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Titolo:
PHASE-I AND PHARMACOLOGICAL TRIAL OF FAZARABINE (ARA-AC) WITH GRANULOCYTE COLONY-STIMULATIAG FACTOR
Autore:
GOLDBERG RM; REID JM; AMES MM; SLOAN JA; RUBIN J; ERLICHMAN C; KUFFEL MJ; FITCH TR;
Indirizzi:
MAYO CLIN & MAYO FDN,DIV MED ONCOL,200 1ST ST SW ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DIV DEV ONCOL RES ROCHESTER MN 55905 MAYO CLIN & MAYO FDN,DIV CANC STAT ROCHESTER MN 55905 MAYO CLIN,DIV HEMATOL & ONCOL SCOTTSDALE AZ 85259
Titolo Testata:
Clinical cancer research
fascicolo: 12, volume: 3, anno: 1997,
parte:, 1
pagine: 2363 - 2370
SICI:
1078-0432(1997)3:12<2363:PAPTOF>2.0.ZU;2-N
Fonte:
ISI
Lingua:
ENG
Soggetto:
SOUTHWEST-ONCOLOGY-GROUP; ANTI-TUMOR ACTIVITY; CONTINUOUS-INFUSION; CELL-CARCINOMA; ARABINOSYL-5-AZACYTOSINE; CANCER; 1-BETA-D-ARABINOFURANOSYL-5-AZACYTOSINE; ARABINOFURANOSYL-5-AZACYTOSINE; NSC-281272; LEUKEMIA;
Tipo documento:
Article
Natura:
Periodico
Citazioni:
29
Recensione:
Indirizzi per estratti:
Citazione:
R.M. Goldberg et al., "PHASE-I AND PHARMACOLOGICAL TRIAL OF FAZARABINE (ARA-AC) WITH GRANULOCYTE COLONY-STIMULATIAG FACTOR", Clinical cancer research, 3(12), 1997, pp. 2363-2370

Abstract

Fazarabine (1-beta-D-arabinofuranosyl-5-aza-cytosine, or Ara-AC) is anucleoside analogue that consists of the arabinoside ring of 1-beta-D-arabinofuranosylcytosine and the pyrimidine base of 5-azacytidine, InPhase I and Phase II trials, neutropenia was dose limiting, with minimal nonhematological toxicity, The in vitro cytotoxic concentrations of Ara-AC could not be achieved in these studies; neutropenia precludeddose escalation, The objectives of this study were: to determine either the maximum tolerated dose of Ara-AC or to safely achieve target plasma levels of 2-5 mu g/ml when Ara-AC was administered as a 24-h infusion with granulocyte colony-stimulating factor (G-CSF) to patients with advanced refractory malignancies; to characterize the pharmacokinetic behavior of Ara-AC with G-CSF; and to define the relationship of Ara-AC pharmacokinetics to toxicity, Twenty-four patients received 67 courses of Ara-AC at doses of 54-112 mg/m(2)/h, Dose-limiting toxicity was approached but not reached, Grade 3 or 4 neutropenia and nausea were the principle side effects, Steady-state plasma concentrations exceeded the minimum target concentration of 2 mu g/ml in all patients who received greater than or equal to 78 mg/m(2)/h for 24 h, The maximum target concentration was approached during administration of 112 mg/m(2)/h for 24 h, The mean steady-state clearance was 475 +/- 103 ml/min/m(2) and did not change with dose, One partial response was seen. One patient received 16 courses and another received 7 courses of therapy before progression. Ara-AC can be safely administered in doses that result in plasma concentrations of 2-5 mu g/ml, if it is given with G-CSF, Phase II trials of Ara-AC in selected malignancies are planned.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 16:47:11