Abstract

Simple SummaryWe studied children with cancer who receive vincristine chemotherapy as a one-hour infusion and compared them to children who received vincristine as a push injection. We investigated if there was a difference in the development of vincristine induced peripheral neuropathy, the most common side effect of vincristine. We found that in general there were no differences between the two groups (one-hour group versus push group). However, in children using both vincristine and azole antifungals, we noticed that children who received vincristine as a one-hour infusion experienced less severe vincristine induced peripheral neuropathy compared to children who received vincristine as a push injection. Therefore, in children who require both azole antifungal medication as well as vincristine it might be beneficial to administer the vincristine as a one-hour infusion instead of a push injection. However, this finding needs to be confirmed in other studies as well.Vincristine (VCR) is a frequently used chemotherapeutic agent. However, it can lead to VCR-induced peripheral neuropathy (VIPN). In this study we investigated if one-hour infusions of VCR instead of push-injections reduces VIPN in pediatric oncology patients. We conducted a multicenter randomized controlled trial in which participants received all VCR administrations through push injections or one-hour infusions. VIPN was measured at baseline and 1–5 times during treatment using Common Terminology Criteria of Adverse Events (CTCAE) and pediatric-modified Total Neuropathy Score. Moreover, data on co-medication, such as azole antifungals, were collected. Overall, results showed no effect of administration duration on total CTCAE score or ped-mTNS score. However, total CTCAE score was significantly lower in patients receiving one-hour infusions concurrently treated with azole antifungal therapy (β = -1.58; p = 0.04). In conclusion, generally VCR administration through one-hour infusions does not lead to less VIPN compared to VCR push injections in pediatric oncology patients. However, one-hour infusions lead to less severe VIPN compared to push-injections when azole therapy is administered concurrently with VCR. These results indicate that in children treated with VCR and requiring concurrent azole therapy, one-hour infusions might be beneficial over push injections, although larger trials are needed to confirm this association.

Highlights

  • Vincristine (VCR) is a frequently-used chemotherapeutic agent in pediatric oncology since many decades [1,2]

  • OR: odds ratio; 95% CI: 95% confidence interval; Common Terminology Criteria of Adverse Events; ped-mTNS: pediatric modified Total Neuropathy Score; VCR-induced peripheral neuropathy (VIPN): vincristine-induced peripheral neuropathy; a : Push administration group served as reference group, b No VIPN group served as reference group

  • Our results show that one-hour infusions result in lower total CTCAE scores when VCR is concurrently used with azole antifungals

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Summary

Introduction

Vincristine (VCR) is a frequently-used chemotherapeutic agent in pediatric oncology since many decades [1,2]. VCR inhibits the mitotic spindle in the cell, thereby blocking cell division [3,4]. In the liver, it is metabolized into M1 by the cytochrome P450 (CYP) 3A enzymes [5]. Symptoms of VCR-induced peripheral neuropathy (VIPN) include paresthesia, muscle weakness, areflexia, pain, and diminished sensibility [9,10,11,12]. It usually starts after a few administrations and symptoms often reside several months after treatment cessation [1,2].

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