Sirs, Chemotherapy-induced peripheral neuropathy (CIPN) is currently acknowledged as a major and potentially doselimiting adverse event in patients exposed to commonly administered chemotherapeutic agents [1]. As a result, the prevention of CIPN remains a very challenging area broadly in the field. 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, e.g., channelopathy, and induces two clinically distinct forms of peripheral neurotoxicity, i.e., 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 cisplatinand paclitaxel-induced peripheral neuropathy [3–5], this is not the case for oxaliplatin-induced peripheral neuropathy. In our knowledge, the efficacy of vitamin E against CIPN has never to date been tested in oxaliplatin-treated patients. We might agree that the chronic neuropathy caused by oxaliplatin is not necessarily a channelopathy. Nevertheless, the rationale for neuroprotection with antioxidants in oxaliplatin-treated patients should be clarified. Moreover, the limited number of patients treated with cisplatin (n=8), carboplatin (n=2), or combination (n=20) certainly lacked the statistical power to detect significant differences between groups in outcome measures. Nonetheless, a significant proportion of the study sample (n=50) appears to be inappropriate, whereas the remaining number of patients already stratified in subgroups (n=30) was too small for being further divided into treatment and control arms. The effect of vitamin E supplementation on the incidence of CIPN was primarily assessed using the National Cancer Institute Common Toxicity Criteria (NCI-CTC) version 3. Some standardized questions regarding neurotoxic symptoms, ranging the severity of CIPN in a visual analog scale, were also employed. One would expect a meaningful prophylactic agent for CIPN to reduce the incidence of grade II+ neuropathy in the NCI-CTC version 3 grading. However, this seems that might not be the case in the Kottschade et al. study [2]. Bearing in mind that CIPN is characterized by a great variability in symptom characterA. A. Argyriou (*) Department of Neurology, “Saint Andrew’s” General Hospital of Patras, 26335 Patras, Greece e-mail: andargyriou@yahoo.gr
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Apr 1, 2024
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