Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations
Autore:
Boland, I; Vassal, G; Morizet, J; Terrier-Lacombe, MJ; Valteau-Couanet, D; Kalifa, C; Hartmann, O; Gouyette, A;
Indirizzi:
Inst805stave Roussy, CNRS URA147, Lab Pharmacotoxicol & Pharmacogenet, F-94 Inst Gustave Roussy Villejuif France F-94805 xicol & Pharmacogenet, F-94 Inst Gustave Roussy, Dept Pediat Oncol, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France Inst Gustave Roussy, Dept Anatomopathol, F-94805 Villejuif, France Inst Gustave Roussy Villejuif France F-94805 , F-94805 Villejuif, France
Titolo Testata:
BRITISH JOURNAL OF CANCER
fascicolo: 5-6, volume: 79, anno: 1999,
pagine: 787 - 792
SICI:
0007-0920(199902)79:5-6<787:BIAANA>2.0.ZU;2-L
Fonte:
ISI
Lingua:
ENG
Soggetto:
HIGH-DOSE BUSULFAN; BONE-MARROW TRANSPLANTATION; HUMAN-TUMOR XENOGRAFTS; THERAPEUTIC ACTIVITY; PHASE-II; CHILDREN; CYCLOPHOSPHAMIDE; STABILITY; MYLERAN; CPT-11;
Keywords:
brain tumours; childhood cancer; bone marrow transplantation; pharmacokinetics;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Clinical Medicine
Life Sciences
Citazioni:
31
Recensione:
Indirizzi per estratti:
Indirizzo: Vassal, G Instueustave Roussy, CNRS URA147, Lab Pharmacotoxicol & Pharmacogenet, 39 R Inst Gustave Roussy 39 Rue C Desmoulins Villejuif France F-94805
Citazione:
I. Boland et al., "Busulphan is active against neuroblastoma and medulloblastoma xenografts in athymic mice at clinically achievable plasma drug concentrations", BR J CANC, 79(5-6), 1999, pp. 787-792

Abstract

High-dose busulphan-containing chemotherapy regimens have shown high response rates in children with relapsed or refractory neuroblastoma, Ewing's sarcoma and medulloblastoma. However, the anti-tumour activity of busulfan asa single agent remains to be defined, and this was evaluated in athymic mice bearing advanced stage subcutaneous paediatric solid tumour xenografts. Because busulphan is highly insoluble in water, the use of several Vehiclesfor enteral and parenteral administration was first investigated in terms of pharmacokinetics and toxicity. The highest bioavailability was obtained with busulphan in DMSO administered i.p. When busulphan was suspended in carboxymethylcellulose and given orally or i.p., the bioavailability was poor. Then, in the therapeutic experiments, busulphan in DMSO was administered i.p. on days 0 and 4. At the maximum tolerated total dose (50 mg kg(-1)), busulphan induced a significant tumour growth delay, ranging from 12 to 34 days in the three neuroblastomas evaluated and in one out of three medulloblastomas. At a dose level above the maximum tolerated dose, busulphan induced complete and partial tumour regressions. Busulphan was inactive in a peripheral primitive neuroectodermal tumour (PNET) xenograft. When busulphan pharmacokinetics in mice and humans were considered, the estimated systemic exposure at the therapeutically active dose in mice (113 mu g h ml(-1)) was close to the mean total systemic exposure in children receiving high-dose busulphan (102.4 mu g h ml(-1)). In conclusion, busulphan displayed a significant anti-tumour activity in neuroblastoma and medulloblastoma xenografts at plasma drug concentrations which can be achieved clinically in children receiving high-dose busulphan-containing regimens.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/11/20 alle ore 04:04:01