Vincristine-induced peripheral neuropathy in children with cancer:new insights on an old problem

Vincristine induced peripheral neuropathy is the most common type of toxicity in patients using vincrstine. Vincristine is chemotherapeutic agent used in a diverse range of pediatric oncology treatment protocols. In this thesis we take a multidimensional view on the topic of vincristine induced peripheral neuropathy. We describe a validation study reporting on the validity of the Dutch translated version of the pediatric-modified total neuropathy score (ped-mTNS). Furthermore we report on the effects of vincristine induced peripheral neuropathy on quality of life during treatments. This showed that children with cancer and vincrstine induced peripheral neuropathy report a lower quality of life than children with cancer without vincristine induced peripheral neuropathy. Furthermore we report the outcomes of a randomized clinical trial studying the effect of administration duration (push injections versus one-hour infusions) of vincristine on the development of vincristine induced peripheral neuropathy. This trial reported no overall effect, but showed that when vincristine in concomitantly used with azole antifungals (which is generally avoided to their drug-drug interaction leading to an increase in vincristine induced peripheral neuropathy) in case of an invasive fungal infection requiring treatment next to vincristine, one-hour administration resulted in a significant reduced peripheral neuropathy compared to push injections. We also report on the outcomes of pharmacokinetics of vincrstine related to administration duration and describes genetic single nucleotide polymorphisms related to vincristine induced peripheral neuropathy. Finally, we describe the research protocol of an dose escalation trial with close toxicity monitoring in pediatric oncology patients in Kenyan patients.