We read with great interest the results of a large phase III trial, conducted by the Mayo Clinic [2], on the neuroprotective effect of vitamin E against CIPN. The results of this study showed that vitamin E failed to reduce the incidence of grade 2+ sensory CIPN, thoroughly disputing our own and other previously published data, which were strongly supportive of its neuroprotective role against CIPN [3–5]. However, the methodology applied by the Kottschade study [2] raises a number of questions that, to our opinion, might hamper the general interpretability of results. To address the important clinical issue of CIPN prevention with vitamin E, the researchers enrolled patients with many different types of cancer who were treated with five different schedules, different combinations of drugs, and different doses. The cumulative dose for each drug was not reported, thoroughly suggesting that the two groups of patients have not been stratified for different dose intensities.

Bearing in mind that oxaliplatin has a different pathogenetic mechanism to evoke peripheral nerve damage, eg, channelopathy, and induces two clinically distinct forms of peripheral neurotoxicity, ie, acute and chronic syndromes, it remains unclear why one third of the study sample (n= 50) was composed of oxaliplatintreated patients. Although there are promising data on the prophylactic effect of vitamin E against cisplatin-and paclitaxel-induced peripheral neuropathy [3–5], this is not the case for oxaliplatin-induced peripheral neuropathy. In