Delto Joan C, Kobayashi Takashi, Benson Mitchell, McKiernan James, Abate-Shen Cory
Department of Urology, Columbia University Medical Center, New York, NY, USA.
Oncotarget. 2013 Feb;4(2):269-76. doi: 10.18632/oncotarget.852.
There is a critical need to identify treatment options for patients at high risk for developing muscle invasive bladder cancer that avoid surgical removal of the bladder (cystectomy). In the current study, we have performed preclinical studies to investigate the efficacy of intravesical delivery of chemotherapy for preventing progression of bladder cancer. We evaluated three chemotherapy agents, namely cisplatin, gemcitabine, and docetaxel, which are currently in use clinically for systemic treatment of muscle invasive bladder cancer and/or have been evaluated for intravesical therapy. These preclinical studies were done using a genetically-engineered mouse (GEM) model that progresses from carcinoma in situ (CIS) to invasive, metastatic bladder cancer. We performed intravesical treatment in this GEM model using cisplatin, gemcitabine, and/or docetaxel, alone or by combining two agents, and evaluated whether such treatments inhibited progression to invasive, metastatic bladder cancer. Of the three single agents tested, gemcitabine was most effective for preventing progression to invasive disease, as assessed by several relevant endpoints. However, the combinations of two agents, and particularly those including gemcitabine, were more effective for reducing both tumor and metastatic burden. Our findings suggest combination intravesical chemotherapy may provide a viable bladder-sparing treatment alternative for patients at high risk for developing invasive bladder cancer, which can be evaluated in appropriate clinical trials.
迫切需要为有发展为肌肉浸润性膀胱癌高风险的患者确定避免膀胱手术切除（膀胱切除术）的治疗方案。在当前的研究中，我们进行了临床前研究，以调查膀胱内化疗预防膀胱癌进展的疗效。我们评估了三种化疗药物，即顺铂、吉西他滨和多西他赛，这些药物目前临床上用于肌肉浸润性膀胱癌的全身治疗和/或已进行膀胱内治疗评估。这些临床前研究是使用一种从原位癌（CIS）进展为侵袭性、转移性膀胱癌的基因工程小鼠（GEM）模型进行的。我们在这个GEM模型中使用顺铂、吉西他滨和/或多西他赛单独或联合两种药物进行膀胱内治疗，并评估这种治疗是否抑制进展为侵袭性、转移性膀胱癌。在所测试的三种单一药物中，根据几个相关终点评估，吉西他滨在预防进展为侵袭性疾病方面最有效。然而，两种药物的联合，特别是那些包括吉西他滨的联合，在减轻肿瘤和转移负担方面更有效。我们的研究结果表明，联合膀胱内化疗可能为有发展为侵袭性膀胱癌高风险的患者提供一种可行的保留膀胱的治疗选择，这可以在适当的临床试验中进行评估。
