Cardiotoxic effects of anthracycline-taxane combinations.
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.
Perotti
Antonella
A
Division of Medical Oncology, Istituto Nazionale per lo Studio e la Cura dei Tumouri, 20133 Milan, Italy.
Cresta
Sara
S
Grasselli
Giacomo
G
Capri
Giuseppe
G
Minotti
Giorgio
G
Gianni
Luca
L
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
D018943:Anthracyclines; D001952:Bridged-Ring Compounds; D043823:Taxoids; C080625:taxane; D004317:Doxorubicin; D017239:Paclitaxel