Electromotive Mitomycin Research Articles

Single ablative intravesical electromotive mitomycin C administration for small non-muscle-invasive bladder cancer: a prospective study

Objectives To explore the effect of electromotive drug administration of mitomycin C (EMDA-MMC) using a single dose of intravesical mitomycin C (MMC) to avoid transurethral resection (TURBT) for small non-muscle-invasive bladder cancer.Material and methods All patients presenting small (<2 cm), single or multiple papillary bladder tumors were proposed to undergo a single EMDA-MMC instillation with 60 mg MMC before planning TURBT. The end point is complete disappearance of all papillary tumors at 2–4 weeks after EMDA-MMC.Results Thirty-six instillations were given to 32 patients. In general the treatment was well supported, except for two patients who had severe bladder spasms, resulting in early evacuation of the MMC. Complete response occurred in 28% (10/36 instillations). In 4 EMDA-MMCs with multiple tumors some tumors disappeared while others remained. In 61% (22/36) the tumors remained unchanged.Conclusion A single EMDA-MMC in l papillary bladder tumors <2 cm gives insufficient ablative effect.

Contemporary cost-effectiveness analysis comparing sequential bacillus Calmette-Guerin and electromotive mitomycin versus bacillus Calmette-Guerin alone for patients with high-risk non-muscle-invasive bladder cancer.

Sequential bacillus Calmette-Guerin (BCG) and electromotive mitomycin (sequential therapy) have been shown in a randomized prospective trial to be superior to therapy with BCG alone in patients with high-risk non-muscle-invasive bladder cancer. The objective of the current study was to compare the costs and benefits of these 2 treatment strategies by performing a 5-year and 10-year cost-effectiveness study. A Markov model was developed to estimate the incremental cost-effectiveness ratio over a 5-year and 10-year period. Estimates of disease progression, death, and treatment efficacy were obtained from what to the authors' knowledge is the only randomized trial comparing the 2 therapies. Costs included: 1) medical costs (physician fees); 2) drug costs (preparation and instillation); and 3) hospital costs (procedure fees, admission fees, and tests and procedures done during surveillance). Patients were allowed a second course of induction therapy. Sequential therapy was found to be associated with a higher initial material cost for induction and maintenance. The average effectiveness for the patients treated with therapy with BCG alone was 4.39 years with a mean cost of $9236 (95% confidence interval, $9118-$9345) per patient. The sequential group resulted in an average effectiveness of 4.65 years, with a mean cost of $16,468 (95% confidence interval, $16,371-$16,527). The 5-year incremental cost-effectiveness ratio of sequential versus BCG-alone therapy was $27,815 per life-year gained. The corresponding figure over a 10-year period was $8618 per life-year gained. The results of the current study suggest that sequential therapy is a cost-effective treatment for patients with high-risk non-muscle-invasive bladder cancer.

698 Intravesical sequential BCG and electromotive mitomycin versus BCG alone for stage pT1 urothelial bladder cancer

698 Intravesical sequential BCG and electromotive mitomycin versus BCG alone for stage pT1 urothelial bladder cancer

Intravesical sequential BCG and electromotive mitomycin versus BCG alone in high risk non-muscle invasive bladder cancer.

4572 Background: In 2006, we reported that intravesical sequential bacillus Calmette-Guérin (BCG) and electromotive mitomycin in high risk non-muscle invasive bladder cancer leads to higher disease-free interval, lower recurrence and progression, and to improved overall survival and disease-specific survival compared with BCG alone. After an additional 6 years of follow-up, we now report estimated 16-year results. Methods: From 1994 through 2002, we randomly assigned 212 patients with high risk non.muscle invasive bladder cancer to 81 mg BCG infused over 120 min once a week for 6 weeks (n=105) or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval. Analyses were done by intention to treat. Results: Median follow-up was 121 months (IQR 70.5–163.5). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (79 months [95% CI 27–139] vs 26 months [11–113]; difference between groups 53 months [39–67], log-rank p=0.0002). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (45% [35–55] vs 62% [50–72], difference between groups 17% [6–28], log-rank p=0.0002); progression (12% [3–21] vs 28% [17.5–38.5], difference between groups 16% [5–27], log-rank p=0.003); overall mortality (44% [33–55] vs 59% [43–75], difference between groups 15% [2–28], log-rank p=0.01); and disease-specific mortality (9% [2.5– 15.5] vs 23% [11–34], difference between groups 14% [4–24], log-rank p=0.0055). Conclusions: In patients with high risk non-muscle invasive bladder cancer intravesical BCG combined with electromotive mitomycin provided better results than BCG alone in terms of higher remission rates and longer remission times.

1670 INTRAVESICAL SEQUENTIAL BACILLUS CALMETTE-GUÉRIN AND ELECTROMOTIVE MITOMYCIN VERSUS BACILLUS CALMETTE-GUÉRIN ALONE FOR STAGE PT1 UROTHELIAL BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Superficial I1 Apr 20121670 INTRAVESICAL SEQUENTIAL BACILLUS CALMETTE-GUÉRIN AND ELECTROMOTIVE MITOMYCIN VERSUS BACILLUS CALMETTE-GUÉRIN ALONE FOR STAGE PT1 UROTHELIAL BLADDER CANCER Savino Mauro Di Stasi, Cristian Verri, Emanuele Liberati, Francesco Masedu, Luca Topazio, and Marco Valenti Savino Mauro Di StasiSavino Mauro Di Stasi Rome, Italy More articles by this author , Cristian VerriCristian Verri Rome, Italy More articles by this author , Emanuele LiberatiEmanuele Liberati Rome, Italy More articles by this author , Francesco MaseduFrancesco Masedu L'Aquila, Italy More articles by this author , Luca TopazioLuca Topazio Rome, Italy More articles by this author , and Marco ValentiMarco Valenti L'Aquila, Italy More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2012.02.1528AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES In 2006, we reported that intravesical sequential bacillus Calmette-Guérin (BCG) and electromotive mitomycin, in patients with stage pT1 urothelial bladder cancer, leads to higher disease-free interval, lower recurrence and progression, and to improved overall survival and disease-specific survival compared with BCG alone. After an additional 6 years of follow-up, we now report estimated 16-year results. METHODS From January 1994 through June 2002, we randomly assigned 212 patients with stage pT1 urothelial bladder cancer to 81 mg BCG infused over 120 min once a week for 6 weeks (n=105) or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. RESULTS Median follow-up was 121 months (IQR 70.5–163.5). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (79 months [95% CI 27–139] vs 26 months [11–113]; difference between groups 53 months [39–67], log-rank p=0.0002). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (45% [35–55] vs 62% [50–72], difference between groups 17% [6–28], log-rank p=0.0002); progression (12% [3–21] vs 28% [17.5–38.5], difference between groups 16% [5–27], log-rank p=0.003); overall mortality (44% [33–55] vs 59% [43–75], difference between groups 15% [2–28], log-rank p=0.01); and disease-specific mortality (9% [2.5– 15.5] vs 23% [11–34], difference between groups 14% [4–24], log-rank p=0.0055). Side-effects were mainly localised to the lower urinary tract. Mitomycin pharmacokinetics showed that plasma levels remained well below toxic concentrations. CONCLUSIONS In patients with stage pT1 urothelial bladder cancer intravesical BCG combined with electromotive mitomycin provided better results than BCG alone in terms of higher response rates and longer remission times. © 2012 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 187Issue 4SApril 2012Page: e674 Advertisement Copyright & Permissions© 2012 by American Urological Association Education and Research, Inc.MetricsAuthor Information Savino Mauro Di Stasi Rome, Italy More articles by this author Cristian Verri Rome, Italy More articles by this author Emanuele Liberati Rome, Italy More articles by this author Francesco Masedu L'Aquila, Italy More articles by this author Luca Topazio Rome, Italy More articles by this author Marco Valenti L'Aquila, Italy More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Electromotive mitomycin in superficial bladder cancer

In a recent randomized trial, electromotive intravesical administration of mitomycin before transurethral resection was shown to be effective in the prevention of bladder cancer recurrence. Although this treatment seems to be promising, one question remains: can these results be reproduced by other research groups? If this is the case, it could become a new standard.

