09O6-BENZYLGUANINE AND BCNU--A BIOCHEMICAL MODULATION TRIAL

抗癌药物的早期评估传统上使用毒性（通常是血液学）而不是疗效终点来建立适当的给药方案。 为了建立克服烷基鸟嘌呤DNA烷基转移酶（AGT）介导的肿瘤细胞对1，3-双（2-氯乙基）-1-亚硝基脲耐药性的生化疗效终点，我们对AGT消耗剂06-苄基鸟嘌呤（BG）进行了一项新的剂量递增临床试验。 测定BG前和BG后18 h连续计算机断层扫描引导肿瘤组织活检中将AGT消耗至不可检测水平（BMD（T））所需的BG剂量。30例患者在GCRC上接受的BG剂量范围为10 - 120 mg/m2。

Early phase evaluation of anticancer drugs has traditionally used toxicity (usually hematological) rather than efficacy end points to establish appropriate dosing schedules. To establish a biochemical efficacy end point for overcoming alkylguanine DNA alkyltransferase (AGT)-mediated tumor cell resistance to 1,3-bis(2-chloroethyl)-1-nitrosourea, we performed a novel dose escalation clinical trial for the AGT-depleting agent 06-benzylguanine (BG). The dose of BG required to deplete AGT to undetectable levels (BMD(T) in sequential computed tomography-guided tumor tissue biopsies before BG and 18 h after BG was determined. Thirty patients received doses of BG ranging from 10 to 120 mg/m2 on the GCRC.