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Body-surface area-based dosing does not increase accuracy of predicting cisplatin exposure
F E de Jongh1, J Verweij, W J Loos
1Department of Medical Oncology, Rotterdam Cancer Institute (Daniel den Hoed Kliniek), Rotterdam, The Netherlands.
Summary
Body-surface area (BSA) dosing for anticancer drugs like cisplatin shows high interpatient variability. This study found no rationale for BSA-based cisplatin dosing, recommending fixed-dosing regimens instead for improved cancer treatment.
Area of Science:
- Pharmacology
- Oncology
- Clinical Trials
Background:
- Anticancer drug dosing commonly relies on body-surface area (BSA) to minimize interindividual variability.
- Cisplatin is a widely used chemotherapeutic agent, and its dosing strategy requires careful consideration.
Purpose of the Study:
- To evaluate the relevance of body-surface area (BSA) for cisplatin dosing.
- To analyze cisplatin pharmacokinetics in a large patient population to assess interindividual variability.
Main Methods:
- Pharmacokinetic data from 268 adult patients with advanced solid tumors were analyzed.
- Cisplatin was administered as monotherapy or in combination with other agents.
- Plasma concentrations of unbound and total cisplatin were measured using atomic absorption spectrometry.
Main Results:
- No pharmacokinetic interactions were observed between cisplatin and combination chemotherapy agents.
- Interpatient variability in unbound cisplatin clearance (CL(free)) was 25.6%, while BSA variability was 10.4%.
- Correcting CL(free) for BSA did not significantly reduce interindividual variability, with a weak correlation (r=0.42) between CL(free) and BSA.
Conclusions:
- The high interpatient variability in unbound cisplatin clearance relative to BSA variation provides no rationale for continuing BSA-based dosing.
- Fixed-dosing regimens for cisplatin are recommended based on these pharmacokinetic findings.