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Role of body-surface area in Cisplatin pharmacokinetics

Li Liu, MD

University of Pennsylvania Cancer
Last Modified: May 12, 2001

Presenter: F. de Jongh
Affiliation: Rotterdam Cancer Institute, Rotterdam, Netherlands

Background:

Dosages of anticancer drugs are usually calculated on the basis of a uniform standard, the body surface area (BSA). Although many physiological functions are proportionate to BSA, overall drug clearance is only partially related to this parameter. Consequently, following administration of equivalent drug dosages based on BSA, a wide variability in plasma drug concentrations can be found between patients, as a result of which some patients experience little toxicity while others may show severe toxic symptoms.

Materials and Methods:

-A total of 268 adult patients with advanced solid tumors who were treated with cisplatin based chemotherapy were included in this retrospective study -Cisplatin was given either weekly or every 3 weeks -Pharmocokenitics of cisplatin was studied

Results:

-The relationship between the AUCs of unbound and total cisplatin was linear -The interpatient variability of the plasma clearance of unbound Cisplatin (Clfree) was 25.6%, whereas the BSA variability was 10.4% -There was no strong correlation between Clfree and BSA

Authors' Conclusions

-There appeared to be a high interpatient variability relative to variation in observed BSA -BSA-based dosing of Cisplatin may not be necessary

Clinical/Scientific Implications:

-Since a high proportion of the patients received combination therapy with other chemotherapy agents, this study should be interpreted with caution -A clear pharmacokinetic/pharmacodynamic correlation has been demonstrated for some anticancer drugs, and this relationship provides a background against which rational dose optimisation should be implemented for individual patients