pirarubicin and Urinary-Bladder-Neoplasms

The European Association of Urology non-muscle-invasive bladder cancer (NMIBC) guidelines recommend that all low- and intermediate-risk patients receive a single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB), but its use remains controversial.. To identify which NMIBC patients benefit from a single immediate instillation.. A systematic review and individual patient data (IPD) meta-analysis of randomized trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC patients was carried out.. A total of 13 eligible studies were identified. IPD were obtained for 11 studies randomizing 2278 eligible patients, 1161 to TURB and 1117 to a single instillation of epirubicin, mitomycin C, pirarubicin, or thiotepa. A total of 1128 recurrences, 108 progressions, and 460 deaths (59 due to bladder cancer [BCa]) occurred. A single instillation reduced the risk of recurrence by 35% (hazard ratio [HR]: 0.65; 95% confidence interval [CI], 0.58-0.74; p<0.001) and the 5-yr recurrence rate from 58.8% to 44.8%. The instillation did not reduce recurrences in patients with a prior recurrence rate of more than one recurrence per year or in patients with an European Organization for Research and Treatment of Cancer (EORTC) recurrence score ≥5. The instillation did not prolong either the time to progression or death from BCa, but it resulted in an increase in the overall risk of death (HR: 1.26; 95% CI, 1.05-1.51; p=0.015; 5-yr death rates 12.0% vs 11.2%), with the difference appearing in patients with an EORTC recurrence score ≥5.. A single immediate instillation reduced the risk of recurrence, except in patients with a prior recurrence rate of more than one recurrence per year or an EORTC recurrence score ≥5. It does not prolong either time to progression or death from BCa. The instillation may be associated with an increase in the risk of death in patients at high risk of recurrence in whom the instillation is not effective or recommended.. A single instillation of chemotherapy immediately after resection reduces the risk of recurrence in non-muscle-invasive bladder cancer; however, it should not be given to patients at high risk of recurrence due to its lack of efficacy in this subgroup.

Topics: Administration, Intravesical; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Disease Progression; Doxorubicin; Epirubicin; Humans; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Staging; Randomized Controlled Trials as Topic; Risk Factors; Survival Rate; Thiotepa; Time Factors; Urinary Bladder Neoplasms

We performed a network meta-analysis of randomized controlled trials (RCTs) to compare the efficacy of several intravesical chemotherapeutic (IVC) agents after transurethral resection of bladder tumor (TURB) in non-muscle invasive bladder cancer patients. The literature search was conducted using the Embase, Scopus and PubMed databases for RCTs, including patients with single or multiple, primary or recurrent stage Ta or T1 urothelial carcinoma of the bladder managed with a single, immediate instillation of IVC after TURB. Thirteen RCTs met the eligibility criteria. Pair-wise meta-analysis (direct comparison) showed that pirarubicin [hazard ratio (HR): 0.31], epirubicin (HR: 0.62), and MMC (HR: 0.40) were the most effective drugs for reducing tumor recurrence. Bayesian network meta-analysis (indirect comparison) revealed that treatment with pirarubicin (HR: 0.31), MMC (HR: 0.44), or epirubicin (HR: 0.60) was associated with prolonged recurrence-free survival. Among the drugs examined, only pirarubicin reduced disease progression compared to controls. These results suggest that a single, immediate administration of IVC with pirarubicin, MMC, or epirubicin is associated with prolonged recurrence-free survival following TURB in non-muscle invasive bladder cancer patients, though only pirarubicin also reduced disease progression.

Topics: Administration, Intravesical; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cyclophosphamide; Doxorubicin; Epirubicin; Humans; Melphalan; Network Meta-Analysis; Semustine; Treatment Outcome; Urinary Bladder Neoplasms

The circadian timing of surgery, anticancer drugs, radiation therapy, and biologic agents can result in improved toxicity profiles, tumor control, and host survival. Optimally timed cancer chemotherapy with doxorubicin or pirarubicin (06:00h) and cisplatin (18:00h) enhanced the control of advanced ovarian cancer while minimizing side effects, and increased the response rate in metastatic endometrial cancer. Therapy of metastatic bladder cancer with doxorubicin-cisplatin was made more tolerable by this same circadian approach resulting in a 57% objective response rate. This optimally timed therapy is also effective in the adjuvant setting, decreasing the expected frequency of metastasis from locally advanced bladder cancer. Circadian fluorodeoxyuridine (FUDR) continuous infusion (70% of the daily dose given between 15:00h and 21:00h) has been shown effective for metastatic renal cell carcinoma resulting in 29% objective response and stable disease of more than 1 yr duration in the majority of patients. Toxicity is reduced markedly when FUDR infusion is modulated to circadian rhythms. In a multicenter trial in patients with metastatic renal cell cancer, patients were randomized to a flat or a circadian-modified FUDR infusion. This study confirmed a significant difference in toxicity and dose intensity, favoring the circadian-modified group. Hormone refractory metastatic prostate cancer has been treated with circadian-timed FUDR chemotherapy; however, without objective response. Biological agents such as interferon-alpha and IL-2 have shown low but effective disease control in metastatic renal cell cancer, however, with much toxicity. Each of these cytokines shows circadian stage dependent toxicity and efficacy in model systems. In summary, the timing of anthracycline, platinum, and fluoropyrimidine-based drug therapies during the 24h is relevant to the toxic therapeutic ratio of these agents in the treatment of gynecologic and genitourinary cancers.

Topics: Animals; Antineoplastic Agents; Carcinoma, Renal Cell; Cell Cycle; Chronotherapy; Circadian Rhythm; Cisplatin; Doxorubicin; Endometrial Neoplasms; Female; Floxuridine; Genital Neoplasms, Female; Humans; Kidney Neoplasms; Male; Ovarian Neoplasms; Prostatic Neoplasms; Rats; Urinary Bladder Neoplasms; Urogenital Neoplasms

Intravesical instillation of pirarubicin (THP) was performed on 66 patients with superficial bladder cancer after transurethral resection to evaluate the prophylactic effect against tumor recurrence. Intravesical chemotherapy was carried out at the concentration of 20mg/40ml. THP was initially instilled three times for one week, following instillation of every two weeks for ten times, and then every one month for seven times. Bladder irritability was demonstrated 21 of 66 cases (31.8%). Although there was a case of contracted bladder, generalized side effect was no case. Eligible cases for evaluation of efficacy were 43 out of 66 patients. The non-recurrence rate (by Kaplan-Meier's method) at one and two years were 90.4% and 77.8%, respectively. Intravesical THP instillation seems to be effective for the purpose of prophylaxis against the recurrence of superficial bladder tumor.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Urinary Bladder Neoplasms

To assess the prophylactic efficacy of postoperative single intravesical instillation with pirarubicin (THP) and mitomycin C (MMC) for low-risk non-muscle-invasive bladder cancer (NMBC).. A total of 103 clinically low-risk NMBC patients were preoperatively randomized into either THP (n=49) or MMC (n=54) groups. The primary endpoint was recurrence-free survival.. The median follow-up periods of the THP and MMC groups were 955 and 1008 days, respectively (p=0.76). Twelve patients (24.5%) in the THP group and 7 (13%) in the MMC group had bladder cancer recurrences. The two-year recurrence-free survival of the THP group and the MMC group was 77.8% and 86.4%, respectively (p=0.20). Neither groups had severe toxicity.. In low-risk NMBC, the prophylactic effect against postoperative single intravesical instillation with THP was not superior to that with MMC.

Topics: Administration, Intravesical; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Combined Modality Therapy; Cystoscopes; Doxorubicin; Female; Humans; Male; Middle Aged; Mitomycin; Neoplasm Grading; Neoplasm Staging; Postoperative Care; Recurrence; Treatment Outcome; Tumor Burden; Urinary Bladder Neoplasms

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Combined Modality Therapy; Doxorubicin; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Treatment Outcome; Urinary Bladder Neoplasms; Urologic Surgical Procedures

Observation is the current standard for managing cases of Stage 0a-III upper tract urothelial carcinoma after radical nephroureterectomy. A randomized Phase III trial commenced in Japan during October 2016. The trial is designed to investigate the superiority of a single early intravesical instillation of pirarubicin, compared with observation, in terms of relapse-free survival after radical nephroureterectomy for Stage 0a-III upper tract urothelial carcinoma. During a 5-year period, 310 patients will be recruited from 43 Japanese institutions. The primary endpoint is defined as relapse-free survival, and the secondary endpoints are overall survival, intravesical relapse-free survival, adverse events, and serious adverse events. This trial has been registered in the UMIN Clinical Trials Registry (UMIN000024267, http://www.umin.ac.jp/ctr/index.htm).

Topics: Administration, Intravesical; Doxorubicin; Follow-Up Studies; Humans; Japan; Neoplasm Recurrence, Local; Nephrectomy; Nephroureterectomy; Urinary Bladder Neoplasms

Single immediate intravesical instillation of chemotherapy after transurethral resection of bladder tumor (TURBT) has been the gold standard treatment for patients with low- and intermediate-risk non-muscle invasive bladder cancer (NMIBC). Herein, we conducted a multicenter prospective randomized controlled trial in Japan, comparing recurrence-free survival between single and two-time instillation of pirarubicin (THP) for solitary NMIBC.. Between 2005 and 2009, 257 patients with solitary NMIBC were enrolled and randomized to single instillation of THP (30 mg/50 mL) immediately after TURBT (Group A) or two-time instillation of THP immediately after and 1 day after TURBT (Group B). The primary endpoint was recurrence-free survival. Secondary endpoints included rates of recurrence and adverse effects, including hematuria, micturition pain, difficult urination, pollakiuria, systemic symptoms, and other complications. This study was registered as UMIN C000000266.. Of 257 patients, 99 in Group A and 102 in Group B could be evaluated for recurrence. Median follow-up was 71 months. The overall recurrence rate was 39 and 31%, respectively (p = 0.2704). Although the 5-year recurrence-free survival rates were 55.9% and 67.7% in groups A and B, respectively, the difference between groups was not significant (p = 0.2031). No significant differences in adverse effects were observed between groups, except for pollakiuria (7 vs 22%, p = 0.0031). Multivariate analyses did not show that the treatment group was a significant risk factor for bladder cancer recurrence.. Postoperative two-time intravesical instillation of THP was not superior to single immediate instillation for preventing recurrence after complete resection of a solitary NMIBC.

Topics: Administration, Intravesical; Aged; Analysis of Variance; Antineoplastic Agents; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Humans; Japan; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Prospective Studies; Urinary Bladder Neoplasms

The objective of this study was to evaluate the efficacy, defined by the 3-year tumor recurrence-free survival rate, of intravesical chemotherapy using pirarubicin (THP) in patients with low or intermediate-risk nonmuscle-invasive bladder cancer (NMIBC).. Between October 2010 and January 2015, 206 patients were enrolled, and finally 113 were randomized to receive either a single immediate postoperative intravesical instillation of THP (30 mg) (Group A), or 8 additional weekly intravesical instillations of THP (30 mg) after a single postoperative instillation (Group B). The patients were examined by performing cystoscopy and urine cytology every 3 months after transurethral resection to determine bladder tumor recurrence. The primary endpoint was 3-year-recurrence-free survival rate.. All 113 patients were bacillus Calmette-Guérin (BCG)-naïve. The 3-year recurrence free survival rate was 63.7% for Group A and 85.3% for Group B (log-rank test, P = .0070). In patients with intermediate recurrence risk, the 3-year recurrence-free survival rate was 63.4% in Group A and 86.1% in Group B (log-rank test, P = .0036). Cox regression analysis revealed that only additional instillation of THP was a significant independent factor for recurrence-free rate in patients with intermediate risk. No patient with progression was noted during this period. Frequent adverse effects (AEs) were frequent urination and micturition pain, and no severe AEs (Grade 3 or more) occurred.. Additional instillation of THP (30 mg) weekly for 8 weeks reduced the risk of tumor recurrence without severe AEs in BCG-naïve NMIBC patients with intermediate risk.

Topics: Administration, Intravesical; Aged; Antineoplastic Agents; Chemotherapy, Adjuvant; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Female; Humans; Japan; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Prospective Studies; Regression Analysis; Risk Factors; Time Factors; Treatment Outcome; Urinary Bladder; Urinary Bladder Neoplasms; Urologic Surgical Procedures

To verify the efficacy and safety of intravesical instillation of pirarubicin combined with hyaluronic acid after TURBT in non-muscle invasive bladder cancer patients.. We conducted a prospective study recruiting 127 eligible patients from 2008 to 2010. Patients were randomly assigned to Group A (pirarubicin combined with hyaluronic acid) and Group B (pirarubicin alone). Patients' demographics, treatment efficacy on recurrence, visual analog scale score, and postoperative complications were evaluated and analyzed during observation.. After the first month of intravesical chemotherapy, a perceptible relief of pelvic pain and urinary symptoms was detectable in Group A when compared with Group B (Fig. 2; P = 0.04). From objective analysis, the clinicians observed a consistent better improvement in Group A than in Group B on clinical conditions (P = 0.02). Frequency, urgency, and odynuria are relieved effectively in Group A (21/64 32.9%) and in Group B (41/63 65.1%), with significant difference observed (P = 0.001). No statistical evidence of benefit was observed in terms of recurrence. No obvious hyaluronic acid-related adverse event was observed.. As compared to intravesical instillation of pirarubicin alone, the administration of pirarubicin combined with HA for prevention from postoperative recurrence was satisfactory and safe. The relief of pelvic pain and urinary symptoms is more rapid and more durable.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Antineoplastic Agents; Carcinoma, Transitional Cell; Cystectomy; Dose-Response Relationship, Drug; Doxorubicin; Drug Therapy, Combination; Female; Humans; Hyaluronic Acid; Immunosuppressive Agents; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Postoperative Care; Prospective Studies; Therapeutic Irrigation; Urinary Bladder Neoplasms

We evaluated the efficacy of a single early intravesical instillation of pirarubicin (THP) in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma (UUT-UC).. From December 2005 to November 2008, 77 patients clinically diagnosed with UUT-UC from 11 institutions participating in the Tohoku Urological Evidence-Based Medicine Study Group were preoperatively enrolled in this study. Patients were randomly assigned to receive or not receive a single instillation of THP (30 mg in 30 mL of saline) into the bladder within 48 hours after nephroureterectomy. Cystoscopy and urinary cytology were repeated every 3 months for 2 years or until the occurrence of first bladder recurrence.. Seventy-two patients were evaluable for efficacy analysis, 21 of whom had a subsequent bladder recurrence. Significantly fewer patients who received THP had a recurrence compared with the control group (16.9% at 1 year and 16.9% at 2 years in the THP group v 31.8% at 1 year and 42.2% at 2 years in the control group; log-rank P = .025). No remarkable adverse events were observed in the THP-treated group. Based on multivariate analysis, THP instillation (hazard rate [HR], 0.26; 95% CI, 0.07 to 0.91; P = .035) and open surgery (HR, 0.28; 95% CI, 0.09 to 0.84; P = .024) were independently predictive of a reduced incidence of bladder recurrence.. In this prospective randomized phase II study, a single intravesical instillation of THP seemed to reduce bladder recurrence after nephroureterectomy. A phase III, large-scale, multicenter study is needed to confirm these observations.

Topics: Administration, Intravesical; Aged; Antineoplastic Agents; Carcinoma, Transitional Cell; Cystoscopy; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Male; Multivariate Analysis; Neoplasm Recurrence, Local; Prospective Studies; Treatment Outcome; Ureter; Urinary Bladder Neoplasms; Urinary Tract; Urologic Surgical Procedures

Immediate intravesical instillation of chemotherapeutic agents after transurethral resection (TUR) of nonmuscle invasive transitional cell bladder cancer has recently been suggested and has been proven to decrease the tumor recurrence rate significantly. This study is to evaluate the efficacy and safety of immediate intravesical instillation combined with regular instillations of Pirarubicin (THP(®)) as prophylaxis compared to regular instillations only after TUR operation.. This was a prospective, randomized, multi-center, clinical study. Patients diagnosed with non-muscle invasive bladder cancer (Ta and T1) pathologically and suitable for TUR were enrolled randomly into two groups. In the study group, the patients received intravesical instillation within 24-hour post TURBT, followed by regular intravesical therapy using 30 mg/50 ml of THP(®) once a week for 8 weeks, and then once a month to 1 year postoperatively Among the patients. In the control group, patients received regular instillation only.. A total of 403 patients were enrolled into this study from 26 institutions in China. Among the potients, 210 were enrolled into the study group and 193 were enrolled into the control group. At the median follow-up of 18 months, the recurrence rate was 7.8% in the study group, significantly lower than that in the control group (14.3%; P = 0.042). Subgroup analysis showed that the recurrence rate in low and intermediate-risk patients was significantly lower in the study group (6.8%) than in the control group (14.0%; P = 0.047), although no significant differences were found in high-risk patients.. One immediate dose of THP(®) 30 mg after TURBT followed by regular intravesical therapy appears well tolerated and more effective than regular intravesical therapy for preventing tumor recurrence, especially in low and intermediate-risk patients.

Topics: Administration, Intravesical; Antineoplastic Agents; Carcinoma, Transitional Cell; Cystectomy; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Urinary Bladder Neoplasms

The Pirarubicin Monotherapy Study Group trial was a randomized Phase II study that evaluated the efficacy of intravesical instillation of pirarubicin in the prevention of bladder recurrence after nephroureterectomy for upper urinary tract urothelial carcinoma. This study conducted further analysis of the Pirarubicin Monotherapy Study Group cohort, focusing on intravesical seeding of cancer cells.. Using the data from the Pirarubicin Monotherapy Study Group trial, bladder recurrence-free survival rates and factors associated with bladder recurrence in the control group were analyzed.. Of 36 patients in the control group, 14 with positive urine cytology had more frequent recurrence when compared with the 22 patients with negative cytology (P = 0.004). Based on the multivariate analysis in the control group, voided urine cytology was an independent predictive factor of bladder recurrence (hazard ratio, 5.54; 95% confidence interval 1.12-27.5; P = 0.036). Of 72 patients in the Pirarubicin Monotherapy Study Group trial, 31 had positive urine cytology. Among the 31 patients, 17 patients who received pirarubicin instillation had fewer recurrences when compared with 14 patients who received control treatment (P = 0.0001). On multivariate analysis, pirarubicin instillation was an independent predictor of better recurrence-free survival rates in the patients with positive urine cytology (hazard ratio, 0.02; 95% confidence interval, 0.00-0.53; P = 0.018). Of 21 patients with bladder recurrence, 17 had recurrent tumor around cystotomy or in the bladder neck compromised by the urethral catheter, supporting the notion that tumor cells seeded in the injured urothelium.. Intravesical instillation of pirarubicin immediately after nephroureterectomy significantly reduced the bladder recurrence rate in patients with positive voided urine cytology. The results suggest that intravesical seeding of upper urinary tract urothelial carcinoma occurs during nephroureterectomy.

Topics: Administration, Intravesical; Adult; Aged; Antineoplastic Agents; Carcinoma, Transitional Cell; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Seeding; Nephrectomy; Odds Ratio; Risk Assessment; Risk Factors; Secondary Prevention; Ureter; Urinary Bladder Neoplasms; Urine; Urologic Neoplasms

Fluorescence cystoscopy (FC) with intravesical instillation of a photosensitizing agent has emerged as an adjunctive and safe diagnostic tool with high sensitivity and reasonable specificity; however, it has not been widely accepted, because it is time-consuming and expensive. The aim of the present study was to determine whether the use of the fluorescent dye pirarubicin [(2"R)-4'-O-tetrahydropyranyl doxorubicin] (THP) in endoscopy can improve detection of nonmuscle invasive urothelial carcinoma of the bladder.. Forty-eight patients with known or suspected bladder urothelial carcinoma were enrolled in this prospective study between January 2008 and April 2009. The Storz D-light system was used to detect fluorescence 15 minutes after intravesical instillation with 30 mg THP. Endoscopic findings, histopathologic evaluation of biopsy lesions, and adverse effects of THP were recorded.. After THP uptake, the lesions appear bright orange under white light, and produce bright red fluorescence under blue light. Among 238 biopsies evaluated (84 malignant, 20 dysplasia, and 134 benign), sensitivity of overall tumors, carcinoma in situ (CIS), and dysplasia detection using FC was 96% (81/84), 100% (6/6), and 90% (18/20), respectively. The specificity of FC was 74.7% (115/154), and its false-positive rate was 32.5% (39/120). No significant systemic side effects or allergic reactions were observed other than a few cases of mild cystitis.. THP endoscopy may improve the detection of nonmuscle invasive urothelial carcinoma of the bladder, especially CIS and flat lesions. Results indicate that THP is a promising fluorescent dye for diagnosis and follow-up of nonmuscle invasive bladder carcinoma. Moreover, it is inexpensive, easily available, simple to administer, and is associated with few side effects.

Topics: Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma, Transitional Cell; Cystoscopy; Doxorubicin; Fluorescence; Humans; Middle Aged; Muscles; Neoplasm Invasiveness; Neoplasm Staging; Prospective Studies; Urinary Bladder Neoplasms

To evaluate the efficacy and safety of intravesical instillation of high-dose pirarubicin during perioperative period to prevent bladder carcinoma recurrence.. A prospective randomized controlled clinical trial was carried out. A total of 120 patients with bladder transitional cell carcinoma (TNM I-II) underwent partial cystectomy or transurethral resection of bladder tumour were randomly divided into 2 groups, which were chosen from the patients were hospitalized during June 2003 to May 2009. There were 62 patients were in group A and 58 patients were in group B. In group A, intravesical instillation of high-dose pirarubicin during perioperative period was conducted. In group B, intravesical perfusion of pirarubicin was performed regularly after operation. All the patients were followed up in order to record the relapse rates and adverse reaction.. No significant difference was found between group A and group B from gender, age, pathological stage and operation methods (P > 0.05). The recurrence rates were 8.1% in group A, and 20.7% in group B. The adverse effect rates of urethrostenosis in group A and group B were 3.2% and 18.9%. The adverse effect rates of cystic stimulation including irritation signs of bladder and hematuria in group A and group B were 4.8% and 27.6%. There were significant differences in recurrence rates and adverse effect rates between the two groups (P > 0.05).. Intravesical instillation of high-dose pirarubicin during perioperative period is an effective procedure for the prevention of bladder cancer recurrence.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Doxorubicin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Perioperative Period; Prospective Studies; Treatment Outcome; Urinary Bladder Neoplasms; Young Adult

To evaluate the apoptosis-inducing effect of intravesical instillation of pirarubicin (THP) on bladder cancer and normal bladder tissue, and explore the mechanism of such treatment for preventing recurrence of non-muscle invasive bladder cancer.. Forty patients with primary non-muscle invasive bladder cancer were treated in our hospital from January 2006 to October 2008. The patients were divided into three groups, including 15 cases treated by intravesical instillation of THP (30 mg/50 ml, 0.5 hours) at 1 hour, 15 cases at 24 hours before transuretheral resection of bladder tumor (TUR-BT), and 10 cases in control group who received TUR-BT only. The THP uptake of the tumor and normal bladder tissues was observed by fluorescence microscopy, the apoptosis was assessed with TUNEL staining, and immunohistochemistry was used to detect the expression of bcl-2 and bax.. Seldom fluorescence of THP in normal bladder tissues and some diffuse fluorescence reaching the muscular layer in the tumor area were observed after THP instillation at 1 hour before TUR-BT. The fluorescence of THP could still be observed in the tumor tissues at 24 hours after THP instillation. The apoptosis indexes (AI) of tumors in the chemotherapy groups were significantly higher than that in the control group (P < 0.01). There was a correlation between bcl-2/bax ratio and AI.. Pirarubicin can be uptaken by bladder cancer tissue selectively and induces apoptosis of tumor cells. The changes of expression of bcl-2 and bax and decreasing of the bcl-2/bax ratio may be an important mechanism of action of the intravesical instillation of THP for preventing recurrence of non-muscle invasive bladder cancer.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Antineoplastic Agents; Apoptosis; bcl-2-Associated X Protein; Cystectomy; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Preoperative Care; Proto-Oncogene Proteins c-bcl-2; Urinary Bladder; Urinary Bladder Neoplasms

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of pirarubicin (THP) prior to transurethral resection (TUR) of superficial bladder cancer. A total of 63 patients were randomized into two groups, the THP group and the control group. In the THP group, 30 mg of THP dissolved in 50 ml saline was administered 4 times intravesically for 4 consecutive days before TUR. In the control group, no instillation was performed before TUR. The patients were followed by cystoscopy and urinary cytology every 3 months. The non-recurrence rates in the THP group and control group were 54.1% versus 37.6% at 1 year and 40.4% versus 26.8% at 2 years, respectively (P = 0.086). Time to recurrence for tumors larger than 1 cm was significantly longer in the THP group (P = 0.0137). Time to recurrence for single and grade 1+2 tumors tended to be longer in the THP group (P = 0.09, P = 0.079). No significant adverse effects were observed in any patient. Our findings suggest that intravesical THP instillation prior to TUR would be effective for patients with single, low grade lesions larger than 1 cm of superficial bladder cancer.

Topics: Administration, Intravesical; Aged; Antineoplastic Agents; Cystectomy; Doxorubicin; Female; Humans; Male; Neoplasm Recurrence, Local; Prospective Studies; Urinary Bladder Neoplasms

Superficial transitional cell carcinoma (TCC) of urinary bladder tends to recur after transurethral surgery. This study was designed to evaluate the effect of interferon-alpha (IFN-alpha)and pirarubicin (THP) on decreasing postoperative recurrence of superficial bladder cancer.. Recombinant IFN-alpha and THP has been used in clinical study. One week After operation, 68 patients were prospectively enrolled and divided into two groups randomly: IFN-alpha plus THP group and THP group. The protocols of chemoimmunoprophylaxis include 8 weekly and 10 monthly instillation of 3 x 10(7) IU IFN-alpha plus 40 mg THP in 40 ml 5% glucose via catheter.. The follow-up period ranged from 6 to 32 months (median 18.2 months). The cytoscopy and cytology with cold cup biopsies had been carried out every 3 months for 2 years. Recurrence after instillation of IFN-alpha combining THP was observed in only 4 cases (12.1%), bladder irritation was found in 4 cases, fatigue in 3 cases, and rash in 1 case as well. Among the 35 cases in THP group, recurrence was found in 8 cases (22.8%), bladder irritation in 5 cases, fatigue in 3 cases. IFN-alpha plus THP yielded better effect than THP alone (P< 0.05),especially in grade 3 and stage PT1 bladder cancer.. IFN-alpha working in coordination with THP would be an effective remedy to prevent the recurrence of bladder cancer. The intravesical IFN-alpha plus THP appears to be more effective against recurrence than THP alone. Further study is needed for side-effect and popularization in such way.

Topics: Administration, Intravesical; Adult; Age Factors; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cystectomy; Doxorubicin; Female; Follow-Up Studies; Humans; Interferon-alpha; Male; Middle Aged; Neoplasm Recurrence, Local; Neoplasm Staging; Postoperative Period; Prospective Studies; Urinary Bladder Neoplasms

Although transurethral resection of a bladder tumor (TUR-Bt) alone has been standard treatment for single superficial bladder carcinoma, some authors reported a certain prophylactic effect of a single immediate intravesical instillation of chemotherapeutic agent after TUR-Bt. A prospective randomized study was conducted to determine whether a single (2"R)-4'-O-tetrahydropyranyl-doxorubicin (THP) instillation immediately after TUR-Bt is beneficial to patients with a single superficial bladder carcinoma.. One hundred seventy patients with a single resectable superficial bladder carcinoma (Ta-1, primary or recurrent with no recurrence during the last 1 year) were enrolled in this study. THP (30 mg/30 mL of normal saline) was administered into the bladder within 6 hours after TUR-Bt in arm A, while TUR-Bt alone was done in arm B.. Of the 170 patients, 160 (94.1%) were eligible and were followed up for a median time of 40.8 months. There was a significant difference in the recurrence free curve between the 2 arms (log-rank test; P = 0.0026), with 92.4% recurrence free rate at 1 year, 82.7% at 2 years, and 78.8% at 3 years in arm A (84 patients) and 67.0%, 55.7%, and 52.6%, respectively, in arm B. The recurrence rate per year was 0.11 +/- 0.22 in arm A and 0.24 +/- 0.36 in arm B, with a significant difference (P = 0.007). Toxicity included pain with micturition in 9 patients (10.7%), urinary frequency/urgency in 5 patients (6.0%), and macroscopic hematuria in 7 patients (8.3%).. These data indicate that a single THP instillation immediately after TUR reduces the recurrence of superficial bladder carcinoma.

Topics: Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Follow-Up Studies; Humans; Middle Aged; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

In order to determine the modality of prophylactic intravesical instillation of pirarubicin (THP = tetrahydropyranyladriamycin) following transurethral resection (TUR) of superficial bladder cancer, a prospective randomized study was performed. A total of 79 patients were randomized into "2-hour instillation" (A), "5-min instillation" (B) and "control" (C) groups. Prophylactic efficacy and side effects were analyzed in each group. In groups A and B, 20 mg of THP was first dissolved in 10 ml of distilled water, adjusted to 40 ml with saline and was administered intravesically once a week for 10 weeks, starting from 1 week after TUR. The recurrence-free rate was calculated in 65 evaluable patients. The one-year recurrence-free rate was 70.2% in group A, 62.8% in group B and 52.1% in group C. The one-year recurrence-free rate was significantly higher in group A than in group C. Adverse effects were observed in 21.4% of the patients in group A and 40.7% in group B. There was no significant difference in the occurrence rate of side effects between these two groups. Taking the prophylactic efficacy and side effects into consideration, "2-hour instillation" seemed to be better than "5-min instillation".

Topics: Administration, Intravesical; Adult; Aged; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Prospective Studies; Time Factors; Urinary Bladder Neoplasms

Fifty-six patients with locally invasive bladder cancer were treated by chemotherapy with intermittent arterial infusion from an implanted reservoir and alteration of intrapelvic blood flow. The tip of an infusion catheter was inserted selectively into an internal iliac artery by an angiographic technique. Superior gluteal artery and the other internal iliac artery were then embolized with steel coils so that the drugs would perfuse throughout the tumor through a single catheter. Treatment consisted of intermittent injection of cisplatin (10 mg/body) and doxorubicin (10 mg/body) or epirubicin (10 mg/body) or pirarubicin (10 mg/body) in a ten-minute period every week (for the first 8 weeks) or every two weeks (after the 8th week). Fifty patients were objectively evaluated and the response rate was 80%. The overall survival rate in 54 patients at 1, 3, 5 and 8 years was 83.7%, 61.2%, 52.6%, and 52.6%. The 1-, 2-, 3-, 5- and 7-year disease free survival rate in evaluable 22 patients who showed a complete response (CR) was 91.8%, 85.2%, 65.6%, 58.3% and 58.3%. No serious side effects, such as severe myelosuppression or renal and/or liver dysfunction, were noted during treatment. These findings suggest that intermittent arterial chemotherapy with an implanted reservoir is clinically useful. This procedure appears safe and is easily performed in the outpatient clinic for the treatment of locally advanced bladder cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Female; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Male; Middle Aged; Neoplasm Invasiveness; Prognosis; Quality of Life; Survival Rate; Urinary Bladder Neoplasms

Forty-five patients with muscle-invasive bladder cancer treated with intra-arterial doxorubicin chemotherapy plus low-dose radiotherapy between September 1979 and March 1990 were retrospectively studied. Twenty-eight (62%) patients achieved a complete response (CR) and in all of them, a functional bladder could be preserved. The 10-year cause-specific survival rate of patients with CR was 95.5%, but that of patients not achieving a CR was 39%. These results demonstrate that in patients who achieve a CR with this treatment, we may be able to preserve a functional bladder. In a prospective study, we designed a new intra-arterial chemotherapy regimen in order to achieve a higher degree of effectiveness and to preserve a functional bladder. Twenty-three patients were treated with concurrent pirarubicin/cisplatin intra-arterial chemotherapy and radiotherapy after complete transurethral resection. Twenty-one (91%) patients achieved CR. One of these patients had relapse with lung metastases and was treated surgically. Two patients who did not achieve a CR died of cancer, and 21 patients are alive with preservation of functional bladder. For treatment of prostate cancer, we now administer only adjuvant intra-arterial chemotherapy plus irradiation for patients after radical prostatectomy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Prospective Studies; Prostatic Neoplasms; Retrospective Studies; Urinary Bladder Neoplasms

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) was performed on 51 patients with superficial bladder cancer after transurethral resection (TUR) for prophylaxis of recurrence. The instillation was carried out with 20 mg of THP dissolved in 40 ml of distilled normal saline. Instillation was performed once 24 hours postoperatively, 9 times every 2 weeks, and 8 times every 4 weeks. These drugs were instilled for 30 to 60 minutes. The recurrence-free survival at 1, 2 and 3 years was 74.5%, 64.6% and 58.0%, respectively. Side effects of THP instillation were observed in only 4 cases (7.8%) as slight urinary frequency or micturition pain. Cases involving 5 or more tumors, or tumors measuring 3 cm or larger, more frequently demonstrated recurrence. The cases that did not respond to preoperative intravesical instillation of THP demonstrated a high frequency of recurrence. Intravesical instillation of THP as a prophylaxis against recurrence of superficial bladder cancer was effective in selected patients.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Antibiotics, Antineoplastic; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Urinary Bladder Neoplasms

