randomized, placebo-controlled crossover trial was conducted, with patients randomized to receive either 8 weeks of duloxetine followed by 8 weeks of placebo, or the reverse. Eligibility criteria included daily CIPN symptoms for at least 3 months following chemotherapy. The primary outcome measure was change in patient-reported neuropathy via the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG-NTx) questionnaire. Secondary outcomes were change in objective neurophysiological parameters via the Total Neuropathy Score (TNS) and sural amplitude.Results 20 patients completed the trial, of which 35% reported painful CIPN. While both duloxetine and placebo demonstrated reduced FACT-GOG-NTx score after 8 weeks, only the mean score change in the placebo group exceeded the threshold of 2.8 for clinical importance (duloxetine mean score change; -1.41; 95% CI -3.65 to 0.838 vs. placebo -3.27; 95% CI -5.11 to -1.43; p=0.189). No significant difference in TNS score or sural amplitude were observed between duloxetine and placebo groups.Conclusions In this small cohort, duloxetine did not demonstrate efficacy in improving symptom burden or neurophysiological parameters in CIPN.