Evaluation of the Safety and Efficacy of N-acetylcysteine in the Prevention of Paclitaxel-induced Peripheral Neuropathy: A Randomized, Double-blind, and Placebo-controlled Trial.

Abstract

Objective: Paclitaxel-induced peripheral neuropathy (PIPN) is a disabling condition that leads to discontinuation or dose reduction of chemotherapy and reduces the patient's quality of life (QOL). We investigated the effect of N-acetylcysteine (NAC) in preventing PIPN.

Methods: This study was a randomized, double-blind, and placebo-controlled clinical trial conducted at a chemotherapy center of Mazandaran University of Medical Sciences. Breast cancer patients receiving the Adriamycin/Cyclophosphamide-Taxol regimen were enrolled. All patients received 1200 mg NAC or placebo in two doses before each cycle of paclitaxel. Response to treatment was assessed based on improvements in the Numeric Pain Rating Scale (NRS), NCI-CTCAE, NPS, FACT/GOG-Ntx, and EORTC-QLQ. Two blood samples were taken at baseline and last cycle to determine the oxidative factors.

Findings: Sixty patients were enrolled. At the last cycle, changes in NRS were decreasing in the NAC group but increasing in the placebo group. Thirteen patients (44.8%) in the NAC group and only one patient (3.4%) in the placebo group still reported no neuropathy in the end. A significant difference was observed between the two groups in the Ntx subscale and the Fact-G total score at the last cycle (P < 0.001). The QOL increased in the NAC and decreased in the placebo group. Glutathione levels, MDA, and TAC differed significantly between the two groups (P < 0.001, <0.001, and 0.04, respectively), but no significant difference in NO levels (P = 0.5).

Conclusion: Oral NAC at a dose of 1200 mg daily for two doses can reduce the incidence and severity of PIPN and improve patients' QOL.