Between July 1993 and May 1999, 36 patients with invasive bladder cancer were treated with intra-arterial chemotherapy using cisplatin and pirarubicin, and their treatment outcome was evaluated. Clinical CR was obtained in 18 patients, PR in 13, and NC in 5, for an overall response rate of 86%. The median follow-up for evaluating patients was 24 months (2-70 months). The bladder was preserved in 13 of 18 patients showing CR and in 4 of 13 patients showing PR. The 5-year cause-specific survival rate for the 36 patients was 56%. The grade factor did not effect the survival rate significantly. Compared with stage T2, stage T3 yielded a significantly poor prognosis, especially with grade 3. Intra-arterial chemotherapy was confirmed useful as a regional treatment, but not sufficient as a systemic treatment. Thus the selection of patients for this therapy was considered to require exact staging and assessment of the effectiveness.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Female; Follow-Up Studies; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Survival Rate; Treatment Outcome; Urinary Bladder Neoplasms

Polyamines are recognized as cell growth factors. We attempted to determine whether blood polyamines are useful biochemical makers for monitoring the efficacy of the chemotherapy on bladder tumors.. The blood concentrations of three polyamines, diamine, spermidine and spermine, were determined in 31 patients with invasive urinary bladder carcinoma, following chemotherapy with cisplatin, methotrexate and pirarubicin. Clinical response was evaluated by CT after 3 weeks. In 26 patients who underwent subsequent surgical therapy, the effectiveness of the chemotherapy were histopathologically evaluated by a pathologist according to the response criteria for bladder cancer treatment.. Mean regression rate in the size of the tumor after the chemotherapy was 40.8%. Of 31 patients, clinical CR was observed in 2, PR in 11, and NC in 18. Of 26 patients who were histopathologically evaluated, grade 3 was observed in 5, grade 2 in 4, grade 1b in 4, grade 1a in 12, and grade 0 in 1. One week after chemotherapy, the levels of spermine and total polyamine in the patients with CR and PR were significantly lower than those in the patients with NC. Similarly one week after chemotherapy, the levels of spermine and total polyamine in the patients with grade 3 and grade 2 were significantly lower than those in the patients with grade 1b, grade 1a and grade 0.. The study suggested that the levels of blood polyamines could be used as biochemical markers for monitoring the efficacy of the chemotherapy on bladder tumors.

Topics: Adenocarcinoma; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biomarkers, Tumor; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Female; Humans; Male; Methotrexate; Middle Aged; Monitoring, Physiologic; Polyamines; Treatment Outcome; Urinary Bladder Neoplasms

We previously reported favorable results of intraarterial doxorubicin chemotherapy in combination with low-dose radiotherapy for locally-advanced bladder cancer. We have now designed a new intraarterial chemotherapy regimen to achieve a higher tumor response rate while preserving a functional bladder.. Twenty-one patients with muscle-invasive bladder cancer (T2,10; T3,7; T4,4) were treated with concurrent intraarterial chemotherapy and radiotherapy after an initial complete transurethral resection. Induction therapy consisted of concomitant pirarubicin (THP; 15 mg/m2/day on days 1 to 3), cisplatin (CDDP; 25 mg/m2/day on days 8 to 10) and irradiation (2 Gy/session on days 1 to 3 and 8 to 10). Maintenance treatment consisted of THP administered at 20 or 30 mg with or without 50 mg CDDP every month for 2 years.. Nineteen of the 21 patients (90.5%) achieved a complete response (CR). One of these 19 relapsed with lung metastases 24 months after treatment and was treated surgically. The 2 patients who did not achieve a CR died of cancer, while the remaining 19 patients are alive with preservation of a functional bladder.. These findings suggest that a higher tumor response rate with bladder preservation for patients with muscle-invasive bladder cancer is achieved by intraarterial THP/CDDP chemotherapy plus radiotherapy.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cisplatin; Combined Modality Therapy; Doxorubicin; Female; Humans; Male; Middle Aged; Muscle, Smooth; Neoplasm Invasiveness; Treatment Outcome; Urinary Bladder Neoplasms

The present study was designed to investigate the appropriate intravesical retention time of pirarubicin (THP) for the treatment of bladder tumor in terms of its anti-tumor effect and side effect. We administered THP to 22 patients with superficial bladder tumor intravesically and measured the THP concentration in the tumor tissues. Patients were divided into 3 groups by retention time; 8 for 30 minutes, 8 for 1 hour and 7 for 2 hours. Tumor tissues were obtained by transurethral resection 30 min., 1 or 2 hours after the intravesical instillation of THP at the fixed concentrations of 30 mg/30 ml. There was no significant difference in THP concentration between 3 groups. This indicates that the anti-tumor effect of intravesical instillation of the THP would be expected by only 30 min. of intravesical retention time at the THP concentration of 30 mg/30 ml. Then, we administered 30 mg/30 ml of THP solution for 30 min. to 10 patients intravesically 6 times every 48 hours to investigate its clinical anti-tumor effect and side effect. There were 2 complete responses, 3 partial responses and 5 cases with no changes for a total response rate of 50%. No side effect was observed. It is considered that 30 min. of intravesical retention time at the THP concentration of 30 mg/30 ml would be appropriate in terms of its anti-tumor effect and side effect.

Topics: Administration, Intravesical; Antibiotics, Antineoplastic; Doxorubicin; Drug Administration Schedule; Humans; Urinary Bladder Neoplasms

We conducted a prospective randomized controlled study on the prophylactic effects of short-term intravesical instillation of pirarubicin (THP) against recurrence to determine the effective administration schedule. All patients gave their informed consent. The subjects included bladder cancer patients who had pTa or pT1, and G1 or G2 cancer, and became tumor-free after transurethral resection of the bladder tumor (TUR-BT). After dissolving 30 mg of THP into 5 ml of distilled water, physiological saline was added to adjust the total volume to 50 ml, which was then instilled into the bladder, and was retained for 5 minutes. The schedule of instillation was for daily for 7 consecutive days from the day of TUR-BT and subsequently once a week for 10 weeks, 17 times in total for Group I, and once every two weeks for 6 months (12 times) starting 2 weeks after TUR and subsequently once a month until one year had passed after surgery (6 times), 18 times in total for Group II. The total number of cases was 69 (36 in Group I, 33 in Group II). The tumor-free ratios determined by the Kaplan-Meier analysis were 93.9% in Group I and 72.7% in Group II for one year, and 86.8% in Group I and 59.5% in Group II for two years. There was a statistically significant difference in the tumor-free ratios between the two groups by the generalized Wilcoxon test and the Log rank test (p = 0.0145 and 0.0107, respectively). Multivariated analysis using Cox's comparison hazard model produced p-values of 0.0002, 0.0007, 0.0009 and 0.0040 in the order of therapeutic mode, initial onset/recurrence, stage and number of tumor. Adverse events that forced discontinuation of the therapy for a while occurred in 4.3%. These results demonstrated that short-term intensive intravesical instillation of THP immediately after TUR-BT was a safe and effective therapy.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotic Prophylaxis; Antibiotics, Antineoplastic; Cystectomy; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Proportional Hazards Models; Prospective Studies; Urinary Bladder Neoplasms

A prospective randomized study was conducted to evaluate the efficacy of prophylactic intravesical instillation of tetrahydropyranyladriamycin (THP) following complete transurethral resection (TUR) of superficial bladder cancer. A total of 80 patients were randomized into "THP" or "control" group. In the THP group, 20 mg of THP dissolved in 40 ml saline (or 5% dextrose) was administered intravesically once a week for 10 weeks, starting from about 7 days after TUR. In the control group, 40 ml saline was given with the same schedule. The patients were followed up by cystoscopy and urinary cytology every 3 months. The number of evaluable patients was 36 for the THP group and 37 for the control group. The non-recurrence rates in the THP group and control group were 79.4% versus 63.2% at 1 year and 69.8% versus 47.4% at 3 to 5 years, respectively. These figures were not statistically significant. However, THP instillation significantly reduced tumor recurrence rates for multiple tumors, and also tended to decrease recurrence rates for primary and pT1 tumors. Adverse effects were observed in 53.6% of the patients in the THP group, but they were tolerable. Our results suggest that intravesical THP instillation would not be effective for all patients with superficial bladder cancer. Further study is warranted in a selected group of patients.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Cystectomy; Doxorubicin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Prospective Studies; Urinary Bladder Neoplasms

In order to study its safety and anti-cancer dose-effectiveness in the prevention of cancer recurrence, two groups of patients having superficial bladder cancer (TUR-Bt) had their bladder intravesically irrigated post-surgically with 20 or 30 mg aliquots of (2''R)-4'-0-tetrahydropyranyl-adriamycin (THP). A total of 74 patients with bladder cancer were entered in the study. Four cases proved ineligible, and 30 could not complete the planned treatment. THP vesical irrigation of 14-17 sessions was regarded as a condition for eligibility: Clinical evaluation was feasible with 19 patients of 20 mg and 21 of 30 mg THP. Non-recurrence rates at 1, 2, 3 and 4 years were 89.5, 53.3, and 26.6%, respectively, for the 20 mg group, and 95.2, 84.3, 75.9 and 75.9%, respectively, for the 30 mg THP group. The incidence of side effects appeared slightly greater in the 30 mg THP group than in the 20 mg group, and there were no systemic adverse reactions. Topical reaction of cystitis was noted to be as low as 12.5%. Thus, THP vesical irrigations at 30 mg were found tolerable and effective for the prevention of local recurrence following TUR-Bt.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Cystectomy; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Period; Urinary Bladder Neoplasms

Thirteen patients with invasive bladder cancer treated by induction intra-arterial chemotherapy in combination with radiotherapy achieved a complete response (CR). All of them were treated by prophylactic intra-arterial chemotherapy using pirarubicin (10), epirubicin (2) and carboplatin (1). The treatment was given once a month for 2 years. In the followup period from 14 to 43 months (median; 22.5 months), only one of the 13 patients had an invasive recurrence of bladder cancer and died of it. Ten of the 13 patients are now disease-free and alive with functional bladder. The complications of this therapy were mild and tolerable. The results suggest that prophylactic intra-arterial chemotherapy is a useful regimen for CR patients with invasive bladder cancer after induction therapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Disease-Free Survival; Doxorubicin; Drug Administration Schedule; Epirubicin; Female; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Male; Middle Aged; Neoplasm Recurrence, Local; Remission Induction; Urinary Bladder Neoplasms

Forty patients with bladder cancer who underwent radiotherapy with angiotensin II, a hypertensor, and two cycles of arterial infusion of anticancer chemotherapies, including cisplatin 100 mg/body, were randomly assigned to a granisetron group and a non-granisetron group for comparative study of its prophylactic effect on nausea, vomiting and anorexia. Granisetron proved significantly effective in preventing nausea, as 75% of granisetron-administered patients experienced either only slight nausea or none at all, against only 22.5% in the non-granisetron group. The number of vomiting episodes was zero during the three-day observation period in 28 out of 40 (70%) granisetron-administered patients compared with 6 patients (15%) in the non-granisetron group. A significant difference in prophylactic effect on anorexia was demonstrated between the granisetron and non-granisetron group, indicating that control of alimentary symptoms such as nausea and vomiting influences the severity of anorexia. As to the safety, nausea was lengthened and deteriorated in one patients. Though the physician in charge judged it to be an adverse event too minor to question the safety of granisetron. Thus, granisetron proved to be highly effective and safe in preventing nausea, vomiting and anorexia in patients under concomitant administration of radiotherapy with hypertensor and arterial infusion of anticancer chemotherapies.

Topics: Aged; Angiotensin II; Anorexia; Antineoplastic Combined Chemotherapy Protocols; Blood Pressure; Child; Cisplatin; Doxorubicin; Female; Granisetron; Humans; Infusions, Intra-Arterial; Methylprednisolone; Nausea; Tegafur; Urinary Bladder Neoplasms; Vomiting

A multicentric randomized trial was conducted to evaluate the efficacy of intravesical chemoprophylaxis for primary superficial bladder cancer. The 299 eligible patients with primary superficial bladder cancer were randomized into four groups (A, B, C, and D) after pathological confirmation. Intravesical instillation of drugs, which were dissolved in 20 ml physiological saline (PS; group A, 20 mg Adriamycin; group B, 20 mg epirubicin; group C, 20 mg pirarubicin; group D (control), PS alone], was performed once a week for 2 weeks after trasurethral resection and then once every 2 weeks for 14 weeks, once monthly for 8 months, and once every 3 months for 1 year. No significant difference in the patients' characteristics was found among the four groups. The follow-up period ranged from 3 to 31 months (mean, 14 months). The nonrecurrence rates were estimated by the method of Kaplan and Meier. The relative effects of five variables (the tumor status, size, grade, and stage and the treatment) on the efficacy of the chemoprophylaxis regimens were evaluated using a multiple regression model. Although the nonrecurrence rates determined for groups A and B were significantly higher than that found for group D (P < 0.05), no significant difference in the nonrecurrence rate was detected among groups A, B, and C. The multiple regression model indicated that the most important factors in preventing tumor recurrence at 12 or 24 months were the intravesical instillation of an anthracycline and the tumor status (solitary). These results demonstrate that intravesical instillation of the tested anthracyclines is effective for at least 2 years as prophylactic chemotherapy for primary superficial bladder cancer.

Topics: Administration, Intravesical; Aged; Antibiotics, Antineoplastic; Chemotherapy, Adjuvant; Doxorubicin; Epirubicin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Regression Analysis; Urinary Bladder Neoplasms

Twenty-one patients with superficial bladder cancer entered an analysis of single dose (2'R)-4'-O-tetrahydropyranyladriamycin (THP) or adriamycin (ADM) administration. The patients in each group that have been or not have been treated previously with anti-cancer drugs were randomized into two groups, one was given THP and the other ADM. Thirty-mg of THP or ADM dissolved in 30 ml of physiologic saline was instilled into the bladder, and retained for 1 hour. After 1 hour retention of the drugs, tumor tissues and normal mucosas were removed by punch biopsy forceps transurethrally. The tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. The tissue concentrations of THP and ADM in the tumors were significantly greater (p < 0.05) than those in the normal bladder mucosas. The tissue concentration of THP in the tumors were greater than that of ADM. The tissue concentrations of THP and ADM in the tumor of patients who have been treated with anti-cancer drugs previously were less than those of patients who have not. This results demonstrated that prior therapy with anti-cancer drug may cause a resistance for intravesical instillation chemotherapy. However in patients with prior therapy, the tissue concentration of THP in the tumors were greater than that of ADM. Based on these findings, THP has been shown to be were effective as an intravesical instillating agent especially, in cases with prior chemotherapy.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

In the present series of trials, Adriamycin (ADM) intravesical instillation therapy was found to be effective against tumors of papillary morphology measuring less than 10 mm in diameter that were of low pathological stage and low histological grade. The rate of complete disappearance increased in proportion to the concentration of ADM and the duration of retention of the drug, although the efficacy rates were almost the same in each trial. On the other hand, side effects on the bladder were reduced when the instilled solution was lower in concentration and the retention time was short.

Topics: Administration, Intravesical; Carcinoma, Papillary; Clinical Trials as Topic; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Epirubicin; Humans; Time Factors; Urinary Bladder Neoplasms

Doxorubicin is one of the standard drugs in the chemotherapy of advanced urothelial tumors. Pirarubicin, a new anthracycline, turned out to be equally active and less toxic than its parent compound in preclinical studies. Twenty one patients with either metastatic or inoperable locally advanced bladder carcinoma were treated with intravenous infusion of pirarubicin: 25 mg/m2/day for 3 days every 4 weeks in the first 15 patients and 20 mg/m2/day for 3 days every 3 weeks in the others. Fifteen patients were not pretreated and 6 received prior chemotherapy (5 patients with doxorubicin containing regimen). Twenty patients were evaluable for response; there were 2 partial response, 8 stable disease and 10 progressive disease. All pretreated patients progressed. Hematological toxicity was moderate, however there was one toxic death with grade 4 neutropenia which occurred in a heavily pretreated patient receiving a dose of 25 mg/m2/day for 3 days. There was no clinical cardiac toxicity. Single agent Pirarubicin displays an objective response rate of 10% (95% of CI 0 to 23%) which reaches 14% (95% CI 0 to 29%) when non pretreated patients are analyzed separately. This rate is in the range of doxorubicin activity.

