Novel prophylactic effect of doxifluridine in superficial bladder cancer.
OBJECTIVE
The prophylactic effect of 5'-deoxy-5-fluorouridine (5'-DFUR) has not been fully studied in superficial bladder cancer. The aims of this work were to investigate the prophylactic effects of 5'-DFUR in terms of tumor recurrence after transurethral resection of bladder tumor (TURBT) and to study whether thymidine phosphorylase (TdRPase) immunostaining predicts tumor recurrence.


METHODS
A total of 112 patients with pTa or pT1 bladder cancer were eligible for the analysis and were allocated to either an adjuvant group (TURBT+5'-DFUR; n = 47; initial 23 months) or a control group (TURBT alone; n = 65, final 23 months). Tumor specimens were studied immunohistochemically using anti-TdRPase antibody.


RESULTS
Tumor recurrence was observed in 54 of the patients (48%) after a median follow-up period of 26.8 months. No significant clinico-pathologic bias was observed between the two groups. Although patients in the adjuvant group had a significantly higher recurrence-free survival rate than those in the control group when considering 78 patients with pathological T1 tumors (p = 0.0272) and 65 patients who did not recur within 12 months (p = 0.001), overall there was no significant difference between the two groups. Multivariate analysis revealed that 5'-DFUR administration was the strongest predictor of late tumor recurrence, which was defined as development of recurrence 12 months after TURBT (hazard ratio 5.744; 95% CI 1.495-30.45; p = 0.0094). Immunostaining did not predict prophylactic effects of 5'-DFUR. Mild, reversible toxicity was found in 9/58 (15.5%) of the cases evaluated.


CONCLUSIONS
Oral administration of 5'-DFUR after TURBT did not prevent tumor recurrence in the overall cohort, although this novel drug may have a prophylactic effect in patients belonging to several subgroups.
Matsuyama
Hideyasu
H
Department of Urology, Yamaguchi University School of Medicine, Yamaguchi, Japan. hidde@yamaguchi-u.ac.jp
Baba
Yoshikazu
Y
Shimabukuro
Tomoyuki
T
Uchiyama
Koichi
K
Aoki
Akihiko
A
Suga
Akinobu
A
Jojima
Kazutaka
K
Suyama
Ken-ichi
K
Yamamoto
Norio
N
Naito
Katsusuke
K
D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery; D015653:Cystectomy / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D005260:Female; D005467:Floxuridine / Q000627:therapeutic use*; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality / Q000517:prevention & control*; D009367:Neoplasm Staging; D011336:Probability; D016016:Proportional Hazards Models; D011446:Prospective Studies; D012016:Reference Values; D018570:Risk Assessment; D016019:Survival Analysis; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy / Q000401:mortality / Q000473:pathology* / Q000601:surgery
D005467:Floxuridine; C025034:doxifluridine