O3.06 * THE EFFECT OF ACETYL-L-CARNITINE IN REDUCING THE TAXANES INDUCED NEUROPATHY

Abstract

Design Prospective randomized controlled open-label pilot study. INTRODUCTION: Paclitaxel is one of the most commonly used chemotherapeutic agents in breast cancer. Studies showed that about 70- 80% of breast cancer patients treated with paclitaxel had persistent neuropathic symptoms at 2 years. The neurotoxicity-related symptoms might result in severe limitation in daily activity and compromise patient's quality of life. Acetyl L-carnitine (ALC) is the ester acetylated form of carnitine, a well characterized amino acid involved in fatty acid beta-oxidation in mitochondria. Animal studies using ALC have shown that it is useful in the prevention and treatment of chemotherapy induced peripheral neuropathy. The potential role of ALC in PIPN is not well evaluated and needs further investigations. OBJECTIVES: This study aims to evaluate the impact of administering acetyl L-carnitine on the incidence and severity of paclitxel induced peripheral sensory and motor neuropathy in patients with breast cancer. PATIENTS AND METHODS: Forty eligible patients with breast cancer were randomized in a 1:1 ratio to one of 2 groups. Control group (n = 20) received three cycles of paclitaxel 135 mg/m2 alone cycled every 21 days. Test group received same regimen plus 1000 mg of oral ALC 3 times/ day for 8 weeks. At baseline, patients in both groups were assessment by clinical examination, nerve conduction velocity (NCV) and serum nerve growth factor (NGF) estimation. Incidence and severity of sensory and motor neuropathy were assessed after each cycle using the CTAC version 4. RESULTS: At baseline, both groups were comparable in age, sex and total dose. In the first cycle, both groups showed no significant difference in frequency of sensory or motor neuropathy or adverse events occurrence. In the 2nd cycle, test group showed a significantly lower frequency of; sensory neuropathy (10 vs 17, p= 0.018) and motor neuropathy (3 vs 12, p= 0.003) versus control. In the 3rd cycle, test group showed a significantly lower frequency of; sensory neuropathy (6 versus 18, p < 0.001) and motor neuropathy (3 vs 17, pp < 0.001) versus control. The frequency of vomiting was significantly higher in the control group (5 vs 0, p= 0.047) versus test in the 3rd cycle. At baseline, the median NGF levels were significantly lower in test group versus control (1.9 vs 9.5, p < 0.001). At the end of the study the median NGF levels were significantly lower (2.4, p = 0.02) in the control group versus their initial baseline levels. While, the test group median levels were higher than their baseline levels. The delta change in NGF was significantly different between the 2 groups (p < 0.001). The NCV was not significantly different between 2 groups neither at baseline nor at the end. CONCLUSION: ALC administration reduced the frequency of paclitaxel induced motor and sensory peripheral neuropathy, and was accompanied with lesser side effects and an improvement in NGF levels.