Combined Intravesical Chemotherapy with Mitomycin C and
Local Bladder Microwave-Induced Hyperthermia as a
Preoperative Therapy for Superficial Bladder Tumors

Rigatti, Patrìzio; Lev, A.; Colombo, Renzo

doi:10.1159/000471701

Cited by 38 publications

(17 citation statements)

References 7 publications

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“…Although the most common adverse effects described in the literature are bladder spasms (2–40%) and pain (8–27%), urgency‐frequency was the most common adverse effect (>50% of patients) in the present cohort. As all our patients had had multiple previous TURB and 71% had also undergone intravesical instillation therapies with either BCG or a chemotherapeutic agent, it is probable that they had an increased vulnerability to additional chemotherapy compared with chemo‐naïve patients because of their compromised bladder mucosa.…”

Section: Discussionmentioning

confidence: 63%

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non‐muscle‐invasive bladder cancer?

et al. 2014

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Abbreviations & Acronyms BC = bladder cancer BCG = bacillus Calmette-Guérin CIS = carcinoma in situ HT = hyperthermia MMC = mitomycin C NMIBC = non-muscle-invasive bladder cancer TUR = transurethral resection TURB = transurethral resection of the bladder Objectives: To prospectively evaluate the outcome of combined microwave-induced bladder wall hyperthermia and intravesical mitomycin C instillation (thermochemotherapy) in patients with recurrent non-muscle-invasive bladder cancer. Methods: Between 2003 and 2009, 21 patients (median age 70 years, range 35-95 years) with recurrent non-muscle-invasive bladder cancer (pTaG1-2 n = 9; pTaG3 n = 3; pT1 n = 9; concurrent pTis n = 8) were prospectively enrolled. Of 21 patients, 15 (71%) had received previous intravesical instillations with bacillus Calmette-Guérin, mitomycin C and/or farmorubicin. Thermochemotherapy using the Synergo system was carried out in 11 of 21 patients (52%) with curative intent, and in 10 of 21 patients (48%) as prophylaxis against recurrence. Results: The median number of thermochemotherapy cycles per patient was six (range 1-12). Adverse effects were frequent and severe: urinary urgency/frequency in 11 of 21 patients (52%), pain in eight of 21 patients (38%) and gross hematuria in five of 21 patients (24%). In eight of 21 patients (38%), thermochemotherapy had to be abandoned because of the severity of the adverse effects (pain in 3/8, severe bladder spasms in 2/8, allergic reaction in 2/8, urethral perforation in 1/8). Overall, six of 21 patients (29%) remained free of tumor after a median follow up of 50 months (range 1-120), six of 21 patients (29%) had to undergo cystectomy because of multifocal recurrences or cancer progression and seven of 21 patients (33%) died (2/7 of metastatic disease, 5/7 of non-cancer related causes). Conclusions: Given the high rate of severe side-effects leading to treatment discontinuation, as well as the limited tumor response, thermochemotherapy should be offered only in highly selected cases of recurrent non-muscle-invasive bladder cancer.

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Section: Discussionmentioning

confidence: 63%

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non‐muscle‐invasive bladder cancer?

et al. 2014

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“…A description of this technique as well as its advantages over earlier methods of inducing hyperthermia, have been extensively reported by us [7–12].…”

Section: Methodsmentioning

confidence: 99%

“…Since 1987 many clinical trials have shown that administration of mitomycin C (MMC) combined with LHT is safe and more effective in tumour ablation and in preventing recurrences after TUR than using ICT alone. Furthermore, the procedure can prevent or at least delay the need for cystectomy in a large number of patients affected by multifocal and unresectable bladder tumours [7‐13].…”

Section: Introductionmentioning

confidence: 99%

Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma

Paroni¹,

Salonia²,

Lev

et al. 2001

Brit J Clinical Pharma

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Aims To assess the effect of local hyperthermia on the systemic absorption of mitomycin C (MMC) during intravesical chemotherapy for the treatment of super®cial 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 ®rst 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. Results The highest MMC plasma concentration (67.9 ng ml x1 ) occurred in a patient in group 3. This value was well below the threshold concentration (400 ng ml x1 ) for myelosuppression. Local hyperthermia associated with the intravesical chemotherapy enhanced plasma MMC concentrations at 30, 45 and 60 min compared with chemotherapy alone (Group 1 vs 2, Pj0.008). Systemic exposure to MMC was not signi®cantly increased by doubling the intravesical dose when intravesical chemotherapy alone was administered. Patients in group 3 displayed the highest degree of MMC absorption and the greatest variability in pharmacokinetics between patients. Conclusions Local hyperthermia enhances the systemic absorption of MMC during intravesical chemotherapy for bladder cancer. In the doses used, plasma MMC concentrations were always more than six times lower than those shown to cause toxicity.

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“…Synergo, operating at a frequency of 915 MHz [10, 13, 14], externally heated chemotherapy fluid circulation in the bladder [15], intravesical magnetic nanoparticles [16], and external deep regional radiofrequency transmission with 70–110 MHz [17]. While the intravesical heating methods are more commonly used and produce uniform temperatures across the urothelial lining of the bladder, there is a significant temperature gradient measured through increasing depth of the bladder wall.…”

Section: Introductionmentioning

confidence: 99%

A systematic review of regional hyperthermia therapy in bladder cancer

Longo

Gopalakrishna

Tsivian

et al. 2016

International Journal of Hyperthermia

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Context Bladder cancer therapy remains suboptimal as the morbidity and mortality remains high amongst those with non-muscle invasive and muscle-invasive disease. Regional hyperthermia therapy (RHT) is a promising adjunctive therapy being tested in multiple clinical contexts. Objective To systematically review the literature on the efficacy and toxicity of RHT. Evidence Acquisition The systematic review was registered with the PROSPERO database (Registration number: CRD42015025780) and was conducted according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. We queried PubMed, EMBASE, and Cochrane libraries. Two reviewers reviewed abstracts independently and a third reviewer arbitrated disagreements. The last search was performed on August 28, 2015. A descriptive analysis was performed and quality assessment was conducted using the Newcastle-Ottawa Quality Assessment Scale for observational studies, and the Cochrane Risk of Bias Assessment Tool for trials. Evidence Synthesis We identified 859 publications in the initial search, of which 24 met inclusion criteria for full-text review. Of these, we were able to obtain data on the outcomes of interest for 15 publications. Conclusions The review underscores the limited nature of the evidence; definitive conclusions are elusive. However, the promising results of RHT in the setting of intravesical chemotherapy, chemotherapy and radiotherapy show a trend towards legitimate efficacy.

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Combined Intravesical Chemotherapy with Mitomycin C and Local Bladder Microwave-Induced Hyperthermia as a Preoperative Therapy for Superficial Bladder Tumors

Cited by 38 publications

References 7 publications

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non‐muscle‐invasive bladder cancer?

Is thermochemotherapy with the Synergo system a viable treatment option in patients with recurrent non‐muscle‐invasive bladder cancer?

Effect of local hyperthermia of the bladder on mitomycin C pharmacokinetics during intravesical chemotherapy for the treatment of superficial transitional cell carcinoma

A systematic review of regional hyperthermia therapy in bladder cancer

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