Vol.:(0123456789) 1 3 Breast Cancer Research and Treatment https://doi.org/10.1007/s10549-020-05762-8 CLINICAL TRIAL Evaluation of the efect of N‑acetylcysteine on the prevention and amelioration of paclitaxel‑induced peripheral neuropathy in breast cancer patients: a randomized controlled study Hadeer G. Khalefa 1  · May A. Shawki 2  · Rasha Aboelhassan 3  · Lamia M. El Wakeel 2 Received: 20 January 2020 / Accepted: 20 June 2020 © Springer Science+Business Media, LLC, part of Springer Nature 2020 Abstract Purpose The aim of the current study was to evaluate the efect of N-acetylcysteine (NAC) on the incidence and severity of paclitaxel-induced peripheral neuropathy (PIPN) in breast cancer patients. Method A prospective randomized controlled open label study was conducted on 75 breast cancer patients receiving adjuvant paclitaxel 80 mg/m 2 weekly for 12 weeks. Eligible patients were randomized to either the low dose group; 1200 mg daily NAC, the high dose group; 1200 mg NAC twice daily or the control group; received paclitaxel only. The primary endpoint was the incidence of diferent grades of PIPN using National Cancer Institute’s common toxicity criteria for adverse event (NCI-CTCAE) while secondary endpoints were the severity of PIPN using modifed total neuropathy score (mTNS), quality of life (QOL) using Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT-GOG- NTX) subscale, serum nerve growth factor (NGF), and serum malondialdehyde (MDA). Results At the end of the 12-week period, the incidence of grade (2, 3) peripheral neuropathy was signifcantly lower in the high dose group (28.6%) compared to the low dose group (61.9%) and the control group (100%), p value < 0.001. A signifcant improvement in the mTNS and QOL scores was observed after 6 and 12 weeks in the high dose group and the low dose group compared to the control, p value < 0.001. Signifcantly higher levels of serum NGF in the high dose group and lower level of serum MDA in the high dose and the low dose group were observed. Conclusion Oral NAC (1200 mg once and twice daily) might reduce the incidence and severity of PIPN and improve the patients’ QOL. Trial registry Clinical Trial.gov registration number: NCT03492047. Keywords Paclitaxel · N-Acetylcysteine · Peripheral neuropathy · Oxidative stress · Nerve growth factor Introduction Breast cancer is the second most common cancer in women with an incidence of 1.5 million each year [1]. It accounts for 32% of cancer in Egyptian women [2]. Treatment of early stages breast cancer include surgery followed by adju- vant chemotherapy [3]. Lymph node positive breast cancer patients usually receive four cycles of anthracycline-cyclo- phosphamide based regimen followed by weekly paclitaxel for 12 cycles [4]. Neurotoxicity is the most common dose-dependent side efect of paclitaxel that increases with cumulative doses of > 250 mg/m 2 [5]. The incidence of paclitaxel- induced peripheral neuropathy (PIPN) in breast cancer patients ranges from 11 to 70.8% during treatment and 23–80% after treatment [6]. Neurotoxicity of paclitaxel can be manifested by paresthesia, dysesthesia, tingling, itching, burning and tight, stabbing, sharp, or aching pain in addition to sensory loss in feet and legs leading to sen- sory ataxia and gait disorders [7]. Peripheral neuropathy can afect the patient’s quality of life (QOL) limiting their daily activities like walking, standing, eating, and writ- ing. It can also cause chemotherapy dose reduction or * May A. Shawki mayahmed@pharma.asu.edu.eg 1 Oncology Clinical Pharmacy Department, Nasser Institute for Research and Treatment, Cairo, Egypt 2 Clinical Pharmacy Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt 3 Nasser Institute for Research and Treatment, Cairo, Egypt