Dose-capping, dose-adjustment, full-dose: what to do for antineoplastic drugs in obese patients ?

Introduction
With high increase in the world since the end of last century, obesity can be described as a pandemic. Oncology practitioners are increasingly confronted with this type of patient profile and they face a problem of antineoplastic drugs dosing. Drug adaptations are often based on empirical practices and differ between institutions. The aim of this work is to clarify the pharmacokinetic reasons where antineoplastic drugs adjustment or capping is necessary or not in the hematology unit in our hospital.

Materials & Methods
Bibliographic searches were carried out with MeSH terms “obese”, “cancer drugs” or “pharmacokinetic”. Then, we synthetized these data to provide an approach and recommendations for the specific management of these patients in our hospital. These recommendations are therefore based on 7 major publications on this subject, including reviews and general publications on the pharmacokinetic modifications induced by obesity.

Results
It appears that given the hydrophilic nature of most of anti-cancer drugs, the volume of distribution of these drugs is increased but not in proportion to the weight. In fact, obesity is characterized by an increase in adipose tissue that represents a smaller hydrophilic compartment than lean tissue and therefore a reduced possibility of distribution of these molecules. This suggests that anti-cancer drugs doses should not be based on total body weight.
Most of anti-cancer drugs are prescribed based on body surface area and not body weight. Since the weight has little impact on body surface area, it has much less impact on drug doses calculated according to body surface area. Furthermore, these drugs are intended to be toxic, but they must be tolerable by the patient, so doses must above all be adapted to the toxicities and comorbidities of the patient, especially concerning elimination. However for some cytotoxic drugs used for hematopoietic stem cell transplants conditioning, which dosage is weight-based, a dose adjustment is required in obese patient and can lead to significant concessions.
Since the beginning of the year 2022, we intervened on 6 prescriptions of obese patients: 3 busulfan prescriptions with dose reductions of 20%, 27% and 43%, 1 thiotepa prescription with 20% of reduction, 2 cyclophosphamide prescriptions with dose reductions of 16% and 25 %.

Discussion-Conclusion
Following several cases of obese patients, this work has made it possible to consider obese patients as a population at risk in oncology departments in the same way as elderly patients or patients with renal or hepatic impairment. Now the hematology department contacts us when they have to initiate a chemotherapy protocol in an obese subject to first assess the pharmacokinetic risk and the necessary adaptations.

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