Comparative study of intravesical chemotherapy instillations combined
with hyperthermia versus intravesical chemotherapy instillations for
prophylaxis of recurrences of Superficial Transitional Cell Carcinoma
of the urinary Bladder (STCCB).
The aim of this study was to compare the safety and efficacy of intravesical
instillation of a chemotherapeutic agent combined with local hyperthermia
delivered by the Synergo® System versus intravesical instillation of the
same chemotherapeutic agent.
Intermediate-high risk patients (mostly failures to previous instillations,
including BCG) were enrolled following TUR eradication of superficial
transitional cell bladder tumors. The chemotherapeutic agent used in this
study was Mitomycin C (MMC).
The study was designed as a two-arm randomized study.
The 3 medical centers that participated were:
San Raffaele Hospital. Milan, Italy; University Hospital. Palermo, Italy;
Rabin Medical Center, Beilinson Campus. Petach-Tikva, Israel
Group 1:
Intravesical Chemotherapy & Local Hyperthermia - Synergo®
Two thirty minutes cycles, each consisted of intravesical instillation of 20mg Mitomycin C dissolved in 50cc of sterile distilled water
Hyperthermia at 42±2°C delivered by the Synergo® System.
8 weekly inductive sessions followed by 4 monthly maintenance sessions
42 Patients
Group 2:
Intravesical Chemotherapy Alone
Two thirty minutes cycles, each consisted of intravesical instillation of 20mg Mitomycin C dissolved in 50cc of sterile distilled water
8 weekly inductive sessions followed by 4 monthly maintenance sessions
41 Patients
Follow-up began at the end of the 8th inductive session, and proceeded between 2 to 5 years.
Efficacy Analysis:
The following graph presents the results for the per protocol cohort using the Kaplan-Meier Survival Analysis with the log rank test for statistical significance:
K-M Survival Analysis for per protocol cohort, long-term follow-up
Long-term follow-up results are for ³ 24 months (up to 5 years). The results
clearly demonstrate a highly significant (p=0.0006) difference in the recurrence
rate of STCCB between the two treatment groups, where tumor recurrence was significantly
sooner and more frequent in the intravesical chemotherapy alone group (65%) compared to
the Synergo® group (25.7%).
Side Effects
Most of the side effects were common between both treatment groups:
Dysuria, MMC induced skin allergy, few side effects related to the
procedure (catheter insertion) and hematuria. The only parameters
that presented a significant difference between the treatment groups
were mild pain during session, and posterior bladder wall thermal
reaction (transient, superficial and asymptomatic, that resolved
without medical intervention).
Recurrence
During long-term follow-up a total of 35 patients were reported with
tumor recurrence, 9 in Synergo® group and 26 in the intravesical
chemotherapy group.
Medical Enterprises Europe B.V.
Assumburg 152B
1081GC, Amsterdam, The Netherlands
Tel: +31 (0) 20 6423719
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R&D Center:
MEL Medical Enterprises Ltd.
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