- 作者：Harm C. Arentsen ; M.D.a ; Kees Hendricksen ; M.D.a ; Christina A. Hulsbergen-van de Kaa ; M.D. ; Ph.D.b ; Guru Reddy ; Ph.D.c ; Egbert Oosterwijk ; Ph.D.a ; J. Alfred Witjes ; M.D. ; Ph.D.a ; F.Witjes@uro.umcn.nl
- 关键词：Apaziquone ; Bladder neoplasms ; Rats ; Inbred F344 ; Intravesical therapy ; Urothelial cell carcinoma
- 刊名：Urologic Oncology: Seminars and Original Investigations
- 出版年：2012
- 出版时间：January-February 2012
- 年：2012
- 卷：30
- 期：1
- 页码：64-68
- 全文大小：403 K
Objectives
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.Materials and methods
Female Fischer F344 rats were instilled with 1.5 ¡Á 106 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.
Results
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.
Conclusions
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.