Indeed, there is a growing interest in the literature about neuroprotective strategies for the prevention of peripheral neurotoxicity induced by anticancer drugs. However, the conclusions of this trial contradict recent data indicating that vitamin E and other antioxidants seem to protect against cisplatin neuropathy [2]. The negative results of this trial may be explained by the inclusion in the study of different drugs with very different mechanism of peripheral neurotoxicity: more than 50% of patients enrolled in this trial were treated with taxanes and others with several platinum compounds including cisplatin, carboplatin, and oxaliplatin. The possible neuroprotective effect of vitamin E against cisplatin-induced neurotoxicity and ototoxicity has been investigated in many experimental and clinical studies [3, 4]. The hypothesis is that vitamin E supplementation may protect against the oxidative stress induced by cisplatin on the neuronal cell body in the dorsal root ganglia, the target of cisplatin neurotoxicity [5]. The mechanism of action of paclitaxel-induced neuropathy is completely different: the inhibition of tubulin polymerization induced by paclitaxel leads to an acute distal axonal sensorimotor polyneuropathy related to an alteration of axonal transport that is reversible after the end of chemotherapy. There is no clear evidence of a possible neuroprotective role for vitamin E or other antioxidants in taxane-induced neurotoxicity.

Unfortunately, in Kottschade's study, both the vitamin E arm and the placebo arm included patients treated with platinum compounds and taxanes or both and the cumulative dose was not reported. The dose of platinum administered is relevant because the large fiber sensory neuropathy (neuronopathy) induced by cisplatin is dose-related and most often becomes evident after a cumulative cisplatin dose of at least 300–350 mg/m2 [6]. Moreover, patients were treated with different schedules and different combinations of drugs. The study of Kottschade and colleagues raises a number of questions: were the two groups of patients stratified for different dose intensities? Were patients treated with carboplatin and oxaliplatin evaluated separately from patients treated with cisplatin? And more generally: What is the rationale for neuroprotection with antioxidants in taxaneinduced and oxaliplatin-induced neurotoxicity? Considering the different neurotoxicity mechanisms of the different anticancer drugs evaluated in this trial and the specific effects of antioxidants in preventing cisplatin toxicity, we disagree entirely with the study's conclusion on the lack of activity of vitamin E supplementation for neuroprotection in patients treated with platinum. Large randomized and controlled trials are needed to provide a clearer understanding of neuroprotection in chemotherapy-induced peripheral neurotoxicity (CIPN), but neuroprotective strategies should be tailored to the different mechanism of action of neurotoxic drugs. There is a wide consensus about the need for large trials exploring possible neuroprotective agents. However, the evaluation of agents intended to prevent chemotherapyinduced neurotoxicity should include adequate measures of assessment including nerve conduction study and validated neurotoxicity scale. The assessment of CIPN is still uncertain as several of the most frequently used scales do not rely on a formal neurological evaluation and depend on patients'