Dodion P F, Abrams J, Gérard B, Crespeigne N, Peeters B, Van Berchem C, Kenis Y
Service de Médecine Interne, Institut Jules Bordet, Centre des Tumeurs de l'Université Libre de Bruxelles, Brussels, Belgium.
Eur J Cancer Clin Oncol. 1987 Jun;23(6):837-42. doi: 10.1016/0277-5379(87)90288-4.
The diethylaminoester of flavone acetic acid (LM985) is a new anticancer agent with curative effects against slow growing murine tumors. Thirty-one adult patients with solid tumors received a total of 57 courses of LM985 given on days 1 and 8 every 4 weeks. The drug was given as a short infusion (1-2 hr) at doses ranging from 120 to 1900 mg/sq.m/day. The dose-limiting toxicity consisted of acute expressive aphasia; this neurotoxicity usually appeared at the end of the infusion and resolved spontaneously within a few minutes to 1 hr after the end of the infusion. In some patients, neurotoxicity was avoided by reducing the infusion rate. Neurotoxicity was observed in 5 out of 6 patients receiving 960 mg/sq.m over 1 hr and in 3 out of 3 patients receiving 1900 mg/sq.m over 2 hr. The drug did not induce any significant myelosuppression. Other side-effects were very mild and consisted mainly of occasional nausea and/or vomiting at all dose levels. One patient with breast cancer resistant to several hormonal and chemotherapy regimens had stable disease for 6 months. LM985 was detected in plasma in very small concentrations (0-2.5 micrograms/ml) but there was extensive formation of flavone acetic acid (peak concentration ranging between 8.3 and 64 micrograms/ml). A dose of 1500 mg/sq.m on days 1 and 8 every 4 weeks could be recommended for phase II studies with LM985; however, since LM985 is a prodrug of flavone acetic acid, phase II studies with LM985 should not be activated prior to the completion of the ongoing phase I trials with flavone acetic acid, which may be devoid of the acute toxicity of LM985.
黄酮乙酸的二乙氨基酯（LM985）是一种新型抗癌药物，对生长缓慢的鼠类肿瘤具有治疗作用。31例成年实体瘤患者每4周在第1天和第8天共接受了57个疗程的LM985治疗。药物通过短时间输注（1 - 2小时）给药，剂量范围为120至1900毫克/平方米/天。剂量限制性毒性表现为急性表达性失语；这种神经毒性通常在输注结束时出现，并在输注结束后几分钟至1小时内自行缓解。在一些患者中，通过降低输注速度可避免神经毒性。在6例1小时内接受960毫克/平方米的患者中有5例观察到神经毒性，在3例2小时内接受1900毫克/平方米的患者中全部观察到神经毒性。该药物未引起任何显著的骨髓抑制。其他副作用非常轻微，主要在所有剂量水平下偶尔出现恶心和/或呕吐。1例对多种激素和化疗方案耐药的乳腺癌患者病情稳定6个月。血浆中检测到的LM985浓度非常低（0 - 2.5微克/毫升），但黄酮乙酸大量生成（峰值浓度在8.3至64微克/毫升之间）。每4周在第1天和第8天给予1500毫克/平方米的剂量可推荐用于LM985的II期研究；然而，由于LM985是黄酮乙酸的前体药物，在正在进行的黄酮乙酸I期试验完成之前不应启动LM985的II期研究，因为黄酮乙酸可能没有LM985的急性毒性。
