title: Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer.
abstract: OBJECTIVE
  The study aims to evaluate the efficacy and toxicity of fenretinide in preventing tumor recurrence in patients with transitional cell carcinoma (TCC) of the bladder.
  
  
  METHODS
  We conducted a multicenter phase III, randomized, placebo-controlled trial of fenretinide (200 mg/day orally for 12 months) in patients with non-muscle-invasive bladder TCC (stages Ta, Tis, or T1) after transurethral resection with or without adjuvant intravesical Bacillus Calmette-Guerin (BCG). Patients received cystoscopic evaluation and bladder cytology every 3 months during the 1-year on study drug and a final evaluation at 15 months. The primary endpoint was time to recurrence.
  
  
  RESULTS
  A total of 149 patients were enrolled; 137 were evaluable for recurrence. The risk of recurrence was considered to be "low" in 72% (no prior BCG) and intermediate or high in 32% (prior BCG) of the evaluable patients. Of the lower-risk group, 68% had solitary tumors and 32% had multifocal, low-grade papillary (Ta, grade 1 or grade 2) tumors. The 1-year recurrence rates by Kaplan-Meier estimate were 32.3% (placebo) versus 31.5% (fenretinide; P = 0.88 log-rank test). Fenretinide was well tolerated and had no unexpected toxic effects; only elevated serum triglyceride levels were significantly more frequent on fenretinide (versus placebo). The Data Safety and Monitoring Board recommended study closure at 149 patients (before reaching the accrual goal of 160 patients) because an interim review of the data showed a low likelihood of detecting a difference between the two arms, even if the original accrual goal was met.
  
  
  CONCLUSIONS
  Although well tolerated, fenretinide did not reduce the time-to-recurrence in patients with Ta, T1, or Tis TCC of the bladder.
authors.affiliation: Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1439, USA. asabichi@mdanderson.org
authors.forename: Anita L
authors.initials: AL
authors.lastname: Sabichi
authors.forename: Seth P
authors.initials: SP
authors.lastname: Lerner
authors.forename: E Neely
authors.initials: EN
authors.lastname: Atkinson
authors.forename: H Barton
authors.initials: HB
authors.lastname: Grossman
authors.forename: Nancy P
authors.initials: NP
authors.lastname: Caraway
authors.forename: Colin P
authors.initials: CP
authors.lastname: Dinney
authors.forename: David F
authors.initials: DF
authors.lastname: Penson
authors.forename: Surena
authors.initials: S
authors.lastname: Matin
authors.forename: Ashish
authors.initials: A
authors.lastname: Kamat
authors.forename: Louis L
authors.initials: LL
authors.lastname: Pisters
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Lin
authors.forename: Ruth L
authors.initials: RL
authors.lastname: Katz
authors.forename: Dean E
authors.initials: DE
authors.lastname: Brenner
authors.forename: George P
authors.initials: GP
authors.lastname: Hemstreet
authors.forename: Mary
authors.initials: M
authors.lastname: Wargo
authors.forename: Archie
authors.initials: A
authors.lastname: Bleyer
authors.forename: William H
authors.initials: WH
authors.lastname: Sanders
authors.forename: John L
authors.initials: JL
authors.lastname: Clifford
authors.forename: Howard L
authors.initials: HL
authors.lastname: Parnes
authors.forename: Scott M
authors.initials: SM
authors.lastname: Lippman
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001500:BCG Vaccine / Q000008:administration & dosage; D002295:Carcinoma, Transitional Cell / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery; D005260:Female; D017313:Fenretinide / Q000627:therapeutic use*; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000517:prevention & control*; D010919:Placebos; D016019:Survival Analysis; D001749:Urinary Bladder Neoplasms / Q000473:pathology / Q000517:prevention & control* / Q000601:surgery
chemical_list: D000970:Antineoplastic Agents; D001500:BCG Vaccine; D010919:Placebos; D017313:Fenretinide