Randomized controlled trial on the effect of 1‐hour infusion of vincristine versus push injection on neuropathy in children with cancer (final analysis)

Abstract

IntroductionVincristine is an integral component of treatment for children with cancer. Its main dose‐limiting side effect is vincristine‐induced peripheral neuropathy (VIPN). The VINCA trial was a randomized controlled trial that explored the effect of 1‐hour infusion compared with push injection of vincristine on the development of VIPN in children with cancer. The short‐term outcomes (median follow‐up 9 months) showed that there was no difference in VIPN between the randomization groups. However, 1‐hour infusion was less toxic in children who also received azoles. We now report the results of the final analyses (median follow‐up 20 months), which includes treatment outcome as a secondary objective (follow‐up 3 years).MethodsVIPN was measured 1–7 times per participant using the Common Terminology Criteria for Adverse Events (CTCAE) and the pediatric‐modified total neuropathy score. Poisson mixed model and logistic generalized estimating equation analysis for repeated measures were performed.ResultsForty‐five participants per randomization group were included. There was no significant effect of 1‐hour infusion compared with push injection on VIPN. In participants receiving concurrent azoles, the total CTCAE score was significantly lower in the one‐hour group (rate ratio 0.52, 95% confidence interval 0.33–0.80, p = 0.003). Four patients in the one‐hour group and one patient in the push group relapsed. Two patients in the one‐hour group died.Conclusion1‐hour infusion of vincristine is not protective against VIPN. However, in patients receiving concurrent azoles, 1‐hour infusion may be less toxic. The difference in treatment outcome is most likely the result of differences in risk profile.