title: Efficacy of escalating doses of intravesical interferon alpha-2b in reducing recurrence rate and progression in superficial transitional cell carcinoma.
abstract: OBJECTIVE
  To compare the efficacy of three different doses of intravesical interferon alpha-2b (IFN alpha-2b) in reducing recurrence and progression rates in superficial grade II, transitional cell carcinoma (TCC).
  
  
  METHODS
  Eighty-nine patients with primary or recurrent TCC stage Ta/T1, grade II, were randomly allocated into four groups after transurethral resection (TUR) of the tumour. Group A (20 patients) received no further treatment, serving as the control group; group B (22 patients) received 40 MU of IFN alpha-2b, group C (24 patients) 60 MU and group D (23 patients) 80 MU. The instillations started within 48-72 h after TUR and were performed weekly for 2 months, bimonthly for the next 4 months and thereafter monthly for 6 months. The patients were followed for 36 months. The four groups were compared for the number of recurrences (simple recurrence rate), progression in stage, disease-free interval and recurrence rate per 100 patient-months.
  
  
  RESULTS
  During the follow-up, 33 patients had recurrence (13, eight, seven and five in groups A to D, respectively). The simple recurrence rate was 65% for group A, compared with 36% (P = 0.06), 29% (P < 0.05) and 22% (P < 0.01) for groups B, C and D, respectively. The differences in simple recurrence rates between the groups treated with IFN alpha-2b were not statistically significant. Eleven patients experienced progression in stage, with six, there, one and one in groups A to D, respectively. The differences were statistically significant only between groups A and C (P < 0.05) and groups A and D (P < 0.05). The disease-free interval was 15 months for group A, compared with 21.4 (P < 0.05), 26.1 (P < 0.001) and 30 months (P < 0.001) for groups C to D, respectively. The disease-free intervals of the groups treated with IFN alpha-2b were significantly different between all patients in groups B and D (P < 0.01) and only for those with stage T1 between groups C and D (P < 0.01). Finally the recurrence rate per 100 patient-months was 2.91, 1.19, 0.88 and 0.63 for groups A to D, respectively (all P < 0.001). The results were always in favour of the patients treated with the high dose, the only exception being the difference between groups C and D (P = 0.026). No side-effects of the drug were noted, nor was any adverse reaction reported from any patient.
  
  
  CONCLUSIONS
  These results show a significant advantage for adjuvant intravesical IFN alpha-2b treatment over TUR alone for the 36 months of follow up and indicate that IFN alpha-2b can modify the clinical course of superficial TCC at least in the short term. The appropriate dose was apparently 80 MU, for although 40 MU was better than TUR alone, it was less effective than 60 MU and 80 MU; the 80 MU dose was slightly better than 60 MU and thus this regimen is recommended.
authors.affiliation: Department of Urology, University of Athens, School of Medicine, Sismanoglio Hospital, Greece.
authors.forename: S
authors.initials: S
authors.lastname: Giannakopoulos
authors.forename: A
authors.initials: A
authors.lastname: Gekas
authors.forename: G
authors.initials: G
authors.lastname: Alivizatos
authors.forename: F
authors.initials: F
authors.lastname: Sofras
authors.forename: T
authors.initials: T
authors.lastname: Becopoulos
authors.forename: C
authors.initials: C
authors.lastname: Dimopoulos
mesh_terms: D000283:Administration, Intravesical; D000328:Adult; D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002295:Carcinoma, Transitional Cell / Q000628:therapy*; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D006417:Hematuria / Q000209:etiology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011446:Prospective Studies; D011994:Recombinant Proteins; D016896:Treatment Outcome; D001749:Urinary Bladder Neoplasms / Q000628:therapy*
chemical_list: D000970:Antineoplastic Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins