title: Systemic therapy for unresectable and metastatic transitional cell carcinoma of the urothelium: first-line and beyond.
abstract: OBJECTIVE
  The review aims to provide an overview of recent advances and future research direction in the management of patients with advanced transitional cell carcinoma.
  
  
  RESULTS
  Early data of the randomized phase III study comparing paclitaxel, cisplatin, and gemcitabine with gemcitabine plus cisplatin for advanced urothelial cancer detected no survival difference. A phase II study investigated the safety and efficacy of trastuzumab, carboplatin, gemcitabine, and paclitaxel in human epidermal growth factor receptor-2/neu-positive advanced urothelial carcinoma and reported promising results. Renal-sparing regimens are under active development. A nonrandomized comparison of the 3-week with the 4-week schedule for gemcitabine and cisplatin showed that the 3-week schedule had less hematological toxicity and better dose intensity. Potential molecular markers such as excision repair cross-complementation group 1, emmprin, and survivin for survival and/or platinum resistance in patients with transitional cell carcinoma showed promise.
  
  
  CONCLUSIONS
  Recent data do not support change in the current standard of care for advanced transitional cell carcinoma. Clinical testing of emerging anticancer therapies using new agents, new combinations, and new approaches is under active investigation. Rational combination and new strategy in clinical trial design are critical for new drug development for transitional cell carcinoma.
authors.affiliation: Department of Medicine, Tom Baker Cancer Centre, University of Calgary, Calgary, Alberta, Canada. tinachen@cancerboard.ab.ca
authors.forename: Tina
authors.initials: T
authors.lastname: Cheng
mesh_terms: D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D061067:Antibodies, Monoclonal, Humanized; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000378:metabolism / Q000556:secondary; D002945:Cisplatin / Q000008:administration & dosage; D002986:Clinical Trials as Topic; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D004334:Drug Administration Schedule; D006801:Humans; D017239:Paclitaxel / Q000008:administration & dosage; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000096:biosynthesis; D000068878:Trastuzumab; D014571:Urologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D019459:Urothelium / Q000473:pathology*; D000093542:Gemcitabine
chemical_list: D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D016190:Carboplatin; D002945:Cisplatin; D003841:Deoxycytidine; D017239:Paclitaxel; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab; D000093542:Gemcitabine