Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG)

The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Therefore, we studied the relationship between vincristine antileukaemic effect and pharmacokinetics in children newly diagnosed with ALL before the start of standard induction chemotherapy. Vincristine plasma concentration was measured by high-pressure liquid chromatography analysis with electrochemical detection. Primary pharmacokinetic parameters were estimated by maximum a posteriori parameter estimation with a Bayesian algorithm using the ADAPT II software package. Secondary pharmacokinetic parameters were calculated from the model. Response to a single dose of vincristine was determined on bone marrow (BM) and peripheral blood (PB) smears after 3 days. Variability of vincristine pharmacokinetics did not explain variability of response to vincristine monotherapy. Our results do not support the clinical application of pharmacokinetically guided adaptation of a standard body surface area-based dose of vincristine.