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Calvert's formula for dosing carboplatin: overview and concerns of applicability in high-dose setting.

The uniqueness of carboplatin as a chemotherapy drug is in the fact that the systemic drug exposure produced by any dose in a patient can be reasonably estimated on the basis of his or her renal function. Calvert’s formula (1) of delivering a calculated dose in terms of target carboplatin area under the time– concentration curve (AUC) and a measured or estimated glomerular filtration rate (GFR) has been widely used. Here, we describe the derivation of Calvert’s formula and point out some limitations in its development, including violation of an underlying assumption of linear regression theory. We also discuss the related published literature and recommend practicing caution in its use for a high-dose setting. Calvert et al. (1) derived the dosage formula in three stages. Analysis at stage I involved a retrospective look at data from pharmacokinetic studies and produced a preliminary dosing relationship as