Intravesical Instillation Of Epirubicin Research Articles

Single Early Intravesical Instillation of Epirubicin for Preventing Bladder Recurrence after Nephroureterectomy in Upper Urinary Tract Urothelial Carcinoma.

We aimed to assess the effectiveness of early single intravesical administration of epirubicin in preventing intravesical recurrence after radical nephroureterectomy for upper tract urothelial carcinoma. Patients with upper tract urothelial carcinoma who underwent radical nephroureterectomy between November 2018 and May 2022 were retrospectively reviewed. Intravesical epirubicin was administered within 48 hours if no evidence of leakage was observed. Epirubicin (50 mg) in 50 mL normal saline solution was introduced into the bladder via a catheter and maintained for 60 minutes. The severity of adverse events was graded using the Clavien-Dindo classification. We compared intravesical recurrence rate between the two groups. Multivariate analyses were performed to identify the independent predictors of bladder recurrence following radical nephroureterectomy. Epirubicin (n=55) and control (n=116) groups were included in the analysis. No grade 1 or higher bladder symptoms have been reported. A statistically significant difference in the intravesical recurrence rate was observed between the two groups (11.8% at 1 year in the epirubicin group vs. 28.4% at 1 year in the control group; log-rank p=0.039). In multivariate analysis, epirubicin instillation (hazard ratio [HR], 0.43; 95% confidence interval [CI], 0.20 to 0.93; p=0.033) and adjuvant chemotherapy (HR, 0.29; 95% CI, 0.13 to 0.65; p=0.003) were independently predictive of a reduced incidence of bladder recurrence. This retrospective review revealed that a single immediate intravesical instillation of epirubicin is safe and can reduce the incidence of intravesical recurrence after radical nephroureterectomy. However, further prospective trials are required to confirm these findings.

The value of immediate postoperative intravesical epirubicin instillation as an adjunct to standard adjuvant treatment in intermediate and high-risk non–muscle-invasive bladder cancer: A preliminary results of randomized controlled trial

PurposeWe aimed at this study to test the value of immediate postoperative intravesical epirubicin instillation in intermediate and high-risk non–muscle-invasive bladder cancer patients. Materials and MethodsAfter approval of Institutional Review Board, 260 patients were randomly allocated into 2 groups, including transurethral resection of bladder tumor (TURBT) alone in control group and TURBT plus immediate postoperative epirubicin (50 mg) in test group. Patients were monitored for postoperative complications. Adjuvant instillation therapy was administered according to risk categorization. Patients were followed every 3 months by cystourethroscopy and urine cytology. The primary end points were recurrence, progression, and/or death from cancer. ResultsOf the 260 patients, 236 were eligible and followed for a mean of 29 months. The 2 study groups were comparable regarding perioperative baseline demographic criteria. There was no statistically significant difference between the 2 groups regarding recurrence rate (27.1% vs. 26.2%), interval to first recurrence (16.3 ± 6.6 vs. 16.4 ± 6.4 months) or progression rate to muscle invasion (8.5% vs. 5.9%). Site, size, and number of recurrences were also comparable between the 2 groups. Recurrences and progression-free survival were comparable between the 2 groups (Log-rank P = 0.88 and 0.47, respectively). Postoperative complications were all low-grade according to modified Dindo–Clavian system, with no significant difference in their rate between the 2 groups. ConclusionsImmediate post-TURBT epirubicin instillation is ineffective in intermediate and high-risk non–muscle-invasive bladder cancer. It neither prolongs time to recurrence and/or progression nor reduces number of recurrences. We advocate strict specification of patient and tumor criteria in which immediate instillation is indicated.

Symptoms Control for Patients with Superficial Bladder Cancers Before and After TURBT and Intravesical Epirubicin Instillation

Bladder cancer is one of the most common cancers among urologic cancers. Intravesical instillation following transurethral resection of bladder tumor (TURBT) is used as a treatment of bladder cancer. According to results of this study, before and after intravesical instillations following TURBT have no effect on symptom outcomes of patients with superficial bladder cancer.

AB143. Pharmacogenetic association between XRCC1 polymorphisms and improved outcomes in bladder cancer patients following intravesical instillation of epirubicin

ObjectiveXRCC1 is a multi-domain protein associated with bladder cancer. We investigated the relationship between the distribution of XRCC1 polymorphisms (rs915927 and rs2854501) and clinical outcomes following intravesical instillation with epirubicin (EPI) or mitomycin C (MMC).MethodsA TaqMan assay was performed to determine genotypes of 240 individuals diagnosed with bladder cancer. Logistic regression was used to assess the association between polymorphisms and relapse-free survival (RFS) of patients. Quantitative real-time polymerase chain reaction was performed to determine expression of XRCC1 polymorphisms. Survival curves were generated using the Kaplan-Meier method.ResultsRisk of bladder cancer recurrence was significantly reduced in patients receiving EPI who had higher incidences of XRCC1 polymorphisms (P=0.009 for rs915927, P=0.001 for rs2854501). In participants administered MMC, results were not statistically significant.ConclusionsPolymorphisms in XRCC1 SNP variants (rs915927 and rs2854501) were associated with improved clinical outcomes following EPI treatment.

390 ROLE OF KI-67 PROLIFERATION MARKER IN PREDICTING RECURRENCE OF HIGH GRADE TA & T1 BLADDER TRANSITIONAL CELL CARCINOMA

You have accessJournal of UrologyUrothelial Cancer: Natural History, Markers & Pathophysiology1 Apr 2013390 ROLE OF KI-67 PROLIFERATION MARKER IN PREDICTING RECURRENCE OF HIGH GRADE TA & T1 BLADDER TRANSITIONAL CELL CARCINOMA Mohamed Abdallah, Ahmed Abdelhalim, Hala Said, Tarek Abdelbakey, Nancy Assad, and Abdelaliem Eldorey Mohamed AbdallahMohamed Abdallah Quesna, Egypt More articles by this author , Ahmed AbdelhalimAhmed Abdelhalim Shibin Elkom, Macedonia More articles by this author , Hala SaidHala Said shibin elkom, Egypt More articles by this author , Tarek AbdelbakeyTarek Abdelbakey shibin elkom, Egypt More articles by this author , Nancy AssadNancy Assad shibin elkom, Egypt More articles by this author , and Abdelaliem EldoreyAbdelaliem Eldorey shibin elkom, Egypt More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1779AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Ki-67, an established proliferation marker expressed in G1, S, G2, M phases of cell cycle. We previously found an association between Ki-67 index & urothelial tumor grade, muscle invasion & positive lymph nodes. In this study, we focused on high grade non-muscle invasive urothelial tumor to predict recurrence after complete TURBT with 1 year follow up. This can aid decision of urologist either to follow up or to schedule his patient for radical cystectomy. METHODS 87 patients with high grade non-muscle invasive TCC did complete TURBT with immediate intravesical instillation of Epirubicin® 50 mg, Ki-67 index was estimated using purified rabbit polyclonal antibody raised against the C-terminal fragment of the human Ki67 nuclear antigen (Lab vision, USA). Intravesical immunotherapy by instillation of BCG & follow up cystoscopy & immunohistochemical determination of Ki-67 index at 3, 6, 9 & 12 months. RESULTS The Age of the patients (Range, Mean ± SD)45-60, 56.72 ± 4.81. The gender (Male%, Female%)86.1, 13.9.The Ki-67 index was(Range, Median)30-90,70.The table shows the recurrence rates. CONCLUSIONS The higher the Ki-67 index, the higher the probability of recurrence of high grade Ta & T1 transitional cell carcinoma of bladder with 56% recurrence with Ki-67 index 81-90% at 1 year follow up. New recurrence at 3 months 6 months 9 months 12 months total Ki-67 index 30-40% (N=15) 0 (0%) 0 (0%) 0 (0%) 2 (13.33%) 2 (13.33%) Ki-67 index 41-60% (N=21) 0 (0%) 0 (0%) 4 (19.05%) 4 (19.05%) 8 (38.1%) Ki-67 index 61-80% (N=26) 1 (3.85%) 1 (3.85%) 4 (15.38%) 4 (30.77%) 10 (38.46%) Ki-67 index 81-90% (N=25) 2 (8.0%) 4 (16%) 2 (8.0%) 6 (24.0%) 14 (56.0%) Overall recurrence at 1 year 34 (39.08%) © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e158 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Mohamed Abdallah Quesna, Egypt More articles by this author Ahmed Abdelhalim Shibin Elkom, Macedonia More articles by this author Hala Said shibin elkom, Egypt More articles by this author Tarek Abdelbakey shibin elkom, Egypt More articles by this author Nancy Assad shibin elkom, Egypt More articles by this author Abdelaliem Eldorey shibin elkom, Egypt More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

2‐micrometer continuous wave laser treatment for multiple non‐muscle‐invasive bladder cancer with intravesical instillation of epirubicin

We have reported the efficacy and safety of 2-micrometer continuous wave laser resection of non-muscle-invasive bladder tumor (NMIVBC) (World J Urology 2010;28:157-161). In this study, we evaluated the use of 2-micrometer continuous wave laser resection in combination with intravesical instillation of epirubicin for the treatment of multiple NMIVBC. From September 2007 to April 2008, sixty patients with multiple NMIVBC were included in this study (44 cases of low grade papillary urothelial carcinoma, 10 cases of high grade papillary urothelial carcinoma, and six cases of papillary urothelial neoplasm with low malignant potential). Imaging examinations including pelvic computer tomography (CT) and intravenous urography showed no extravesical extension, lymphatic metastasis or any lesions of upper urinary tract. All patients received 2-micrometer continuous wave laser therapy under continuous epidural anesthesia, and intravesical chemotherapy with epirubicin 1 week later (intravesical instillation weekly for 8 weeks, followed by monthly maintenance to 12 months). Totally 211 tumors in 60 patients were successfully removed with 2-micrometer continuous wave laser. The mean operation time was 48 minutes per patient (ranged 20-90 minutes) and 13.6 minutes per tumor (range 5-25 minutes). No obturator nerve reflection or bladder perforation occurred during the procedure. All patients finished 12 months of intravesical chemotherapy without severe complications. The mean followed-up time was 23 months. Tumor recurrences were found in 13 patients (22%). The combination of 2-micrometer continuous wave laser and intravesical chemotherapy is feasible, safe, and efficacious for the treatment of multiple NMIVBC.

Long-term efficacy results of EORTC Genito-Urinary Group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder

Long-term efficacy results of EORTC Genito-Urinary Group randomized phase 3 study 30911 comparing intravesical instillations of epirubicin, bacillus Calmette-Guérin, and bacillus Calmette-Guérin plus isoniazid in patients with intermediate- and high-risk stage Ta T1 urothelial carcinoma of the bladder

1352 SYNERGISTIC EFFECT OF IMMEDIATE INTRAVESICAL CHEMOTHERAPY AND SUBSEQUENT INDUCTION COURSE OF BCG FOR NON-MUSCLE INVASIVE BLADDER CANCER

You have accessJournal of UrologyBladder Cancer: Superficial1 Apr 20101352 SYNERGISTIC EFFECT OF IMMEDIATE INTRAVESICAL CHEMOTHERAPY AND SUBSEQUENT INDUCTION COURSE OF BCG FOR NON-MUSCLE INVASIVE BLADDER CANCER Kazuhiro Matsumoto, Hiroyuki Yamanaka, Masayuki Hagiwara, Akiharu Ninomiya, and So Nakamura Kazuhiro MatsumotoKazuhiro Matsumoto More articles by this author , Hiroyuki YamanakaHiroyuki Yamanaka More articles by this author , Masayuki HagiwaraMasayuki Hagiwara More articles by this author , Akiharu NinomiyaAkiharu Ninomiya More articles by this author , and So NakamuraSo Nakamura More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.979AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES BCG is currently the most effective intravesical agent at preventing the recurrence of non-muscle invasive bladder cancer. However, some patients treated with BCG still unfortunately experience tumor recurrence. To date, multiple clinical trials have focused on the efficacy of single immediate instillation of chemotherapeutic agents. The aim of this study was to evaluate the synergistic effect of immediate intravesical chemotherapy and a subsequent induction course of BCG. METHODS Between 1993 and 2007, 526 cases with diagnosed non-muscle invasive bladder cancer were treated with transurethral resection at our institution. Of these 526 cases, 115 low risk patients who had initially been diagnosed with a solitary Ta G1/2 tumor and 41 patients treated with induction courses of intravesical chemotherapy were excluded. The remaining 370 patients, consisting of 193 intermediate risk patients and 177 high risk patients, were the subjects in this retrospective study. The median follow-up interval was 3.1 years. RESULTS No adjuvant intravesical therapy was performed in 115 patients (Group A). Only immediate epirubicin 40 mg instillation was performed in 56 patients (Group B), and 125 patients received only an induction course of 6 BCG instillations (Group C). The remaining 74 patients were treated with both immediate epirubicin instillation and a subsequent induction course of BCG (Group D). Initially there was no significant difference in the clinicopathological backgrounds of Group A and Group B, but the 3-year recurrence-free survival rate in Group A (31.9%) was less than in Group B (57.5%) (p<0.001), which proved the efficacy of immediate intravesical therapy using epirubicin. In Group C, the 3-year recurrence-free survival rate was 57.9%, which was almost the same as that in Group B (p=0.533), although statistically Group C included more high risk patients (72 of 125 patients) than Group B (17 of 56 patients) (p<0.001). Next, we compared Group C and Group D. No significant difference in their respective backgrounds was observed. However, the 3-year recurrence-free survival rate in Group D was significantly higher than that in Group C (75.5% vs 57.9%) (p<0.001), which suggested the combination therapy had a synergistic effect. CONCLUSIONS For intermediate and high risk patients, our results indicate that the combination of immediate intravesical epirubicin instillation with a subsequent induction course of BCG exhibited a synergistic effect against potential tumor recurrence and is thus recommended. Tokyo, Japan© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e522 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Kazuhiro Matsumoto More articles by this author Hiroyuki Yamanaka More articles by this author Masayuki Hagiwara More articles by this author Akiharu Ninomiya More articles by this author So Nakamura More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Comparison of the Efficacy of Single or Double Intravesical Epirubicin Instillation in the Early Postoperative Period to Prevent Recurrences in Non-Muscle-Invasive Urothelial Carcinoma of the Bladder: Prospective, Randomized Multicenter Study

Objectives: To investigate the efficacy of single or double epirubicin instillation during the early postoperative period (EPP) in intermediate-risk non-muscle-invasive urothelial cancer. Methods: Patients with primary and solitary or multiple (3 or less) Ta (grade 2–3) or T1 (grade 1–2) tumors were enrolled. Patients were randomized to receive either a single dose of 100 mg epirubicin instillation within 6 h or a second 100 mg epirubicin instillation during the 12th–18th hours after a complete TUR-BT. At the end of the 60-month follow-up period, the available data were statistically analyzed. The end-points of the study were determined as disease-free survival, progression and recurrence rates, time to recurrence, and time to progression. Results: A total of 299 patients from 24 institutions were randomized between January 2002 and June 2004. There were 143 patients from 18 institutions who met the eligibility criteria. The follow-up and disease-free survival periods were 16.9 months and 16 months, respectively. There was no statistical difference in the demographic properties and the end-points between the groups. Conclusions: A single dose of intravesical 100 mg epirubicin chemotherapy during the early postoperative period for primary intermediate-risk non-muscle-invasive urothelial cancer achieved 16 months of mean disease-free survival. A second intravesical epirubicin instillation did not provide any significant benefit.

Should Patients With Primary Upper Urinary Tract Cancer Receive Prophylactic Intravesical Chemotherapy After Nephroureterectomy?

We assessed the efficacy of prophylactic intravesical chemotherapy for primary upper urinary tract urothelial cancer after nephroureterectomy during long-term followup. From January 1985 to June 2007, 196 patients with primary upper urinary tract urothelial cancer were included in this study. Patients were divided into group 1-31 who received intravesical epirubicin instillation, group 2-27 who received intravesical mitomycin C instillation and group 3-138 who did not receive prophylactic instillation after nephroureterectomy. We compared the bladder tumor recurrence rate, number of recurrence episodes, time to first bladder tumor recurrence, tumor type, percent of patients with cystectomy and percent who died of urothelial cancer, and the recurrence-free survival rate. Of the 196 patients 73 had subsequent bladder recurrence at a mean followup of 55.6 months. There were no significant differences in recurrence type, mean number of bladder tumor recurrences, percent of patients with cystectomy and the cancer specific survival rate. The bladder recurrence rate was lower in group 1 and 2 than in group 3. Mean time to first bladder tumor recurrence was longer in groups 1 and 2. Kaplan-Meier curves of recurrence-free survival rates were significantly increased in groups 1 and 2. Intravesical instillation of epirubicin or mitomycin C appears to be well tolerated and effective for preventing bladder recurrence and prolonging time to first bladder recurrence. Patients should receive prophylactic intravesical chemotherapy after nephroureterectomy.

Drug eruption due to intravesical instillations of both epirubicin and mitomycin C

We present the first patient to develop drug eruption due to intravesical instillations of both epirubicin and mitomycin C. A 58-year-old-man underwent transurethral resection (TUR) for superficial bladder carcinoma followed by instillations of intravesical chemotherapy. Immediately after TUR, the first instillation of epirubicin was performed. Two days after the first instillation, the patient developed generalized erythema of the face, trunk, upper and lower limbs. Two days after the second instillation, the patient developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillations of epirubicin by the dermatologist. Instead of epirubicin, mitomycin C was instilled 2 weeks postoperatively. Two days after the first instillation of mitomycin C, the patient again developed severe generalized erythema and was diagnosed as having drug eruption due to intravesical instillation of mitomycin C. Drug eruption after the first instillation of epirubicin might have been due to drug toxicity of the agent. However, drug eruptions after the second instillation of epirubicin and the first instillation of mitomycin C might have been due to allergic reactions to the drugs. The patient has not received any further intravesical chemotherapy and has not demonstrated any such a drug eruption again.

Preventing Bladder Tumor Implantation With Photodynamic Therapy in a Rat Model Mimicking Post-Fluorescence Guided Transurethral Resection

Fluorescence guided transurethral resection has gained acknowledgment from the urological community and it is progressively becoming more applied. It has been shown to decrease the recurrence rate of nonmuscle invasive bladder cancer due to incomplete resection due to lack of visualization. The implantation of viable tumor cells seeded during transurethral resection is another reason for recurrence. We investigated whether applying photodynamic therapy on sensitized tumor cells would decrease the amount of viable intraluminal cells and tumor cell implantation. Two models were designed to mimic the situation after fluorescence guided transurethral resection, including partly or fully de-epithelialized bladders and circulating tumor cells loaded with protoporphyrin IX. Photodynamic therapy was performed. Controls consisted of no drug with no light, light only and drug only. Immediately after photodynamic therapy the intravesical contents were retrieved and clonogenic assays were performed on cells. Bladders were harvested 10 days after cell administration and subjected to pathological analysis. In the photodynamic therapy and control groups tumor volume was proportional to the instilled cell load. Clonogenic assays showed that viable cells were decreased a tenth of the initial administered amount. Tumor implantation decreased to less than a fifth of control values. Photodynamic therapy can effectively decrease the amount of viable tumor cells in the bladder lumen. This results in a significant decrease in tumor implantation. This technique could possibly be used to further decrease the recurrence rate of nonmuscle invasive bladder cancer.

Should All Patients with Non–Muscle-Invasive Bladder Cancer Receive Early Intravesical Chemotherapy after Transurethral Resection? The Results of a Prospective Randomised Multicentre Study

BackgroundTo decrease recurrences in non–muscle-invasive bladder cancer (NMIBC), the European Association of Urology (EAU) guidelines recommend immediate, intravesical chemotherapy after transurethral resection (TUR) for all patients with Ta/T1 tumours. ObjectiveTo study the benefits of a single, early, intravesical instillation of epirubicin after TUR in patients with low- to intermediate-risk NMIBC. Design, setting, and participantsIn this prospective randomised multicentre trial, 305 patients with primary as well as recurrent low- to intermediate-risk (Ta/T1, G1/G2) tumours were enrolled between 1997 and 2004. Patients were randomly allocated to receive 80mg of epirubicin in 50ml of saline intravesically within 24h of TUR or no further treatment after TUR. MeasurementsThe primary end point was time to first recurrence. Results and limitationsA total of 219 patients remained for analysis after exclusions. The median follow-up time was 3.9 yr. During the study period, 62% (63 of 102) of the patients in the epirubicin group and 77% (90 of 117) in the control group experienced recurrence (p=0.016). In a multivariate model, the hazard ratio (HR) for recurrence was 0.56 (p=0.002) for early instillation of epirubicin versus no treatment. In a subgroup analysis, the treatment had a profound recurrence-reducing effect on patients with primary, solitary tumours, whereas it provided no benefits in patients with recurrent or multiple tumours. Furthermore, patients with a modified European Organisation for Research and Treatment of Cancer (EORTC) risk score of 0–2 with and without single instillation had recurrence rates of 41% and 69%, respectively (p=0.003), whereas the corresponding rates for those with a risk score of ≥3 were 81% and 85%, respectively (p=0.35). ConclusionsA single, early instillation of epirubicin after TUR for NMIBC reduces the likelihood of tumour recurrence; however, the benefit seems to be minimal in patients at intermediate or high risk of recurrence. Future trials will determine the value of early instillation in addition to serial instillations in NMIBC.

Prevention of Recurrence With Epirubicin and Lactobacillus Casei After Transurethral Resection of Bladder Cancer

A prospective, randomized, controlled trial was done to evaluate whether oral administration of a preparation of the probiotic agent Lactobacillus casei (Yakult Honsha, Tokyo, Japan) could enhance the prevention of recurrence by intravesical instillation of epirubicin after transurethral resection for superficial bladder cancer. Between August 1999 and December 2002, 207 patients clinically diagnosed with superficial bladder cancer were included as study candidates and underwent transurethral resection, followed by intravesical instillation of 30 mg epirubicin/30 ml saline twice during 1 week. After histological confirmation of superficial bladder cancer they were again included as study participants with 102 randomized to receive treatment with 6 additional intravesical instillations of epirubicin during the 3-month period after transurethral resection (epirubicin group) and 100 randomized to intravesical chemotherapy on the same schedule as the epirubicin group plus oral administration of 3 gm Lactobacillus casei preparation per day for 1 year (epirubicin plus Lactobacillus casei group). Patients were evaluated for intravesical recurrence, disease progression, prognosis and adverse drug reactions. The 3-year recurrence-free survival rate was significantly higher in the epirubicin plus Lactobacillus casei group than in the epirubicin group (74.6% vs 59.9%, p = 0.0234), although neither progression-free nor overall survival differed between the groups. The incidence of adverse drug reactions did not significantly differ between the groups and there were no serious adverse drug reactions. Intravesical instillation of epirubicin plus oral administration of Lactobacillus casei preparation is a novel, promising treatment for preventing recurrence after transurethral resection for superficial bladder cancer.

A Single Instillation of Epirubicin After Transurethral Resection of Bladder Tumors Prevents Only Small Recurrences

We studied whether a single instillation of epirubicin after transurethral bladder tumor resection would influence the interval to and size of the first recurrence. A total of 404 patients from 13 hospitals were randomized to 1 instillation of 50 mg epirubicin or placebo within 6 hours after transurethral resection of bladder tumors. Of 155 evaluable patients in the epirubicin group 79 (51.0%) had recurrence compared to 95 of 152 (62.5%) in the placebo group (p = 0.04). Of the recurrences 63.3% were small (1 to 5 mm). Tumor size was unknown in 5 patients. Of 79 patients with recurrence in the epirubicin arm 33 (42.9%) vs 29 (31.5%) of 95 in the placebo arm had larger (more than 5 mm) first recurrences (p = 0.12). Approximately half of the patients with first recurrences were treated as outpatients and the other half spent a total of 145 days in the hospital with no difference between the groups. We confirmed the results of previous studies showing that 8.5 patients must be treated with a single instillation to prevent 1 recurrence. Furthermore, our data may indicate that only small recurrences are prevented, which could easily be fulgurated using local anesthesia at followup cystoscopy. The benefit of single instillations can be questioned if this finding is confirmed by others.

Meglumine Eicosapentaenoic acid (MeEPA) a new soluble omega-3 fatty acid formulation: In vitro bladder cancer cytotoxicity tests in combination with epirubicin and mitomycin

To determine if Meglumine-Eicosapentaenoic Acid (MeEPA) acts synergistically with epirubicin and mitomycin to enhance cytotoxicity towards bladder cancer cell lines in vitro. Bladder cancer cells were exposed to MeEPA in combination with epirubicin or mitomycin. Residual viable cell biomass was estimated with the methyl-thiazoldiphenyl tetrazolium (MTT) assay following drug exposure. Drug interaction was analysed using median effect analysis to determine levels of synergism. Most combinations of MeEPA with both epirubicin and mitomycin showed a high-level of synergism. At high doses, drug precipitation adversely affected MTT assay analysis suggesting antagonism of action. However, the predominant pattern was of synergism for most dose combinations tested. Bladder cancer treated by endoscopic resection alone is subject to high recurrence rates. Post-operative intravesical instillation of epirubicin and mitomycin can halve recurrence rates, but there is no evidence that disease progression to invasive bladder cancer is altered. Thus, optimisation of current treatment strategies is required. The anti-tumour activity of fatty acids is well established and MeEPA is a new, soluble formulation with the potential to enhance intravesical drug efficacy.

Randomized Study of Single Instillation of Epirubicin for Superficial Bladder Carcinoma: Long-Term Clinical Outcomes

Purpose: Intravesical instillation of epirubicin (EPI) is one of the most effective adjuvant therapies for nonmuscle-invasive bladder cancer postoperation. We evaluated the long-term efficacy of single dose intravesical epirubicin for superficial bladder carcinoma recurrence. Methods: Between June 1997 and May 1998, a total of 47 patients with resectable superficial bladder carcinoma (Ta-1, Grade 1-2), primary or recurrent with no recurrence during last one year, were enrolled in this study. All patients were randomized into 3 study groups: Group A—single epirubicin (80 mg/40 mL of normal saline) was administered into the bladder within 6 hours postoperation; Group B–40 mg Epirubicin consecutively; Group C—40 mg mitomycin C, consecutively. In Group B and C, instillation were given every week for 6∼ 8 weeks and then every one month for 10 months. Patients were followed up at 3, 6, 9, 12, 18, 24, 36, 48, and 60 months of treatment. The analyzed background factors were the therapeutic method, tumor recurrence, and side effects. Results: Of the 47 patients, 43 (91.5 percent) were eligible and were followed up for 5 years postoperation. The disease free intervals of the three groups were found to have no significant differences (F = 10.28, p > 0.05). The recurrence rates were 35.7 percent (5/14), 33.3 percent (5/15), and 40 percent (6/15), respectively (χ2 = 0.83, p > 0.05). Side effects of group A (13.6 percent) was lower than that of Group B or C (53.3 percent and 46.7 percent, respectively) significantly (χ2 test, p < 0.01). Conclusions: These data indicate that single dose of epirubicin instillation postoperation can reduce the recurrence of superficial bladder carcinoma and has low side effects.

BACILLUS CALMETTE-GUERIN VERSUS EPIRUBICIN FOR PRIMARY, SECONDARY OR CONCURRENT CARCINOMA IN SITU OF THE BLADDER: RESULTS OF A EUROPEAN ORGANIZATION FOR THE RESEARCH AND TREATMENT OF CANCER—GENITO-URINARY GROUP PHASE III TRIAL (30906)

We compared the efficacy and side effects of intravesical instillations of bacillus Calmette-Guerin (BCG) and epirubicin in patients with carcinoma in situ (CIS) of the bladder. Patients with primary, secondary or concurrent CIS of the bladder were randomized to 81 mg BCG-Connaught (6 weekly instillations) or 50 mg epirubicin (8 weekly instillations). When a complete response (CR), defined as no Ta/T1 or CIS on biopsy and negative cytology, was obtained, patients in the 2 groups received maintenance instillations at months 3, 6, 12, 18, 24, 30 and 36. When no complete response was observed, the original treatment was repeated, followed again by cystoscopy and biopsies plus cytology. A total of 168 patients were randomized between March 1993 and April 1999 to receive BCG (84) or epirubicin (84), while 4 on epirubicin and 3 on BCG were ineligible. The majority (52%) had concurrent CIS. Primary and secondary CIS was found in 23% and 24% of cases, respectively. The overall CR rate was 56% for epirubicin and 65% for BCG (p = 0.21, 90% CI 21.5 to -2.9). When tumor was found following 2 instillation courses, further treatment was left to the investigator (BCG in 29 cases and epirubicin in 37). Time to bladder tumor recurrence after CR was longer in patients treated with BCG vs epirubicin (median 5.1 vs 1.4 years). CIS recurrences were more frequently observed in complete responders to epirubicin (45% vs 16%). No differences in time to progression or duration of survival were observed. Side effects were more frequently seen in patients on BCG with 26 on BCG and 8 on epirubicin stopping treatment due to side effects. No significant difference in CR rates could be demonstrated with intravesical instillations of epirubicin or BCG. Time to recurrence was significantly longer in patients treated with BCG after having achieved a CR. More CIS recurrences were found in patients treated with epirubicin. For time to progression and survival longer followup is warranted. Side effects were more frequent in patients on BCG.

