|The following article features coverage from the European Society for Medical Oncology (ESMO) Congress 2019. Click here to read more of Oncology Nurse Advisor‘s conference coverage.
Prior to allogenic hematopoietic cell transplantation (allo-HCT), the drug busulfan needs to accumulate to a given therapeutic range of 80-100 mg*hr/L. However, there is known to be within-person variability in how quickly busulfan is cleared from the body. Therapeutic drug monitoring may prevent severe under and/or over exposure of busulfan in patients undergoing allo-HCT, according to study results presented at ESMO Congress 2019 in Barcelona, Spain.
The study included 239 participants — both children and adults — who underwent allo-HCT with intravenous busulfan between July 2011 and July 2016 at the University Medical Center in Utrecht, Netherlands. Patients received busulfan daily for 4 consecutive days, and busulfan levels were measured on days 1 and 4.
The researchers compared cumulative exposure to 3 possible models: 1) a model without therapeutic drug monitoring based on hypothetical drug levels, 2) actual therapeutic drug monitoring with fixed clearance over time, and 3) therapeutic drug monitoring with an adapted pharmacokinetic model accounting for age and temporal changes in drug clearance.
A significantly higher percentage (76.2%) of patients reached their busulfan target with therapeutic drug modeling using a pharmacokinetic model than with no therapeutic modeling (49.8%). Interestingly, the use of other drugs, such as paracetamol and anticonvulsants, predicted the decline in busulfan clearance over time. As such, therapeutic drug monitoring also resulted in significantly lower variation in cumulative exposure.
“We strongly advocate for the use of a [pharmacokinetic] model aided therapeutic drug monitoring anticipating a decrease in busulfan clearance,” write the researchers.
Boss J, Langenhorst J, Lalmohamed A, Van Der Linden P, Boelens JJ, Van Maarseveen E. The influence of TDM on achieving busulfan target exposure and related determinants, in both children and adults who underwent an allogeneic hematopoietic cell transplantation. Presented at: ESMO Congress 2019; September 27-October 1, 2019; Barcelona, Spain. Abstract 1067O.