Topics: Adult; Aged; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Doxorubicin; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

To determine the antitumor action by intravesical instillation prior to transurethral resection TUR, a randomized study on pirarubicin (THP) versus adriamycin (ADM) was performed for superficial, papillary and initially detected bladder cancers with participation of 21 Urological Clinics in 3 Tokai Prefectures. The instillation dose of 500 micrograms/ml was given 3 times per week for 3 weeks in both THP (n = 33) and ADM (n = 30) groups. The complete and partial response rates were 56.3% in THP group and 26.7% in ADM group. THP instillation was more effective against multiple tumors than a single tumor, stage Ta than T1 and grade G1 than G2 and G3. However, these findings were not statistically significant. Untoward effects were mainly bladder irritability and its frequency was 60.6% in the THP group and 23.3% in the ADM group. Contracted bladder was found in 2 of the 33 patients in the THP group and 2 of the 30 patients in the ADM group. The antitumor effect of a half dose of THP was equivalent to that of one dose of ADM, and the THP group showed a twofold higher frequency of side effects. Therefore, a clinical trial should be made comparing the effect of 500 micrograms/ml of THP and that of 1,000 micrograms/ml of ADM.

Topics: Administration, Intravesical; Aged; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Remission Induction; Urinary Bladder Neoplasms

Intravesical instillation of pirarubicin (THP) was performed on 66 patients with superficial bladder cancer after transurethral resection to evaluate the prophylactic effect against tumor recurrence. Intravesical chemotherapy was carried out at the concentration of 20mg/40ml. THP was initially instilled three times for one week, following instillation of every two weeks for ten times, and then every one month for seven times. Bladder irritability was demonstrated 21 of 66 cases (31.8%). Although there was a case of contracted bladder, generalized side effect was no case. Eligible cases for evaluation of efficacy were 43 out of 66 patients. The non-recurrence rate (by Kaplan-Meier's method) at one and two years were 90.4% and 77.8%, respectively. Intravesical THP instillation seems to be effective for the purpose of prophylaxis against the recurrence of superficial bladder tumor.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Urinary Bladder Neoplasms

Intravesical instillation therapy with (2"R)-4'-O-tetrahydropyranyl adriamycin [pirarubicin (THP)], a new anthracycline agent, was performed to examine its direct effect on superficial bladder cancer in a six-center cooperative Phase II study. There were 50 evaluable cases, for which a response rate of 50% was obtained. The main side effects that occurred were bladder irritation symptoms such as pollakisuria (50%) and pain on urination (38%). Intravesical pirarubicin instillation therapy was administered to eight cases that had not responded to doxorubicin therapy or that had experienced recurrence after such therapy. For six evaluable cases, the response rate was 50%, and the incidence of side effects was 88%.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Doxorubicin; Drug Evaluation; Female; Humans; Male; Middle Aged; Neoplasm Staging; Urinary Bladder Neoplasms

To investigate the value of gemcitabine and pirarubicin in patients with non-muscle-invasive bladder cancer (NMIBC).. 405 patients with non-muscle invasive bladder cancer admitted to our hospital from January 2012 to December 2020 who underwent transurethral bladder tumor electronic resection were studied. 177 patients were treated with gemcitabine (Gemcitabine group) and 228 patients were treated with pirarubicin (Pirarubicin group) after surgery. The efficacy and adverse effects of the two groups were observed and the patients were followed up.. No differences were found when comparing age, gender, smoking, bladder mass, number of masses, hypertension, diabetes, coronary artery disease, hematuria and tumor diameter between the 2 groups (P > 0.05). In the Gemcitabine group, bladder irritation signs, meatus hematuria, fever, nausea and vomiting were lower than those in the Pirarubicin group (P < 0.05). The recurrence rates were 6.21% and 12.28% at 1 year, 11.86% and 23.68% at 2 years, 15.82% and 25.88% at 3 years in the Gemcitabine and Pirarubicin groups respectively, with the Gemcitabine group having a significantly lower recurrence rate than the Pirarubicin group (P < 0.05). The tumor recurrence-free survival rate for 5 years of gemcitabine was significantly higher than that of the Pirarubicin group (P < 0.05).. Gemcitabine and pirarubicin are both effective in treating patients with non-muscle invasive bladder cancer, with gemcitabine having a lower incidence of adverse reactions, a higher safety rating, a lower recurrence rate and an improved survival outcome.

Topics: Administration, Intravesical; Gemcitabine; Hematuria; Humans; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Non-Muscle Invasive Bladder Neoplasms; Urinary Bladder Neoplasms

Improving urinary bladder cancer diagnosis, follow-up, and therapy tools to overcome existing limitations and increase survival rates is a highly desirable goal. In the current investigation, pirarubicin, a new generation antineoplastic anthracycline, was labeled with [

Topics: Cell Proliferation; Dose-Response Relationship, Drug; Doxorubicin; Humans; Iodine Radioisotopes; Precision Medicine; Urinary Bladder Neoplasms

To investigate the relationships between non-muscle invasive bladder cancer molecular subtypes and predict the efficacy of intravesical chemotherapy with pirarubicin, pharmorubicin and gemcitabine.. A total of 160 patients with T1 stage non-muscle invasive bladder cancer were enrolled in this study. Fifty-three patients underwent anthracycline (Pirarubicin and Pharmorubicin) therapy and 107 patients accepted gemcitabine therapy. Uroplakin II and CK20 were categorized as immunohistochemistry (IHC) markers for luminal subtype, whereas CK5/6 and CD44 were categorized as immunohistochemistry markers for basal subtype. The cluster results with immunohistochemical score indicated that non-muscle invasive bladder cancer can be subgrouped into three major classes.. Class 2 showed the luminal-like characteristics, whereas class 3 showed the basal-like characteristics. Class 1 showed no high expression of luminal or basal-associated immunohistochemistry markers. The molecular subtype is an independent risk factor for recurrence-free survival (P = 0.030) and progression-free survival (P = 0.006) in patients with T1 stage non-muscle invasive bladder cancer. In class 1 and class 2 (luminal-like) subtypes, gemcitabine and anthracycline show no difference in recurrence-free survival and progression-free survival. Gemcitabine was associated with reduced recurrence compared with anthracycline (P = 0.039) in class 3 (basal-like) subtypes and show no difference in decreasing progression.. The molecular classification based on immunohistochemical results is an independent risk factor for the prognosis of non-muscle invasive bladder cancer with T1 stage. Different therapeutic methods should be selected according to different molecular subtypes.

Topics: Administration, Intravesical; Anthracyclines; Antibiotics, Antineoplastic; Deoxycytidine; Doxorubicin; Epirubicin; Gemcitabine; Humans; Immunohistochemistry; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

To compare the efficacy and safety of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) against intravesical BCG immunotherapy in high-risk non-muscle-invasive bladder cancer (NMIBC) after transurethral resection of the bladder tumor (TURBT).. 130 patients with high-risk NMIBC who had underwent TURBT were divided into two groups, of which IAC + IVC group received four courses of IAC (cisplatin and epirubicin) combined with IVC (epirubicin or pirarubicin) after surgery and BCG group received intravesical BCG immunotherapy. Recurrence rate and progression rate were assessed by Chi-square test, while recurrence-free survival and progression-free survival were calculated using the Kaplan-Meier method.. In this study, the recurrence rate was 27.9% (12/43) in IAC + IVC group and 26.4% (14/53) in BCG group, while progression rate was 9.3% (4/43) in IAC + IVC group and 9.4% (5/53) in BCG group. Both of the recurrence and progression rate did not show a significant difference. In the Kaplan-Meier plot, no difference was found with respect to recurrence-free survival and progression-free survival. Moreover, 46.5% (20/43) patients suffered from adverse events of IAC and 83.1% (49/59) patients suffered from adverse events associated with BCG, of which 6 patients discontinued treatment due to serious adverse events of BCG. Univariate analysis suggested that only recurrent tumor could be an independent risk factor related to recurrence.. IAC combined with IVC used in high-risk NMIBC could reduce the recurrence and progression as effective as BCG instillation with lower adverse events.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Cystectomy; Doxorubicin; Epirubicin; Female; Humans; Immunotherapy; Infusions, Intra-Arterial; Male; Middle Aged; Neoplasm Invasiveness; Retrospective Studies; Risk Factors; Urinary Bladder Neoplasms

We carried out structure-activity relationship study on anti-cancer effects of naftopidil (1) and its metabolites, resulted in identification of 1-(4-hydroxy-2-methoxyphenyl)piperazin-1-yl)-3-(naphthalen-1-yloxy) propan-2-ol (2, HUHS190), a major human metabolite of 1, which exhibited the most selective toxicities between against normal and cancer cells (Table 1). 2 was more hydrophilic compared to 1, was enough to be prepared in high concentration solution of more than 100 μM in saline for an intravesical instillation drug. Moreover, serum concentration of 2 was comparable to that of 1, an oral preparation drug, after oral administration at 32 mg/kg (Fig. 3). Both of 1 and 2 showed broad-spectrum anti-cancer activities in vitro, for example, 1 and 2 showed inhibitory activity IC

Topics: Animals; Antineoplastic Agents; Female; Humans; Male; Mice; Naphthalenes; Piperazines; Structure-Activity Relationship; Urinary Bladder Neoplasms

The objective of this study was to evaluate which patients might benefit from a single immediate postoperative intravesical instillation (SII) compared to maintenance intravesical instillations (MII) in primary non-muscle-invasive bladder cancer (NMIBC) after transurethral en bloc resection of bladder tumors (ERBT). A total of 141 patients with primary NMIBC who underwent ERBT with thulium laser between January 2012 and May 2016 were retrospectively enrolled. All the patients were categorized into two groups based on the duration of postoperative intravesical instillation of pirarubicin (THP): single intravesical instillation (SII) group, patients received a single immediate postoperative intravesical instillation of THP (30 mg), and maintenance intravesical instillations (MII) group, patients received a 1-year MII of THP (30 mg). Prognosis and recurrence data of each group were analyzed. One hundred and four (73.8%) patients received MII, and other 37 (26.2%) patients received SII. There was no significant difference in recurrence-free survival (RFS) between the two groups (P = 0.105). Following recurrence risk-stratified analysis, patients with high recurrence risk who accepted SII had a significantly lower RFS rate than those who received MII (P = 0.027). However, there were no significant differences in RFS rate between the two groups in patients with low and intermediate recurrence risk. In the multivariate analysis, the number of tumors was found to be an independent prognostic factor for RFS in NMIBC patients [hazard ratio, 5.665; 95% confidence interval (CI), 2.577-12.454; P < 0.001]. SII seems not to be inferior to MII in patients with initial low-risk and intermediate-risk NMIBC after ERBT.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Doxorubicin; Female; Humans; Lasers; Male; Middle Aged; Multivariate Analysis; Muscles; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Risk Factors; Survival Analysis; Thulium; Urethra; Urinary Bladder Neoplasms

This study aimed to evaluate the efficacy of transurethral thulium laser en bloc resection of the bladder tumor (TmLRBT) in patients with non-muscle invasive bladder cancer (NMIBC) and to investigate whether a second resection can be avoided.. From June 2012 to June 2018, 251 newly diagnosed patients with NMIBC were enrolled in this retrospective study; all patients received regular administration of pirarubicin after the initial resection. A second transurethral resection (TUR) was performed in patients within 2-6 weeks after the initial TmLRBT in group 1. Patients in group 2 only underwent cystoscopy at 3 months.. Second surgery results indicate that recurrence was detected histopathologically in 6/108 and 11/143 patients in group 1 and 2, respectively (P = 0.52); Progression was observed in 2 patients in each group (P = 0.34). The mean follow-up duration was 40.1 months, with no significant difference between the groups (P = 0.32). Recurrence was observed in 23 (21.3%) and 39 (27.3%) patients in groups 1 and 2 during the follow-up, respectively (P = 0.34); disease progression occurred in 4 (3.8%) patients in group 1 compared with 7 (4.0%) in group 2 (P = 0.20).. Complete removal of tumors can be achieved by TmLRBT. This technique may decrease the number of second TURs.

Topics: Administration, Intravesical; Aged; Antineoplastic Agents; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Cystoscopy; Doxorubicin; Female; Humans; Laser Therapy; Male; Margins of Excision; Middle Aged; Neoplasm Invasiveness; Reoperation; Retrospective Studies; Thulium; Urinary Bladder; Urinary Bladder Neoplasms

To evaluate the safety and efficacy of intensive intravesical instillation of low-dose pirarubicin (THP) for 6 times vs. bacillus Calmette-Guérin (BCG) without maintenance therapy after transurethral resection of bladder tumor (TURBT) in patients with primary high-risk non-muscle-invasive bladder cancer (NMIBC).. We retrospectively evaluated 370 patients with primary high-risk NMIBC who underwent TURBT from November 1993 to April 2019. The patients were divided into 2 groups: patients treated with intravesical instillation of BCG without maintenance therapy (BCG group) and intensive intravesical instillation of low-dose (20 mg) THP for 6 times within 10 days after TURBT (THP group). Safety was assessed using the Common Terminology Criteria for Adverse Events version 5.0. Background-adjusted multivariate analyses were performed to evaluate the effect of intensive intravesical instillation of low-dose THP on oncological outcomes, including intravesical recurrence-free survival (RFS), upper urinary tract RFS, muscle-invasive bladder cancer-free survival, metastasis-free survival, cancer-specific survival, and overall survival.. Of the 370 patients with primary high-risk NMIBC, 180 (49%) and 190 (51%) were stratified into the BCG and THP groups, respectively. The incidence rate of adverse events of any grade in the BCG group was significantly higher than that in the THP group (P < 0.001). In the background-adjusted multivariate analyses, no significant differences were observed in oncological outcomes between the BCG and THP groups.. Intensive intravesical instillation of low-dose THP for 6 times may be one of the treatment options in view of safety and efficacy after TURBT in patients with primary high-risk NMIBC.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Aged; Antineoplastic Agents; BCG Vaccine; Combined Modality Therapy; Cystectomy; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Retrospective Studies; Risk Assessment; Treatment Outcome; Urethra; Urinary Bladder Neoplasms

This study will aim to appraise the efficacy and safety of pirarubicin for the treatment of patients with nonmuscle invasive bladder cancer (NMIBC).. We will perform a comprehensive literature search in MEDLINE, EMBASE, Cochrane Library, Scopus, PsycINFO, Web of Science, Allied and Complementary Medicine Database, Chinese Biomedical Literature Database, and China National Knowledge Infrastructure from their beginning to the February 29, 2020. All randomized controlled trials of pirarubicin for NMIBC will be included regardless limitations related to the language and publication time. Two researchers will independently select studies from searched records, extract data from included randomized controlled trials, and assess study quality using Cochrane risk of bias tool. Any differences between them will be solved with the help of another researcher. RevMan 5.3 software will be utilized for statistical analysis.. This study will provide a synthesis of current evidence to investigate the efficacy and safety of pirarubicin for NMIBC using overall survival, progression-free survival, recurrence-free survival, quality of, rates of recurrence, and adverse events.. This study will explore whether or not pirarubicin can be used as an effective and safety treatment for patients with NMIBC.. INPLASY202040113.

Topics: Doxorubicin; Humans; Meta-Analysis as Topic; Research Design; Systematic Reviews as Topic; Treatment Outcome; Urinary Bladder Neoplasms

Because of the failure, shortage and related toxicities of Bacillus Calmette-Guérin (BCG), the other intravesical chemotherapy drugs are also widely used in clinical application. Gemcitabine and anthracycline antibiotics (epirubicin and pirarubicin) are widely used as first-line or salvage therapy, but which drug is better is less discussed.. A total of 124 primary NMIBC patients administered intravesical therapy after transurethral resection of bladder tumor (TURBT) at Nanjing Drum Tower hospital from January 1996 to July 2018. After TURBT, all patients accepted standard intravesical chemotherapy. Recurrence was defined as the occurrence of a new tumor in the bladder. Progression was defined as confirmed tumor invading muscular layer. Treatment failure was defined as need for radical cystectomy (RC), systemic chemotherapy and radiation therapy.. Of the 124 patients who underwent intravesical chemotherapy, 84 patients were given gemcitabine, 40 patients were given epirubicin or pirarubicin, with mean follow-up times (mean ± SD) of (34.8 ± 17.9) and (35.9 ± 22.1) months respectively. The clinical and pathological features of patients show no difference between two groups. Recurrence rate of patients given gemcitabine was 8.33% (7 out of 84), the recurrence rate was 45% (18 out of 40) for epirubicin or pirarubicin (P < 0.0001). The progression rates of gemcitabine, anthracycline antibiotics groups were 2.38% (2 out of 84) and 20% (8 out of 40), respectively (P < 0.001). The rate of treatment failure is 8.33% (7 out of 84) and 25% (10 out of 40), respectively (P = 0.012). Gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence (HR = 0.165, 95% CI 0.069-0.397, P = 0.000), progression (HR = 0.160, 95% CI 0.032-0.799, P = 0.026) and treatment failure (HR = 0.260, 95% CI 0.078-0.867, P = 0.028).. In conclusion, gemcitabine intravesical chemotherapy group was significantly related to a lower rate of recurrence, progression and treatment failure. Gemcitabine could be considered as a choice for these patients who are not suitable for BCG.

Topics: Aged; Anthracyclines; Antineoplastic Agents; Deoxycytidine; Doxorubicin; Epirubicin; Female; Gemcitabine; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Treatment Outcome; Urinary Bladder Neoplasms

To assess the efficacy of intra-arterial chemotherapy (IAC) combined with intravesical chemotherapy (IVC) in T1G3 bladder cancer (Bca) after transurethral resection of bladder tumor (TURBT).. Our study retrospectively reviewed 200 patients with T1G3 BCa who had all undergone TURBT. The patients' medical records were divided into two groups, one group only had IVC with pirarubicin after surgery, and the other group had IAC (cisplatin and epirubicin) combined with IVC after surgery. The patients were monitored regularly by urine cytology and cystoscopy. Survival and recurrence curves were calculated using the Kaplan-Meier method. Tumor recurrence, progression and tumor-specific death rate were compared with Chi-square test. A multivariate analysis was carried out to find out potential confounders.. A total of 200 medical record was analyzed, 131 patients received IVC, 69 IAC + IVC treatment, tumor-specific death rate between the combined IAC and IVC compared to IVC alone was 7.25 and 17.6%, respectively (p < 0.05); the tumor recurrence rate between the two groups was 31.8% (22/69) and 44.3%, respectively (58/131) (p < 0.05), and tumor recurred later in the IAC + IVC group (p < 0.05), tumor progression rate was 18.8% (13/69) and 28.2% (37/131), respectively, with p < 0.05. Overall survival was longer in IAC + IVC group (p < 0.05). Using the multivariable regression model, IAC was significantly related to disease recurrence (p < 0.05) and overall survival (p < 0.05).. T1G3 BCa post-TURBT surgery patients who underwent IAC combined with IVC had a longer overall survival and increased time interval to first recurrence, lower tumor recurrence rate, progression rate and tumor-specific death rate than compared with those who only underwent IVC alone.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Cisplatin; Cystoscopy; Doxorubicin; Epirubicin; Female; Humans; Injections, Intra-Arterial; Male; Middle Aged; Neoplasm Recurrence, Local; Organ Sparing Treatments; Retrospective Studies; Treatment Outcome; Urinary Bladder Neoplasms

Prophylactic intravesical chemotherapy can decrease bladder cancer recurrence rate after nephroureterectomy for upper tract urothelial carcinoma. We aimed to compare the effect of different prophylactic intravesical chemotherapy regimens in bladder recurrence-free survival. From 2000 to 2016, a total of 270 patients treated with radical nephroureterectomy at both institutions were enrolled. Patients were divided into 3 groups: multiple-instillation group, single-instillation group, and no-instillation group. Univariable and multivariable analyses with Cox regression methods were performed to calculate hazard ratios for bladder recurrence using clinicopathologic data, including our different instillation strategies. Sixty-three (23.3%) of 270 patients had subsequent intravesical recurrence. Significantly fewer patients in both the instillation groups had a recurrence compared to in the no-instillation group (13.1% vs 25.4% vs 41.5%, P = .001). Furthermore, there was a significant difference between both the instillation groups ( P = .016). In different subsets of patients with upper tract urothelial carcinoma, intravesical chemotherapy, either multiple or single instillation, was a protective factor of bladder recurrence in pT2-4 ( P = .002) and high grade ( P < .0001). Importantly, Kaplan-Meier curves of bladder recurrence-free survival rate were increased observably in multiple-instillation group compared to that in single-instillation group ( P = .053 in pT2-4 subgroup; P = .048 in high-grade subgroup, respectively). On multivariable analysis, intravesical chemotherapy ( P < .001), especially multiple instillations (hazard ratio 0.230; 95% confidence interval 0.110-0.479), was identified an independent predictor of bladder recurrence-free survival. In conclusion, prophylactic intravesical chemotherapy effectively prevents bladder recurrence after nephroureterectomy, especially with multiple instillations, in patients with invasive upper tract urothelial carcinoma or at high-grade status.

Topics: Administration, Intravesical; Aged; Combined Modality Therapy; Cystoscopy; Disease-Free Survival; Doxorubicin; Female; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Nephroureterectomy; Treatment Outcome; Urinary Bladder Neoplasms; Urothelium

Pyruvate kinase M2 (PKM2) regulates the final step of glycolysis levels that are correlated with the sensitivity of anticancer chemotherapeutic drugs. THP is one of the major drugs used in non-muscle-invasive bladder cancer instillation chemotherapy. However, low response ratio of THP (19.7%) treatment to human genitourinary tumours using collagen gel matrix has been observed. This study aims to investigate the effect of down-regulation of PKM2 on THP efficiency. Via inhibitor or siRNA, the effects of reduced PKM2 on the efficiency of THP were determined in 2 human and 1 murine bladder cancer cell lines, using MTT, cologenic and fluorescence approaches. Molecular mechanisms of PKM2 on THP sensitization were explored by probing p-AMPK and p-STAT3 levels via WB. Syngeneic orthotopic bladder tumour model was applied to evaluate this efficiency in vivo, analysed by Kaplan-Meier survival curves, body and bladder weights plus immunohistochemistric tumour biomarkers. PKM2 was overexpressed in bladder cancer cells and tissues, and down-regulation of PKM2 enhanced the sensitivity of THP in vitro. Activation of AMPK is essential for THP to exert anti-bladder cancer activities. On the other hand, down-regulating PKM2 activates AMPK and inhibits STAT3, correlated with THP sensitivity. Compared with THP alone (400 μmol L

Topics: Adenylate Kinase; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Down-Regulation; Doxorubicin; Drug Synergism; Female; Gene Expression Regulation, Neoplastic; Humans; Inhibitory Concentration 50; Metformin; Mice, Inbred C57BL; Phosphorylation; STAT3 Transcription Factor; Urinary Bladder Neoplasms

Topics: Administration, Intravesical; Antineoplastic Agents; Disease Progression; Doxorubicin; Humans; Neoplasm Recurrence, Local; Postoperative Care; Risk Assessment; Risk Factors; Time Factors; Urinary Bladder Neoplasms

This study was conducted to evaluate the efficacy and necessity of repeat transurethral resection (re-TUR) treatment for selected patients with muscle-invasive bladder cancer and to investigate the possibility of bladder sparing.. The study included 61 selected patients with invasive bladder cancer who were treated by re-TUR and in whom biopsies of the muscle layer of the tumour bed were negative. Re-TUR was performed within 4-6 weeks of the initial resection. Pirarubicin instillation was scheduled for the bladder-preserving group. The prognosis was compared with that of patients in our previous research, which included 93 selected patients with invasive bladder cancer who were treated by radical TUR. In that research, we found that the overall survival and disease-specific survival rates were 59.1 and 65.2%, respectively. The clinical stage of tumour influenced the survival rates.. Of the 61 patients who underwent re-TUR, 31 never had disease relapse, 19 had disease recurrence and 11 had disease progression. The clinical stage of the tumour influenced the overall survival and disease-specific survival. The 5-year overall survival rate was 70% and disease-specific survival rate was 74%, respectively. Compared with the TUR group, both the overall survival and disease-specific survival rates of the re-TUR group both increased significantly (P < 0.05).. Re-TUR combined with pirarubicin instillation is a suitable bladder-preserving treatment for selected patients with muscle-invasive bladder cancer, based on good overall survival and disease-specific survival rates demonstrated in this research. The clinical stage of tumour has a major influence on the survival rates.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Transitional Cell; Combined Modality Therapy; Cystectomy; Disease-Free Survival; Doxorubicin; Female; Humans; Male; Middle Aged; Natural Orifice Endoscopic Surgery; Neoplasm Invasiveness; Neoplasm Staging; Organ Sparing Treatments; Prognosis; Survival Rate; Urethra; Urinary Bladder Neoplasms

To analyze the correlation between pharmacogenomic biomarkers and the efficacy of pirarubicin (THP, also named 4'-O-tetrahydropyranyl-adriamycin) and to explore potential associations of individual genetic backgrounds with the clinical outcomes of non-muscle-invasive bladder cancer (NMIBC) patients.. Between July 2003 and June 2011, a total of 91 patients were treated with transurethral resection (TUR) of the bladder tumor and were histopathologically confirmed to have NMIBC. Patients received an immediate instillation and maintenance therapy with THP. All patients underwent follow-up for recurrence. We genotyped 13 single nucleotide polymorphisms (SNPs) from blood and saliva DNA samples of all patients.. The associations of patients' genotypes with tumor recurrence risks were analyzed by survival analysis. A total of 16 (17.6%) of the 91 patients with NMIBC had tumor recurrences with a median follow-up of 17 months (range, 2-83 months). We confirmed the effect of the European Organization for Research and Treatment of Cancer (EORTC) risk score for predicting tumor recurrence (p = 0.002, log-rank test). We adjusted for the EORTC score and found that 2 SNPs, NOS3 895G>T (rs1799983) (p = 0.02, HR = 4.32, 95% CI, 1.30-14.39, GT+TT vs. GG) and CBR3 730G>A (rs1056892) (p = 0.04, HR = 2.57, 95% CI, 1.07-6.18, GA+AA vs. GG), were significantly associated with a higher recurrence risk after TUR and instillations of THP in NMIBC patients.. Our results suggest that NOS3 895G>T and CBR3 730G>A are genetic markers that can be used to predict tumor recurrence in NMIBC patients receiving intravesical instillations of THP. The effects of those 2 SNPs are independent of the EORTC scores. Further studies with larger sample sizes and longer follow-ups are needed to confirm our results.

Topics: Administration, Intravesical; Aged; Alcohol Oxidoreductases; Antineoplastic Agents; Biomarkers, Tumor; Doxorubicin; Female; Genotype; Humans; Kaplan-Meier Estimate; Male; Middle Aged; Neoplasm Recurrence, Local; Nitric Oxide Synthase Type III; Polymorphism, Single Nucleotide; Risk Factors; Saliva; Urinary Bladder Neoplasms

We evaluated the efficacy of single-dose instillation of pirarubicine hydrochloride (THP) in the chemoprophylaxis of non-muscle-invasive bladder cancer(NMIBC). In a retrospective study, 135 evaluable patients were assigned to three groups after transurethral resection of bladder tumors (TURBT). In group 1, patients received no adjuvant therapy after TURBT. In group 2, patients received a single-dose of 30 mg THP in 30 ml normal saline immediately after TURBT. In group 3, patients received 30 mg THP in 30 ml normal saline 2 weeks after TURBT , and the instillations were repeated for 4 weeks, then every other week twice and successively monthly for 6 months. Patients were followed with cystoscopy and urine cytology every 3 months for the first 2 years and every 6 months thereafter. The 3- and 5-year non-recurrence rates were 66.9%, and 66.0%, respectively, in group 1, 85.6%, and 85.6%, respectively, in group 2, and 93.6%, and 77.9%, respectively, in group 3. There was a significant difference only between group 1 and group2 (P ＝0.048). With respect to the recurrence per month, there was a significant difference between the 3 groups (P＝0.014) for the first 2 years. However, there was no significant difference thereafter. Limitations of our study are its retrospective and nonrandomized nature with a limited number of patients.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Invasiveness; Recurrence; Retrospective Studies; Secondary Prevention; Urinary Bladder Neoplasms

Bladder cancer is a common malignant tumor with a very high recurrence rate after surgery. Intravesical instillation can help clear up the residual tumor cells after surgery and thereby reduce the recurrence rate.. To establish a bladder tumor transplantation animal model and to evaluate the inhibitory effects of a novel perfusate, Su Fu'ning Lotion (SFN), on bladder tumor.. SFN was compared with several commonly used chemotherapy drugs, including mitomycin (MMC) and pirarubicin (THP) for anticancer effects on the bladder cancer cell lines T24, BTT, and BIU-87 and SFN half inhibitory concentrations (IC50) were determined after 48 hours of treatment. In addition, bladder cancer orthotopic transplantation tumor models were established in BALB/C nude mice and T739 mice, and SFN anticancer effects were assessed in vivo, with normal saline and MMC as negative and positive controls, respectively.. SFN, MMC, and THP were all lethal to bladder cancer cells, in vitro, with SFN and THP significantly superior to MMC. IC50 values for SFN were 13.22, 11.22, and 12.5 µg/mL on T24, BTT, and BIU-87 cells, respectively. In vivo, SFN significantly reduced the mouse bladder wet weight and prolonged the animal survival compared with controls (P < .05), suggesting that SFN significantly inhibited T24/BTT cell growth in mice.. SFN inhibited the bladder cancer cell proliferation in vitro and in vivo and significantly prolonged the survival of mice with bladder cancer xenografts, indicating that SFN could be used as a perfusate after surgery for removal of residual bladder cancers cells.

Topics: Administration, Intravesical; Animals; Antineoplastic Agents; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Doxorubicin; Female; Humans; Medicine, Chinese Traditional; Mice; Mice, Inbred BALB C; Mice, Nude; Mitomycin; Neoplasm Recurrence, Local; Neoplasm Transplantation; Urinary Bladder Neoplasms

We report the first case of anaphylaxis induced by intravesical administration of pirarubicin hydrochloride during spinal anesthesia. The patient was a 64-year-old woman being followed up for transitional cell carcinoma of the bladder. Anaphylaxis occurred the fifth time pirarubicin hydrochloride was administered intravesically. Pirarubicin hydrochloride, an anthracycline antitumor antibiotic that is widely used for intravesical instillation chemotherapy, is administered at the end of surgery. Because this is about the time that the patient is leaving the operating room, attention to patient monitoring tends to be divided. Because anaphylaxis may occur at this time, staff should remain vigilant of the risk of anaphylaxis.

Topics: Administration, Intravesical; Anaphylaxis; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Doxorubicin; Epinephrine; Female; Humans; Middle Aged; Treatment Outcome; Urinary Bladder Neoplasms; Urologic Surgical Procedures; Vasoconstrictor Agents

Pirarubicin is widely used in intravesical chemotherapy for bladder cancer, but its efficacy is limited due to drug resistance; the mechanism has not been well studied. Emerging evidence shows that autophagy can be a novel target for cancer therapy. This study aimed to investigate the role of autophagy in pirarubicin-treated bladder cancer cells. Bladder cancer cells EJ and J82 were treated with pirarubicin, siRNA, 3-methyladenine or hydroxychloroquine. Cell proliferation and apoptosis were tested by cell survival assay and flow cytometric analysis, respectively. Autophagy was evaluated by immunoblotting before and after the treatments. The phosphorylated mammalian target of rapamycin, serine/threonine kinase p70 S6 kinase, and eukaryotic translation initiation factor 4E binding protein 1 were also investigated by immunoblotting. We found that pirarubicin could induce autophagy in bladder cancer cells. Inhibition of autophagy by 3-methyladenine, hydroxychloroquine or knockdown of autophagy related gene 3 significantly increased apoptosis in pirarubicin-treated bladder cancer cells. Pirarubicin-induced autophagy was mediated via the mTOR/p70S6K/4E-BP1 signaling pathway. In conclusion, autophagy induced by pirarubicin plays a cytoprotective role in bladder cancer cells, suggesting that inhibition of autophagy may improve efficacy over traditional pirarubicin chemotherapy in bladder cancer patients.

Topics: Antineoplastic Agents; Apoptosis; Autophagy; Doxorubicin; Humans; Signal Transduction; TOR Serine-Threonine Kinases; Urinary Bladder Neoplasms

There is a high frequency of tumor recurrence in non-muscle invasive bladder cancer (NMIBC) after transurethral resection and postoperative intravesical chemotherapy, however, the molecular mechanisms leading to the chemoresistance and tumor re-growth remain largely unknown. In this study, we observed a significant decrease of DAB2IP expression in high-grade and recurrent NMIBC specimens, which was negatively correlated with Twist1 expression and predicted a lower recurrence-free survival of patients. Mechanistically, DAB2IP could inhibit the phosphorylation and transactivation of STAT3, and then subsequently suppress the expression of Twist1 and its target gene P-glycoprotein, both of which were crucial for the pirarubicin chemoresistance and tumor re-growth of bladder cancer cells. Overall, this study reveals a new promising biomarker modulating the chemoresistance and tumor recurrence of NMIBC after bladder preservation surgery.

Topics: Animals; Antineoplastic Agents; ATP Binding Cassette Transporter, Subfamily B, Member 1; Cell Line, Tumor; Cell Survival; Down-Regulation; Doxorubicin; Drug Resistance, Neoplasm; Female; Humans; Kaplan-Meier Estimate; Mice, Inbred BALB C; Mice, Nude; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Nuclear Proteins; ras GTPase-Activating Proteins; Signal Transduction; STAT3 Transcription Factor; Twist-Related Protein 1; Urinary Bladder Neoplasms; Urothelium; Xenograft Model Antitumor Assays

We retrospectively evaluated 23 patients who had been administered pirarubicin by intravesical instillation once weekly for 5 weeks, after undergoing surgery for upper urinary tract cancer between May 2003 and October 2008. We compared their clinical records with those of 19 patients with upper urinary tract cancer subjected to nephroureterectomy between 1998 and 2008, and who did not receive intravesical instillation of pirarubicin. This prophylactic therapy was well tolerated and contributed to reduce the rate of bladder recurrence. The non-recurrence rate at 2 years was 87.0% in the instillation group and 68.4% in the non-instillation group (P＝0.0025). The overall analysis of the study population did not reveal any statistically significant risk factors of bladder recurrence.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Antineoplastic Agents; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Nephrectomy; Retrospective Studies; Ureterocele; Urinary Bladder Neoplasms; Urologic Neoplasms

This study was aimed to establish rat bladder tumor animal models to investigate the in viva antitumor effect of polyanhydride-pirarubicin (PAD-THP), a long-lasting anti-cancer implant, in the bladder tumor of animal models. The model of bladder cancer was set up with N-butly-N-(4 hydroxybutyl) nitrosamine (BBN) feeding into rats. The PAD-THP long-acting anti-cancer implants containing the drugs and the same dose of the THP naked drug were placed under the bladder mucosa of bladder tumor model in vivo. The pirarubicin plasma concentration was measured with high performance liquid chromatography (HPLC) detection in vivo. The effective drug concentration and lasting period were observed and compared in the animal bodies. The tumor sizes were measured before and after the treatment. The in viva antitumor effects were analyzed and compared. The results showed that more significant antitumor effect of PAD-THP implants on the local drug release characteristics were presented compared with that of the same dose of THP bare drug group and there were significant differences (P<0. 05) between the two methods. All the results indicated that the PAD-THP anti-cancer implants in the postoperative local treatment of bladder tumors would show prosperous in the future for clinical application.

Topics: Animals; Antineoplastic Agents; Butylhydroxybutylnitrosamine; Delayed-Action Preparations; Disease Models, Animal; Doxorubicin; Female; Implants, Experimental; Polyanhydrides; Rats; Rats, Sprague-Dawley; Urinary Bladder Neoplasms

Intravesical chemotherapy is an important part of the treatment for superficial bladder cancer. However, the response to it is limited and its side effects are extensive. Functional single-walled carbon nanotubes (SWNT) have shown promise for tumor-targeted accumulation and low toxicity. In the present study, we performed in vivo and in vitro investigations to determine whether SWNT-based drug delivery could induce high tumor depression in rat bladder cancer and could decrease the side effects of pirarubicin (tetrahydropyranyl-adriamycin, THP). We modified SWNT with phospholipid-branched polyethylene glycol and constructed an SWNT-THP conjugate via a cleavable ester bond. The cytotoxicity of SWNT-THP against the human bladder cancer cell line BIU-87 was evaluated in vitro. Rat bladder cancer in situ models constructed by N-methyl-N-nitrosourea intravesical installation (1 g/L, 2 mg/rat once every 2 weeks for 8 weeks) were used for in vivo evaluation of the cytotoxicity of SWNT and SWNT-THP. Specific side effects in the THP group including urinary frequency (N = 12), macroscopic hematuria (N = 1), and vomiting (N = 7) were identified; however, no side effects were observed with SWNT-THP treatment. Flow cytometry was used to assess the cytotoxicity in vitro and in vivo. Results showed that SWNT alone did not yield significant tumor depression compared to saline (1.74 ± 0.56 and 1.23 ± 0.42%) in vitro. SWNT-THP exhibited higher tumor depression than THP-saline in vitro (74.35 ± 2.56 and 51.24 ± 1.45%) and in vivo (52.46 ± 2.41 and 96.85 ± 0.85%). The present findings indicate that SWNT delivery of THP for the treatment of bladder cancer leads to minimal side effects without loss of therapeutic efficacy. Therefore, this nanotechnology may play a crucial role in the improvement of intravesical treatment of bladder cancer.

Topics: Administration, Intravesical; Animals; Antineoplastic Agents; Doxorubicin; Female; Humans; Nanotubes, Carbon; Rats; Rats, Sprague-Dawley; Urinary Bladder Neoplasms

We estimated the results of 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) following transurethral resection of bladder tumor (TURBT) for non-muscle-invasive bladder cancer retrospectively.. Through March 1995 to April 2009, a total of 184 patients were instilled 3-day consecutive intravesical instillation of pirarubicine hydrochloride (THP) (30 mg/40 ml in disinfected distilled water) started within a few hours after TURBT. 184 patients were diagnosed as untreated fresh non-muscle-invasive urothelial bladder cancer with no concomitant carcinoma in situ (CIS), no concurrent upper urinary tract urothelial cancer and no past history of upper urinary tract urothelial cancer. Number of tumors, tumor size, tumor grade and clinical tumor stage were analyzed in relation to tumor recurrence by univariate and multivariate analyses. Median follow-up were 55.1 months.. Using EAU guideline on non-muscle invasive urothelial carcinoma of the bladder, 168 patients were classified at intermediate risk of tumor recurrence, 14 patients were at low risk of tumor recurrence and 2 patients were at high risk of tumor recurrence. The shape of non-recurrence rate curve showed two phase decrease pattern, namely, early hasty decrease within 1.5 or two years and late gentle decrease thereafter. The 1, 2, 3, 5-year non-recurrence rate were 82.7%, 75.3%, 72.3% and 67.4% respectively. The 3-year non-recurrence rate of low score group (recurrence score 1-3) at intermediate risk of tumor recurrence was 85.3%. Univariate analysis revealed that number of tumors, tumor grade and clinical tumor stage were related to tumor recurrence (p<0.05). By multivariate analysis, number of tumors and clinical tumor stage were related to tumor recurrence (p<0.05).. In patients of low score group at intermediate risk of tumor recurrence without grade 3 urothelial carcinoma and concomitant bladder CIS, 3-day consecutive intravesical instillation of pirarubicine hyorochloride (THP) following TURBT for non-muscle-invasive bladder cancer would be a significant adjuvant therapy. But in patients of high score group at intermediate risk of tumor recurrence, it seemed better to do additional maintenance intravesical chemotherapy or intravesical BCG therapy.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Combined Modality Therapy; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Retrospective Studies; Urinary Bladder Neoplasms

To analyze the influence of intravesical Pirarubicin (THP) instillation on the prediction results of European Organization for Research and Treatment of Cancer (EORTC) risk tables and to discuss the efficacy of EORTC risk tables in clinical application.. We retrospectively reviewed the clinical data of 389 patients with non-muscle invasive bladder cancer after TURBT treated with intravesical pirarubicin instillation. According to the EORTC Scoring System, all the cases were divided into low risk group, intermediate risk group and high risk group. The 1-year and 5-year recurrence and progression rates of each group were calculated and compared with the prediction results of the EORTC risk tables.. The 1-year recurrence and progression rates of the low risk group were 8.0% and 0, those of the intermediate risk group were 31.0% and 2.8%, and those of the high risk group were 52.5% and 18.6%, respectively. The 5-year recurrence and progression rates of low risk group were 16.0% and 5.3%, those of the intermediate risk group were 42.6% and 10.7%, and those of the high risk group were 63.9% and 41.9%, respectively. The prediction results of progression rate were similar to that of the EORTC risk tables while the overall recurrence rate was lower.. The EORTC risk tables can be effectively used to predict the recurrence rate and progression rate of non-muscle invasive bladder cancer. However, the EORTC risk tables have a tendency to overestimate the recurrence rate. Intravesical pirarubicin instillation is helpful to reduce the recurrence rate, yet has no obvious influence on the tumor progression.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Disease Progression; Doxorubicin; Female; Follow-Up Studies; Humans; Male; Middle Aged; Neoplasm Invasiveness; Neoplasm Recurrence, Local; Retrospective Studies; Risk Assessment; Urinary Bladder Neoplasms

This study was designed to determine the ideal manner (schedule and duration) of intravesical chemotherapy using pirarubicin (THP). At first, T-24 cancer cells were treated with 50, 100, 150, and 200 μg/ml THP for 10, 30 and 60 min. Following the first exposure, at various intervals (3, 6, 12, and 24 h), a second exposure to THP was performed under the same condition in vitro. The cell viability was measured by XTT assay. Further, the cells were scanned with a laser scanning cytometer (LSC) and DNA histograms were analyzed to evaluate the cell-cycle components. A single exposure of T-24 cells to THP resulted in significantly higher inhibition of cell growth for 30 min with 100 μg/ml and higher concentrations of THP; for example, the cell viability was reduced to 15, 2, and 0% by incubating cells with 100, 150, and 200 μg/ml of THP, respectively, whereas it was 49% with 50 μg/ml THP. Double exposure of T-24 cells to THP resulted in significantly higher inhibition of cell growth than single treatment at all intervals. LSC assay demonstrated a higher sub-G(1) peak after double treatment with THP when compared with that after a single treatment. Similar cytotoxic effects following double treatment with THP were observed on other bladder cancer cell lines (UMUC3, TCCSUP, 5637, and 253J cells) in vitro. In conclusion, the double short-term exposure to bladder cancer cells by THP has more remarkable cytotoxic effects than the single exposure in vitro.

Topics: Antineoplastic Agents; Apoptosis; Cell Cycle; Cell Line, Tumor; Cell Survival; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Humans; Laser Scanning Cytometry; Neoplasm Staging; Urinary Bladder Neoplasms

We evaluated antitumoral effect of combined chemotherapy and interleukin-12 (IL-12) gene therapy in in vitro and in vivo experimental urothelial bladder cancer (UBC) model.. EJ UBC cells were transfected with recombinant IL-12 genes using a liposomal transfection agent. Pirarubicin (THP) was added to the experimental samples at a final concentration of 20 mg/l. Four groups were assigned in vitro: untreated cells, transfected cells, untransfected cells plus THP and transfected cells plus THP. Death rates (DR) and cellular micromorphologic changes were evaluated. Bladder tumor model was established by subcutaneous injection of EJ cells to the nude mice. Four groups were assigned in vivo: control group; THP group; IL-12 gene group and IL-12 gene plus THP group. After injection of combined THP and IL-12 gene therapy, tumor size and IL-12 levels were evaluated.. In vitro study: DR in the THP + IL-12 gene therapy group (58.2 ± 15.8%) was significantly higher than transfected group (12.2 ± 5.6%; P = 0.01) and untransfected cells plus THP group (33.4 ± 7.8; P = 0.046). A higher amount of apoptotic changes and necrosis on transmission electron microscope analysis were observed in transfected cells plus THP group. In vivo study: A significant tumor attenuation was found in IL-12 gene in combination with THP group when compared with any other groups that were treated without Il-12 or THP (P < 0.05). IL-12 levels in serum were significant high in IL-12 gene groups (P < 0.01).. The combination of THP chemotherapy and IL-12 gene therapy showed an additive antitumoral effect on bladder cancer cells in vitro and in vivo. Further investigation should be focused on high-level transgene protocols in vivo.

Topics: Animals; Antineoplastic Agents; Apoptosis; Carcinoma; Cell Line, Tumor; Combined Modality Therapy; Doxorubicin; Genetic Therapy; Humans; Interleukin-12; Mice; Mice, Inbred BALB C; Mice, Nude; Models, Animal; Transfection; Tumor Burden; Urinary Bladder Neoplasms

This paper aims to prepare polyanhydride-Pirarubicin dose long-acting sustained-release implants for the treatment of bladder cancer and for the prevention of postoperative recurrence of bladder cancer. Pirarubicin hydrochloride (THP) and polyanhydride, in accordance with a certain proportion, were fully mixed in the agate morta and dissolved in dichloromethane, and then were cast into a film within a mold put in the dryer set at 4 degrees C. Each tablet implanted contained 5.0 mg of THP. Polyanhydride-pirarubicin sustained-release was implanted into the bladder mucosa of the rabbits, and blood and urine samples were taken at different times after the operation. The THP drug concentrations in urine and blood were determined with high-performance liquid chromatography. The THP concentration in urine was significantly higher than the THP concentration in plasma. The drug concentration in urine reached (92.5 +/- 7.4) microg/L at 250 d time after the operation. Polyanhydride-pirarubicin implants possess long-acting sustained-release level dynamics in the body. It can maintain a stable long-term drug release and can be expected to last a year and can effectively prevent recurrence of bladder cancer. The present experiments proved that the implants with sustained-release drug treatment are expected to be useful in the clinical application in prevention of bladder cancer recurrence.

Topics: Absorbable Implants; Animals; Antineoplastic Agents; Chromatography, High Pressure Liquid; Delayed-Action Preparations; Doxorubicin; Female; Implants, Experimental; Male; Neoplasm Recurrence, Local; Polyanhydrides; Postoperative Period; Rabbits; Random Allocation; Urinary Bladder Neoplasms

To investigate whether the location of carcinoma in situ (CIS) of bladder cancer could be macroscopically ascertained by instilling pirarubicin (THP) into urinary bladder.. 50 mg of THP was dissolved into 50 ml of 5% glucose solution. And the resulting solution was instilled into urinary bladder. After 15 min, the urinary bladder was observed by a cystoscopy. The study group consisted of 51 patients with bladder cancer (37 males, 14 females) and 14 patients with hematuria (8 males, 6 females), treated at our hospital from December 2007 to June 2008.. The THP uptake was seen in 67 flat (non-tumorous) areas of bladder mucosa in 37 patients with bladder cancer. Of these, 11 lesions in 7 patients were confirmed to be CIS. The THP uptake was found in 2 flat (non-tumorous) areas of bladder mucosa in 14 patients with hematuria, 1 lesion in 1 patient was confirmed to be CIS. The sensitivity and specificity of THP uptake by CIS were 92.3% (12/13) and 86.7% (371/428) respectively.. This practical method may be employed to ascertain easily the macroscopic location of CIS of bladder cancer.

Topics: Adult; Aged; Carcinoma in Situ; Doxorubicin; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

To evaluate intra-arterial chemotherapy for bladder preservation in patients with locally advanced bladder cancer.. A total of 34 patients with locally advanced bladder cancer (T2, n=25; T3, n=9) were treated with intra-arterial chemotherapy. Chemotherapy was consisted of intraarterial administration of cisplatin (100 mg/body), and adriamycin or pirarubicin (50 mg/body) every 4 weeks for two cycles. The response was evaluated by TUR, urine cytology, CT and/or MRI 4 weeks after the treatment. In 4 patients, we combined this treatment with radiotherapy.. Among all 34 patients, 12 (35%) patients presented complete response (CR) and 24 patients (70%) presented in objective response (OR). During mean follow up period of 28.7 months, five patients had locally advanced recurrence and one had distant metastasis. The 5-year survival rate was 69.3%. Bladder was conserved in 19 (56%) of all 34 patients. Hematological and gastrointestinal toxicity (more than grade 3) was occurred in 5 and 3 patients. Risk factors on the outcome of this therapy were tumor size >20 mm, multiple tumors and clinical stage > or = cT3. Patients with no or one risk factor had favorable outcomes; the OR rates of 75-100%, the bladder preservation rates of 71-75% and the 5-year cancer specific survival rates of 83%. Whereas patients with two or three risk factors had unfavorable outcomes; the OR rates of 50-58%, the bladder preservation rates of 25-42% and the 3-year cancer specific survival rates of 0-69%.. The treatment of locally advanced bladder cancer with intra-arterial chemotherapy seems to be good for patients with less risk factor, but not so good for patients with more risk factors.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Neoplasm Staging; Risk Factors; Treatment Outcome; Urinary Bladder Neoplasms

We herein report the case of a bladder tumor in an 85-year-old man who had been engaged in phenacetin abuse. He had been taking phenacetin owing to migraine headaches since he was 45 year of age. His total intake of phenacetin was approximately 7.3 to 11.5 kg over a period of years. He visited the Department of Urology in our hospital due to gross hematuria and pain on urination. IVP and a pelvic CT scan revealed a tumor mass on the right lateral wall of the urinary bladder. TUR-BT was performed. A histopathological examination of the resected specimen was diagnosed as urotherial carcinoma, grade 2∼3, pT2N0M0. To our acknowledge, only 24 cases of urotherial tumors owing to phenacetin abuse have been previously reported in the Japanese literature, making this the 25 th such case to be reported in Japan.

Topics: Aged, 80 and over; Analgesics, Non-Narcotic; Antineoplastic Combined Chemotherapy Protocols; Doxorubicin; Floxuridine; Humans; Male; Phenacetin; Radiography; Substance-Related Disorders; Urinary Bladder Neoplasms

A 66-year-old woman presented with a coin-size lesion in the right lung. Bronchoalveolar lavage cytology showed class V. Thoracoscopic partial pneumonectomy of right upper lobe was performed and pathologic finding was metastatic transitional cell carcinoma (TCC). She had a history of superficial bladder tumors which were treated with transurethral resection (TURBT). All pathologic findings demonstrated low grade superficial TCC. After the pneumonectomy, recurrent tumors were detected in the bladder after three months' follow up. Intravesical instillations and TURBT were performed and the pathologic finding showed superficial TCC. There have been no signs of recurrence during the six-year follow up. The case reported here is of superficial cancer with a metastatic lesion in the lung without local invasion in the urinary bladder.

Topics: Administration, Intravesical; Administration, Oral; Aged; Antineoplastic Agents; BCG Vaccine; Carcinoma, Transitional Cell; Combined Modality Therapy; Cystectomy; Doxorubicin; Drug Administration Schedule; Drug Combinations; Female; Humans; Immunosuppressive Agents; Lung Neoplasms; Pneumonectomy; Tegafur; Thoracoscopy; Uracil; Urinary Bladder Neoplasms

We report our second patient treated successfully with a new combined chemotherapy regimen of intra-arterial pirarubicin and nedaplatin plus intravenous methotrexate and vincristine for squamous cell carcinoma (SCC) of the bladder. A 57-year-old man consulted our hospital in September 2005 for treatment of bladder tumors diagnosed in another hospital. Magnetic resonance imaging (MRI) showed an extravesical invasive tumor on the anterior wall of the bladder, and clinical stage T2bN0M0 was diagnosed. Transurethral cold-cup biopsy was performed, and pathological examination revealed SCC. After he received two courses of this new combined intra-arterial chemotherapy regimen using nedaplatin, tumors were detected in MRI and cystoscopy. We performed partial cystectomy in January 2006. Postoperative pathological examination revealed no tumor cells (pathological CR). There were no severe adverse reactions by this chemotherapy regimen. He has been alive without evidence of disease.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Chemotherapy, Adjuvant; Cystectomy; Doxorubicin; Drug Administration Routes; Humans; Infusions, Intra-Arterial; Infusions, Intravenous; Male; Methotrexate; Middle Aged; Organoplatinum Compounds; Remission Induction; Urinary Bladder Neoplasms; Vincristine

To evaluate the anticancer effects of exogenous human WT-PTEN overexpression on bladder transitional carcinoma cell line EJ.. The plasmid containing WT-PTEN or mutant PTEN was separately transfected into bladder transitional carcinoma cell line EJ, and the protein expression of PTEN in the EJ cells was detected by Western blot. Cell morphological changes were observed under the inverted microscope and transmission electron microscope. MTT test was used to assess the effect of PTEN on proliferation and anticancer effects for mitomycin and theraubicin. The change of bcl-2 expression in the cells was measured by Western blot. The empty plasmid was used as control.. Western blot analysis showed that EJ cells expressed high level of PTEN protein after transfection with WT-PTEN or mutant PTEN plasmid. Abnormal morphological changes of the cells were observed in WT-PTEN transfected groups. The growth of EJ cells treated with WT-PTEN was significantly inhibited by 40.1% and anticancer effects were enhanced by mitomycin and theraubicin, but the cells transfected with mutant PTEN plasmid did not show such similar biological behavior.. WT-PTEN gene transfection can suppress the in vitro growth and induce apoptosis of bladder transitional carcinoma cell line EJ cells. Mutant PTEN does not show similar biological behavior. Overexpression of WT-PTEN inhibits cancer cell proliferation by down-regulating bcl-2 expression in the cells.

Topics: Antibiotics, Antineoplastic; Antineoplastic Agents; Apoptosis; Blotting, Western; Carcinoma, Transitional Cell; Cell Line, Tumor; Cell Proliferation; Doxorubicin; Green Fluorescent Proteins; Humans; Microscopy, Electron, Transmission; Mitomycin; Mutation; Plasmids; Proto-Oncogene Proteins c-bcl-2; PTEN Phosphohydrolase; Recombinant Fusion Proteins; Transfection; Urinary Bladder Neoplasms

Patients with locally advanced bladder cancer are at significant risk for metastases. We aimed to evaluate the usefulness of intra-arterial chemotherapy (IAC) combined with angiotensin-II (AT-II) in such patients. The possibility of bladder preservation is also discussed. Patients were enrolled if they had muscle-invasive bladder cancer (stage T2 to T4NxM0). Cisplatin, pirarubicin, and AT-II were infused through the tumor-feeding arteries. Cause-specific survival was the end point. We enrolled 37 patients who were treated with neoadjuvant IAC and 5 patients with adjuvant IAC. There were 7 patients (16.7%) with pathological complete remission. Overall 5-year and 10-year survival rates of the patients were 61.3% and 47.7%, respectively. The 5-year cause-specific survival rate was 100% for the clinical T2 group and 63% for the T3-4 group, and the 8-year survival rate was 33% and 63%, respectively. There was no statistically significant difference between these two groups (P=0.445). Multivariable analysis using tumor number, pattern of growth, and tumor size seemed to independently correlate with cause-specific survival, but there were no significant differences. Our results suggest that intra-arterial chemotherapy combined with AT-II is a useful treatment for patients with locally advanced bladder cancer, since this modality achieves a favorable response rate without severe toxicity or mortality.

Topics: Aged; Aged, 80 and over; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Neoadjuvant Therapy; Neoplasm Invasiveness; Neoplasm Staging; Survival Rate; Urinary Bladder Neoplasms

We studied prophylactic intravesical instillation of mitomycin C (MMC) and pirarubicin (THP) following transurethral resection of bladder tumor (TUR-Bt) for superficial bladder cancer.. Forty-six evaluable patients were administered intravesically 20 mg of MMC dissolved in 20 ml saline on day 1 and 20 mg of THP dissolved 20 ml 5% dextrose on day 2. The patients were followed up by cystscopy and urinary cytology. Intravesical instillations were performed once a month and continued for 5 years.. The non-recurrence rates at 1, 3 and 5 years were 88.8%, 79.5% and 67.0%, respectively. No significant differences were observed between grade 1-2 and 3, male and female, and solitary and multiple tumors. Although the side effects were relatively mild, 6 patients were stopped intravesical instillation.. Because non-recurrence rates of our report is not better than previous reports with shorter treatment periods, intravesical MMC and THP instillation for 5 years is not beneficial to the patients with superficial bladder cancer.

Topics: Administration, Intravesical; Adult; Aged; Antibiotic Prophylaxis; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Time Factors; Urinary Bladder Neoplasms

Patients with superficial bladder tumors sometimes have long recurrence-free intervals. We evaluated whether patients with long recurrence-free periods had subsequent recurrences. We also clarified how these patients should be followed.. We enrolled 244 patients with superficial bladder cancer (62 pTa and 182 pT1) treated by transurethral resection of bladder tumor (TURBT) and adjuvant chemotherapy with pirarubicin. Median follow up was 75.5 months. Patients were stratified by the length of their recurrence-free interval.. Recurrences occurred in 124 patients (50.8%). Of 185 patients who did not have a recurrence for the first 3 years, subsequent recurrences occurred in 65 patients; in more than half the first recurrence developed after 5 years or more. Ta tumors had a low recurrence rate (14.5%) with the first recurrence often developing after a long recurrence-free period. Of 40 patients who remained recurrence-free for 3 years or more after at least one recurrence occurred, 16 patients (40%) had subsequent recurrences. Furthermore, most of these patients who remained free of recurrence for more than 5 years eventually had a recurrence. The overall progression rate was 15.6%, and this did not relate to the length of the recurrence-free interval.. When patients did not have a recurrence for the first 3 years, tumors subsequently often recurred, even in pTa tumors. In patients with at least once recurrence, subsequent recurrences appear to occur irrespective of the length of the recurrence-free period. Thus, we recommend that all patients with superficial bladder tumors be followed for as long as possible.

Topics: Adult; Aged; Aged, 80 and over; Chemotherapy, Adjuvant; Disease-Free Survival; Doxorubicin; Female; Follow-Up Studies; Humans; Immunosuppressive Agents; Male; Middle Aged; Neoplasm Recurrence, Local; Survival Rate; Urinary Bladder Neoplasms

Thymidine phosphorylase (TP), also known as platelet-derived endothelial cell growth factor, has been implicated in the angiogenesis of bladder cancer. The aim of this study is to investigate the association between TP expression and the clinicopathologic findings, and the prognostic value.. TP immunohistochemical staining was performed in specimens from 71 patients (50 men and 21 women) with superficial bladder cancer (pTa or pT1). Thirty-nine patients had received intravesical instillation of tetrahydropyranyladriamycin (THP) after transurethral resection (TUR) and the other 32 had not. For immunohistochemistry, paraffin-embedded specimens were stained with mouse monoclonal antibody against TP. When more than 10% of tumor cells were positively stained, staining was defined as positive. The correlations between TP immunostaining and clinicopathological features were analyzed. Multivariate analysis, using the Cox proportional hazard model, was performed to determine the risk factors for intravesical recurrence.. Specimens from 29 of the 71 patients (19 men and 10 women) were positive for TP. The expression of TP was not correlated with age, sex, histological grade, multiplicity, or morphology. Also, TP expression was not associated with whether the cases were primary or recurrent. Multivariate analysis demonstrated that the decreased expression of TP and the use of THP instillation could be independent predictors of a higher rate of intravesical recurrence-free bladder cancer.. The present study suggests that immunohistochemical TP staining is useful for predicting the intravesical recurrence of superficial bladder cancer after Transurethral resection of bladder tumor (TUR-Bt).

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Biomarkers, Tumor; Carcinoma, Papillary; Carcinoma, Transitional Cell; Disease-Free Survival; Doxorubicin; Female; Humans; Immunohistochemistry; Male; Middle Aged; Multivariate Analysis; Neoplasm Recurrence, Local; Neoplasm Staging; Predictive Value of Tests; Preventive Medicine; Prognosis; Proportional Hazards Models; Regression Analysis; Thymidine Phosphorylase; Urinary Bladder Neoplasms

We report a case of squamous cell carcinoma (SCC) of the bladder treated successfully with intraarterial chemotherapy using nedaplatin. A 75-year-old woman was admitted to our hospital in March 2004 with gross hematuria. Cystoscopic examination showed tumors on the anterior bladder wall. Computed tomography (CT) scans and magnetic resonance imaging (MRI) revealed extravesical invasion of the tumors, and a clinical diagnosis of T3bN0M0 was made. Transurethral biopsy was performed, and histopathological examination revealed SCC, grade 2-3, invasive. The patient received a new combined chemotherapy, intraarterial nedaplatin and pirarubicin plus intravenous methotrexate and vincristine. After two courses of the chemotherapy, CT scans and MRI demonstrated no tumor in the bladder. Transurethral bladder-wall biopsy was performed in November 2004, and histopathological examination of the specimen revealed no definite tumors. The patient is alive without evidence of disease more than 1 year after the chemotherapy.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Doxorubicin; Drug Administration Routes; Female; Humans; Infusions, Intra-Arterial; Injections, Intravenous; Magnetic Resonance Imaging; Methotrexate; Neoplasm Invasiveness; Organoplatinum Compounds; Remission Induction; Tomography, X-Ray Computed; Urinary Bladder Neoplasms; Vincristine

Bladder carcinoma with skin metastasis is extremely rare. We herein report a case of a bladder tumor with skin metastasis. A 68-year-old man was referred to our hospital with macroscopic hematuria. Cystoscopy revealed a trigone papillary tumor. Transurethral resection of bladder tumor (TURBT) was performed and the pathological diagnosis was transitional cell carcinoma (TCC), pT1, G3. Thereafter, he received several courses of TURBT, intravesical chemotherapy (pirarubicin, bacillus Calmette-Guerin and mitomycin C) and intra-arterial chemotherapy because of recurrence. Thirteen years later, he underwent total cystoprostatectomy with neobladder formation. Histological examination revealed muscle-invasive bladder cancer with a staging of T3bNOM0. Two years and three months later, multiple firm nodules with eruptions appeared on the skin in several regions; they were resected and the histological findings revealed TCC. This indicated metastatic spread from the primary bladder TCC. He received only supportive treatment during this period due to renal dysfunction. He died four months after the manifestation of the skin metastasis due to multiple metastases.

Topics: Administration, Intravesical; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Combined Modality Therapy; Cystectomy; Doxorubicin; Humans; Infusions, Intra-Arterial; Male; Methotrexate; Mitomycin; Skin Neoplasms; Urinary Bladder Neoplasms

No established technique for locating solitary carcinoma in situ (CIS) of the urinary bladder or CIS accompanying bladder cancer has been determined. Here we investigated whether the location of CIS of the urinary bladder can be macroscopically ascertained by instilling pirarubicin hydrochloride (THP) into the urinary bladder.. We dissolved 50 mg of THP in 50 ml of distilled water, and instilled the resulting solution into the urinary bladder. After 5 min, the urinary bladder is examined using a cystoscope. The study group consisted of 30 subjects (23 men and 7 women).. THP uptake was seen in 19 flat (nontumorous) areas of the bladder mucosa in 13 patients. Of these, 11 lesions in 6 patients were confirmed to be CIS. THP uptake was also seen in flat malignant lesions such as bladder cancer invasion into the prostatic urethra, and in benign lesions such as chronic cystitis and urothelial hyperplasia.. The present method can be useful to find easily and macroscopically the location of flat malignant lesions such as CIS.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Biopsy; Carcinoma in Situ; Cystoscopy; Doxorubicin; Female; Humans; Immunosuppressive Agents; Male; Microscopy, Fluorescence; Middle Aged; Mucous Membrane; Neoplasm Staging; Sensitivity and Specificity; Urinary Bladder; Urinary Bladder Neoplasms

The patient was a 63-year-old woman who had been diagnosed with advanced bladder cancer with renal dysfunction and bilateral bulky pulmonary metastasis. Initially, the primary lesion was resected and the implantation of an infusion catheter and port system was performed. Following surgery, she received intermittent intra-arterial (IA) low-dose CDDP chemotherapy via the infusion port and concurrent bronchial arterial infusion and radiation (40 Gy for the left lung). About 3 months later, the right and left lung metastases were reduced 63% and 91%, respectively, and a right lower lobectomy was performed. CDDP was administered through the outpatient clinic ever since. From January 2001, we began to use docetaxel (TXT) for CDDP because of continuous grade 2 nausea and appetite loss. There were no adverse effects by TXT. Repeated IA chemotherapy was discontinued from June 2001 because of neurological symptoms. In September 2001, a left skull base metastasis was detected and was treated by radiation 40 Gy. In November 2002, a left patella metastasis appeared and was treated by IA chemotherapy with angiotensin II and radiation 30 Gy. We confirmed that multidisciplinary treatment contributed to her approximately 3-year survival with good QOL. The cancers in both lungs could be kept under control until her death.

Topics: Antineoplastic Combined Chemotherapy Protocols; Bone Neoplasms; Carcinoma, Transitional Cell; Cisplatin; Combined Modality Therapy; Docetaxel; Doxorubicin; Female; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Lung Neoplasms; Lymph Nodes; Lymphatic Metastasis; Middle Aged; Quality of Life; Taxoids; Urinary Bladder Neoplasms

A 75-year-old man was admitted to our hospital for treatment of superficial bladder tumor. Transurethral resection (TUR) was performed and histopathological examination revealed a transitional cell carcinoma (G2). Despite one course of post-TUR bladder instillation therapy using pirarubicin hydrochloride, carcinoma in situ (CIS) was found 4 months later. CIS disappeared after another course of bladder instillation therapy using BCG; but, it recurred a month later. BCG bladder instillation therapy was performed again, and no malignant cells were detected in the urinary tract thereafter. Four months later, lung metastasis was diagnosed and an MVAC regimen (cisplatin, methotrexate, vinblastin adriamycin) was administered. However, anaphylactic shock was induced by intravenous injection of pirarubicin hydrochloride, so this therapy was stopped in the middle of the second course. Even though the lung metastasis disappeared once after the same MVAC treatment, it recurred the following year. At that time, 3 courses of a cisplatin-methotrexate-vinblastin regimen were administered, and a complete response was achieved.

