Electromotive Drug Administration Research Articles

Botulinum Toxin Type A Therapy: Intravesical Injection or Electromotive Drug Administration

To compare the outcomes of intravesical injection of botulinum toxin A (BoNTA) with intravesical electromotive drug administration (EMDA) of BoNTA on urinary incontinence secondary to neuropathic detrusor overactivity (NDO) in children with myelomeningocele (MMC). A total of 26 children with MMC (11 boys, 15 girls) who had urinary incontinence secondary to NDO were retrospectively enrolled in the study. Patients in EMDA group (n = 14), using an electrode-catheter, 10 IU/kg of BoNTA were inserted into the bladder for EMDA without anesthesia and on an outpatient basis. The EMDA equipment was connected to the electrode of indwelling catheter and 2 dispersive electrodes, a pulsed current generator delivered 10-20 mA for 20 minutes. Patients in injection group (n = 12) were received interavesical injection of 10 IU/kg of BoNTA via rigid cystoscope on an inpatient basis. All patients had been evaluated by a voiding diary, urodynamic study, renal, and bladder ultrasounds before, 6 months and 1 year after the treatment. Six months after the treatment, 12 of 14 (85.7 %) and 8 of 12 (66.6%) patients in EMDA and injection groups respectively became completely dry between 2 consecutive clean intermittent catheterizations, which maintained in 11 of 14 (78.5%) of patients in EMDA group compared to 6 of 12 (50%) of patients in injection group, 1 year after the treatment. Patients in both groups improved after the treatment; however improvement in EMDA group was more prominent with better sustained effects. BoNTA/EMDA is a feasible, reproducible, cost benefit, and pain free method as an outpatient basis and no need for anesthesia.

Treatment options and results of adjuvant treatment in nonmuscle-invasive bladder cancer (NMIBC) during the Bacillus Calmette-Guérin shortage.

Given the worldwide shortage of Bacillus Calmette-Guérin (BCG), we review the efficacy of alternative BCG application schedules, doses or strains and intravesical chemotherapy in patients with nonmuscle-invasive bladder cancer (NMIBC). Modifying BCG schedules by reducing the dose is preferable to reducing the frequency of BCG that increases recurrence rates and should be avoided if possible. Changing the BCG substrain represents a reasonable option, as current evidence does not suggest different oncological outcomes with specific BCG substrains. Mitomycin C (MMC) alone is inferior to BCG with maintenance, but promising results have been demonstrated when used with chemohyperthermia and electromotive drug administration. Several other intravesical chemotherapies including Gemcitabine and Epirubicin should be used when both BCG and MMC are in short supply. In case of BCG shortage, much will depend on the severity and length of the BCG shortage, but our review supports several solutions: First, we recommend contacting the local pharmacist or BCG supplier to consider alternative BCG strains or sterile splitting of BCG doses. In the complete absence of BCG, consideration should be given to MMC with chemohyperthermia or electromotive drug administration where available or other intravesical chemotherapy. High-risk patients should be considered for cystectomy.

The role of device-assisted therapies in the management of non-muscle invasive bladder cancer: A systematic review

Despite optimal treatment, patients affected by non-muscle invasive bladder cancer (NMIBC) suffer from high risk of recurrence and progression. Intravescical device assisted therapies such as radiofrequency induced thermochemotherapeutic effect (RITE) and electromotive drug administration (EMDA) have shown promising effect in enhancing the effect of intravescical chemotherapies. The aim of the study was to assess clinical outcomes of these two devices in non-muscle invasive bladder cancer. A systematic literature review was performed in December 2019 using the Medline, Embase, and Web of Science databases. Only articles published in the last 10 years were considered (2009-2019). The articles were selected using the following keywords association: "bladder cancer" AND "EMDA' AND "synergo" AND "hyperchemotherapy" AND "electromotive drug administration", AND "radiofrequency induced thermochemotherapeutic" AND "RITE". We found 16 studies published in the last ten years regarding the efficacy of RITE (12 studies) and EMDA (4 studies) in the treatment of NMIBC. Both RITE and EMDA showed promising results in the treatment of intermediate and high risk NMIBC as well as in patients affected by recurrent BCa after BCG failure. In high-risk BCG naïve NMIBC patients treated with EMDA recurrence and progression rates were 68% and 95%, respectively. Considering RITE, recurrence and progression range rates were 43%-88% and 62%-97%, respectively. Discordance results were reported regarding its effect on patients with carcinoma in situ. However, only few studies could be compared since differences exist regarding inclusion criteria with high patients' heterogeneity. Considering recurrence after BCG, recurrence and progression range rates were 29%-29.2% and 62%-83% for RITE and 25% and 75% for EMDA, respectively. Delivery of intravescical hyperthermia seems to enhance the normal effect of intravescical chemotherapy instillation. Although prospective trials supported its effect on both BCG naïve and BCG failure patients, data are urgently required to validate these findings and to understand its effect on patients with carcinoma in situ. 3.

MP73-01 SEQUENTIAL ADMINISTRATION OF BACILLUS CALMETTE-GUERIN (BCG) AND ELECTROMOTIVE DRUG ADMINISTRATION (EMDA) OF MITOMYCIN C (MMC) FOR THE TREATMENT OF HIGH GRADE NON MUSCLE INVASIVE BLADDER CANCER AFTER BCG FAILURE

You have accessJournal of UrologyBladder Cancer: Non-invasive IV (MP73)1 Apr 2020MP73-01 SEQUENTIAL ADMINISTRATION OF BACILLUS CALMETTE-GUERIN (BCG) AND ELECTROMOTIVE DRUG ADMINISTRATION (EMDA) OF MITOMYCIN C (MMC) FOR THE TREATMENT OF HIGH GRADE NON MUSCLE INVASIVE BLADDER CANCER AFTER BCG FAILURE Tristan Juvet*, Christopher Wallis, Lior Krimus, Cynthia Kuk, Annette Erlich, Andrea Mari, Girish Kulkarni, Neil Fleshner, and Alexandre Zlotta Tristan Juvet*Tristan Juvet* More articles by this author , Christopher WallisChristopher Wallis More articles by this author , Lior KrimusLior Krimus More articles by this author , Cynthia KukCynthia Kuk More articles by this author , Annette ErlichAnnette Erlich More articles by this author , Andrea MariAndrea Mari More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , Neil FleshnerNeil Fleshner More articles by this author , and Alexandre ZlottaAlexandre Zlotta More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000000959.01AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: There is a need for effective non-surgical treatment options in patients with non-muscle invasive bladder cancer (NMIBC) in whom Bacillus Calmette-Guerin (BCG) therapy has failed. We aimed to determine the efficacy of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) in BCG unresponsive patients. METHODS: A retrospective review of NMIBC BCG unresponsive patients who received BCG/EMDA-MMC between 2013 and 2017 was performed. Patients had received at least one full regimen of BCG. Progression and overall survival time were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment. RESULTS: 26 patients were included. Initial pathology was carcinoma in situ (CIS) in 53.8% (14/26), pT1 in 34.6% (9/26) and pTa HG disease in 11.6% (3/26). 12/26 patients progressed (46.2%). Following BCG/EMDA-MMC treatment, progression-free survival rates were 62.2% (95% CI 43.4-81.0) at 1 year and 53.2% (95% CI 33.4-80.0) at 2 years from the date of induction of BCG/EMDA-MMC, respectively. Side effects included dysuria (19.2%), hematuria (19.2%), and frequency (11.5%). 3 patients were admitted for side effects but managed conservatively. Four patients (15.4%) died of bladder cancer over the course of the study. CONCLUSIONS: BCG/EMDA-MMC represents a viable option in patients with BCG unresponsive NMIBC with over 50% progression-free survival at 2 years. However, the window of curability is narrow with 15% cancer specific mortality in these high-risk patients. Source of Funding: none © 2020 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 203Issue Supplement 4April 2020Page: e1121-e1121 Advertisement Copyright & Permissions© 2020 by American Urological Association Education and Research, Inc.MetricsAuthor Information Tristan Juvet* More articles by this author Christopher Wallis More articles by this author Lior Krimus More articles by this author Cynthia Kuk More articles by this author Annette Erlich More articles by this author Andrea Mari More articles by this author Girish Kulkarni More articles by this author Neil Fleshner More articles by this author Alexandre Zlotta More articles by this author Expand All Advertisement PDF downloadLoading ...

Botulinum toxin therapy in children with neurogenic detrusor overactivity.

Special birth defects and neurological diseases can cause neurogenic detrusor overactivity (NDO). First-line pharmacotherapy is the antimuscarinic therapy, which can be limited by side effects or non-effectiveness. Therefore, pharmacological treatment of NDO in children includes off-label use of intravesical injections of botulinum toxin type A (BTA). In this review article, various clinical studies in which BTA was used for the treatment of NDO of different etiologies in children are discussed, including studies about children with acquired NDO. An electronic literature search was performed using PubMed, and studies published prior to March 2019 are reported. BTA injections are a clinically and urodynamically effective and safe treatment for NDO in children. The treatment is also important in protecting the upper urinary tract from damage and improving concomitant bowel dysfunctions. Fibrotic, acontractile bladders with poor bladder compliance and/or a very small initial bladder capacity and/or the presence of an open bladder neck all contributed to poor responses. A combined injection into the detrusor and external urethral sphincter may improve the clinical outcome in the detrusor-sphincter dyssynergia. New application methods are promising, such as the electromotive drug administration, to avoid general anesthesia. Furthermore, the minimal clinically effective dosage, inclusion criteria, and prognostic factors remain to be established.

