Duloxetine for Prevention of Oxaliplatin-Induced Neuropathy (OIPN): JCO Oncology Advances | April 2026

Introduction

Oxaliplatin-induced peripheral neuropathy (OIPN) is a common, dose-limiting toxicity in colorectal cancer treatment, significantly impacting quality of life and long-term functional outcomes. Duloxetine, already proven effective for the treatment of established chemotherapy-induced neuropathy, has been explored as a preventive strategy.

Problem Statement

Despite multiple attempts, there is no established therapy to prevent OIPN. Whether early initiation of duloxetine (30 mg or 60 mg) can reduce the incidence or severity of neuropathy during oxaliplatin-based chemotherapy remains unclear, representing a critical unmet clinical need.

Summary

This randomised, double-blind phase II trial demonstrated that duloxetine, at both 30 mg and 60 mg doses, did not significantly reduce the incidence or severity of OIPN compared to placebo. Response rates were similar across all groups (~65–68%), indicating no preventive benefit. Importantly, duloxetine was well-tolerated with manageable toxicity. Overall, the study confirms that duloxetine should not be used for the prevention of OIPN and highlights the continued lack of effective preventive strategies in this setting.