Evaluation of body‐surface area based dosing of cisplatin in patients with extreme BSA values
2005
Background
In view of their small therapeutic window, cytotoxic drugs for adults are dosed based on body-surface area (BSA), aiming to reduce interpatient variability in drug exposure. In a retrospective analysis no rationale was found for continuing of BSA-based dosing for cisplatin (CDDP) in the average patient[JCO 19 (2001), 3733]. Here, we studied the usefulness of this dosing strategy in patients at lower and upper extremes of BSA values.
Methods
Patients were randomized to receive a fixed dose of CDDP (based on an average BSA of 1.86m2) in course 1 and a BSA-adjusted dose in course 2 or vice versa. Plasma concentrations of unbound platinum (Pt) were determined and analyzed by noncompartmental analysis.
Results
18 Patients are evaluable so far; 10 large patients (9 M> 2.05m2, 1 F >1.90m2) and 8 small patients (5 M 0.37), however with a large variability in CL. The average CL in large patients was approximately 30% faster than the average CL in small patients. Correction of CL for the BSA in both populations, resulted in a reduction of only 10–13% in the variability.
Conclusion
Unless better predictors for CL are identified, fixed dose regimens per BSA-cluster are recommended.
Clinical Pharmacology & Therapeutics (2005) 77, P37–P37; doi: 10.1016/j.clpt.2004.12.033
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