Perifere neuropathie als gevolg van vincristine bij kinderen met leukemie: een vergelijking van twee toedieningsvormen

Vincristine (VCR) is a commonly used chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). The main dose-limiting side effect of VCR is peripheral neuropathy (PNP). PNP is often seen in the form of weakness of lower limbs, areflexia, neuropathic pain, and/or sensory loss. The quality of life of children who suffer from VCR-induced PNP is severely affected.
There is a lack of information regarding the optimal therapeutic dosing and method of administration of VCR for children with cancer. High peak plasma concentrations seem to be correlated with PNP. However, the exact mechanism underlying VCR-induced PNP is not clear.
This study aims to investigate whether the administration of VCR in children with ALL by one-hour infusions leads to less PNP compared to bolus injections. In addition, quality of life, medical costs, and therapeutic effectiveness associated with bot administration methods will be evaluated. Moreover, it will be investigated whether other factors, such as pharmacokinetics and genetic susceptibility to drug-induced side-effects, also influence the degree of PNP.
The study is set up as a prospective, multi-center, randomized trial with a duration of 42 months. In the Netherlands all children diagnosed with ALL are treated according to the same treatment protocol. Patients will receive all VCR administrations of this protocol either by bolus injections or by one-hour infusions. Study measurements will be performed at 7 points in time.

To evaluate whether the administration of vincristine (VCR) in children with acute lymphoblastic leukemia (ALL) by one-hour infusions leads to less peripheral neuropathy (PNP) compared to the administration by bolus injections.

Secondary objectives:

• To compare self-reported quality of life (QoL) associated with both administration methods.

• To compare the direct and indirect medical costs involved in both administration methods.

• To compare the treatment efficacy of both administration methods.

• To compare the pharmacokinetic parameters of patients receiving both administration methods and to relate these parameters to the degree of PNP.

• To correlate genetic factors known to be associated with VCR-induced PNP (either through influencing pharmacokinetics of VCR or through genetically increased susceptibility) to the degree of PNP of patients receiving both administration methods.

Study measurements will be performed at 7 points in time: at baseline, four times during the two years of vincristine-therapy, at the end of therapy, and 6 months after the end of VCR-therapy.

Group A: patients receiving all VCR administrations by bolus injections ("push injections").

Group B: patients receiving all VCR administrations by one-hour infusions.