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Titolo:
Influence of the interval between the administration of doxorubicin and paclitaxel on the pharmacokinetics of these drugs in patients with locally advanced breast cancer
Autore:
Moreira, A; Lobato, R; Morais, J; Silva, S; Ribeiro, J; Figueira, A; Vale, D; Sousa, C; Araujo, F; Fernandes, A; Oliveira, J; Passos-Coelho, JL;
Indirizzi:
Inst Portugues Oncol Francisco Gentil, Dept Med Oncol, P-1093 Lisbon, Portugal Inst Portugues Oncol Francisco Gentil Lisbon Portugal P-1093 n, Portugal Fac Farm, Lisbon, Portugal Fac Farm Lisbon PortugalFac Farm, Lisbon, Portugal
Titolo Testata:
CANCER CHEMOTHERAPY AND PHARMACOLOGY
fascicolo: 4, volume: 48, anno: 2001,
pagine: 333 - 337
SICI:
0344-5704(200110)48:4<333:IOTIBT>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
BOLUS DOXORUBICIN; CREMOPHOR EL; PHASE-I; MICE;
Keywords:
breast cancer; cardiac toxicity; doxorubicin; paclitaxel; pharmacokinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
12
Recensione:
Indirizzi per estratti:
Indirizzo: Moreira, A Inst Portugues Oncol Francisco Gentil, Dept Med Oncol, Rua ProfLima Basto, P-1093 Lisbon, Portugal Inst Portugues Oncol Francisco Gentil Rua Prof Lima Basto Lisbon Portugal P-1093
Citazione:
A. Moreira et al., "Influence of the interval between the administration of doxorubicin and paclitaxel on the pharmacokinetics of these drugs in patients with locally advanced breast cancer", CANC CHEMOT, 48(4), 2001, pp. 333-337

Abstract

Purpose: The combination of bolus doxorubicin followed by a 3-h infusion of paclitaxel has high antitumor activity in patients with metastatic breastcancer, but is limited by unexpected cardiac toxicity. In contrast, the administration of the two drugs 16 li apart has similar antitumor activity but less cardiac toxicity. The purpose of this study was to compare the pharmacokinetics of these drugs when doxorubicin administration preceded paclitaxel by 30 min or by 24 h. Patients and methods: Women with locally advanced2 breast cancer were treated with doxorubicin (60 mg/m(2) i.v. bolus) followed 24 h later by paclitaxel (200 mg/m(2) i.v. over 3 h) for six cycles (four before and two after surgery). In one of the first two cycles doxorubicin preceded paclitaxel by 30 min instead of 24 h, with plasma sampling for pharmacokinetic analysis up to 48 h. Determination of drug levels in plasmawas done by HPLC. Results: A total of 28 patients were included. No clinical cardiac toxicity was observed but five patients discontinued doxorubicin-paclitaxel treatment after four cycles because of a decrease in LVEF of atleast 15% from baseline or to less than 50%. While paclitaxel pharmacokinetics were not changed, there was a 30% and an 80% increase in the AUC(0-24h) for doxorubicin and doxorubicinol., respectively, when the drugs were administered 30 min instead of 24 h apart. Even when paclitaxel was given 24 It after doxorubicin, there was a rebound 24% increase in the plasma concentration of doxorubicinol. Conclusions: Paclitaxel interferes with the pharmacokinetics of doxorubicin leading to higher systemic exposure to both doxorubicin and doxorubicinol, which is more evident when the plasma concentration or the anthracyclines is higher. This interference may explain the higher incidence of cardiac toxicity observed when the two drugs are administered within a short interval.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 29/01/20 alle ore 19:09:18