The objectives of this study were to investigate the disposition of gemcitabine, epirubicin, paclitaxel, 2',2'-difluorodeoxyuridine and epirubicinol, and characterize the pharmacokinetic and pharmacodynamic profile of treatment in patients with breast cancer. PATIENTS AND METHODS: The drug dispostion in 15 patients who received gemcitabine 1000 mg/m2, epirubicin 90 mg/m2 and paclitaxel 175 mg/m2 (GEP) on day 1 of a 21-day cycle, was compared with that of patients treated with epirubicin 90 mg/m2 and paclitaxel 175 mg/m2 (EP, n = 6) and epirubicin 90 mg/m2 alone (n = 6). Drug and metabolite levels in plasma and urine were assessed by high-performance liquid chromatography and parameters of drug exposure were related to hematological toxicity by a sigmoid-maximum effect (Emax) model. RESULTS: Paclitaxel administration significantly increased the epirubicinol area under the concentration-time curve, from 357+/-146 (epirubicin) to 603+/-107 (EP) and 640+/-81 h x ng/ml (GEP), and reduced the renal clearance of epirubicin and epirubicinol by 38 and 52.2% and 34.5 and 53% in GEP- and EP-treated patients, respectively, compared with epirubicin alone. Gemcitabine had no apparent effect on paclitaxel and epirubicin pharmacokinetics, and renal clearance of epirubicin and epirubicinol. The only pharmacokinetic/pharmacodynamic relationship observed was between neutropenia and the time spent above the threshold plasma level of 0.1 micromol/l (tC0.1) of paclitaxel, with the time required to obtain a 50% decrease in neutrophil count (Et50) of GEP being 7.8 h, similar to that of EP. CONCLUSIONS: Paclitaxel and/or its vehicle, Cremophor EL, interferes with the disposition and renal excretion of epirubicin and epirubicinol; gemcitabine has no affect on epirubicin and paclitaxel plasma pharmacokinetics and renal excretion of epirubicin, while neutropenia is not enhanced by gemcitabine.
Gemcitabine, epirubicin and paclitaxel: pharmacokinetic and pharmacodynamic interactions in advanced breast cancer / S., Fogli; R., Danesi; A., Gennari; S., Donati; Conte, Pierfranco; M., DEL TACCA. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 13(2002), pp. 919-927.
Data di pubblicazione: | 2002 |
Titolo: | Gemcitabine, epirubicin and paclitaxel: pharmacokinetic and pharmacodynamic interactions in advanced breast cancer. |
Autore/i: | S., Fogli; R., Danesi; A., Gennari; S., Donati; Conte, Pierfranco; M., DEL TACCA |
Autore/i UNIMORE: | |
Rivista: | |
Volume: | 13 |
Pagina iniziale: | 919 |
Pagina finale: | 927 |
Codice identificativo ISI: | WOS:000176557900021 |
Codice identificativo Scopus: | 2-s2.0-0035990106 |
Codice identificativo Pubmed: | 12123338 |
Citazione: | Gemcitabine, epirubicin and paclitaxel: pharmacokinetic and pharmacodynamic interactions in advanced breast cancer / S., Fogli; R., Danesi; A., Gennari; S., Donati; Conte, Pierfranco; M., DEL TACCA. - In: ANNALS OF ONCOLOGY. - ISSN 0923-7534. - STAMPA. - 13(2002), pp. 919-927. |
Tipologia | Articolo su rivista |
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