Antineoplastic dosing in overweight and obese cancer patients: an Associazione Italiana Oncologia Medica (AIOM)/Associazione Medici Diabetologi (AMD)/Società Italiana Endocrinologia (SIE)/Società Italiana Farmacologia (SIF) multidisciplinary consensus position paper

Abstract

Most anticancer molecules are administered in body-size-based dosing schedules, bringing up unsolved issues regarding pharmacokinetic data in heavy patients. The worldwide spread of obesity has not been matched by improved methods and strategies for tailored drug dosage in this population. The weight or body surface area (BSA)-based approaches may fail to fully reflect the complexity of the anthropometric features besides obesity in cancer patients suffering from sarcopenia. Likewise, there is a lack of pharmacokinetic data on obese patients for the majority of chemotherapeutic agents as well as for new target drugs and immunotherapy. Therefore, although the available findings point to the role of dose intensity in cancer treatment, and support full weight-based dosing, empirical dose capping often occurs in clinical practice in order to avoid toxicity. Thus a panel of experts of the Associazione Italiana Oncologia Medica (AIOM), Associazione Medici Diabetologi (AMD), Società Italiana Endocrinologia (SIE), and Società Italiana Farmacologia (SIF), provides here a consensus statement for appropriate cytotoxic chemotherapy and new biological cancer drug dosing in obese patients.

Keywords: BSA; cancer drug dosing; chemotherapy dose; obesity; pharmacokinetic parameters.

Figure 1

Summary of the most common weight and size descriptors and their limits. Drug dose administration usually follows one of the three illustrated approaches: weight-based dosing, body-surface-area-based dosing, or fixed dosing. The first two strategies assume that drug PK parameters increase in proportion to increasing body size, whereas dosing drugs on a fixed basis presumes that body size does not influence drug PK parameters. Although commonly used to scale drug therapy in overweight or obese patients, each of these descriptors has important limitations. BMI and BSA are not informative as regards body composition and do not differentiate fat from lean tissue mass. IBW seems inappropriate as a dosing metric as it predicts the same dose for people of the same height, regardless of weight. LBW requires specialized equipment as it is measured with methods such as dual-energy X-ray absorptiometry, bioelectrical impedance analysis, underwater weighing and skinfold thickness. BW, body-weight.

Figure 2

Graphic summary of the complex changes induced by obesity in all pharmacokinetic (PK) parameters. The dose of each drug is determined by the plasma concentration required to achieve the desired effect. The plasma concentration of each drug following administration is dependent on its absorption (if not administered via the intravenous route), distribution, metabolism and excretion from the body. The duration of administration will also affect drug plasma concentration. In obese individuals, anthropometric changes in body proportions of water, fat and muscle mass are accompanied by variations in cardiac output, regional blood flow, alterations in liver and renal function and a chronic, low-grade inflammatory state. GFR, glomerular filtration rate.