Applications of electromotive drug administration in urology.

To review all published evidence regarding the use of Electromotive Drug Administration (EMDA) for the management of urological conditions, focusing on efficacy and safety, and highlighting areas that require further study. The PubMed and Medline databases were searched up to July 23, 2019. All studies reporting the use of EMDA to enhance the intravesical administration of therapeutic drugs for urological conditions were included. Two reviewers independently screened all articles, searched the reference lists of retrieved articles, and performed the data extraction. Thirty-two studies were included. The use of EMDA has been reported in the following urological conditions: (1) nonmuscle-invasive bladder cancer (NMIBC); (2) overactive bladder; (3) bladder pain syndrome; (4) radiation cystitis; (5) detrusor acontractility; and (6) for analgesia prior to transurethral procedures. Overall, most studies are nonrandomized trials with small numbers of patients. The use of EMDA is reported to be safe and effective in all these conditions, with the highest level of evidence in NMIBC in the neoadjuvant and adjuvant setting. However, the low overall quality of evidence limits the conclusions that can be reached. The use of EMDA to improve the efficacy of intravesical treatments is promising, but the low overall quality of the evidence base has limited its widespread use. Future studies should compare EMDA to passive diffusion and current standard of care in large, randomized, and long-term studies to determine the efficacy, safety, and cost-effectiveness of this modality.

BCG-Unresponsive Bladder Cancer: New Frontiers in the Treatment Landscape

This Ferring-organised Meet-The-Expert symposium at the European Society of Medical Oncology (ESMO) 2019 meeting aimed to discuss new treatment modalities in the management of high-risk, non-muscle invasive bladder cancer (NMIBC). The chairperson Prof Palou commenced the session by discussing the need for newer interventions to address the failure of bacillus Calmette–Guérin (BCG), the first-line treatment against NMIBC, in a substantial proportion of patients. Prof Palou emphasised the need to clearly define refractory disease to optimise second-line treatments, before introducing immune checkpoint inhibitors as a promising class of drug for the treatment of BCG-unresponsive NMIBC. Prof Shariat discussed a case study to define key clinical timepoints for evaluating therapeutic outcomes of BCG treatment. He further outlined factors to be considered before deciding on radical cystectomy in BCG-unresponsive NMIBC. Prof Babjuk listed some of the landmark trials conducted recently to investigate chemotherapeutic agents such as mitomycin C (MMC) and docetaxel in BCG-unresponsive patients before highlighting the role of advanced drug delivery technologies such as electromotive drug administration (EMDA), hyperthermic intravesical chemotherapy, and radiofrequency-induced thermo-chemotherapy effect (RITE) in improving the effectiveness of these agents. Prof Powles shared data from some of the trials investigating immune checkpoint inhibitors such as PURE-01, ABACUS, KEYNOTE, to underscore the importance of biomarkers in selecting appropriate treatment strategies for NMIBC.

Intravesical Treatment with Electro-Mediated Administration of Mytomicin C as Prophylaxis for Intermediate and High-Risk Nonmuscle-Invasive Bladder Cancer: A Retrospective Multicenter Study

Background: Topical therapy of nonmuscle-invasive bladder cancer (NMIBC) is based on immunotherapy with Bacillus Calmette-Guerin and chemotherapy administered by passive instillation, but an active drug administration achieves a better concentration of the drugs in the bladder. Aim: This study aimed to investigate the effectiveness of electromotive drug administration (EMDA) of mitomycin C (EMDA/MMC) in intermediate- and high-risk NMIBC patients 6 months after the end of induction treatment. Materials and Methods: Sixty-five patients diagnosed with histologically confirmed NMIBC, with a complete transurethral resection of all visible tumors underwent EMDA/MMC. Primary endpoint was the proportion of responders at 3 or 6 months. Results: Data on follow-up were available for 62 subjects at 3 months and 45 at 6 months. EMDA was effective in intermediate- and high-risk patients: because of the small number of cases no conclusions can be drawn on the efficacy in the low-risk group. No difference in the response to treatment between intermediate- (83.3%) and high-risk (84%) patients could be seen. Conclusions: EMDA/MMC is a useful technique for an effective and safe treatment of primary and recurrent NMIBC, and a valuable therapeutic option in intermediate- and high-risk NMIBC patients.

Efficacy of electromotive drug administration in delivering botulinum toxin a in children with neuropathic detrusor overactivity—outcomes of a pilot study

Intravesical botulinum toxin A (BtA) injection is well established in managing paediatric neuropathic detrusor overactivity (NDO). Electromotive drug administration (EMDA) is a less invasive method, which can be performed in the clinic, using pulsed electrical current for drug delivery via a urethral catheter. Few small studies report good outcomes following BtA via EMDA (BtA/EMDA) into bladders of children with NDO. The objective of this study is to assess the efficacy of BtA/EMDA in children with NDO, reduced bladder capacity and compliance. Twelve children with NDO on baseline urodynamic study were prospectively included. Pre-BtA/EMDA and post-BtA/EMDA results compared the following four parameters: maximal cystometric capacity, bladder compliance, maximal detrusor pressure (pDetmax) during detrusor overactivity and pDetmax at capacity. The Wilcoxon matched-pairs signed-rank test using Graphpad Prism 8 was used for analysis. Secondary outcomes include adverse effects and symptomatic improvement. Fourteen episodes of BtA/EMDA were performed. Five patients received 3.3 IU/kg of Botox®, and five received 10 IU/kg (maximum 300 IU). Four patients received 10 IU/kg of Dysport®. Two patients in the Dysport®/EMDA group also received Botox®/EMDA more than six months previously. Thirteen of 14 post-EMDA results were completed and included in the paired analysis. No statistically significant improvements in any cystometric parameters were demonstrated. Eight patients subsequently had intravesical BtA injections with significant improvements in both cystometric parameters and symptoms. Two patients subsequently transitioned to adult services; one was commenced on mirabegron, and one has undergone ileocystoplasty with Mitrofanoff appendicovesicostomy. Despite some evidence to support BtA/EMDA in children with NDO, the authors were unable to replicate previously published positive cystometric and symptomatic outcomes. In addition, BtA/EMDA performed poorly when compared with conventional intravesical BtA injections. This implies failure of EMDA to deliver BtA correctly to the target tissue. The large size of the BtA moleculeor the abnormal bladder wall in NDO could account for the negative results. Thorough preparation and consultation was undertaken before this study with BtA/EMDA, and it is discouraging that the authors were unable to reproduce the positive results of other groups. Although safe and acceptable to most patients, the authors cannot recommend the use of BtA/EMDA for NDO in children at present.

Intravesical electromotive administration of botulinum toxin type A in improving the bladder and bowel functions: Evidence for novel mechanism of action

Objective: To examine the hypothesis that what is the concomitant mechanism of action botulinum toxin type A (BoNTA) administration by intravesical electromotive into the bladder resulting in bladder function improvement. We also tried to confirm the possibility of retrograde trans-axonal transportation of toxin. Design: Animal study. Setting: Ten male rabbits were divided into two groups. Participants: Group 1 (G1) (n = 5) (BoNTA/EMDA), and group 2 (G2) (n = 5) the control group. Interventions: Animals in G1received 10 IU/Kg of intravesical BoNTA through a specific catheter for electromotive drug administration (BoNTA/EMDA). About 0.1–0.15 ml of toxin was diluted in 1 ml of distilled water. The maximum frequency of the device for drug solution delivery was set at 4 mA for 15 min. In G2 as the control group, the same procedure was performed to deliver normal saline to the bladder. Outcome measures: Multiple biopsies were taken from bladder’s contiguous structures one month postoperatively. The immunohistochemical (IHC) evaluation was performed with anti-clostridium botulinum toxoid type A mouse IgM monoclonal antibody. Results: In specimens of G1, BoNTA penetrated through muscular layers of the bladder wall and the staining was uniform in the urothelium, interstitium, and muscular layers. Positive IHC staining showed that BoNTA was traced in the upper and lower spinal cord in addition to pelvic nerve, sacral nerve plexus, intestine wall, and pelvic floor muscle. In G2, all the specimens were intact in IHC staining. Conclusions: The presence of BoNTA in lower and upper spinal cord suggests the possibility of retrograde trans-axonal transfer of toxin to lower and upper neural pathways which may result in simultaneous improvement in bladder and bowel functions.

Device-assisted intravesical therapy for non-muscle invasive bladder cancer.

Non-muscle invasive bladder cancer (NMIBC) is a challenging disease, with a high risk of recurrence and even progression to muscle invasive disease. The present standard treatment is suboptimal, and consists of a complete transurethral resection of the visible bladder tumour(s), followed by prophylactic intravesical instillations mitomycin-C (MMC) or bacillus Calmette-Guérin (BCG). In search for higher efficacy, several adjuvant device-assisted intravesical therapies are developed. Chemohyperthermia may be based on microwave-/radiofrequency-induced (RF) hyperthermia systems, for which most evidence exists, or on hyperthermic intravesical chemotherapy, which is applied by conductive or loco-regional heating systems. RF-induced CHT has shown superiority over MMC alone, and in one prospective study superiority over BCG in per-protocol analysis, which has led to the ‘weak’ recommendation in the EAU guidelines to consider RF-based CHT as a bladder preservation strategy in patients with BCG-refractory tumours, who are not candidates for radical cystectomy due to comorbidities. Prospective studies on hyperthermic intravesical chemotherapy for patients with intermediate-risk NMIBC are awaited next year. The combination of electromotive drug administration (EMDA) with MMC has shown superiority over MMC as well, and seems promising when combined with BCG in sequential treatment. Photodynamic therapy should still be considered experimental, in which a study with the intravenous photosensitizer Radachlorin® has shown promising results.

Will long-term disease specific outcomes of bladder conservation with sequential Bacillus Calmette-Guérin (BCG) and electromotive drug administration Mitomycin-C (EMDA-MMC) for high-risk non-muscle invasive bladder cancer (HR-NMIBC) influence adoption?

Event Abstract Back to Event Will long-term disease specific outcomes of bladder conservation with sequential Bacillus Calmette-Guérin (BCG) and electromotive drug administration Mitomycin-C (EMDA-MMC) for high-risk non-muscle invasive bladder cancer (HR-NMIBC) influence adoption? Jennifer Lane1*, Zakariya Abdille1, Christine Gan1, Kathryn Chatterton1, Suzanne Amery1, Ramesh Thurairaja1, Shamim Khan1, Sachin Malde1, Timothy O'Brien1 and Rajesh Nair1 1 Guy's and St Thomas' NHS Foundation Trust, United Kingdom Background: Superior short-term outcomes of sequential BCG with EMDA-MMC when treating HR-NMIBC have been reported. Despite this, the regimen has not been widely adopted for bladder conservation and the optimal regimen is yet to be determined. An understanding of long-term oncological outcomes would be important in understanding it’s true role and may encourage wider adoption. Methods: This is a prospective single-centre study of 464 patients, presenting with new HR-NMIBC between June 2009 and July 2017. The bladder conservation schedule followed TURBT with adjuvant 9-week induction consisting of 3 consecutive and identical cycles of; BCG in weeks 1 and 2, followed by EMDA-MMC in week 3. Maintenance was 3-weekly BCG. Cystoscopy was used to assess response at 8 weeks post induction. Primary outcome measures evaluated were recurrence free survival, progression rates and outcomes following salvage treatment. Results: 249 patients received sequential BCG/EMDA-MMC with a median follow-up of 54 months (4-108). 206/249 (83%) received treatment for high-grade (Ta/T1) disease, and 13/249 (5%) for primary carcinoma in situ. A further 30/249 (12%) received treatment for recurrent or large volume low-grade disease. Of the 196/249 (79%) patients who completed the induction course of treatment 123/196 (63%) have remained disease free during follow-up. 53/196 (27%) patients developed bladder recurrence, of which 22/53 (42%) demonstrated stage migration (T2 disease). Of note, 28/53 (53%) developed recurrence within the first three years of treatment. Of the 15/53 (28%) who subsequently underwent radical cystectomy, upstaging on final histopathology was demonstrated in 8/15 (53%) patients, 1/15 (6%) died of metastatic bladder cancer. Conclusion: If induction BCG/EMDA-MMC treatment is completed, over two-thirds of patients remain disease free during long term follow-up. This is twice the efficacy quoted for intravesical BCG alone and adds further weight to the adoption of this sequential regimen in bladder preservation for HR-NMIBC. Keywords: Bladder cancer, BCG - Bacille Calmette-Guérin vaccine, Electromotive drug administration (EMDA), Mitomycin C (Mit-C), Non-muscle invasive bladder cancer Conference: Bladder Cancer Translational Research Meeting, London, United Kingdom, 29 Mar - 29 Mar, 2019. Presentation Type: Poster Topic: Development of personalised treatment Citation: Lane J, Abdille Z, Gan C, Chatterton K, Amery S, Thurairaja R, Khan S, Malde S, O'Brien T and Nair R (2019). Will long-term disease specific outcomes of bladder conservation with sequential Bacillus Calmette-Guérin (BCG) and electromotive drug administration Mitomycin-C (EMDA-MMC) for high-risk non-muscle invasive bladder cancer (HR-NMIBC) influence adoption?. Front. Oncol. Conference Abstract: Bladder Cancer Translational Research Meeting. doi: 10.3389/conf.fonc.2019.01.00015 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 28 Feb 2019; Published Online: 27 Sep 2019. * Correspondence: Dr. Jennifer Lane, Guy's and St Thomas' NHS Foundation Trust, London, United Kingdom, jennifer.lane@gstt.nhs.uk Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Jennifer Lane Zakariya Abdille Christine Gan Kathryn Chatterton Suzanne Amery Ramesh Thurairaja Shamim Khan Sachin Malde Timothy O'Brien Rajesh Nair Google Jennifer Lane Zakariya Abdille Christine Gan Kathryn Chatterton Suzanne Amery Ramesh Thurairaja Shamim Khan Sachin Malde Timothy O'Brien Rajesh Nair Google Scholar Jennifer Lane Zakariya Abdille Christine Gan Kathryn Chatterton Suzanne Amery Ramesh Thurairaja Shamim Khan Sachin Malde Timothy O'Brien Rajesh Nair PubMed Jennifer Lane Zakariya Abdille Christine Gan Kathryn Chatterton Suzanne Amery Ramesh Thurairaja Shamim Khan Sachin Malde Timothy O'Brien Rajesh Nair Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.

ElectroMotive drug administration (EMDA) of Mitomycin C as first-line salvage therapy in high risk \u201cBCG failure\u201d non muscle invasive bladder cancer: 3\u2009years follow-up outcomes

BackgroundIn case of high grade non-muscle invasive bladder cancer (HG-NMIBC), intravesical BCG represents the first-line treatment; despite the “gold” standard therapy, up to 50% of patients relapse, needing radical cystectomy. Hence, alternative therapeutic strategies have been developed. The aim of the study was to evaluate a first-line salvage treatment with EMDA®-MMC in patients with HGNMIBC unresponsive to BCG.MethodsWe carried out a prospective, single-center, single-arm Phase II study in order to evaluate the efficacy (in terms of recurrence and progression) and the safety of the EMDA®-MMC treatment in 26 (21 male, 5 female) consecutive patients with “BCG refractory” HGNMIBC on a 3 years follow-up.EMDA®-MMC treatment consisted of 40 mg of MMC diluted in 100 ml of sterile water retained in the bladder for 30 min with 20 mA pulsed electric current.EMDA®-MMC regimen consisted of an induction course of 6 weekly instillations followed by a maintenance course of 6 monthly instillations.Follow-up was performed with systematic mapping biopsies of the bladder (with sampling in the prostatic urethra for men), voiding and washing urinary cytology, radiological study of the upper urinary tract.We performed Survival Kaplan-Meier curves and Log-rank test in order to analyze high grade disease-free survival.ResultsAt the end of follow-up, 16 patients (61.5%) preserved their native bladder; 10 patients (38.4%) underwent radical cystectomy, in 6 patients (23.1%) for recurrent HGNMIBC and in 4 patients (15.4%) for progression to muscle-invasive disease.At the end of follow-up, stratifying patients based on TNM classification (TaG3, T1G3, Cis, TaT1G3 + Cis), disease-free rates were 75, 71.4, 50 and 25%, respectively; survival curves showed statistically significant differences (p value < 0.05).Regarding toxicity, we reported severe adverse systemic event of hypersensitivity to the MMC in 3 patients (11.5%), and local side effects in 6 patients (26.1%).ConclusionsIn the field of alternative strategies to radical cystectomy, the EMDA®-MMC could be considered safe and effective in high-risk NMIBC unresponsive to BCG, as a “bladder sparing” therapy in selected patients. Multicenter studies with a larger number of patients and a longer follow-up might confirm our preliminary results.Trial registrationEudraCT2017-002585-43. 17 June 2017 (retrospectively registered).

Intravesical device-assisted therapiesfor non-muscle-invasive bladder cancer.

Non-muscle-invasive bladder cancer (NMIBC), the most prevalent type of bladder cancer, accounts for ~75% of bladder cancer diagnoses. This disease has a 50% risk of recurrenceand 20% risk of progression within 5 years, despite the use of intravesical adjuvant treatments (such as BCG or mitomycin C) that are recommended by clinical guidelines. Intravesical device-assisted therapies, such as radiofrequency-induced thermochemotherapeutic effect (RITE), conductive hyperthermic chemotherapy, and electromotive drug administration (EMDA), have shown promising efficacy. These device-assisted treatments are an attractive alternative to BCG, as issues with supply have been a problem in some countries. RITE might be an effective treatment option for some patients who have experienced BCG failure and are not candidates forradical cystectomy. Data from trials using EMDA suggest that it is effective in high-risk disease but requires further validation, and results of randomized trials are eagerly awaited for conductive hyperthermic chemotherapy. Considerable heterogeneity in patient cohorts, treatment sessions, use of maintenance regimens, and single-arm study design makes it difficult to draw solid conclusions, although randomized controlled trials have beenreported for RITE and EMDA.

