The Use of the Calvert Formula to Determine the Optimal Carboplatin Dosage

Carboplatin is a chemotherapeutic agent frequently used in the treatment of various malignancies. The myelotoxicity and clinical efficacy of carboplatin correlate with the clearance of the drug, which is correlated to the glomerular filtration rate (GFR). Dosing of this agent based solely upon the patients body surface area is therefore not accurate enough; the GFR, and thus the clearance of carboplatin differ in each patient irrespective of the body area. Consequently, some patients undergo a higher systemic exposure, expressed as the area under the plasma concentration/time curve (AUC), than others when dosages of carboplatin are given on the basis of the body surface area. A high AUC correlates with increased toxicity, thus increasing the risks of the treatment, but in the case of a low AUC the therapeutical efficacy decreases. This indicates that an individual dosing strategy is warranted to obtain the optimal AUC. In this article, the development and application of a simple equation, known as the Calvert formula, are discussed. This formula can be used to calculate the carboplatin dose accurately in order to obtain a target AUC by using only the GFR. The formula is: dose (mg) = AUC (mg ml-1 min) x [GFR (ml/min) + 25 (ml/min)]. This formula has proven to be, in both retrospective and prospective studies, a reliable tool to calculate the optimal dose of carboplatin Future studies should determine the value of the creatinine clearance as a measure for the GFR.