Document Detail

Influence of alternate sequences of epirubicin and docetaxel on the pharmacokinetic behaviour of both drugs in advanced breast cancer.
MedLine Citation:
PMID:  11886006     Owner:  NLM     Status:  MEDLINE    
BACKGROUND: Previously we observed a pharmacokinetic interference of epirubicin elimination when paclitaxel is given in combination in a sequence-dependent manner (i.e. when paclitaxel is administered as first drug). The aim of this study was to determine whether these sequence-dependent pharmacological effects were also evident when epirubicin was combined with docetaxel.
PATIENTS AND METHODS: Patients who received epirubicin 75 mg/m2 or 90 mg/m2 as an intravenous bolus followed immediately by docetaxel 70 mg/m2 or 80 mg/m2 over a 1-h infusion, or the opposite sequence, every 3 weeks were eligible for this study. The pharmacokinetics of docetaxel, epirubicin and its metabolites were studied at the first and second cycle of treatment. Pharmacokinetic data were normalised to the lower dose of each drug. Toxicity was recorded at nadir and graded according to National Cancer Institute Common Toxicity Criteria.
RESULTS: Twelve consecutive patients, each acting as their own control, entered the study. The sequence of drug administration of docetaxel and epirubicin did not affect the pharmacokinetics of the parent anthracycline. Statistically significant lower glucuronidation metabolism of epirubicin was observed in patients who received docetaxel before epirubicin. The pharmacokinetics of docetaxel were not influenced by the sequence of drug administration. No difference in haematological and non-haematological toxicity was observed in the two sequences of treatment.
CONCLUSIONS: The pharmacokinetics of the parent anthracycline and of docetaxel were similar between the two schemes of treatment. The metabolic variations observed, i.e. differences in the plasma levels of epirubicin glucuronides, seem not to have clinical relevance.
G Lunardi; M Venturini; M O Vannozzi; G Tolino; Mastro L Del; C Bighin; G Schettini; M Esposito
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Annals of oncology : official journal of the European Society for Medical Oncology / ESMO     Volume:  13     ISSN:  0923-7534     ISO Abbreviation:  Ann. Oncol.     Publication Date:  2002 Feb 
Date Detail:
Created Date:  2002-03-11     Completed Date:  2002-08-22     Revised Date:  2013-05-28    
Medline Journal Info:
Nlm Unique ID:  9007735     Medline TA:  Ann Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  280-5     Citation Subset:  IM    
Servizio di Farmacologia e Neuroscienze, Istituto Nazionale per la Ricerca sul Cancro, Genoa, Italy.
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MeSH Terms
Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
Breast Neoplasms / drug therapy*
Epirubicin / administration & dosage*,  adverse effects,  pharmacokinetics
Paclitaxel / administration & dosage*,  adverse effects,  analogs & derivatives*,  pharmacokinetics
Reg. No./Substance:
0/Taxoids; 15H5577CQD/docetaxel; 33069-62-4/Paclitaxel; 56420-45-2/Epirubicin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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