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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!