title: Current and recent clinical trials for perioperative systemic therapy for muscle invasive bladder cancer: a systematic review.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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 Nine trials have been completed and 5 have been terminated early or withdrawn.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.
  
  
  CONCLUSIONS
  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.
authors.forename: Vishal
authors.initials: V
authors.lastname: Vashistha
authors.forename: David I
authors.initials: DI
authors.lastname: Quinn
authors.forename: Tanya B
authors.initials: TB
authors.lastname: Dorff
authors.affiliation: Department of Urology, USC/Norris Comprehensive Cancer Center, USC Institute of Urology, 1441 Eastlake Abe, Suite 7416, Los Angeles, CA 90089, USA. daneshma@med.usc.edu.
authors.forename: Siamak
authors.initials: S
authors.lastname: Daneshmand
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D019496:Cancer Vaccines / Q000627:therapeutic use; D017024:Chemotherapy, Adjuvant; D017322:Clinical Trials, Phase II as Topic; D017326:Clinical Trials, Phase III as Topic; D015653:Cystectomy; D015316:Genetic Therapy; D006801:Humans; D058990:Molecular Targeted Therapy; D009130:Muscle, Smooth; D020360:Neoadjuvant Therapy; D009361:Neoplasm Invasiveness; D019990:Perioperative Care; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D001749:Urinary Bladder Neoplasms / Q000473:pathology* / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D019496:Cancer Vaccines; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases