title: Combined-modality therapy with gemcitabine and radiation therapy as a bladder preservation strategy: long-term results of a phase I trial.
abstract: OBJECTIVE
  A Phase I trial of twice-weekly gemcitabine and concurrent radiation therapy (RT) was performed in patients with muscle-invasive bladder cancer. We present the final analysis of bladder-intact survival (BIS), disease-specific survival (DSS), and overall survival (OS).
  
  
  METHODS
  Eligible patients had muscle-invasive transitional cell carcinoma (cT2-3) and were candidates for cystectomy. Patients underwent maximal transurethral resection of bladder tumor followed by twice-weekly gemcitabine with concurrent RT to the bladder (total of 60 Gy over 6 weeks). Gemcitabine doses ranged from 10 to 33 mg/m(2).
  
  
  RESULTS
  Median follow-up was 5.6 years (range, 0.6-9.5 years). Twenty-three of 24 patients were evaluable for response. All patients were clinical stage T2. Locoregional failure occurred in seven patients (30%), which were successfully salvaged by radical cystectomy (n = 5) or intravesical therapy (n = 2). Four local failures occurred > 5 years after therapy. Most local failures were noninvasive tumors (Ta or Tis, n = 6). Ten patients (43%) experienced optimal outcome (no failures and bladder intact). The 5-year actuarial estimates of survival are BIS 62%, OS 76%, and DSS 82%.
  
  
  CONCLUSIONS
  Twice-weekly gemcitabine with concurrent RT is well tolerated and provides rates of survival and bladder preservation that are comparable to the existing literature. All locoregional failures were successfully salvaged by either radical cystectomy or intravesical therapy. Given the high proportion of late local failures, we recommend long-term monitoring when using this regimen. Future studies comparing the safety and efficacy of gemcitabine- vs. platinum-based bladder preservation protocols are pending.
authors.affiliation: Department of Radiation Oncology, University of Michigan Medical School, Ann Arbor, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Oh
authors.forename: Daniel E
authors.initials: DE
authors.lastname: Soto
authors.forename: David C
authors.initials: DC
authors.lastname: Smith
authors.forename: James E
authors.initials: JE
authors.lastname: Montie
authors.forename: Cheryl T
authors.initials: CT
authors.lastname: Lee
authors.forename: Howard M
authors.initials: HM
authors.lastname: Sandler
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000964:Antimetabolites, Antineoplastic / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D003131:Combined Modality Therapy / Q000379:methods; D015653:Cystectomy; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives*; D004334:Drug Administration Schedule; D006801:Humans; D008297:Male; D008875:Middle Aged; D016879:Salvage Therapy; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000532:radiotherapy* / Q000601:surgery; D000093542:Gemcitabine
chemical_list: D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; D000093542:Gemcitabine