Lectin Mediated Biorecognition as a Novel Strategy for Targeted Delivery to Bladder Cancer

Inadequate urothelial delivery of drugs is considered a primary cause of current shortcomings in adjuvant intravesical chemotherapy for bladder cancer. We report what is to our knowledge a novel biorecognitive approach to achieve more regionally selective targeting of malignant tissue and improve urothelial uptake based on specific interaction between lectins and bladder cell glycocalyces. We assessed the cytoadhesive and cytoinvasive potential of selected plant lectins in 3 human urothelial cell lines, corresponding to healthy tissue, and low and high grade carcinoma, respectively. Flow cytometry and fluorimetry were used to determine binding capacity and specificity in single cells and confluent monolayers. Monensin quenching experiments, microscopic analysis and enzyme treatment allowed further characterization of internalization, the uptake pathway and the potential cause of tumor selectivity. Wheat germ agglutinin had the highest bioadhesive potential while peanut agglutinin was the most potent discriminator between healthy and cancerous tissue (p <0.01). In each case cell interaction was highly specific (greater than 80%) and proved decisive for efficient uptake. Within 60 minutes after exposure greater than 50% of membrane bound lectins were internalized in acidic compartments. Cancer associated aberrant glycosylation likely represents the determining cause of peanut agglutinin selectivity. Given careful choice of the targeting ligand, the development of carbohydrate based delivery strategies for bladder cancer therapy seems feasible. Lectin bioadhesion may not only mediate preferential accumulation in malignant tissue but also promote cellular internalization via increased recruitment of membrane bound material to physiological uptake routes.

Is Electromotive Mitomycin C an Alternative Treatment for Frail Patients with High-Risk Non-Muscle Invasive Bladder Cancer Who Have Failed Intravesical BCG?

Is Electromotive Mitomycin C an Alternative Treatment for Frail Patients with High-Risk Non-Muscle Invasive Bladder Cancer Who Have Failed Intravesical BCG?

Electromotive drug administration with mitomycin C for intravesical treatment of non-muscle invasive transitional cell carcinoma

This article reviews the use and application of electromotive drug administration for the intravesical treatment of bladder cancer. Strong evidence supports the use of passive intravesical chemotherapy in the management of non-muscle invasive bladder cancer. More recently, two published randomised trials have shown therapeutic advantage with protocols that use electromotive drug administration to enhance urothelial penetration of intravesical mitomycin C. The results suggest that the passive intravesical administration of chemotherapeutic drugs may be suboptimal. Further studies are required to demonstrate the feasibility and advantage of electromotive intravesical mitomycin C in the wider uro-oncological community.

Erratum: A combination of intravesical BCG and electromotive mitomycin for high-risk superficial bladder cancer

Nature Clinical Practice Urology (2006) 3: 472–473 [doi: 10.1038/ncpuro0559] In the September 2006 issue, the title of this Practice Point commentary was published as “A combination of intravesical and BCG electromotive mitomycin for high-risk superficial bladder cancer”. This should have appeared as “A combination of intravesical BCG and electromotive mitomycin for high-risk superficial bladder cancer”.

A combination of intravesical and BCG electromotive mitomycin for high-risk superficial bladder cancer

A combination of intravesical and BCG electromotive mitomycin for high-risk superficial bladder cancer

Intravesical bacillus Calmette–Guérin combined with electromotive mitomycin for high-risk superficial bladder cancer

Intravesical bacillus Calmette–Guerin combined with electromotive mitomycin for high-risk superficial bladder cancer

Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: A randomised controlled trial: Di Stasi SM, Giannantoni A, Giurioli A, Valenti M, Zampa G, Storti L, Attisani F, De Carolis A, Capelli G, Vespasiani G, Stephen RL, Department of Surgery/Urology, Tor Vergata University, Rome, Italy

Background The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer. Methods After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website. Findings Median follow-up was 88 months (IQR 63–110). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (69 months [95% CI 55–86] vs 21 months [15–54]; difference between groups 48 months [42–54], log-rank p=0.0012). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (41.9% [32.7–51.5] vs 57.9% [48.7–67.5]; difference between groups 16.0% [2.7–29.3], log-rank p=0.0012); progression (9.3% [3.8–14.8] vs 21.9% [17.9–25.9]; difference between groups 12.6% [3.0–22.2], log-rank p=0.004); overall mortality (21.5% [13.5–29.5] vs 32.4% [23.4–41.4], difference between groups 10.9% [0.6–21.2], log-rank p=0.045); and disease-specific mortality (5.6% [1.2–10.0] vs 16.2% [6.1–23.3], difference between groups 10.6% [2.5–18.7], log-rank p=0.01). Side effects were mainly localised to the bladder. Interpretation BCG-induced inflammation might increase the permeability of the bladder mucosa such that mitomycin can reach the target tissue more easily and exert its anticancer effect.

