Phase I clinical and pharmacokinetic trial of flavone acetic acid
| Autor: | John G. Kuhn, Daniel D. Von Hoff, G. S. Harman, David H. Boldt, J. B. Craig, Gary N. Clark, A. Kathleen Havlin, Geoffrey R. Weiss, Rowena Schwartz, Jim M. Koeller |
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| Rok vydání: | 1991 |
| Předmět: |
Drug
Adult Antigens Differentiation T-Lymphocyte Male Cancer Research medicine.medical_specialty medicine.medical_treatment media_common.quotation_subject Antineoplastic Agents Urine Receptors Fc Pharmacology Pharmacokinetics Neoplasms medicine Humans media_common Aged Flavonoids Chemotherapy Flavone acetic acid business.industry Receptors IgG Middle Aged Antigens Differentiation CD56 Antigen Surgery Oncology Mechanism of action Drug Evaluation Female medicine.symptom Mitoflaxone business Benzopyrone |
| Zdroj: | Journal of the National Cancer Institute. 83(2) |
| ISSN: | 0027-8874 |
| Popis: | Flavone acetic acid is a synthetic benzopyrone derivative with an unknown mechanism of action. Thirty-eight patients (30 men and 8 women) were treated once a week for 4 weeks every 5 weeks with doses of flavone acetic acid ranging from 0.33 to 12.5 g/m2. At doses less than or equal to 3.9 g/m2, the drug was administered intravenously over 1 hour; at doses greater than or equal to 5.28 g/m2, the infusion period was lengthened to 6 hours. Treatment of all patients included hydration before and after treatment and alkalization to maintain urine pH at greater than or equal to 6.5. A dose-limiting toxic effect was hypotension at 10 g/m2. Pharmacokinetic studies revealed linear behavior in the eight patients studied, beginning at 3.9 g/m2. Peak plasma levels ranged from 125 to 630 micrograms/mL, with a mean terminal half-life of 22.4 hours. Immunologic monitoring was performed in three patients at 10 g/m2. A transient increase in CD16- and/or Leu-19-positive cells was noted in all three patients. In one patient, this increase correlated with a 10-fold increase in K562 cell killing. There were no objective tumor responses seen in this trial. The recommended phase II dose on this schedule is 8 g/m2. Further studies to elucidate the drug's mechanism of action and to define its immunologic properties are recommended. |
| Databáze: | OpenAIRE |
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