Flat-fixed dosing versus body surface area based dosing of anticancer drugs: there is a difference.

In a recent review, Mathijssen et al. [1] proposed using flatfixed dosing regimens rather than body surface area (BSA)based dosing for anticancer drugs because “it does not seem worse than using BSA-based dosing” with regard to pharmacokinetic variability. We feel that this statement, together with other recent publications arguing against BSAbased dosing, requires a counterpart. Most cytotoxic drugs have a narrow therapeutic range and are often administered at a dose close to the maximumtolerated dose (MTD) because of the fact that, for many solid tumors and leukemia, increasing systemic exposure often results in higher response rates. In contrast, molecularly targeted cytostatic drugs, like tyrosine kinase inhibitors, should have a greater therapeutic range and an optimal effective dose that can be much lower than the MTD [2]. For classic cytotoxic drugs, every patient should experience the same high systemic exposure close to, but clearly below, the MTD. Systemic exposure can be quantified as the area under the curve (AUC) of the plasma concentration versus time curve. The AUC is determined by the administered dose and the individual clearance of a drug according to the formula: