- WebCafé home
- Newly Diagnosed
- Treatment Options
- Non-Invasive blc
- Invasive bladder cancer
- Upper tract TCC
- Metastatic cancer
- Clinical trials
- Survival Guides
- Resources USA & Canada
- Resources Europe
- Clinical trials
- Alternative medicine
- Financial help
- About Us
|Innovations in bladder cancer p.4|
Synergo® II Workshop Dec. 2005- Rome Synergo® Medical Enterprises
On this page presentations 9, 10, and 11
9.Local hyperthermia and intravesical chemotherapy for superficial TCC of the bladder Clinical studies: An overview; R. Colombo U.O. di Urologia Istituto Scientifico Universitario “Vita e Salute” San Raffaele, Milano
11.Thermochemotherapy - Current Italian Studies Rodolfo Hurle U.O. Urologia Humanitas Gavazzeni Bergamo
Disease-Free Patients: 47/71 Pts 66%, Average Follow-Up: 24 months
Rrecurrent free survival - 57.5% of the combination group (Hyperthermia+chemotherapy) had no recurrences by the 24 month mark as opposed to 17.1% in the group that received chemotherapy alone. Age and sex had no significant (p>0.05) effect on recurrence in either treatment group; previous local CT did not significantly (p>0.05) influence the results; the total number of treatment sessions had a significant (p<0.0001) association with the recurrence rates of the treatment groups pts who received 8+4 treatment sessions had a lower recurrence.
Safety Analysis: thermal reaction of the posterior bladder wall (“posterior-wall medallion”) appeared as a painless, superficial, black discoloration patch surrounded by hyperemia confined (=3cm) and self-healing from a few days to several weeks. “Posterior-wall medallion” corresponds to the location of the radio-frequency antenna inside the bladder during the operative procedure. Overall, local side effects (namely, cystitis symptoms, suprapubic pain and thermal reaction of the posterior bladder wall) were more frequent and more severe in Group 1, however, local side effects did not influence the completion of the treatment and were transitory and self-recovering shortly after the end of treatment. There was no significant difference in side effects and clinical complications observed in the 3 participating centers nor between groups.
Study Limitations: these results were preliminary and needed to be confirmed by large prospective, multicentric studies. LHT+CT was more expensive and cumbersome than routine instillation a larger catheter had to be used and it insertion may become more invasive
Aims: To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma of the bladder, and to establish the likely safety of this procedure.
Methods: Group 1 (n = 12) received 20 mg intravesical MMC plus local hyperthermia, group 2 (n = 13) 20 mg MMC alone, group 3 (n = 16) 40 mg MMC plus local hyperthermia and group 4 (n = 10) 40 mg MMC alone. Patients in groups 1, 2, and 4 underwent post-tumour resection adjuvant treatment, whereas those in group 3 still had tumour present and were treated to eradicate it. Intravesical instillation lasted 60 min, with the solution (50 ml) being replaced after the first 30 min. Blood samples were taken before, and every 15 min during instillation. MMC concentrations in plasma and in urine were determined by h.p.l.c:High Performance Liquid Chromatography (HPLC)
Long Term Follow up - median 8 years AUA 2006, submitted
Overall number of disease progression:
Recent and ongoing trials for local hyperthermia and endovsesical chemotherapy
Patients and methods: Ninety eligible patients from nine European centers received adjuvant treatment with a combination of mitomycin-C (MMC) and local microwave hyperthermia. All patients had multiple or recurrent Ta or T1 TCC of the bladder and were classified as intermediate or high risk (IR, HR) according to EAU criteria. In total, 41 patients were BCG failures. The treatment regimen included 6 to 8 weekly sessions followed by 4 to 6 monthly sessions. Follow-up consisted of video-cystoscopy and urine cytology every 3 months. All patients were observed for 2 years.
Results: Kaplan-Meier analyses of the total group (N = 90) indicated that 1 year after treatment only 14.3% (SE 4.5%) of all patients experienced a recurrence. After 2 years of follow-up the risk of recurrence was 24.6% (SE 5.9%). No progression in stage and grade was observed.
Time to first recurrence.
Time to first recurrence for HR and IR
Time to first recurrent for Pts with prior BCG
Conclusion: Microwave induced hyperthermia combined with MMC has promising value in intermediate or high risk superficial bladder cancer patients compared to literature data of BCG and/or intravesical chemotherapy, particularly where other treatments, i.e. BCG, have failed.
SYNERGO for BCG FAILURES 1996 – Ongoing
Combined local bladder hyperthermia and intravesical chemotherapy for the treatment of high-grade superficial bladder cancer. Gofrit ON, Shapiro A, Pode D, Sidi A, Nativ O, Leib Z, Witjes JA, van der Heijden AG, Naspro R, Colombo R. Department of Urology, Hadassah University Hospital, Jerusalem, Israel. Urology. 2004 Mar;63(3):466-71. PubMed
Objectives: To evaluate the effectiveness of combined local bladder hyperthermia and intravesical chemotherapy for the treatment of patients with high-grade (G3) superficial bladder cancer.
Methods: Patients with G3 bladder tumors (Stage Ta or T1) were treated with combined intravesical chemotherapy with mitomycin-C and local radiofrequency hyperthermia of the bladder wall. The patients were treated with either a prophylactic protocol (40 mg mitomycin-C) after complete transurethral resection of all tumors or with an ablative protocol (80 mg mitomycin-C) when visible tumor was seen on video-cystoscopy or bladder biopsies were positive for carcinoma in situ.
Results: Combined chemo-thermotherapy was administered to 52 patients with high-grade superficial bladder cancer (40 patients with Stage T1 tumor, 11 with Ta, and 3 with concomitant or isolated carcinoma in situ). At a median follow-up of 15.2 months (mean 23, range 6 to 90), no stage progression to T2 or disease-related mortality had occurred. The bladder preservation rate was 86.5%. The prophylactic protocol was administered to 24 patients. After a mean follow-up of 35.3 months, 15 patients (62.5%) were recurrence free. The bladder preservation rate was 95.8%. The ablative protocol was administered to 28 patients. Complete ablation of the tumor was accomplished in 21 patients (75%). After a mean follow-up of 20 months, 80.9% of these patients were recurrence free. The bladder preservation rate for the ablative group was 78.6%.
Conclusions: Combined local bladder hyperthermia and intravesical chemotherapy has a beneficial prophylactic effect in patients with G3 superficial bladder cancer. Ablation of high-grade bladder tumors is feasible, achieving a complete response in about three quarters of the patients.
Background: The purpose of this study was to evaluate the efficacy of combined local hyperthermia and intravesical mitomycin-C (MMC) in a selected group of patients with intermediate or high-risk recurrent transitional cell carcinoma (TCC) of bladder.
Results: Thirty-two patients were eligible for analysis. The prophylactic protocol was administered to 22 patients. After a mean follow-up of 289 days, 20 patients (91%) were recurrence free. Two patients (9%) had tumour recurrence after a mean period of 431 days. The ablative protocol was administered to 10 patients. Complete tumour ablation was achieved in eight patients (80%) after a mean follow up of 104.5 days.
Prophylaxis Protocol, after follow up of 289 days, 20/21 (91%) recurrence-free
Conclusions: Our efficacy and safety results confirm those reported in previously published studies, suggesting the promising value of this combined treatment modality for both prophylactic and ablative patients. The ablative protocol offers an alternative therapy for a selected patient population for whom no other treatment option exists.
Some possible reasons:
In vitro research
2005: Effect of Hyperthermia on the cytotoxicity of 4 chemotherapeutic agents currently used for the treatment of transitional cell carcinoma of the bladder: An in vitro study van der Heijden AG, Verhaegh G, Jansen CFJ, Schalken JA, Witjes JA The Journal of Urology - April 2005 (Vol. 173, Issue 4, Pages 1375-1380:
The human transitional cell carcinoma cell lines used were RT4, RT112, 253J and T24. Cells were seeded in 96-well microtiter plates. After 24 hours cells were treated for 60 minutes with increasing concentrations of mitomycin C, epirubicin, gemcitabine and EO9 at a temperature of 37C or 43C. After treatment cells were rinsed 3 times and left for 24 hours in the incubator at 37C. The influence of chemotherapy and temperature on cell survival was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide) assay.
In vivo research (van der Heijden, submitted)
Tumor Response rate
2005 update: European ablative pts (MMC40/40):All patients: n=156
Some recent prophylactic results (Colombo, JCO, dec 2003)
Multicentric Study Comparing Intravesical Chemotherapy Alone and With Local Microwave Hyperthermia for Prophylaxis of Recurrence of Superficial Transitional Cell Carcinoma Renzo Colombo, Luigi Filippo Da Pozzo, Andrea Salonia, Patrizio Rigatti, Zvi Leib, Jack Baniel, Emanuele Caldarera, and Michele Pavone-Macaluso; From the Department of Urology, University Vita-Salute San Raffaele, Milan, Italy; the Department of Urology, Beilinson Hospital, Tel Aviv, Israel; and the University of Palermo, Palermo, Italy. JCO Dec 1 2003: 4270–4276 pubMed (see above )
Conclusion: In our series, endovesical thermochemotherapy appears to be more effective than standard endovesical chemotherapy as an adjuvant treatment for superficial bladder tumors at 24-month follow-up, despite an increased but acceptable local toxicity.
Synergo in intermediate and high risk patients:
-90 EAU intermediate or high risk patients (41 BCG failures)
Results: Kaplan-Meier analyses of the total group (N = 90) indicated that 1 year after treatment only 14.3% (SE 4.5%) of all patients experienced a recurrence. After 2 years of follow-up the risk of recurrence was 24.6% (SE 5.9%). No progression in stage and grade was observed. CONCLUSION: Microwave induced hyperthermia combined with MMC has promising value in intermediate or high risk superficial bladder cancer patients compared to literature data of BCG and/or intravesical chemotherapy, particularly where other treatments, i.e. BCG, have failed.
Comparisons: Literature in intermediate and high risk patients (vd Heijden et al, Eur Uro '04l]
Clinical trial: 102.1 Synergo® protocol
Some posterior wall necrosis is seen after treatment.
As reviewed by Prof. Witjes in his presentation (above), the costs of treating recurrent bladder tumors is astronomically high. The equipment and costs associated with a new technology like Synergo® can be justified if it defers one cystoscopy and one instillation per year, per patient. That alone would represent a huge savings.
Current Italian Studies Lombardia Synergo Project 2005-2008
N patients - 240; Time span for ° the project, 3 years
A highly selective homogenous subset of female patients affected by SBC "high bladder carcinogenity" do not respond to repeated TUR and instillations.
Objective: The primary objective is to obtain at least 50% of the patient NED at 12 months
|Last Updated ( Sunday, 15 June 2008 )|