title: Cardiotoxic effects of anthracycline-taxane combinations.
abstract: The association of doxorubicin (DOX) and paclitaxel (PTX) is very active in breast cancer. Unfortunately, PTX may potentiate the cardiotoxic effects of anthracyclines: it causes nonlinear disposition of DOX and its metabolites, leading to persistant of elevated plasma concentrations of the anthracyclines. However, this pharmacokinetic interference is not sufficient to explain the enhanced cardiotoxicity of the combination. Recent data suggest that PTX stimulates the conversion of DOX to cardiotoxic metabolites (namely doxorubicinol) inside cardiomyocytes. Docetaxel (DTX) does not have a major influence on DOX plasma concentration because it does not interfere with its elimination. Clinical data suggest that DTX may not enhance anthracycline cardiotoxicity, but patients seldom received a total anthracycline dose compatible with increased risk. Furthermore, there are experimental data indicating that DTX can also stimulate the metabolism of DOX to toxic species in human heart.
authors.affiliation: Division of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumouri, 20133 Milan, Italy.
authors.forename: Antonella
authors.initials: A
authors.lastname: Perotti
authors.forename: Sara
authors.initials: S
authors.lastname: Cresta
authors.forename: Giacomo
authors.initials: G
authors.lastname: Grasselli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Capri
authors.forename: Giorgio
authors.initials: G
authors.lastname: Minotti
authors.forename: Luca
authors.initials: L
authors.lastname: Gianni
mesh_terms: D018943:Anthracyclines / Q000009:adverse effects* / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000009:adverse effects*; D001943:Breast Neoplasms / Q000150:complications / Q000188:drug therapy; D001952:Bridged-Ring Compounds / Q000009:adverse effects*; D002986:Clinical Trials as Topic; D004305:Dose-Response Relationship, Drug; D004317:Doxorubicin; D004334:Drug Administration Schedule; D005260:Female; D006331:Heart Diseases / Q000139:chemically induced*; D006801:Humans; D017239:Paclitaxel / Q000009:adverse effects / Q000627:therapeutic use; D012306:Risk; D043823:Taxoids
chemical_list: D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D004317:Doxorubicin; D017239:Paclitaxel