Phase III prevention trial of fenretinide in patients with resected non-muscle-invasive bladder cancer.
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.
Sabichi
Anita L
AL
Department of Clinical Cancer Prevention, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77230-1439, USA. asabichi@mdanderson.org
Lerner
Seth P
SP
Atkinson
E Neely
EN
Grossman
H Barton
HB
Caraway
Nancy P
NP
Dinney
Colin P
CP
Penson
David F
DF
Matin
Surena
S
Kamat
Ashish
A
Pisters
Louis L
LL
Lin
Daniel W
DW
Katz
Ruth L
RL
Brenner
Dean E
DE
Hemstreet
George P
GP
Wargo
Mary
M
Bleyer
Archie
A
Sanders
William H
WH
Clifford
John L
JL
Parnes
Howard L
HL
Lippman
Scott M
SM
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
D000970:Antineoplastic Agents; D001500:BCG Vaccine; D010919:Placebos; D017313:Fenretinide