Diversity of dose-individualization and therapeutic drug monitoring practices of platinum compounds: a review.

ABSTRACT

Introduction: Platinum-derived drugs are commonly used for the treatment of solid tumors. The differences in chemical structures of these molecules lead to different pharmacological properties, in terms of indication, efficacy, and toxicity. Their pharmacokinetics (PK) differ according to their respective renal elimination and have led to many studies investigating their dose optimization. Area covered This review attempts to summarize and compare PK and pharmacodynamics of cisplatin, carboplatin, and oxaliplatin, with an emphasis on differences of dose calculations and opportunities for therapeutic drug monitoring (TDM) in various patient populations. Expert opinion Although cisplatin and carboplatin can be considered as analogs since they share the same DNA interacting properties, the slower hydrolysis of the latter results in a better safety profile. Carboplatin is the only drug in oncology to be administrated according to a target area under the curve of concentration versus time, considering that its PK variability is almost fully explained by renal function, not by body size. This enables individual dosing based on predicted carboplatin clearance (along with patients renal characteristics) or on actual clearance with TDM, especially in a high-dose protocol.