CARBOPLATIN DOSAGE FORMULAS CAN GENERATE INACCURATE PREDICTIONS OF CARBOPLATIN EXPOSURE IN CARBOPLATIN PACLITAXEL COMBINATION REGIMENS/

Carboplatin is a frequently used antitumour agent recommended to be ad ministered according to the Calvert formula: dose = AUC x (GFR+25), wh ere GFR is the glomerular filtration rate as measured by Cr-51-EDTA cl earance and AUC is the targeted area under the carboplatin concentrati on versus time curve. In several modified Calvert formulae, the GFR is estimated on the basis of serum creatinine levels. We compared AUCs o f carboplatin that were predicted by modified Calvert formulae with ac tual measured AUCs in 75 courses in patients with non-small cell lung cancer or ovarian cancer who were treated with the combination of carb oplatin-paclitaxel. Predictions were made using two modified Calvert f ormulae, in which the GFR was calculated by serum creatinine level-bas ed equations, according to Jelliffe (Eq. 1) and Cockroft-Gault (Eq. 2) . We also studied the performance of a formula for the clearance of ca rboplatin, as proposed by Chatelut (Eq. 3). The actual measured mean A UC was 4.6 mg/ml.min (range 1.9 to 10.4 mg/ml min, SD 1.7). Equation 1 overestimated the AUC by 32.9% with an imprecision of 43.0%, and equa tion 2 overestimated the AUC by 27.6% with an imprecision of 33.4%. Fo r equation 3, an AUC overestimation of only 10.2%, but with an impreci sion of 25.3%, was observed. In conclusion, all three equations overes timated the carboplatin AUCs and had poor precisions. We concluded tha t the real carboplatin AUCs were lower than calculated, using the thre e tested formulae. This may have important consequences for ongoing an d future phase II and III studies with carboplatin-paclitaxel combinat ions, utilising these formulae to calculate the carboplatin dose. Thus far, the original Calvert dosage formula remains the 'golden standard '.