PD66-03 SEQUENTIAL ADMINISTRATION OF BCG AND ELECTROMOTIVE DRUG ADMINISTRATION (EMDA) OF MITOMYCIN C (MMC) IN NON-MUSCLE INVASIVE BLADDER CANCER HAVING PREVIOUSLY RECEIVED INTRAVESICAL THERAPY

You have accessJournal of UrologyBladder Cancer: Non-invasive III1 Apr 2018PD66-03 SEQUENTIAL ADMINISTRATION OF BCG AND ELECTROMOTIVE DRUG ADMINISTRATION (EMDA) OF MITOMYCIN C (MMC) IN NON-MUSCLE INVASIVE BLADDER CANCER HAVING PREVIOUSLY RECEIVED INTRAVESICAL THERAPY Tristan Juvet, Christopher Wallis, Lior Krimus, Annette Erlich, Girish Kulkarni, and Alexandre Zlotta Tristan JuvetTristan Juvet More articles by this author , Christopher WallisChristopher Wallis More articles by this author , Lior KrimusLior Krimus More articles by this author , Annette ErlichAnnette Erlich More articles by this author , Girish KulkarniGirish Kulkarni More articles by this author , and Alexandre ZlottaAlexandre Zlotta More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2999AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES A number of randomized controlled trials have studied the use of Electromotive Drug Administration (EMDA) of mitomycin C (MMC) in the setting of non-muscle invasive bladder cancer (NMIBC). These studies have focused on treatments prior to and following initial bladder tumor resection (TURBT). They have demonstrated potential benefit in terms of recurrence rates, disease free interval and decreased mortality when compared to standard Bacille Calmette-Guerin (BCG) monotherapy. Evidence remains lacking on the use of EMDA-MMC in patients who have become unresponsive to BCG therapy. Our objective was to determine the efficacy of EMDA-MMC in patients having failed treatment with BCG. METHODS After obtaining institutional review board approval, patients presenting to our multi-disciplinary bladder cancer clinic were reviewed to identify those who had received an initial BCG treatment, progressed, and received BCG/EMDA-MMC between 2013 and April 2016. Patients received BCG/EMDA-MMC as per our research protocol. Progression and overall survival time were calculated using Kaplan-Meier curves. Progression was defined as development of muscle invasive disease, presence of metastasis on imaging or treatment (surgery, chemotherapy, radiation). RESULTS A total of 30 patients having undergone BCG/EMDA-MMC over the study course were reviewed. Median age was 63 years. All patients had undergone at least one BCG induction. Initial pathology was carcinoma in situ (CIS) in 43.3% (13/30), pT1 in 26.7 % (8/30) and pTa disease in 30% (9/30). 55.6% (5/9) of pTa patients were found to have low grade disease (WHO 2003). 43.33% (13/30) of all patients progressed, requiring additional treatment. 84.6% of these patients (11/13) had high grade disease. Following BCG/EMDA-MMC treatment, progression-free survival rates were 79.5% (95% CI 0.63.4-95.5%) at 1 year and 61.7% (95% CI 0.41.8-81.5%) at 2 years from the date of induction of BCG/EMDA-MMC. Median survival was not reached at 4 years follow-up. CONCLUSIONS Our study focuses on one of the limited options available to patients having failed to respond to BCG treatment. Although this remains a novel treatment, our early data show evidence of progression free survival in over 60% of patients at the two year mark. Patients with high grade disease were most likely to progress. Treatment with BCG/EMDA-MMC in this setting may delay more aggressive treatments, although further studies are needed in this subset of patients to determine the exact benefits. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1230-e1231 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Tristan Juvet More articles by this author Christopher Wallis More articles by this author Lior Krimus More articles by this author Annette Erlich More articles by this author Girish Kulkarni More articles by this author Alexandre Zlotta More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

738 - ElectroMotive drug administration (EMDA) of mitomycin C as first line salvage therapy in high risk “BCG-failure” non muscle invasive bladder cancer: 3 years followup outcomes

738 - ElectroMotive drug administration (EMDA) of mitomycin C as first line salvage therapy in high risk “BCG-failure” non muscle invasive bladder cancer: 3 years followup outcomes

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.

