Fixed Dosing of Monoclonal Antibodies in Oncology
Open Access
- 28 July 2017
- journal article
- review article
- Published by Oxford University Press (OUP) in The Oncologist
- Vol. 22 (10), 1212-1221
- https://doi.org/10.1634/theoncologist.2017-0167
Abstract
Most monoclonal antibodies in oncology are administered in body–size-based dosing schedules. This is believed to correct for variability in both drug distribution and elimination between patients. However, monoclonal antibodies typically distribute to the blood plasma and extracellular fluids only, which increase less than proportionally with the increase in body weight. Elimination takes place via proteolytic catabolism, a nonspecific immunoglobulin G elimination pathway, and intracellular degradation after binding to the target. The latter is the primary route of elimination and is related to target expression levels rather than body size. Taken together, the minor effects of body size on distribution and elimination of monoclonal antibodies and their usually wide therapeutic window do not support body–size-based dosing. We evaluated effects of body weight on volume of distribution and clearance of monoclonal antibodies in oncology and show that a fixed dose for most of these drugs is justified based on pharmacokinetics. A survey of the savings after fixed dosing of monoclonal antibodies at our hospital showed that fixed dosing can reduce costs of health care, especially when pooling of preparations is not possible (which is often the case in smaller hospitals). In conclusion, based on pharmacokinetic parameters of monoclonal antibodies, there is a rationale for fixed dosing of these drugs in oncology. Therefore, we believe that fixed dosing is justified and can improve efficiency of the compounding. Moreover, drug spillage can be reduced and medication errors may become less likely.Keywords
This publication has 48 references indexed in Scilit:
- Subcutaneous trastuzumab: development of a new formulation for treatment of HER2-positive early breast cancerOncoTargets and Therapy, 2013
- Dose banding as an alternative to body surface area-based dosing of chemotherapeutic agentsBritish Journal of Cancer, 2012
- The Relationship between Drug Clearance and Body SizeClinical Pharmacokinetics, 2012
- A Guide to Rational Dosing of Monoclonal AntibodiesClinical Pharmacokinetics, 2012
- Clinical Pharmacokinetics of Therapeutic Monoclonal AntibodiesClinical Pharmacokinetics, 2010
- Effect of Obesity on the Pharmacokinetics of Drugs in HumansClinical Pharmacokinetics, 2010
- Phase I/II Study of Ipilimumab for Patients With Metastatic MelanomaJournal of Clinical Oncology, 2008
- Flat-Fixed Dosing Versus Body Surface Area–Based Dosing of Anticancer Drugs in Adults: Does It Make a Difference?The Oncologist, 2007
- Effect of Target Dynamics on Pharmacokinetics of a Novel Therapeutic Antibody against the Epidermal Growth Factor Receptor: Implications for the Mechanisms of ActionCancer Research, 2006
- Dosage Adjustments for Antibacterials in Obese PatientsClinical Pharmacokinetics, 2000