Interim results from a national multicenter phase II trial of combination bacillus Calmette-Guerin plus interferon alfa-2b for superficial bladder cancer.
OBJECTIVE
Interim results are provided from a large multicenter trial of combination bacillus Calmette-Guerin (BCG) plus interferon (IFN) alfa-2b for BCG naive (BCG-N) and previous BCG failure (BCG-F) cases of superficial bladder cancer.


METHODS
A total of 490 patients enrolled from May 1999 to May 2000 with a median of 24 months of followup were analyzed. The BCG-N group (259) was treated with a 6-week induction course of standard dose BCG plus 50 million units of IFN followed by 3, 3-week maintenance cycles of reduced dose BCG (1/3 to 1/10) plus 50 million units IFN at 3, 9 and 15 months after induction. The BCG-F group (231) was treated similarly except induction therapy began at a decreased (1/3 to 1/10) BCG dose.


RESULTS
The simple tumor recurrence rates for BCG-N and BCG-F groups were 40% and 52%, and the Kaplan-Meier estimates for disease freedom at 24 months were 57% and 42%, respectively. Progression to muscle invasion occurred in 5% and 4.3% while metastasis occurred in 2.3% and 2.6%, respectively. In each group 3.9% of patients underwent cystectomy and 2 patients in each group died of bladder cancer. Serious adverse events occurred in 5.5% with infection related serious adverse events being less prevalent in the BCG-F group (2.6% vs 5.4%). Toxicity related dropout, treatment delay and/or further BCG dose reduction, and need for symptomatic drugs were similar. Moderate to severe local side effects during induction were higher in the BCG-F group (6.2% vs 16.9%) but equilibrated during maintenance therapy. Systemic reactions were rare.


CONCLUSIONS
This multicenter trial provides a benchmark for the efficacy and safety of combination BCG and IFN as up front and salvage therapy. The incremental value of IFN cannot be determined from this study.
Department of Urology, University of Iowa, 200 Hawkins Drive, 3 RCP, Iowa City, IA 52242-1089, USA. michael-odonnell@uiowa.edu
Michael A
MA
O'Donnell
Kathleen
K
Lilli
Christina
C
Leopold
D000368:Aged; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001500:BCG Vaccine / Q000008:administration & dosage* / Q000009:adverse effects; D002295:Carcinoma, Transitional Cell / Q000188:drug therapy* / Q000473:pathology / Q000556:secondary; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D009364:Neoplasm Recurrence, Local; D011994:Recombinant Proteins; D017211:Treatment Failure; D001749:Urinary Bladder Neoplasms / Q000188:drug therapy* / Q000473:pathology
D000970:Antineoplastic Agents; D001500:BCG Vaccine; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins