In patients with stage pT1 urothelial bladder cancer, intravesical bacillus Calmette-Guérin (TheraCys, TICE BCG) combined with electromotive mitomycin-C produces higher remission rates and longer remission times than BCG alone, Italian researchers reported.
Rome-In patients with stage pT1 urothelial bladder cancer, intravesical bacillus Calmette-Guérin (TheraCys, TICE BCG) combined with electromotive mitomycin-C produces higher remission rates and longer remission times than BCG alone, Italian researchers reported.
Instillation of electromotive mitomycin-C, which is not approved in the U.S., is based on its potential to eliminate malignant cells that escape BCG immunologic surveillance, said Savino Mauro Di Stasi, MD, PhD, of the department of surgery/urology at Tor Vergata University, Rome.
In 2006, Dr. Di Stasi and colleagues reported that intravesical sequential BCG and electromotive mitomycin administered to patients with high-risk nonmuscle-invasive bladder cancer leads to a higher disease-free interval, lower recurrence and progression, and improved overall survival and disease-specific survival compared with BCG alone (Lancet Oncol 2006; 7:43-51).
An additional 6 years of follow-up are now available, allowing for estimated median 10-year results.
The study included 212 patients with high-risk nonmuscle-invasive bladder cancer who were randomly assigned to treatment with 81 mg of BCG infused over 120 minutes once weekly for 6 weeks or to 81 mg of BCG infused over 120 minutes once weekly for 2 weeks, followed by 40 mg of electromotive mitomycin (intravesical electric current 20 mA for 30 minutes) once per week as one cycle for three cycles.
The timing schedule and delivery techniques were selected to “keep the benefits of both drugs at an optimum,” according to Dr. Di Stasi, who presented the findings at the 2012 American Society of Clinical Oncology annual meeting in Chicago.
Patients who experienced a complete response underwent maintenance treatment. Those assigned to BCG alone had one infusion of 81 mg of BCG monthly for 10 months, and those assigned BCG and mitomycin had 40 mg of electromotive mitomycin once per month for 2 months, followed by 81 mg of BCG once per month as one cycle for three cycles.
Significant difference in disease-free interval
Over a median follow-up of 121 months, the median disease-free interval was 79 months in patients assigned to sequential BCG and electromotive mitomycin compared with 26 months in those assigned to BCG alone, for a between-group difference of 53 months (p=.0002).
Patients assigned sequential BCG and electromotive mitomycin, compared with BCG alone, also had lower recurrence (45% vs. 62%, p=.0002); progression to muscle-invasive disease (12% vs. 28%, p=.003); death from bladder cancer (9% vs. 23%, p=.0055); and overall mortality (44% vs. 59%, p=.01).
The enhanced anticancer effect of sequential BCG and electromotive mitomycin may stem from increased permeability of bladder mucosa caused by BCG-induced inflammation, allowing mitomycin-C to reach its target tissue more easily, according to Dr. Di Stasi.
“The overall toxic effects associated with sequential BCG and electromotive mitomycin are no worse than those associated with BCG alone,” he said.
The most frequent adverse events in patients who received at least one intravesical treatment in those assigned to BCG and electromotive mitomycin versus BCG alone were visible hematuria (59.8% vs. 58.1%), dysuria (50.5% vs. 48.6%), and drug-induced cystitis (45.8% vs. 43.8%). Adverse effects required termination of treatment in only about 3% in each group and temporary suspension in about one-third of patients in each group.