PHASE I TRIAL OF BIZELESIN IN PATIENTS WITH ADVANCED CANCER

这项试验正在进行，以评估每四周治疗一次的晚期癌症患者比赛莱辛的最大耐受剂量（MTD）。目前试验已基本完成应计目标。共有19名患者以5种不同的剂量水平入组。迄今为止，在两个最高水平（0.8 ug/m2和1.0 ug/m2）时遇到了剂量限制毒性。在这些剂量水平下观察到几次4级白细胞减少和中性粒细胞减少。我们继续对三名患者进行持续治疗评估。在第一个周期进行药代动力学取样。我们计划描述按此时间表给药的比泽尔辛的毒性，并描述其药代动力学特征。在确定MTD后，还将探讨药效学关系。该研究药物由NCI提供，目前正在等待进一步调查的计划。该试验的初步结果已于1998年6月在阿姆斯特丹举行的NCI/EORTC会议上提出。更新后的结果于1999年4月提交给美国癌症研究协会作摘要报告。

This trial is being conducted to assess the maximum tolerated dose (MTD) of bizelesin in patients with advanced cancer treated once every four weeks. The current trial has nearly complete the accrual goals. A total of 19 patients have been enrolled at five different dose levels. To date, dose limiting toxicities have been encountered at the two highest levels -- 0.8 ug/m2 and 1.0 ug/m2. Several episodes of grade 4 leukopenia and neutropenia have been observed at these dose levels. We continue to follow three patients for ongoing treatment evaluations. Pharmacokinetic sampling is being performed during cycle one. We plan to describe the toxicities of bizelesin given on this schedule and to characterize the pharmacokinetics. Pharmacodynamic relationships will also be explored when the MTD has been determined. The study drug is supplied by the NCI and plans for further investigations are currently pending. The preliminary findings for this trial have been presented at the NCI/EORTC meeting in Amsterdam, June 1998. Updated results were submitted for abstract presentation to American Association for Cancer Research in April 1999.