Institute of Cancer Therapeutics, University of Bradford, United Kingdom.
Br J Pharmacol. 2013 Jan;168(1):11-8. doi: 10.1111/j.1476-5381.2012.01996.x.
EO9 (Apaziquone) is a bioreductive drug that has a chequered history. It underwent clinical trial but failed to show activity in phase II clinical trials when administered i.v. Poor drug delivery to tumours caused by a combination of rapid pharmacokinetic elimination and poor penetration through avascular tissue were the major factors responsible for EO9's poor efficacy. Based upon an understanding of why EO9 failed, a further clinical trial against patients with superficial transitional cell carcinoma of the bladder was conducted. The rationale for this was that intravesical administration directly into the bladder would circumvent the drug delivery problem, and any drug reaching the blood supply would be rapidly cleared thereby reducing the risk of systemic exposure. EO9 was well tolerated, and clinical activity against marker lesions was recorded in both phase I and II clinical trials. This article charts the pharmacological history of EO9 and discusses the potential implications that 'the EO9 story' has for the development of other loco-regional therapies.
EO9（Apaziquone）是一种生物还原药物，其历史曲折。它曾进行过临床试验，但当静脉注射时，在 II 期临床试验中未能显示出活性。由于快速药代动力学消除和穿过无血管组织的能力差的综合作用，导致肿瘤内药物输送不良，这是 EO9 疗效不佳的主要因素。基于对 EO9 失败原因的了解，对患有浅表性移行细胞膀胱癌的患者进行了进一步的临床试验。这样做的理由是，将药物直接注入膀胱进行膀胱内给药可以避免药物输送问题，并且任何到达血液供应的药物都会被迅速清除，从而降低了全身暴露的风险。EO9 耐受性良好，在 I 期和 II 期临床试验中均记录了对标记病变的临床活性。本文描述了 EO9 的药理学历史，并讨论了“EO9 故事”对其他局部区域治疗方法的发展的潜在影响。
