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“Efficacy and safety of a new device for intravesical thermochemotherapy in BCG recurrent NMIBC. A phase I-II study.” Francesco Soria Clinica urologica Università degli Studi di Torino Introduction: state of the art BCG is currently considered the most effective first line intravesical therapy in NMIBC and the standard conservative treatment option in the high risk category Up to 40% of patients will eventually recur after BCG Babjuk M, Eur Urol 2013 Martin FM, Expert Rev Anticancer Ther 2009 Introduction: the problem of BCG failure Gallagher BL, J Urol 2007 Sternberg IA, J Urol 2013 Introduction: thermochemotherapy Intravesical chemotherapy has been combined with hyperthermia in order to improve treatment efficacy by increasing drug permeability and cytotoxic effect "More effective than MMC alone" "Promising response rates in BCG refractory" "Routine clinical use limited by the high costs of the proper catheters and the high skillfulness required to assure a correct positioning of the catheter" Synergo® system Matherials and methods Phase I-II study: to test the efficacy and safety of Unithermia® (Elmedical Ldt, Hod-Hasharon, Israel) a new hyperthermia device for intravesical chemotherapy based on a conductive heating system Treatment schedule • 6 weekly intravesical instillation of Mitomycin C (MMC) 40 mg in 50 cc of 0.9% saline solution (concentration 0.8 mg/ml) with Unithermia® device • 45 minutes each • In the first 11 patients the solution was replaced after 22 minutes in order to assess drug stability Results: Baseline characteristics 34 patients recurrent after BCG, unfit for surgery or asking for conservative treatment Patients characteristics Age (years), median [range] 70 [51-85] No. Males Females Pathology Staging Ta T1 Grading G1 G2 Focality Single Multiple (%) 28 6 (82.3) (17.7) 26 8 (76.5) (23.5) 16 18 23 11 (47) (53) (67.7) (32.3) Results: stability and pharmacokinetics of MMC • MMC is stable during treatment with Unithermia device • Cmax MMC plasmatic levels were considerably lower than the reported threshold concentration for toxicity (400 ng/ml) • Median rate of MMC recovery in the first (0-22 min) and second (23-45) part of the instillation was 66.2 % (range 38.6-92.3) and 99.6 %(range 68.6-136), respectively Milla P, Cancer Chemotherapy and Pharmacol, 2014 Results: Efficacy at 12 months Response Rate 22 (64,7%) Recurrence Rate 11 (32,4%) - 1 CIS - 4 G3 Progression Rate (T2G3) 1 (2,9%) 75% of T1 patients underwent early recurrence Failure to achieve optimal HT condition at the bladder wall with Unithermia Results: tolerability Toxicity according to CTCAEv6 Grade I n Grade II n Grade III n TOT n(%) Bladder spasms 4 1 3 8(27,5) Frequency 2 3 - 5(17) Incontinence - 1 - 1(3,5) Bladder wall injury - - - 0 Haematuria - - - 0 Dysuria 1 3 - 4(14) Skin rashes - 1 1 2(7) Fever - - - 0 Discussion and Conclusions Interesting efficacy and safety profile in non-grade 3 NMIBC recurring after BCG Costs of the device and disposable catheters are significantly lower compared with other devices (i.e. Synergo®) Failure to achieve optimal HT condition at the bladder wall with Unithermia may account for the high early recurrence in the T1 patients “Efficacy and safety of a new device for intravesical thermochemotherapy in BCG recurrent NMIBC. A phase I-II study.” Grazie!