Chemotherapy-induced peripheral neuropathy is a common side effect afflicting patients with cancer treated with neurotoxic chemotherapeutic agents, as oxalipatin. Aim: The study aims at investigating the use of anti-oxidant L-carnosine for prevention of acute oxaliplatin neurotoxicity in colorectal cancer patients by assessing its effect on Nuclear factor-2 erythroid related factor-2 (Nrf2) induced oxidative stress pathways by assessment of serum levels of Malondialdehyde (MDA), Nuclear factor-kappa light chain enhancer of B cells (NF-κB) anti-inflammatory pathway and pro-apoptotic signals Caspase-3 (Casp-3).
In this pilot study 65 patients were recruited using prospective randomized controlled study design and enrolled randomly into to two arms; Arm A (31 patients) received FOLFOX-6 regimen (oxaliplatin, 5FU & leucovorin) and Arm B (34 patients) received FOLFOX-6 regimen and oral L-carnosine 500 mg daily all along the treatment. All recruited patients were followed up for three months, then both arms were analyzed for neuropathy incidence/grade and any additional toxicities according to NCI-CTC version 4.
In both arms the correlation analysis was significantly positive between NF-κ B and either Nrf2 and caspase 3.
Concerning the improving impact of L-Carnosine added to oxaliplatin, represented in Arm B, on inflammatory markers, it caused a significant decrease in the levels of NFkB (27%) compared to Arm A. Intriguingly, this ameliorative anti-inflammatory effect of L-Carnosine was also reflected on its anti-apoptotic and anti-oxidative effects, by reducing caspase activity (49%), MDA level (51.8%) as well as significant elevation of Nrf2 (38.7%), compared to Arm A.
Dietary supplementation with L-Carnosine proved to improve Oxalipaltin induced peripheral neuropathy by amelioration of the pathophysiologic triad of inflammation, oxidative stress and apoptosis. These results led to the recommendation of safe add-on therapy of Carnosine to chemotherapeutic agents, and opens thereby, a new supportive strategy in oncologic diseases.
Clinical trial identification