Sequential BCG ?? electromotive mitomycin in bladder cancer

Sequential BCG ?? electromotive mitomycin in bladder cancer

Sequential BCG and electromotive mitomycin versus BCG alone for high-risk superficial bladder cancer: a randomised controlled trial

The rationale for combining anticancer drugs has not been applied consistently to use of intravesical agents for treatment of superficial bladder cancer, for which immunotherapeutic BCG and chemotherapeutic mitomycin seem to be a potentially effective combination. We aimed to do a prospective, randomised comparison of BCG alone with that of sequential BCG and electromotive mitomycin in patients with stage pT1 bladder cancer. After transurethral resection and multiple biopsies, 212 patients with stage pT1 bladder cancer were randomly assigned to: 81 mg BCG infused over 120 min once a week for 6 weeks (n=105); or to 81 mg BCG infused over 120 min once a week for 2 weeks, followed by 40 mg electromotive mitomycin (intravesical electric current 20 mA for 30 min) once a week as one cycle for three cycles (n=107). Complete responders underwent maintenance treatment: those assigned BCG alone had one infusion of 81 mg BCG once a month for 10 months, and those assigned BCG and mitomycin had 40 mg electromotive mitomycin once a month for 2 months, followed by 81 mg BCG once a month as one cycle for three cycles. The primary endpoint was disease-free interval; secondary endpoints were time to progression; overall survival; and disease-specific survival. Analyses were done by intention to treat. This trial has been submitted for registration at the US National Cancer Institute website . Median follow-up was 88 months (IQR 63-110). Patients assigned sequential BCG and electromotive mitomycin had higher disease-free interval than did those assigned BCG alone (69 months [95% CI 55-86] vs 21 months [15-54]; difference between groups 48 months [42-54], log-rank p=0.0012). Patients assigned sequential BCG and electromotive mitomycin also had lower recurrence (41.9% [32.7-51.5] vs 57.9% [48.7-67.5]; difference between groups 16.0% [2.7-29.3], log-rank p=0.0012); progression (9.3% [3.8-14.8] vs 21.9% [17.9-25.9]; difference between groups 12.6% [3.0-22.2], log-rank p=0.004); overall mortality (21.5% [13.5-29.5] vs 32.4% [23.4-41.4], difference between groups 10.9% [0.6-21.2], log-rank p=0.045); and disease-specific mortality (5.6% [1.2-10.0] vs 16.2% [6.1-23.3], difference between groups 10.6% [2.5-18.7], log-rank p=0.01). Side-effects were mainly localised to the bladder. BCG-induced inflammation might increase the permeability of the bladder mucosa such that mitomycin can reach the target tissue more easily and exert its anticancer effect.

Intravesical Electromotive Mitomycin C Versus Passive Transport Mitomycin C for High Risk Superficial Bladder Cancer: A Prospective Randomized Study

In laboratory studies electromotive mitomycin C (MMC) demonstrated markedly increased transport rates compared with passive transport. We performed a prospective study in patients with high risk superficial bladder cancer to assess the efficacy of intravesical electromotive vs passive MMC using bacillus Calmette-Guerin (BCG) as a comparative treatment. Following transurethral resection and multiple biopsies 108 patients with multifocal Tis, including 98 with T1 tumors, were randomized into 3 equal groups of 36 each who underwent 40 mg electromotive MMC instillation with 20 mA electric current for 30 minutes, 40 mg passive MMC with a dwell time of 60 minutes or 81 mg BCG with a dwell time of 120 minutes. Patients were scheduled for an initial 6 weekly treatments, a further 6 weekly treatments for nonresponders and a followup 10 monthly treatments for responders. Primary end points were the complete response rate at 3 and 6 months. MMC pharmacokinetics were assessed. The complete response for electromotive vs passive MMC at 3 and 6 months was 53% versus 28% (p = 0.036) and 58% versus 31% (p = 0.012). For BCG the responses were 56% and 64%. Median time to recurrence was 35 vs 19.5 months (p = 0.013) and for BCG it was 26 months. Peak plasma MMC was significantly higher following electromotive MMC than after MMC (43 vs 8 ng/ml), consistent with bladder content absorption. Intravesical electromotive administration increases bladder uptake of MMC, resulting in an improved response rate in cases of high risk superficial bladder cancer.