Sequential Bacillus Calmette-Guérin (BCG) and Electromotive Mitomycin-C Versus Bacillus Calmette-Guérin (BCG) Alone for High Risk Superficial Bladder Cancer

• Status: Completed
• Trial end date: 2002-06-01
• Target enrollment: 0
• Participant gender: All

Summary

Intravesical treatment for superficial bladder cancer has been used for the past 4-5 decades. Intravesical chemotherapy is beneficial in terms of recurrence and time to recurrence in grade 1-2 stage Ta tumours, usually non-invasive. Intravesical chemotherapy has negligible effect on disease progression in high-risk superficial bladder cancer-ie, grade 3, stage T1, and carcinoma in situ. However, BCG as induction and maintenance treatment effectively delays progression. Electromotive mitomycin increases tissue uptake compared with that of passive diffusion. Electromotive mitomycin has emerged as an alternative or complementary treatment to BCG. The rationale for combining anticancer drugs is based on the need to increase efficacy and reduce emergence of resistant malignant cells. This approach is not frequently applied to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. Studies have addressed concurrent use of mitomycin and BCG, and assigned two roles to mitomycin: antitumor action and tissue-scarifying (ie, surface-modifying) effect that enables BCG to attach more efficiently to the urothelium. The investigators therefore aimed to assess whether induction of inflammation by use of BCG before mitomycin treatment makes the bladder mucosa more permeable and thus enables mitomycin to reach the target more easily. This randomised trial to compare the efficacy of sequential BCG and electromotive mitomycin with that of the current standard of BCG alone for patients with high-risk superficial bladder cancer.

After transurethral resection and multiple biopsies patients with stage pT1 bladder cancer are randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks; or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were intention to treat.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University of Rome Tor Vergata
• Collaborator: University of L'Aquila
• Treatments: BCG Vaccine; Mitomycin; Mitomycins

Criteria

Inclusion Criteria:

• adequate bone-marrow reserve (ie, white-blood-cell count ≥4000 x106 cells/L and platelet count ≥120 x 109/L)

• normal renal function (ie, serum creatinine ≤123•76 μmol/L)

• normal liver function (ie, serum glutamic-oxaloacetic transaminase ≤42 U/L, serum glutamic-pyruvic transaminase ≤48 U/L, and total bilirubin ≤22•23 μmol/L)

• Karnofsky performance status between 50 and 100.

Exclusion Criteria:

• previous treatment with BCG or electromotive mitomycin

• treatment with any other intravesical cytostatic agent within the past 6 months

• concomitant urothelial tumours of the upper urinary tract;

• previous muscle-invasive (ie, stage T2 or higher) transitional-cell - carcinoma of the bladder

• bladder capacity less than 2 L

• untreated urinary-tract infection

• severe systemic infection (ie, sepsis)

• urethral strictures that would prevent endoscopic procedures and repeated catheterisation

• disease of upper urinary tract (eg, vesicoureteral reflux or urinary-tract stones) that would make multiple transurethral procedures a risk

• previous radiotherapy to the pelvis

• other concurrent chemotherapy

• treatment with radiotherapy-response or biological-response modifiers;

• history of tuberculosis

• other malignant diseases within 5 years of trial registration (except for basal-cell carcinoma)

• pregnancy or nursing

• psychological, familial, sociological, or geographical factors that would preclude study participation.