Havlin K A, Kuhn J G, Craig J B, Boldt D H, Weiss G R, Koeller J, Harman G, Schwartz R, Clark G N, Von Hoff D D
Temple University Comprehensive Cancer Center, Philadelphia, PA 19140.
J Natl Cancer Inst. 1991 Jan 16;83(2):124-8. doi: 10.1093/jnci/83.2.124.
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.
黄酮醋酸是一种合成的苯并吡喃衍生物，作用机制不明。38例患者（30例男性和8例女性）每5周接受一次治疗，为期4周，黄酮醋酸剂量范围为0.33至12.5 g/m²。剂量小于或等于3.9 g/m²时，药物静脉输注1小时；剂量大于或等于5.28 g/m²时，输注时间延长至6小时。所有患者的治疗包括治疗前后的水化和碱化，以维持尿液pH值大于或等于6.5。剂量限制毒性作用为10 g/m²时出现低血压。药代动力学研究显示，在3.9 g/m²开始的8例研究患者中呈现线性行为。血浆峰值水平范围为125至630微克/毫升，平均终末半衰期为22.4小时。对3例10 g/m²的患者进行了免疫监测。所有3例患者均观察到CD16和/或Leu-19阳性细胞短暂增加。在1例患者中，这种增加与K562细胞杀伤增加10倍相关。该试验中未观察到客观肿瘤反应。该方案推荐的II期剂量为8 g/m²。建议进一步开展研究以阐明该药物的作用机制并确定其免疫特性。
