Phase I and pharmacology study of flavone acetic acid administered two or three times weekly without alkalinization.

Autor:	de Forni, M, Chabot, G G, Armand, J P, Gouyette, A, Klink-Alak, M, Recondo, G
Předmět:	ANTINEOPLASTIC agents BIOTRANSFORMATION (Metabolism) CLINICAL trials COMPARATIVE studies DIARRHEA DRUG administration DOSE-effect relationship in pharmacology CLINICAL drug trials FLAVONOIDS HYPOTENSION INTRAVENOUS therapy RESEARCH methodology MEDICAL cooperation RESEARCH SLEEP stages TIME TUMORS VOMITING EVALUATION research THERAPEUTICS
Zdroj:	Cancer Chemotherapy & Pharmacology; May1995, Vol. 35 Issue 3, p219-224, 6p
Abstrakt:	Flavone acetic acid (FAA, NSC 347512) is a synthetic flavonoid compound with a unique form of preclinical antitumor activity, but its mechanism of action is still not known. In an attempt to exploit the remarkable preclinical activity of this compound in such a way as to allow its use as a clinically useful agent, we performed a phase I and pharmacology study with frequent administration and no hyperhydration or alkalinization. Sixteen patients (9 men, 7 women) were given FAA as 6-h i.v. infusions 2 or 3 times a week (10 and 6 patients, respectively), at doses ranging from 2.5 to 8.1 g/m2. A total of 130 doses were administered during this study. Sedation, arterial hypotension, vomiting and diarrhea were the predominant toxicities observed at the highest dose (8.1 g/m2. One patient developed severe but reversible multiple organ failure. No treatment-related deaths occurred. Pharmacokinetics was linear for the doses studied, with peak plasma levels ranging from 39 to 449 micrograms/ml and a mean terminal half-life of 3.1 h. No drug accumulation was observed with this frequent-administration schedule. No objective response was observed. Three FAA infusions per week at 8.1 g/m2 could be recommended as an optimal and tolerable schedule. [ABSTRACT FROM AUTHOR]
Databáze:	Complementary Index
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