Bélanger K, Jolivet J, Maroun J, Stewart D, Grillo-Lopez A, Whitfield L, Wainman N, Eisenhauer E
Department of Medicine, Hôpital Notre-Dame, University of Montréal, Canada.
Invest New Drugs. 1993 Nov;11(4):301-8. doi: 10.1007/BF00874428.
DUP-937 is a new anthrapyrazole intercalator that inhibits DNA synthesis. A phase I trial was conducted in which DUP-937 was given in an intravenous bolus weekly for 3 weeks. Cycles were repeated every 5 weeks. Twenty men and 13 women with median ECOG performance status of 1 completed 74 cycles. The starting dose was 0.55 mg/m2/week and doses were escalated to 16 mg/m2/week. Non-hematological toxicity was generally mild or moderate and consisted mainly of gastro-intestinal effects, fatigue, alopecia and local reactions. Grade 3 neutropenia was first documented at 7.36 mg/m2 and became more common at higher dose levels. Three of four patients had > or = grade 3 neutropenia at the 16 mg/m2 dose level. Thrombocytopenia was minimal. The dose-limiting toxicity was neutropenia and the maximum tolerated dose was 16 mg/m2 weekly for 3 weeks. Mean area under the curve (AUC) values increased with dose. Linear pharmacokinetics were observed as total body clearance (CLtb), half-life (t1/2) and volume of distribution (Vss) did not change with increasing doses. One partial remission in a patient with prostate carcinoma was documented.
DUP - 937是一种新型的蒽吡唑嵌入剂，可抑制DNA合成。开展了一项I期试验，其中DUP - 937每周静脉推注给药一次，共给药3周。每5周重复一个周期。20名男性和13名女性完成了74个周期，其中位东部肿瘤协作组（ECOG）体能状态评分为1。起始剂量为0.55毫克/平方米/周，剂量逐步递增至16毫克/平方米/周。非血液学毒性一般为轻度或中度，主要包括胃肠道反应、疲劳、脱发和局部反应。3级中性粒细胞减少症首次记录于剂量为7.36毫克/平方米时，在更高剂量水平时更为常见。在16毫克/平方米剂量水平时，4名患者中有3名出现≥3级中性粒细胞减少症。血小板减少症很轻微。剂量限制性毒性为中性粒细胞减少症，最大耐受剂量为每周16毫克/平方米，共给药3周。平均曲线下面积（AUC）值随剂量增加而升高。观察到线性药代动力学，因为总体清除率（CLtb）、半衰期（t1/2）和分布容积（Vss）不会随剂量增加而改变。记录到1例前列腺癌患者出现部分缓解。
