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Titolo:
BUSULFAN DISPOSITION AND HEPATIC VENOOCCLUSIVE DISEASE IN CHILDREN UNDERGOING BONE-MARROW TRANSPLANTATION
Autore:
VASSAL G; KOSCIELNY S; CHALLINE D; VALTEAUCOUANET D; BOLAND I; DEROUSSENT A; LEMERLE J; GOUYETTE A; HARTMANN O;
Indirizzi:
INST GUSTAVE ROUSSY,DEPT PEDIAT ONCOL,RUE CAMILLE DESMOULINS F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,CNRS,URA 147,PHARMACOTOXICOL & PHARMACOGENET LAB VILLEJUIF FRANCE INST GUSTAVE ROUSSY,DEPT BIOSTAT & EPIDEMIOL VILLEJUIF FRANCE
Titolo Testata:
Cancer chemotherapy and pharmacology
fascicolo: 3, volume: 37, anno: 1996,
pagine: 247 - 253
SICI:
0344-5704(1996)37:3<247:BDAHVD>2.0.ZU;2-Y
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-DOSE BUSULFAN; VENOOCCLUSIVE DISEASE; SOLID TUMORS; PHASE-I; PHARMACOKINETICS; DOSAGE; MELPHALAN; INDUCTION; TOXICITY; REGIMENS;
Keywords:
BUSULFAN; PHARMACODYNAMICS; HEPATIC VENOOCCLUSIVE DISEASE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
G. Vassal et al., "BUSULFAN DISPOSITION AND HEPATIC VENOOCCLUSIVE DISEASE IN CHILDREN UNDERGOING BONE-MARROW TRANSPLANTATION", Cancer chemotherapy and pharmacology, 37(3), 1996, pp. 247-253

Abstract

Hepatic veno-occlusive disease (HVOD) is a frequent life-threatening toxicity in patients undergoing bone marrow transplantation (BMT) after the administration of a high-dose busulfan-containing regimen. Recent studies have shown that the morbidity and mortality of HVOD may be reduced in adults by pharmacologically guided dose adjustment of busulfan. We analyzed the pharmacodynamic relationship between busulfan disposition and HVOD in 61 children (median age, 5.9 years) with malignantdisease. Busulfan, given at a dose ranging from 16 mg/kg to 600 mg/m(2), was combined with one or two other alkylating agents (cyclophosphamide, melphalan, thiotepa). Only 3 patients received the standard busulfan/cyclophosphamide (BUCY) regimen. A total of 24 patients (40%) developed HVOD, which resolved in all cases. A pharmacokinetics study confirmed the previously reported wide interpatient variability in busulfan disposition but did not reveal any significant alteration in children with HVOD. The mean area under the concentration-time curve (AUG) after the first dose of busulfan was higher in patients with HVOD (6,811 +/- 2,943 ng h ml(-1)) than in patients without HVOD (5,760 +/- 1,891 ng h ml(-1); P = 0.10). This difference reflects the higher dose of busulfan given to patients with HVOD. No toxic level could be defined and, moreover, none of the toxic levels identified in adults were relevant. The high incidence of HVOD in children given 600 mg/m(2) busulfan may be linked to the use of more intensive than usual high-dose chemotherapy regimens and/or drug interactions. Before the prospective evaluation of busulfan dose adjustment in children, further studies are required to demonstrate firmly the existence of a pharmacodynamic relationship in terms of toxicity and allogeneic engraftment, especially when busulfan is combined with cyclophosphamide. The maximal tolerated and minimal effective AUCs in children undergoing BMT are likely to depend mainly upon the disease, the nature of the combined high-dose regimen, and the type of bone marrow transplant.

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Documento generato il 25/11/20 alle ore 03:48:22