Fixed Dosing of Monoclonal Antibodies in Oncology
Open accessAbstract
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.
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Population pharmacokinetic modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of monoclonal antibodies could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment.
“Furthermore, population pharmacokinetic (PopPK) modeling using data from clinical trials of various biotherapeutics has confirmed that fixed dosing of mAbs could be feasible for the majority of molecules assessed, without impairing the safety and efficacy of the treatment [20–23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [23]
mAbs typically distribute within the blood plasma and extracellular fluids only, which increase less than proportionally with an increase in bodyweight.
“Moreover, as described by Hendrikx et al. [23], mAbs typically distribute within the blood plasma and extracellular fluids only, which increase less than proportionally with an increase in bodyweight.”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [23]
Traditionally, mAb treatments in oncology were developed for intravenous infusion based on a bodyweight- or body surface area-adjusted dosing regimen that aimed to correct potential interpatient variability and drug distribution and elimination issues.
“Traditionally, mAb treatments in oncology were developed for intravenous infusion based on a bodyweight- or body surface area-adjusted dosing regimen that aimed to correct potential interpatient variability and drug distribution and elimination issues [23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [23]
There is evidence that fixed dosing of mAbs could generally be justified without impairing the safety and efficacy of the treatment.
“Today, based on emerging knowledge about the pharmacokinetics of mAbs, considerable pharmacokinetic/pharmacodynamic data from clinical studies, and extensive PopPK modeling, there is evidence that fixed dosing of mAbs could generally be justified without impairing the safety and efficacy of the treatment [20, 23].”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [23]
Depending on the mAb, intracellular degradation after binding to the target can be the primary route of elimination and is not affected by body size.
“Depending on the mAb, intracellular degradation after binding to the target can be the primary route of elimination and is not affected by body size.”
From Subcutaneous Administration of Biotherapeutics: An Overview of Current Challenges and Opportunities (2018) · cites this paper as [23]
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References 47 · Cited by 168
- Authors
- Hendrikx, J. J. M. A., Haanen, J. B. A. G., Voest, E. E., Schellens, J. H. M., Huitema, A. D. R., & Beijnen, J. H.
- Affiliations
- Slotervaartziekenhuis (NL)
- The Netherlands Cancer Institute (NL)
- Utrecht University (NL)
- Corresponding author
- Hendrikx, Jeroen J.M.A.
- ORCID
- Venue
- The Oncologist
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-07-28
- Volume
- 22
- Issue
- 10
- Pages
- 1212-1221
- ISSN
- 1083-7159 (ISSN-L)
- 1549-490X
- PMC
- PMC5634778
- OpenAlex
- W2741564119
- Cited by
- 168
- References
- 47
- Citations by year
- 2026: 8 · 2025: 23 · 2024: 18 · 2023: 23 · 2022: 24 · 2021: 23 · 2020: 27 · 2019: 15 · 2018: 6 · 2017: 1
- FWCI
- 2.02
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- The Oncologist (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- Utrecht University Repository (Utrecht University) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Monoclonal and Polyclonal Antibodies Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmaceutical studies and practices
- Life Sciences › Immunology and Microbiology › Immunology › Biosimilars and Bioanalytical Methods
- Keywords
- monoclonal antibodies, fixed dosing, weight-based dosing, pharmacokinetics, volume of distribution, clearance, target expression, interpatient variability, compounding, drug cost savings, medication errors
- MeSH terms
- Antibodies, Monoclonal, Dose-Response Relationship, Drug, Humans
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