Protective effect of N-acetylcysteine on oxaliplatin-induced peripheral neuropathy in colorectal cancer: a randomized controlled trial.

Abstract

Purpose: Oxaliplatin-induced peripheral neuropathy (OIPN) is a dose-limiting adverse effect of FOLFOX chemotherapy in colorectal cancer (CRC) patients. We aimed to evaluate the protective effect of N-acetylcysteine (NAC) against OIPN. Additionally, we investigated its mechanistic effects on serum biomarkers including total antioxidant capacity (TAC), interleukin-6 (IL-6), and neurotensin.

Methods: Forty-six patients with stage III or high-risk stage II CRC receiving adjuvant modified FOLFOX-6 chemotherapy were randomized in a 1:1 ratio to receive either oral NAC 1200 mg (effervescent tablets or granules) or placebo one hour before each oxaliplatin infusion for four cycles. Serum levels of TAC, IL-6, and neurotensin were measured before and after treatment. Neuropathy was assessed using the FACT/GOG-NTX-12 and NCI-CTCAE scales, and pain was estimated by using the Brief Pain Inventory-Short Form.

Results: Neurotensin was significantly decreased in the NAC group compared to controls after treatment (P < 0.001), and was significantly lower post-treatment versus pre-treatment in the NAC group (P = 0.001). IL-6 was significantly reduced in the NAC group versus controls after treatment (P < 0.001), and significantly decreased post-treatment in both groups (P < 0.05). FACT/GOG-NTX-12 and NCI-CTCAE scores were significantly lower in the NAC group at the end of the first two cycles and at the end of treatment (P < 0.05). Pain interference, but not pain severity, was significantly reduced in the NAC group at both time points (P < 0.001).

Conclusion: NAC administration during FOLFOX chemotherapy significantly reduced OIPN severity, pain interference, and serum levels of IL-6 and neurotensin, suggesting both clinical and mechanistic neuroprotective effects.

Clinical registration: The study was is registered on ClinicalTrials.gov (ID: NCT07391163).