Bacillus Calmette-Guérin is superior to a combination of epirubicin and interferon-alpha2b in the intravesical treatment of patients with stage T1 urinary bladder cancer. A prospective, randomized, Nordic study

Eur Urol. 2010 Jan;57(1):25-31. doi: 10.1016/j.eururo.2009.09.038. Epub 2009 Oct 6.

Abstract

Background: Bacillus Calmette-Guérin (BCG) instillation is regarded as the most effective bladder-sparing treatment for patients with high-grade T1 tumours and carcinoma in situ (CIS). The major problem with this therapy is the side-effects, making maintenance therapy difficult, even impossible, in a proportion of patients. Thus, alternative schedules and drugs have been proposed.

Objective: To compare BCG to the combination of epirubicin and interferon-alpha2b as adjuvant therapy of T1 tumours.

Design, setting, and participants: This is a Nordic multicenter, prospective, randomised trial in patients with primary T1 G2-G3 bladder cancer. Initial transurethral resection (TUR) was followed by a second-look resection. Patients were randomised to receive either regimen, given as induction for 6 wk followed by maintenance therapy for 2 yr.

Measurements: The drugs were compared with respect to time to recurrence and progression. Also, side-effects were documented.

Results and limitations: A total of 250 patients were randomised. At the primary end point, 62% were disease free in the combination arm as opposed to 73% in the BCG arm (p=0.065). At 24 mo, there was a significant difference in favour of the BCG-treated patients (p=0.012) regarding recurrence, although there was no difference regarding progression. The subgroup analysis showed that the superiority of BCG was mainly in those with concomitant CIS. In a multivariate analysis of association with recurrence/progression status, significant variables for outcome were type of drug, tumour size, multiplicity, status at second-look resection, and grade. A corresponding analysis was performed separately in the two treatment arms. Tumour size was the only significant variable for BCG-treated patients, while multiplicity, status at second-look resection, and grade were significant for patients treated with the combination.

Conclusions: For prophylaxis of recurrence, BCG was more effective than the combination. There were no differences regarding progression and adverse events between the two treatments.

Publication types

  • Comparative Study
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Intravesical
  • Aged
  • Antineoplastic Combined Chemotherapy Protocols / administration & dosage*
  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • BCG Vaccine / administration & dosage*
  • BCG Vaccine / adverse effects
  • Carcinoma / drug therapy*
  • Carcinoma / pathology
  • Carcinoma / surgery*
  • Chemotherapy, Adjuvant
  • Cystectomy* / methods
  • Disease Progression
  • Disease-Free Survival
  • Epirubicin / administration & dosage
  • Female
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / administration & dosage
  • Kaplan-Meier Estimate
  • Male
  • Neoplasm Recurrence, Local
  • Neoplasm Staging
  • Proportional Hazards Models
  • Prospective Studies
  • Recombinant Proteins
  • Risk Assessment
  • Risk Factors
  • Scandinavian and Nordic Countries
  • Time Factors
  • Treatment Outcome
  • Tumor Burden
  • Urinary Bladder Neoplasms / drug therapy*
  • Urinary Bladder Neoplasms / pathology
  • Urinary Bladder Neoplasms / surgery*

Substances

  • BCG Vaccine
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Epirubicin