Evaluation of body-surface area based dosing of cisplatin in patients with extreme BSA values

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 <1.75m2, 3 F <1.60 m2). In the large patients (average BSA 2.25m2) a lower exposure to unbound Pt (P=0.001) was found after fixed dosing compared to BSA-adjusted dosing, while in small patients (average BSA 1.54m2) a higher exposure was found (P=0.024). CL was correlated with BSA (P<0.005, R2>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