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Method of administration affects drug side effects in certain group of children with cancer

PhD student Aniek Uittenboogaard, together with colleagues, investigated the method of administration of the drug vincristine to see if it reduced side effects such as neuropathy. A certain group of children benefit from an infusion instead of an injection, she says. 

Aniek Uittenboogaard is currently completing her PhD research in the Department of Outreach, in close collaboration with the Huitema group. She explains: ‘My research is about all children who receive vincristine. It's a drug that appears in many treatment regimens. The largest group is children with acute lymphoblastic leukemia (ALL), but children with Wilms' tumor or Hodgkin's lymphoma also receive vincristine. It is an effective drug in the treatment of leukemia or lymphoma, but it has significant side effects. The most common side-effects are neuropathy or nerve symptoms (tingling, pain, loss of strength, often starting in the hands and feet) and constipation. About 20% of children develop severe neuropathy, which greatly reduces quality of life, and about 30-50% have mild symptoms. In most children, symptoms are reversible, but in 15-20% of children, symptoms persist for years after treatment ends. Doctors often consider neuropathy as a relatively mild side effect,’ Aniek continues. ‘This is because the symptoms usually go away. But it can have a big impact. Sometimes children can't walk because of foot drop, or they can't tie buttons because they lost the feeling in their fingers, or they have a lot of constipation symptoms. Unfortunately, pain due to neuropathy is very difficult to treat since pain medication typically does not help. So we are highly motivated to do more research to minimize these long-term effects.’ 

By infusion or by injection 
The aim of this study was to investigate whether the occurrence of side effects due to vincristine could be reduced by changing the mode of administration from injection to infusion. Aniek: "The participants in this study were randomly divided between 1 hour (by infusion) and 2-3 minutes (by injection) of vincristine. We then measured at several times whether they suffered from neuropathy. The expectation was that giving vincristine as a 1-hour infusion would lead to less neuropathy. The reason is that if you give it as a 1-hour infusion, you avoid high peak concentrations in the blood, which would possibly lead to less nerve damage,’ the researcher explains. But this turned out not to be the case.  

Nevertheless, some remarkable conclusions can be drawn from the study, Aniek explains: ‘In children who also receive antifungal treatment with azoles at the same time as vincristine, there is less neuropathy when you give vincristine as a 1-hour infusion. Thus, in this particular group, a longer infusion time has a protective effect against the occurrence of side effects. In addition, the Máxima Center continues to administer vincristine to children by injection. It remains very important to report neuropathy symptoms well.’ In conclusion, Aniek: ‘In line with this research, we are currently conducting a clinical trial in Kenya, one of the Outreach partners. Amongst others, we investigate the influence of genetic factors on the development of neuropathy.’ 

Aniek Uittenboogaard's study, in collaboration with a number of Belgian hospitals, was published September 21 2023 in Cancer Medicine: Randomized controlled trial of the effect of a 1-hour infusion of vincristine versus an injection on neuropathy in children with cancer.