Department of Urology, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Urol Oncol. 2012 Jan-Feb;30(1):64-8. doi: 10.1016/j.urolonc.2009.10.002. Epub 2009 Nov 27.
Apaziquone used intravesically showed significant activity in phase I and II marker lesion studies in non-muscle-invasive bladder cancer. The objective of this study was to assess antitumor activity and safety of 3 different formulations of intravesical apaziquone in an orthotopic rat bladder cancer model.
Female Fischer F344 rats were instilled with 1.5 × 10(6) AY-27 urothelial cell carcinoma cells and divided in 3 treatment groups (n = 10) and 1 placebo group (n = 6). Intravesical treatment was administered for 1 hour on days 2 and 5. Rats were treated with apaziquone in the formulation used in phase I/II clinical trials (group 1); apaziquone with an altered buffering capacity being used in phase III clinical trials (group 2), and apaziquone as in group 2, but without propylene glycol in the diluent (group 3). On days 5 and 14, the bladder wall was inspected by cystoscopy and evaluated for macroscopic tumor growth. After sacrificing the rats (day 14), cystectomy was performed and the bladders were investigated.
There were no signs of any toxicity due to the study drug. On histopathologic examination of the bladders 0, 1, and 2 tumors per group were found in group 1, 2, and 3, respectively. In the placebo-treated group, 60% of animals developed tumor, which is comparable to untreated animals.
Apaziquone showed an excellent antitumor activity. The effectiveness of apaziquone in this orthotopic rat bladder tumor model corroborates the clinical observations and implies the validity of this model.
阿帕齐醌经膀胱内给药在非肌肉浸润性膀胱癌的 I 期和 II 期标志物病变研究中显示出显著的活性。本研究的目的是评估 3 种不同剂型的膀胱内阿帕齐醌在原位大鼠膀胱癌模型中的抗肿瘤活性和安全性。
雌性 Fischer F344 大鼠膀胱内接种 1.5×10(6)个 AY-27 尿路上皮癌细胞，分为 3 个治疗组（n=10）和 1 个安慰剂组（n=6）。在第 2 天和第 5 天，给予膀胱内治疗 1 小时。大鼠分别接受 I/II 期临床试验中使用的阿帕齐醌制剂（第 1 组）；III 期临床试验中使用的缓冲能力改变的阿帕齐醌（第 2 组），以及第 2 组的阿帕齐醌，但在稀释剂中不含丙二醇（第 3 组）。在第 5 天和第 14 天，通过膀胱镜检查检查膀胱壁并评估宏观肿瘤生长情况。处死大鼠（第 14 天）后，行膀胱切除术并检查膀胱。
研究药物无任何毒性迹象。在组织病理学检查中，第 1 组、第 2 组和第 3 组的膀胱中分别发现 0、1 和 2 个肿瘤。在安慰剂治疗组中，60%的动物发生肿瘤，与未治疗动物相当。
阿帕齐醌显示出优异的抗肿瘤活性。阿帕齐醌在这种原位大鼠膀胱癌模型中的有效性证实了临床观察结果，并暗示了该模型的有效性。
