Updates in intravesical electromotive drug administration® of mitomycin-C for non-muscle invasive bladder cancer

Abstract

Electromotive drug administration Ò (EMDA) increases the local drug efficacy by controlling and enhancing transmembranous transport into tissue. EMDA of intravesical mitomycin-C (MMC) has been used for treatment of non-muscle invasive bladder cancer (NMIBC) for about a decade on the basis of laboratory studies that demonstrated an enhanced administration rate of MMC into all bladder wall layers after EMDA compared to standard instillation/passive diffusion (PD). Higher MMC concentrations might have a clinical impact since EMDA was associated with lower recurrence rates than PD in randomized studies. Further data suggest that EMDA/ MMC is at least equivalent to BCG in treatment of highrisk bladder tumours. In addition, BCG combined with EMDA/MMC as well as preoperative EMDA/MMC are new therapeutic strategies with promising preliminary results in terms of higher remission rates and longer remission times. In summary, these findings suggest that EMDA for MMC delivery in the bladder could be a major therapeutic breakthrough in the treatment of NMIBC.

Electromotive instillation of mitomycin immediately before transurethral resection for patients with primary urothelial non-muscle invasive bladder cancer: a randomised controlled trial

“…The mitomycin solution was drained and TURBT was done, subsequently continuous intravesical irrigation with saline for 8-18 h, to prevent clot formation or retention and related complications. As previously described, 19 intravesical EMDA is given by a battery-powered generator delivering a controlled electric current that passes between the active intravesical electrode (integrated into a specifi c transurethral catheter) and dispersive ground electrodes (on skin of the lower abdomen). Operators set active electrode polarity and current intensity on the generator.…”

Optimal Treatment of Non-Muscle Invasive Urothelial Carcinoma Including Perioperative Management Revisited

“…This method utilizes electrical current to impart an accelerated, directional movement of ionized drugs into tissues to achieve greater local concentrations and depth of penetration than achievable by passive diffusion alone. Though MMC is mostly non-ionized at urinary pH, electroosmosis still occurs carrying Na + ions and the accompanying water and soluble drug with it [20]. Di Stasi and colleagues reported a reduction in recurrence rates using EMDA MMC for patients with pTa and pT1 urothelial carcinoma from 59 % in controls using passive instillation to 38 % using EMDA [21•].…”

Second-Line Intravesical Therapy. What is the Present Role of Device-Assisted Therapy?

“…Numerosi studi in vitro e in vivo hanno dimostrato come le concentrazioni di MMC nella parete della vescica siano significativamente aumentate applicando una corrente elettrica. I dati suggeriscono inoltre che l'EMDA abbia tassi di risposta quasi equivalenti al BCG nel trattamento di tumori della vescica ad alto rischio (10). Diversi studi hanno evidenziato la sicurezza e l'efficacia della metodica.…”

“…Dal confronto tra trattamenti con EMDA e con solo MMC non si evidenziano differenze in termini di risposta completa dopo 8 settimane di trattamento, ma i pazienti sottoposti a EMDA mostrano tassi di recidiva più bassi e intervalli liberi da malattia più lunghi, con scarsi effetti collaterali (9). In pazienti con neoplasia vescicale non muscoloinfiltrante multifocale ad alto rischio, sottoposti a tre schemi terapeutici (EMDA, MMC e BCG), il tasso di risposta completa a 3 e 6 mesi dopo EMDA è stato significativamente maggiore rispetto alla MMC, ma non rispetto al BCG (10). Nuove strategie come BCG combinato con EMDA ed EMDA come trattamento neoadiuvante delle neoplasie vescicali non muscolo-infiltranti hanno fornito risultati preliminari promettenti in termini di tassi di remissione più elevati e tempi più lunghi di remissione di malattia (9).…”