Comparative study evaluating the efficacy of duloxetine, gabapentin, and lacosamide on oxaliplatin-induced peripheral...

Peripheral neuropathic pain limits oxaliplatin use and negatively impacts patients' quality of life.

This study was conducted to assess the impact of gabapentin and lacosamide on oxaliplatin-induced peripheral neuropathy compared with duloxetine.

In this randomized, double-blind study, 93 patients receiving oxaliplatin-based chemotherapy (FOLFOX-4 regimen: folinic acid, fluorouracil, and oxaliplatin) were assigned to 1 of 3 groups. Group 1 received duloxetine 30 mg/d, group 2 received gabapentin 300 mg/d, and group 3 received lacosamide 50 mg/d throughout 12 chemotherapy cycles. Neuropathy was assessed using the McGill Pain Questionnaire, 12-item neurotoxicity questionnaire (NTX-12), the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire, and grading according to the Common Terminology Criteria for Adverse Events. Serum neuroinflammatory biomarkers, including nuclear factor kappa B, neurotensin, neurofilament light chain, and heme oxygenase-1, were also evaluated, along with adverse drug effects.

At cycles 10 and 12, the incidence of grade 2 to 3 neuropathy was significantly lower with duloxetine and lacosamide compared with gabapentin (45.2% and 32.2% vs 70.9%, P = 0.005; 51.6% and 38.8% vs 80.7%, P = 0.002), respectively. Patients receiving gabapentin showed lower 12-item neurotoxicity questionnaire scores at cycles 8, 10, and 12 (all P < 0.01), indicating greater neurotoxicity than duloxetine and lacosamide, as the scale is inversely scored. Consistently, serum levels of nuclear factor kappa B, neurotensin, and neurofilament light chain were reduced in the duloxetine and lacosamide groups relative to gabapentin.

Lacosamide demonstrated neuroprotective efficacy comparable with duloxetine and may represent a promising therapeutic option for oxaliplatin-induced peripheral neuropathy.