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Titolo:
PHASE-I AND PHARMACOKINETIC STUDY OF BREQUINAR (DUP-785 NSC-368390) IN CANCER-PATIENTS
Autore:
DEFORNI M; CHABOT GG; ARMAND JP; FONTANA X; RECONDO G; DOMENGE C; CARDE P; BARBU M; GOUYETTE A;
Indirizzi:
INST GUSTAVE ROUSSY,UNITE LA GRANGE F-77176 SAVIGNY TEMPLE FRANCE INST GUSTAVE ROUSSY,DEPT ADULT MED F-94805 VILLEJUIF FRANCE INST GUSTAVE ROUSSY,CLIN PHARMACOL LAB,CNRS,URA 147,INSERM,U140 F-94805 VILLEJUIF FRANCE DUPONT PHARMA SA GENEVA SWITZERLAND
Titolo Testata:
European journal of cancer
fascicolo: 7, volume: 29A, anno: 1993,
pagine: 983 - 988
SICI:
0959-8049(1993)29A:7<983:PAPSOB>2.0.ZU;2-K
Fonte:
ISI
Lingua:
ENG
Soggetto:
ACID SODIUM-SALT; 4-QUINOLINECARBOXYLIC ACID; ANTICANCER AGENT; NSC 368390; INHIBITION; BIOSYNTHESIS; SCHEDULE; INVIVO;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
17
Recensione:
Indirizzi per estratti:
Citazione:
M. Deforni et al., "PHASE-I AND PHARMACOKINETIC STUDY OF BREQUINAR (DUP-785 NSC-368390) IN CANCER-PATIENTS", European journal of cancer, 29A(7), 1993, pp. 983-988

Abstract

Brequinar (DUP 785, NSC 368390) is a 4-quinoline carboxylic acid derivative with broad spectrum antitumour activity in experimental models that acts as an antimetabolite by specific inhibition of de novo pyrimidine synthesis. We performed a phase I study of brequinar administered as a 10 min intravenous (i.v.) infusion for 5 consecutive days, every 4 weeks. 67 evaluable patients were entered in this study and a total of 130 courses were administered at doses ranging from 2 to 350 mg/ml. The dose-limiting toxicity was myelosuppression with predominant thromobocytopenia. Myelosuppression was dose-related and non-cumulative,with considerable interpatient variability depending on haematological risk factors. The maximum tolerated dose of brequinar was 210 mg/m2/day in poor risk patients whereas patients with good risk haematological profile tolerated higher doses (up to 350 mg/m2/day). Other non-limiting toxicities included nausea and vomiting, mucositis and skin reactions. Brequinar plasma pharmacokinetic profiles were biphasic with alpha half-life ranging from 0.1 to 0.7 h, and beta half-life ranging from 1.5 to 8.2 h. Increase in brequinar area under the plasma concentration versus time curves (AUC) was nonlinear. Day 5 brequinar pharmacokinetics obtained in 21 patients indicated a significant increase in AUC (47%) and half-life beta (133%) compared to day 1 pharmacokinetics in the same patient. Brequinar plasma AUC and the per cent change in platelet count at nadir were correlated (P < 0.001). Although no objective response was observed in this study, one minor response was noted in cervical lymph nodes of a Hodgkin's disease patient.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 25/11/20 alle ore 14:13:09