Dose optimization of anthracyclines.
Despite the fact that anthracyclines are one of the most commonly used and active classes of anticancer agents and that their pharmacokinetic behavior has been extensively studied, optimal anthracycline dosage regimens have not yet been defined. Only a few pharmacokinetic-pharmacodynamic (toxicity and response) relationships have been determined so far for anthracyclines and are here reviewed. The use of prolonged continuous infusion and fractionated schedules reduces doxorubicin cardiotoxicity but no sufficient data are available to date to demonstrate if those schedules result in equivalent antitumor efficacy to that achieved by IV bolus. Not enough data are available to conclude which is the best pharmacokinetic parameter to use in order to predict anthracycline-induced myelosuppression, other toxicities and/or clinical tumor response. Dosing adjustments of anthracyclines in the presence of liver dysfunction are still based on empirical guidelines instead of a more rational basis. Much work still remains to be done if we are to improve our knowledge of anthracyclines' pharmacodynamics. Limited sampling strategies will be of great help in the establishment of pharmacokinetic-pharmacodynamic relationships, which is essential to optimize the dosage regimen of anthracyclines in order to maximize their efficacy and/or minimize their toxicity in individual patients.
de Valeriola
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Institut Jules Bordet, Unité d'Oncopharmacologie, Brussels, Belgium.
D000903:Antibiotics, Antineoplastic / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006801:Humans; D008657:Metabolic Clearance Rate
D000903:Antibiotics, Antineoplastic