Natural products - alpha-lipoic acid and acetyl-L-carnitine - in the treatment of chemotherapy-induced peripheral neuropathy

OBJECTIVE: Cancer patients frequently experience Chemotherapy-Induced Peripheral Neuropathy (CIPN), as a typical side effect related to time of administration and dose of anticancer agents. Yet, CIPN pathophysiology is poorly understood, and there is a lack of well-tolerated pharmacological remedies helpful to prevent or treat it. Therefore, new safe and effective compounds are highly warranted, namely if based on an adequate understanding of the pathogenic mechanisms.MATERIAL AND METHODS: Herein we reviewed and discussed scientific data related to the beneficial role of some non-conventional treatments able to counteract CIPN, focusing our attention on alpha-lipoic acid (ALA) and L-acetyl-carnitine (LAC), two natural products that have been demonstrated to be promising preventive drugs.RESULTS: Although a growing body of in vitro and in vivo studies support ALA as a molecule able to counteract CIPN symptoms, mostly due to its antioxidant and anti-inflammatory properties, only two randomized clinical trials evaluated ALA usefulness in preventing chemotherapy-related neuropathy. Unfortunately, these studies were inconclusive and clinical outcomes showed to be highly dependent on the route of administration (oral versus or intravenous injection). LAC has demonstrated beneficial effects on both in vitro and in animal studies. Yet, some controversies aroused from randomized clinical trials. Indeed, while CIPN-patients treated with Taxane showed no benefit from LAC treatment, CIPN-patients treated with platinum compounds exhibit significant improvement of CIPN-related symptoms. Therefore, LAC treatment should be used, and thoroughly investigated only in patients treated with chemotherapy protocols Taxanes-free.CONCLUSIONS: Mechanisms of toxicity triggered by each single drug need to be deeply explored to better identify effective compounds to prevent or treat them. Moreover, additional experiments are mandatory to establish effective doses and length of treatment for each clinical situation in order to perform large and long-term randomized studies.