Anticancer drug treatment in pediatric patients : studies on optimizing dosage and on parental guidance for improved drug handling at home

Abstract: Background: Every year about 370 children are diagnosed with cancer in Sweden. The treatment includes both inpatient and outpatient care with anticancer drugs. At the clinic, the optimal anticancer drug dosage is usually derived from the patient’s body surface area (BSA). However, several formulae for calculating BSA are available and knowledge about their accuracy and precision in children is scarce. Information on the best formula to use when the height of the patient is missing or cannot be measured is also lacking. Moreover, poor access to age-appropriate drug formulations can force parents to manipulate and handle oral anticancer drugs (OADs) at home without proper drug handling knowledge and skills. Aims: The overall aim of the thesis was to increase knowledge on the adjustment of anticancer drug dosages for children in clinical practice and to optimize OAD handling procedures by parents in the home setting. The specific aims were: I. to validate Mosteller’s formula for calculating BSA; II. to test potential alternative formulae for estimating BSA using bodyweight (BW) alone; III. to observe the effects of risk-reducing strategies when handling high risk substances in the home setting; and IV. to describe parents’ experiences when handling OADs in the home setting. Methods: Different methods were used in each of the four studies. Study I was an analytical retrospective study based on measured BSA values. Study II was a retrospective cohort study based on registered data from electronic health records. In Study III, we used an observational intervention study to observe parents while they handled OADs at home. In Study IV, we used qualitative methods with semi-structured interviews to obtain parents’s views. Results: Study I showed that Mosteller’s formula underestimated BSA by 4.1 % in pediatric patients, and that inter-individual variability in the BSA measurements was most pronounced in neonates and infants. Study II showed that all three of the tested alternative formulae had good accuracy and precision for estimating BSA in children, using BW alone. Study III showed that many parents were handling OADs incorrectly at home before they were given an intervention. The intervention, which included practical training and information presented in different formats, improved the parents’ handling procedures significantly. Study IV resulted in four categories for the experiences of parents handling OADs at home: parents views on the provided information, with two subcategories: lack of, too little or contradictory information, and parents preferences for information delivery; safety over time; correct drug dosage; and drug administration. Conclusions: In Study I we found that Mosteller’s formula should be used with caution in clinical practice because it underestimates the BSA of children, especially neonates and infants. Study II showed that any of the three tested alternative equations, using only BW, can be used as a substitute for Mosteller’s formula to calculate the BSA of children, including term neonates and infants, with the best fit from the Meeh-type equation. In Study III we found that an intervention comprising practical training and information presented in different formats should be provided to parents to enable them to handle OADs correctly at home. In Study IV we concluded that parents need to be provided with timely, clear, nonconflicting and repeated infor