Houy N, and Le Grand F from the University of Lyon, Lyon, France; the CNRS, GATE Lyon Saint-Etienne, France and the emlyon business school, Écully, France and ETH Zurich, Zurich, Switzerland have published in the Journal of Theoretical Biology a research article entilted : Administration of temozolomide: comparison of conventional and metronomic chemotherapy regimens.

In this article they report an innovative methodology for characterizing optimal chemotherapy regimens and used it to compare the Maximum Tolerated Dose (MTD) and Metronomic Chemotherapy (MC) protocols for temozolomide administration.

They used a PK/PD model based on Faivre and coauthors (Faivre et al., 2013) for the pharmacokinetics of temozolomide, as well as the pharmacodynamics of its efficacy and combined it for toxicity, (measured by the nadir of the normalized absolute neutrophil count) with the physiological model of Panetta and coauthors (Panetta et al., 2003) for myelosuppresion. They introduce a multi-criteria tool for comparing protocols regarding efficacy and toxicity.

RESULTS : they show that the toxicity of the MC regimen proposed by Faivre and coauthors (Faivre et al., 2013) can greatly be reduced without affecting its efficacy, while the standard MTD protocol efficacy cannot be improved without impairing its toxicity. We also show that for any acceptable toxicity level, the optimal protocol remains closely related to standard MTD.

CONCLUSIONS: Overall, this new method enables a rich comparison between protocols along multiple dimensions. We can rank protocols for temozolomide administration. It is a first step toward building optimal individual protocols.