Feasibility of chemotherapy and regional hyperthermia in patients with intermediate/high risk non-muscle invasive transitional cell carcinoma of the bladder

Intermediate/high risk non-muscle invasive transitional cell carcinoma of the
bladder has a high recurrence rate and considerable risk on progression despite
intravesical chemotherapy and immunotherapy. Applying local hyperthermia in
combination with intravesical Mitomycin C is a promising development. A higher
thermal dose is expected using locoregional hyperthermia instead of local
hyperthermia supported by hyperthermia treatment planning.
As there is a significant relation between thermal dose and response rate the
clinical outcome will be improved.

The following protocol has been established in order to evaluate and compare
the feasibility and safety of 70 MHz locoregional hyperthermia applied with
concomitant Mitomycin C intravesically.

Primary objective: to study the feasibility and toxicity of the combination of
intravesical chemotherapy with Mitomycin C and regional 70 MHz microwave therapy

Secondary objective: to develop a new bladder catheter with sufficient
thermocouples to measure accurately the temperature on the bladder wall.

This study is designed as a pilot study to evaluate the feasibility and
toxicity of the combination of two well known treatments, in non-muscle
invasive bladder cancer. When feasible, a phase II study will be started in
which this treatment will be optimised by the application of new hyperthermia
techniques. The expectation is that in this way higher tumor temperatures can
be reached and therefore local tumor control can be improved.

The intervention consists of 6 weekly courses of intravesical chemotherapy with
MMC, 40 mg. MMC will be concomitantly given with locoregional 70 MHz microwave
hyperthermia, given for 1 hour at a temperature of at least 41°C.
This induction phase will be followed by a maintenance period of 12 months
during which 4 single courses of hyperthermia in combination with MMC will be
given: at 3, 6, 9 and 12 months.

The conventional treatment of intermediate/ high risk non-muscle invasive
bladder carcinoma is a TURB followed by intravesical therapy with either
chemotherapy or immunotherapy. This is installed in the bladder with a standard
bladder catheter. During this treatment hyperthermia is started. Because of
this combination, treatment takes half an hour more. Hyperthermia can cause
feelings of heat and discomfort. Cooling will be done with a fan and/or wet
towels.
From previous studies we know that toxicity and risks are minimal when given
hyperthermia to the pelvis. Side effects will be scored with the Common
toxicity scale.
Higher temperatures may lead to less recurrences and therefor less progression
of disease leading to a better overall survival.