Background: Patients with BCG-refractory non-muscleinvasive bladder cancer (NMIBC) represent a widely argued therapeutic challenge. Many conservative treatments have been proposed. Bladder wall thermochemotherapy seems to be an interesting treatment option. UniThermia is a new device that provides bladder wall thermochemotherapy with uniform hyperthermia (44.5˚C) all over the bladder with a high flow of a heated mitomycin C (MMC) solution. The aim of this study was to evaluate drug stability, pharmacokinetics, tolerability and activity of this technique. Patients and Methods: A total of 28 patients with BCG-refractory NMIBC (intermediate and high risk) were treated with a course of six instillations after transurethral resection of bladder tumor (TURBT): one early single and five weekly instillations. The drug solution was completely replaced at the halfway point of each instillation. After the treatment, patients underwent cystoscopy every three months for the first year and every six months afterwards. Results: There was a significant loss of MMC in the first half of instillation, while in the second half, most of the drug was retrieved. This observation suggests that there was a significant absorption of MMC during the first half of instillation which was minimal in the second half. Plasmatic Cmax was considerably lower than the reported threshold concentration for toxicity (400 ng/ml). Most side-effects were not beyond grade II, showing a good safety profile. Data about activity are partial, with 1-year follow-up available for only 16 patients. Among them, six were disease-free, six presented progression and four recurrence.
PHARMACOKINETICS, PHARMACOLOGICAL STABILITY, SAFETY AND ACTIVITY OF MMC ADMINISTERED WITH A NEW HYPERTHERMIA DEVICE (UNITHERMIA)
FIORITO, CHIARA;Soria F;CATTEL, Luigi;MILLA, Paola;GONTERO, Paolo
2011-01-01
Abstract
Background: Patients with BCG-refractory non-muscleinvasive bladder cancer (NMIBC) represent a widely argued therapeutic challenge. Many conservative treatments have been proposed. Bladder wall thermochemotherapy seems to be an interesting treatment option. UniThermia is a new device that provides bladder wall thermochemotherapy with uniform hyperthermia (44.5˚C) all over the bladder with a high flow of a heated mitomycin C (MMC) solution. The aim of this study was to evaluate drug stability, pharmacokinetics, tolerability and activity of this technique. Patients and Methods: A total of 28 patients with BCG-refractory NMIBC (intermediate and high risk) were treated with a course of six instillations after transurethral resection of bladder tumor (TURBT): one early single and five weekly instillations. The drug solution was completely replaced at the halfway point of each instillation. After the treatment, patients underwent cystoscopy every three months for the first year and every six months afterwards. Results: There was a significant loss of MMC in the first half of instillation, while in the second half, most of the drug was retrieved. This observation suggests that there was a significant absorption of MMC during the first half of instillation which was minimal in the second half. Plasmatic Cmax was considerably lower than the reported threshold concentration for toxicity (400 ng/ml). Most side-effects were not beyond grade II, showing a good safety profile. Data about activity are partial, with 1-year follow-up available for only 16 patients. Among them, six were disease-free, six presented progression and four recurrence.
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