The risk of malignancy of atypical urothelial cells of undetermined significance in patients treated with chemohyperthermia or electromotive drug administration

Chemohyperthermia (C-HT) or electromotive drug administration (EMDA) are alternative therapies to radical cystectomy in patients with non-muscle-invasive bladder cancer who do not respond to intravesical therapy with bacille Calmette-Guérin. The authors investigated a group of 87 patients with a diagnosis of high-grade non-muscle-invasive bladder carcinoma or carcinoma in situ. Of these, 45 patients received EMDA of mitomycin (EMDA/MMC) and 42 patients were treated with C-HT and mitomycin therapy (C-HT/MMC). In accordance with the Paris System for Reporting Urinary Cytology, a cytological diagnosis was made and patients with diagnoses of atypical urothelial cells (AUC), suspicious high-grade urothelial carcinoma (SHGUC), or high-grade urothelial carcinoma also underwent histological bladder biopsies. In accordance with the Paris System for Reporting Urinary Cytology, the AUC cases may have cytological features of SHGUC present on atypical degenerated cells. In analyzing the AUC group without the SHGUC cases diagnosed on the basis of degenerated urothelial cells, the authors found a significant association between the AUC category and a negative histological biopsy. The SHGUC group, including cases with a SHGUC diagnosis rendered on degenerated urothelial cells, was associated with high-grade urothelial carcinoma or carcinoma in situ (P = .0269 for patients treated with EMDA/MMC and P = .0049 for patients treated with C-HT/MMC). In the urine samples from patients treated with EMDA/MMC or C-HT/MMC, a diagnosis of SHGUC could be made even on degenerated urothelial cells when considering cellular degeneration as a "physiological" consequence of the treatment that involves either normal or neoplastic cells. Cancer Cytopathol 2018;126:200-6. © 2018 American Cancer Society.

Intravesical Electromotive Drug Administration®(EMDA)with Mitomycin-C for non-muscle invasive bladder cancer

Electromotive Drug Administration® (EMDA) offers a means of controlling and enhancing the tissue transport of certain drugs, when applied to a surface epithelium, where they have a local therapeutic effect, in order to increase their efficacy. One application option is the treatment of non-muscle invasive bladder cancer with intravesical mitomycin-C (MMC). Laboratory studies demonstrated that EMDA/MMC can reduce the variability and enhance the drug administration rate into all layers of the bladder wall, and that the applied electric current causes no histological damage to tissue and no chemical modification of MMC. A prospective randomized study, performed in patients with in situ carcinoma, validated the prediction that electromotive enhancement of MMC delivery would provide results superior to those achieved using passive MMC transport. A further randomized study in patients with pT1 bladder cancer demonstrated that a regimen combining intravesical BCG and EMDA/MMC increased the disease-free interval and reduced the recurrence rate, as well as the disease progression and mortality rate if compared with BCG alone. The possibility that BCG may enhance the efficacy of MMC against high-grade pT1 transitional cell carcinoma and in situ carcinoma represents an important new therapeutic perspective in the high-risk non-muscle invasive bladder cancer.

Intravesical Electromotive Botulinum Toxin Type “A” Administration for Management of Urinary Incontinence Secondary to Neuropathic Detrusor Overactivity in Children: Long-term Follow-up

To investigate the long-term efficacy and success rate of intravesical electromotive botulinum toxin type A (BoNTA) "Dysport" administration in patients with myelomeningocele who had urinary incontinence due to neuropathic detrusor overactivity (NDO). Twenty-four patients with myelomeningocele (mean age: 9 ± 3.6 years, range: 3-16) were included in the study and followed up for 6 years. Using an electrode bladder catheter, 10 IU/kg of Dysport (BoNTA) was inserted into the bladder for electromotive drug administration (EMDA) without anesthesia on outpatient basis. The EMDA equipment was connected to the electrode of an indwelling catheter and 2 dispersive electrodes, and a pulsed current generator delivered 10 mA for 20 minutes. The preliminary assessments were voiding diary, urodynamic study, kidney and bladder ultrasounds which were also performed annually. Prior to the treatment, all patients had NDO and urinary incontinence. During the follow-up, 18 of 24 (75%), 11 of 24 (45.5%), 9 of 24 (37.5%), 8 of 24 (33%), and 7 of 24 (29.1%) of the patients were completely dry between 2 consecutive clean intermittent catheterizations after once BoNTA-EMDA treatment at 1, 2, 3, 5, and 6 years of follow-up, respectively. The mean maximum detrusor pressure significantly decreased and mean maximal cystometric capacity significantly increased at follow-ups (P <.05). The results of the present study have shown that BoNTA-EMDA is a feasible, safe, reproducible, cost-effective, long-lasting, and pain free method on an outpatient basis, with long-term duration of effects without anesthesia or cystoscopy procedure. This novel delivery system resulted in considerable improvement in urinary incontinence and urodynamic study parameters in patients with refractory NDO.