A randomized comparative dose-ranging study of interferon-α and mitomycin-C as an internal control in primary or recurrent superficial transitional cell carcinoma of the bladder

Objective To compare, in a phase II study, the activity and toxicity of three dose levels of interferon-alpha, and of mitomycin-C given intravesically (as an internal control to validate the results), the primary objective being to investigate the percentage of complete responses (complete disappearance of a marker lesion) induced by the three interferon-alpha dose levels on a marker lesion: a secondary objective was to compare the interferon-alpha doses for toxicity. Patients and methods In all, 115 patients were enrolled, with the inclusion criteria being multiple grade 1 or 2, stage Ta or T1, primary or recurrent transitional cell carcinoma of the bladder. Interferon-alpha (30, 50 and 80 MU) and mitomycin-C (40 mg) intravesical treatments were given as follows. Patients randomized to one of three interferon-alpha dose levels were treated weekly for 12 weeks. However, in week 9 (first cystoscopy after baseline) interferon-alpha treatment was Stopped if there was a complete response or disease progression. Patients randomized to mitomycin-C were treated weekly for 8 weeks only and in week 9 underwent follow-up cystoscopy. Results Interferon-alpha at doses of 30, 50 and 80 MU gave response rates at 13 weeks of 19%, 33% and 41%, respectively. Although the response rates were higher for 50 and 80 MU than for 30 MU, the differences were not statistically significant. All three interferon-alpha groups had significantly lower response rates than the internal control, mitomycin-C (72%). The safety analysis showed that most of the adverse events were of mild to moderate severity. Adverse events were experienced by 37%, 37% and 48% of patients receiving 30, 50 and 80 MU interferon-alpha, respectively, and by 55% of patients receiving mitomycin-C. The corresponding rates for severe adverse events related to treatment were 9% for interferon-alpha and 10% for mitomycin-C. Conclusion Ablative therapy with interferon-alpha was less effective than mitomycin-C in patients with superficial bladder cancer. Both drugs were well tolerated, although interferon-alpha appeared to have a slightly better overall safety profile.