Vashistha Vishal, Quinn David I, Dorff Tanya B, Daneshmand Siamak
Department of Urology, USC/Norris Comprehensive Cancer Center, USC Institute of Urology, 1441 Eastlake Abe, Suite 7416, Los Angeles, CA 90089, USA.
BMC Cancer. 2014 Dec 16;14:966. doi: 10.1186/1471-2407-14-966.
Although Muscle Invasive Bladder Cancer (MIBC) is increasing in incidence, treatment has largely remained limited to radical cystectomy with or without cisplatin-based neoadjuvant and/or adjuvant chemotherapy. We reviewed the current and recent clinical trials evaluating perioperative chemotherapy, targeted therapy, and novel therapeutic regimens for MIBC patients undergoing radical cystectomy.
An overview of perioperative MIBC management was conducted initially using MEDLINE. The Clinical Trials Registry and MEDLINE were further searched specifically for perioperative MIBC chemotherapy, targeted therapy, and other novel therapeutic approaches. Trials involving non-perioperative management, operative management other than radical cystectomy, multiple tumors, or purely superficial or metastatic disease were excluded from selection. These criteria were not specifically fulfilled for mTOR inhibitor and immune therapy trials. Only phase III chemotherapy and phase II targeted therapy trials found in the Clinical Trials Registry were selected. MEDLINE searches of specific treatments were limited to January 2009 to January 2014 whereas the Clinical Trials Registry search had no timeline. Systematic MEDLINE searches had no phase restrictions. Trials known by the authors to fulfill search criteria but were not found via searches were also selected.
Twenty-five trials were selected from the Clinical Trials Registry including 7 phase III chemotherapy trials, 11 Phase II targeted therapy trials, 3 immune therapy trials, 1 mammalian target of rapamycin (mTOR) inhibitor trial, and 3 gene and vaccine therapy trials. Nine trials have been completed and 5 have been terminated early or withdrawn. Nine trials have data available when individually searched using MEDLINE and/or Google. Systematic searches of MEDLINE separately found 12 trials in the past 5 years. Two phase III chemotherapy trials were selected based on knowledge by the authors. No phase III trials of targeted therapy have been registered or published.
New trials are currently being conducted that may revolutionize MIBC treatment preceding or following cystectomy. Head-to-head phase III trials of perioperative chemotherapy and further phase II and phase III trials of targeted therapy and other therapeutic approaches are necessary before the current cisplatin-based perioperative chemotherapy paradigm is altered.
尽管肌层浸润性膀胱癌（MIBC）的发病率在上升，但其治疗方法在很大程度上仍局限于根治性膀胱切除术，可联合或不联合以顺铂为基础的新辅助和/或辅助化疗。我们回顾了目前及近期评估接受根治性膀胱切除术的MIBC患者围手术期化疗、靶向治疗及新型治疗方案的临床试验。
最初使用MEDLINE对围手术期MIBC管理进行概述。进一步专门在临床试验注册库和MEDLINE中搜索围手术期MIBC化疗、靶向治疗及其他新型治疗方法。涉及非围手术期管理、除根治性膀胱切除术之外的手术管理、多发肿瘤或单纯浅表或转移性疾病的试验被排除在选择范围之外。mTOR抑制剂和免疫治疗试验未完全符合这些标准。仅选择在临床试验注册库中找到的III期化疗试验和II期靶向治疗试验。对特定治疗方法的MEDLINE搜索限于2009年1月至2014年1月，而临床试验注册库搜索没有时间限制。系统性MEDLINE搜索没有阶段限制。作者已知符合搜索标准但未通过搜索找到的试验也被选中。
从临床试验注册库中选择了25项试验，包括7项III期化疗试验、11项II期靶向治疗试验、3项免疫治疗试验、1项雷帕霉素哺乳动物靶点（mTOR）抑制剂试验和3项基因与疫苗治疗试验。9项试验已完成，5项已提前终止或撤回。当单独使用MEDLINE和/或谷歌搜索时，有9项试验可获取数据。MEDLINE的系统性搜索在过去5年中分别找到了12项试验。基于作者的了解选择了2项III期化疗试验。尚无靶向治疗的III期试验注册或发表。
目前正在进行新的试验，这些试验可能会彻底改变膀胱切除术前后的MIBC治疗。在改变当前以顺铂为基础的围手术期化疗模式之前，有必要进行围手术期化疗的直接比较III期试验以及靶向治疗和其他治疗方法的进一步II期和III期试验。
