title: Phase II study of conformal hypofractionated radiotherapy with concurrent gemcitabine in muscle-invasive bladder cancer.
abstract: OBJECTIVE
  The aim of this prospective, phase II trial was to determine the response of muscle-invasive bladder cancer (MIBC) to concurrent chemoradiotherapy of weekly gemcitabine with 4 weeks of radiotherapy (RT; GemX).
  
  
  METHODS
  Fifty patients with transitional cell carcinoma, stage T2-3, N0, M0 after transurethral resection and magnetic resonance imaging, were recruited. Gemcitabine was given intravenously at 100 mg/m(2) on days 1, 8, 15, and 22 of a 28-day RT schedule that delivered 52.5 Gy in 20 fractions. Chemotherapy was stopped for Radiation Therapy Oncology Group (RTOG) grade 3 bladder or bowel toxicity. The primary end points were tumor response, toxicity, and survival.
  
  
  RESULTS
  All patients completed RT; 46 tolerated all four cycles of gemcitabine. Two patients stopped after two cycles, and two stopped after three cycles, because of bowel toxicity. Forty-seven patients had a post-treatment cystoscopy; 44 (88%) achieved a complete endoscopic response. At a median follow-up of 36 months (range, 15 to 62 months), 36 patients were alive, and 32 of these had a functional and intact bladder. Fourteen patients died; seven died as a result of metastatic MIBC, five died as a result of intercurrent disease, and two died as a result of treatment-associated deaths. Four patients underwent cystectomy; three because of recurrent disease and one because of toxicity. One patient required a bowel resection for late toxicity. By using Kaplan-Meier analyses, 3-year cancer-specific survival was 82%, and overall survival was 75%.
  
  
  CONCLUSIONS
  Concurrent gemcitabine-based chemoradiotherapy (ie, GemX) produces a high response rate in MIBC and has durable local control and acceptable toxicity, which allows patients to preserve their own bladder. This treatment modality warrants additional investigation in a phase III setting.
authors.affiliation: The Christie NHS Foundation Trust, Wilmslow Rd, Manchester, M20 4BX United Kingdom.
authors.forename: Ananya
authors.initials: A
authors.lastname: Choudhury
authors.forename: Ric
authors.initials: R
authors.lastname: Swindell
authors.forename: John P
authors.initials: JP
authors.lastname: Logue
authors.forename: P Anthony
authors.initials: PA
authors.lastname: Elliott
authors.forename: Jacqueline E
authors.initials: JE
authors.lastname: Livsey
authors.forename: Marcus
authors.initials: M
authors.lastname: Wise
authors.forename: Paul
authors.initials: P
authors.lastname: Symonds
authors.forename: James P
authors.initials: JP
authors.lastname: Wylie
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramani
authors.forename: Vijay
authors.initials: V
authors.lastname: Sangar
authors.forename: Jeanette
authors.initials: J
authors.lastname: Lyons
authors.forename: Ian
authors.initials: I
authors.lastname: Bottomley
authors.forename: Damian
authors.initials: D
authors.lastname: McCaul
authors.forename: Noel W
authors.initials: NW
authors.lastname: Clarke
authors.forename: Anne E
authors.initials: AE
authors.lastname: Kiltie
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cowan
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D002295:Carcinoma, Transitional Cell / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D003131:Combined Modality Therapy; D003841:Deoxycytidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D019042:Muscle Neoplasms / Q000401:mortality / Q000556:secondary / Q000628:therapy*; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D020266:Radiotherapy, Conformal / Q000009:adverse effects / Q000379:methods*; D001749:Urinary Bladder Neoplasms / Q000401:mortality / Q000473:pathology / Q000628:therapy*; D000093542:Gemcitabine
chemical_list: D000970:Antineoplastic Agents; D003841:Deoxycytidine; D000093542:Gemcitabine