Legha S S, Ring S, Raber M, Felder T B, Newman R A, Krakoff I H
Department of Medical Oncology, University of Texas System Cancer Center, M.D. Anderson Hospital and Tumor Institute, Houston 77030.
Cancer Treat Rep. 1987 Dec;71(12):1165-9.
A phase I study of benzisoquinolinedione (amonafide) was conducted in 30 patients with advanced solid tumors refractory to conventional therapy. The starting dose was 10 mg/m2/day X 5 days and the highest tolerated dose was 625 mg/m2/day X 5. The daily dose was mixed in 100 ml of normal saline and infused over 30-60 minutes. The dose-limiting toxicity was myelosuppression with nadirs of blood counts reached on Day 15 and recovery by Day 21-28. Other side effects included mild nausea and vomiting, mild phlebitis, skin rashes, and alopecia in some patients. A majority of the patients experienced dizziness, tinnitus, and hot flushes occurring predominantly at the higher dose levels. These were related to the rate of drug infusion and resolved on prolonging the infusion to 60 minutes. Pharmacokinetic studies of amonafide revealed a monoexponential plasma disappearance curve with a mean half-life of 3.5 +/- 1.9 hours. The recommended dose of amonafide for phase II studies in solid tumors is 400 mg/m2/day X 5 for good-risk and 300-320 mg/m2/day X 5 days for poor-risk patients with courses repeated at 21-28-day intervals.
对30例对传统治疗无效的晚期实体瘤患者进行了苯并异喹啉二酮（氨萘非特）的I期研究。起始剂量为10mg/m²/天×5天，最大耐受剂量为625mg/m²/天×5天。每日剂量溶于100ml生理盐水中，在30 - 60分钟内输注。剂量限制性毒性为骨髓抑制，血细胞计数最低点在第15天出现，第21 - 28天恢复。其他副作用包括轻度恶心、呕吐、轻度静脉炎、皮疹，部分患者出现脱发。大多数患者在较高剂量水平时出现头晕、耳鸣和潮热。这些与药物输注速度有关，延长输注至60分钟后症状缓解。氨萘非特的药代动力学研究显示血浆呈单指数消除曲线，平均半衰期为3.5±1.9小时。对于实体瘤II期研究，氨萘非特推荐剂量为，低风险患者400mg/m²/天×5天，高风险患者300 - 320mg/m²/天×5天，疗程每21 - 28天重复一次。