Effect of intravesical instillation on performance of uCYT+ test

Objectives To assess the influence of intravesical instillation of epirubicin or bacille Calmette-Guérin (BCG) in patients with bladder cancer on the clinical performance of the uCyt+ test, which traces the three monoclonal antibodies M344, LDQ 10, and 19A211 in urothelial cells. Methods A total of 267 patients with a mean age of 70.5 years (range 35 to 87) were included in this prospective study. All patients were being followed up after complete transurethral resection of superficial urothelial cancer. All patients received a single instillation of 80 mg epirubicin within 24 hours of transurethral resection and 163 underwent subsequent cycles of chemotherapy with epirubicin or immunotherapy with BCG. This was because of multifocality, high-recurrence, or high-grade urothelial cancer. At the next control, all patients underwent urinary cytology, with the uCyt+ test performed on liquid-based cytology (ThinPrep), subsequent cystoscopy, and evaluation of any suspicious lesion by biopsy. Patients who underwent intravesical BCG therapy underwent random bladder cold biopsy after every instillation series. Results Of the 267 patients, 8 could not be evaluated by uCyt+ because of insufficient cells. Of the remaining 259 patients under assessment, 86 had proven urothelial cancer. In the 101 patients under assessment with only a single intravesical instillation of epirubicin (group 1), the overall sensitivity for cytology and the uCyt+ test was 44.7% and 76.6%, respectively. Cytology had a specificity of 90.7% and uCyt+ of 64.8%. The negative predictive value for cytology and uCyt+ was 65.3% and 76.1%, respectively. Of the 158 patients under evaluation who were treated with long-term intravesical therapy (group 2), the overall sensitivity and specificity for cytology and the uCyt+ test was 37.8% and 84.6% and 94.9% and 70.6%, respectively. The negative predictive value for cytology and the uCyt+ test was 83.1% and 93.3%, respectively. Statistical analysis showed no statistically significant difference between the overall sensitivity ( P = 0.512) and specificity ( P = 0.558) for the uCyt+ test in the two groups of patients. Conclusions The sensitivity and specificity of the uCyt+ test are not significantly affected by intravesical long-term treatment with epirubicin or BCG.

A Randomized Controlled Trial of Short-Term Versus Long-Term Prophylactic Intravesical Instillation Chemotherapy for Recurrence After Transurethral Resection of Ta/T1 Transitional Cell Carcinoma of the Bladder

In a prospective randomized controlled study, we investigated the optimal schedule for intravesical instillation of epirubicin for maximizing its effect on prophylaxis and disease progression after transurethral resection of newly diagnosed Ta/T1 bladder cancer. The patients were instilled with epirubicin (30 mg/30 ml in normal saline) within 24 hours after transurethral resection and then randomized into 2 groups after a definite histopathological diagnosis of Ta/T1 bladder cancer. One group of 77 patients received 19 intravesical instillations of epirubicin in the year after transurethral resection (group 1). The second group of 73 patients received 9 intravesical instillations of epirubicin during the 3 months after transurethral resection (group 2). Nonrecurrence rates and toxicity were compared. In the followup period, 10 group 1 patients (13.0%) and 23 group 2 patients (31.5%) had recurrent disease. The 3-year nonrecurrence rate was 85.2% in group 1, whereas it was 63.9% in group 2. The nonrecurrence rate of group 1 was significantly higher than that of group 2 throughout the observation period (p = 0.005). The incidence and severity of toxicity were not significantly different between the 2 groups. Our study indicates that long-term instillation of epirubicin is more effective than short-term instillation in preventing recurrence after transurethral resection of Ta/T1 bladder cancer.