Topics: Administration, Intravesical; Aged; Anaphylaxis; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Drug Administration Schedule; Humans; Injections, Intravenous; Male; Methotrexate; Urinary Bladder Neoplasms; Vinblastine

The objective of this study was to retrospectively investigate the effectiveness of transurethral resection of bladder tumor (TURBT) and intravesical instillation therapy for stage T1, grade 3 (T1G3) transitional cell carcinoma (TCC) of the urinary bladder.. Between January 1995 and December 1997, 97 patients with T1G3 TCC of the urinary bladder were treated by TURBT and adjuvant intravesical instillation with bacillus Calmette-Guérin (BCG) or other anticancer agents. The recurrence-free survival rates were evaluated according to several clinicopathological factors. The cases that progressed to muscle invasive disease were also analysed.. In this series, the median follow-up period was 25 months (range, 5- 41) after the initial TURBT. Intravesical recurrence was noted in 44 patients (45%), and the 1, 2, and 3 year recurrence-free survival rates were 72%, 58%, and 42%, respectively. Multivariate analyses revealed that the risk of intravesical recurrence was significantly higher for patients who did not receive BCG therapy, irrespective of age, gender, tumor size, multiplicity, pathological stage, concomitant carcinoma in situ, and lymphovascular involvement. Moreover, after a median of 10 months, disease progression occurred in seven patients (7%), of which only one patient was treated by BCG therapy after initial TURBT.. These findings suggest that intravesical instillation with BCG combined with TURBT is an effective conservative treatment for T1G3 TCC of the bladder. Patients with negative prognostic factors should be treated by BCG rather than other anticancer agents after TURBT.

Topics: Adjuvants, Immunologic; Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; BCG Vaccine; Carcinoma, Transitional Cell; Combined Modality Therapy; Disease-Free Survival; Doxorubicin; Female; Humans; Male; Middle Aged; Mitomycin; Multivariate Analysis; Neoplasm Recurrence, Local; Neoplasm Staging; Proportional Hazards Models; Retrospective Studies; Risk Factors; Urinary Bladder Neoplasms

Superficial bladder transitional cell carcinoma is aggressive and tends to recurrence after operation. In order to prevent the relapse of bladder neoplasms,this study was designed to explore the effect of intravesical instillation of pirarubicin (THP) together with polyvinylpyrrolidone (PVP) on patients with superficial bladder cancer who had undergone surgical operation.. A total of 34 cases were enrolled from October 1999 to May 2002. After one week of operation, pirarubicin (20 mg) dissolved in 10 ml normal saline plus 20 ml PVP was instilled into bladder, and was retained for 60 minutes. In the following 7 weeks, intravesical instillation of pirarubicin was administered once a week. Subsequently it was done bi-monthly, finally once a month for 6 months.. Follow-up was performed for 5-26 months (mean:17.2 months). Among the 34 cases, recurrence was found in 2 cases (5.8%),bladder irritation in 6 cases (17.6%) and hematuria in 4 cases (11.7%) as well.. Intravesical instillation of THP/PVP is effective for prevention of postoperative recurrence of superficial bladder cancer with fewer side effects. Further study is needed for wide use in such way.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Pharmaceutic Aids; Postoperative Period; Povidone; Recurrence; Urinary Bladder Neoplasms

A 68-year-old man was admitted to our hospital for treatment of a recurrent bladder tumor. Histological examination performed after transurethral resection of the bladder tumor (TUR-BT) revealed a nephrogenic adenoma without any evidence of malignancy. After TUR-BT, total cystectomy was performed to control severe irritative symptoms. Prolonged cystitis and intravesical pirarubicin therapy after TUR-BT may have played an etiological role. Our case is the 25th case of nephrogenic adenoma of the bladder reported in the Japanese literature.

Topics: Adenoma; Administration, Intravesical; Aged; Antibiotics, Antineoplastic; Cystectomy; Cystitis; Diagnosis, Differential; Doxorubicin; Humans; Male; Urinary Bladder Neoplasms

We report a case of regionally metastatic pure squamous cell carcinoma of the urinary bladder successfully treated with combined radiation and chemotherapy in a 46-year-old man. Clinical staging was T3bN2M0. The patient received 50 Gy external radiation combined with intraarterial and systemic chemotherapy. Pathological complete response was found both in bladder and regional lymph nodes when he underwent radical cystectomy and lymph node dissection. The patient has been alive without evidence of disease for two years postoperatively.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Cisplatin; Combined Modality Therapy; Doxorubicin; Humans; Lymph Nodes; Lymphatic Metastasis; Male; Middle Aged; Peplomycin; Radiotherapy Dosage; Urinary Bladder Neoplasms

The prognosis of patients with bladder cancer with pelvic lymph node metastasis is poor, and only 30% of them have been reported to achieve 5- and 10-year survival rates. Prognosis of the patients with pelvic lymph node metastasis larger than 5 cm (N3) is especially poor. and no patient has been reported to have survived more than 3 years. The authors report the successful treatment of two patients with pelvic N3 bladder cancer by internal iliac arterial infusion chemotherapy combined with whole-pelvis irradiation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Humans; Iliac Artery; Infusions, Intra-Arterial; Lymphatic Metastasis; Male; Methotrexate; Neoplasm Staging; Urinary Bladder Neoplasms

Prognostic factors for survival in transitional cell carcinoma of the upper urinary tract have been extensively evaluated, but detailed analyses of patterns of bladder recurrence after surgery have been rare.. The outcome and tumor recurrence of 93 patients with transitional cell carcinoma of the upper urinary tract surgically treated between 1975 and 1999 were reviewed, retrospectively. Disease-specific survival by pathologic stage and grade were analyzed by the Kaplan-Meier. Prognostic factors for survival and bladder recurrence were examined by univariate and multivariate analysis.. The 5-year disease-specific survival rates of the patients with pTa, T1 and T2 were 92.9%, 100% and 88.9%, respectively. However, that of the pT3 patients was 61.9% and the median survival of the pT4 cases was only 7 months. Bladder recurrence was seen in 40 cases and recurrences occurred within 1 year in 32 of these patients. The stage and grade of metachronous bladder tumors usually resembled those of primary tumors, but invasive recurrences were seen in 19% of recurrent cases with primary pTa, pT1 tumors. The significant prognostic factor for survival was pathologic stage (pT3, pT4), but no significant variables were detected for bladder recurrence by multivariate analysis.. The prognosis of pT3, pT4 patients is poor and effective systemic adjuvant therapy is necessary. Invasive bladder recurrence occurred in 19% of patients with superficial primary tumors. As no significant prognostic variables for bladder recurrence were identified, careful follow up for bladder recurrence is important even if the primary tumors are non-invasive.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; BCG Vaccine; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Female; Humans; Male; Methotrexate; Middle Aged; Neoplasm Recurrence, Local; Prognosis; Retrospective Studies; Survival Analysis; Urinary Bladder Neoplasms; Vinblastine

A 70-year-old man developed a skin rash in his right lower abdominal wall after an intra-arterial infusion chemotherapy for carcinoma of the bladder. A CT with a direct infusion of contrast material via the implanted reservoir showed a marked enhancement of the right inferior epigastric artery and a significantly large artery in the right inguinal region. Radionuclide imaging with a direct infusion of Tc-99m macroaggregated albumin (MAA) revealed an abnormal accumulation in the right anterior abdominal wall. These findings implied a collateral pathway from the right internal iliac artery to the right inferior epigastric artery, i.e., the corona mortis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Collateral Circulation; Doxorubicin; Drug Eruptions; Epigastric Arteries; Humans; Iliac Artery; Infusions, Intra-Arterial; Male; Technetium Tc 99m Aggregated Albumin; Tomography, X-Ray Computed; Urinary Bladder Neoplasms

To assess the validity of the prophylactic use of pirarubicin ([2'R]-4-O-tetrahydropyranyl-doxorubicin) immediately after transurethral resection of bladder tumour (TURBT), using pharmacodynamic studies.. The study included 20 consecutive patients with superficial bladder cancer. Pirarubicin (30 mg/50 mL or 30 mg/100 mL, 10 patients each) was instilled immediately after TURBT and retained in the bladder for 1 h. Blood samples were obtained before and at 15, 30, 60 and 120 min after the instillation. After retaining the drug for 1 h all the intravesical fluid was collected and assayed for pirarubicin.. The plasma pirarubicin concentration in those receiving either dose was below detectable levels at any time after instillation. The mean recovery rate of pirarubicin in the drained fluid was 73%.. The intravesical instillation of pirarubicin immediately after TURBT caused no detectable plasma concentration and few systemic side-effects.

Topics: Absorption; Administration, Intravesical; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

Resistance to conventional anticancer chemotherapeutic agents remains one of the major problems in the treatment of bladder cancer. Hence, new therapeutic modalities are necessary to treat the drug-resistant cancers. Apo-2 ligand (Apo-2L) is member of the tumor necrosis factor ligand family, and it induces apoptosis in cancer cells. Several cytotoxic anticancer drugs, including Adriamycin (ADR), also mediate apoptosis and may share the common intracellular pathways leading to cell death. We reasoned that combination treatment of the drug-resistant cancer cells with Apo-2L and drugs might overcome their resistance. Here, we examined whether bladder cancer cells are sensitive to Apo-2L-mediated cytotoxicity and whether Apo-2L can synergize with ADR in cytotoxicity and apoptosis against bladder cancer cells. Recombinant human soluble Apo-2L (sApo-2L), which carries the extracellular domain of Apo-2L, was used as a ligand. Cytotoxicity was determined by a 1-day microculture tetrazolium dye assay. Synergy was assessed by isobolographic analysis. Human T24 bladder cancer line was relatively resistant to sApo-2L. Treatment of T24 line with combination of sApo-2L and ADR resulted in a synergistic cytotoxic effect. Synergy was also achieved in the ADR-resistant T24 line (T24/ADR), two other bladder cancer lines, and three freshly derived human bladder cancer cell samples. In addition, T24 cells were sensitive to treatment with sApo-2L combined with epirubicin or pirarubicin. The synergy achieved in cytotoxicity with sApo-2L and ADR was also achieved in apoptosis. Intracellular accumulation of ADR was not affected by sApo-2L. Incubation of T24 cells with sApo-2L down-regulated the expression of glutathione S-transferase-pi mRNA. This study demonstrates that combination treatment of bladder cancer cells with sApo-2L and ADR overcomes their resistance. The sensitization obtained with established ADR-resistant bladder cancer cells and freshly isolated bladder cancer cells required low subtoxic concentrations of ADR, thus supporting the in vivo potential application of combination of sApo-2L and ADR in the treatment of ADR-resistant bladder cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; Apoptosis Regulatory Proteins; Bisbenzimidazole; Down-Regulation; Doxorubicin; Drug Synergism; Epirubicin; Fluorescent Dyes; Glutathione S-Transferase pi; Glutathione Transferase; Humans; Isoenzymes; Membrane Glycoproteins; Recombinant Proteins; RNA, Messenger; Staining and Labeling; TNF-Related Apoptosis-Inducing Ligand; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Urinary Bladder Neoplasms

A case of transitional cell carcinoma of the bladder in a 18-year-old female is presented. Cystoscopic examination revealed a papillary tumor on the left lateral wall. Histopathology of the excised tumor showed transitional cell carcinoma, G1 > 2, pT1a. Recurrence has not been observed for about 1 year, after intravesical pirarubicin therapy.

Topics: Administration, Intravesical; Adolescent; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Doxorubicin; Female; Humans; Neoplasm Staging; Treatment Outcome; Urinary Bladder Neoplasms

We investigated the clinical usefulness of individualization of chemotherapeutic regimen in neoadjuvant intra-arterial chemotherapy for locally invasive bladder cancer. Anticancer drugs were selected according to the results of an in vitro chemosensitivity test (collagen matrix assay or succinic dehydrogenase inhibition test). Nine patients with locally invasive bladder cancer received 1 to 4 courses of neoadjuvant intra-arterial chemotherapy, followed by radical cystectomy. Histopathological responses in the cystectomized specimens were grade 3 in 3 cases, grade 2 in 2, grade 1b in 2 and no response in 2. Pathologically, a complete response and downstaging were observed in 3 and 4 cases, respectively. Seven of the 9 patients were alive no evidence of disease with a mean follow-up period of 38.9 months, whereas 2 patients died of metastasis within 2 years. Six of the 7 patients who showed a complete response or down staging have been free of recurrence. These findings suggest that our chemotherapeutic strategy may improve the prognosis for locally invasive bladder cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Drug Administration Schedule; Drug Screening Assays, Antitumor; Epirubicin; Etoposide; Female; Fluorouracil; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Mitomycin; Peplomycin; Prognosis; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Vinblastine

Internal iliac arterial infusion (IA) chemotherapy has been used clinically for locally invasive bladder cancer, but there have been no experimental studies to actually demonstrate whether IA is more effective than intravenous infusion (i.v.) chemotherapy in this setting.. We compared the effects of IA and i.v. using a rabbit invasive bladder cancer model. A 0.2 mL suspension containing 2 x 10(6) VX2 cancer cells was inoculated into the posterior submucosa of the bladder. Two weeks later the rabbits were divided into 3 treatment groups of 8 rabbits each: controls, a group treated with IA consisting of 10 mg/kg carboplatin and 1 mg/kg pirarubicin once a week for 3 weeks (days 14, 21, and 28), and the third treated with the same regimen intravenously.. All bladder tumors of the rabbits in the IA group decreased in size, and 3 of the tumors totally disappeared (37.5%). There was also no evidence of lung metastasis. All tumors in the rabbits in the i.v. treatment group increased in size (tumor volume of IA vs. i.v., P = 0.008) and 2 rabbits had lung metastases. All tumors of the control group increased in size and all rabbits had lung metastases. The concentrations of platinum and pirarubicin in the bladder tumors were significantly higher in the IA treatment group than those in the i.v. treatment group at time points from 5 to 10 minutes (P < 0.05) after drug infusion.. The antitumor effect of IA may be due to higher drug concentrations in the early stage after drug delivery, and the initial circulation of high concentrations of drugs may be the most important factor in suppressing tumor growth.

Topics: Animals; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Doxorubicin; Iliac Artery; Infusions, Intra-Arterial; Infusions, Intravenous; Lung Neoplasms; Male; Neoplasm Invasiveness; Platinum; Rabbits; Urinary Bladder Neoplasms

To establish a method for reasonable clinical use of adriamycin (ADM) and pirarubicin (THP) in the intravesical chemotherapy for superficial bladder cancer, intracellular concentrations of these drugs were examined in culture cell lines (T-24, T-24/ADM and FHS736b1) with variable durations of contamination. The intracellular concentration of THP showed a plateau at 15-30 min. contamination in T-24, and in T-24/ADM, and showed the time dependence of contamination in FHS736b1, human normal bladder mucosa cell line. The intracellular concentration of ADM showed the time dependence of contamination in T-24, T-24/ADM and FHS736b1. And these concentrations of THP were 20 times higher than those of ADM. In conclusion, it seems better that THP was retained for 5-15 min. in the bladder in the intravesical chemotherapy, from the point of view of drug efficacy and preventing side effects. And it seems good that ADM was retained for more than 30 min. in the case with drug sensitive tumors.

Topics: Antibiotics, Antineoplastic; Cell Line; Doxorubicin; Humans; Mucous Membrane; Tumor Cells, Cultured; Urinary Bladder; Urinary Bladder Neoplasms

We evaluated the usefulness of in vitro tumor culture system using a specialized collagen gel matrix (CGM assay) as a chemosensitivity test.. Chemosensitivity results of CGM assay were compared with other in vivo and in vitro assays on an implantable murine bladder tumor cell line (MBT-2). In addition we investigated the possibility of the clinical use of CGM assay using clinical specimens obtained from urogenital malignant tumor patients by comparing the result with that of the other chemosensitivity test, SDI testing using single cells (conventional SDI test). Methods of CGM assay were as follows. Tumor tissues on the collagen gel matrices were incubated under the existence of anticancer drugs following 4 days preculture. Drug sensitivities were evaluated by counting the number of viable cells adjusted to the tumor weight.. Inhibition rates in MBT-2 were high in the order of mitomycin C, cisdiamminedichloroplatinum (II), (2"R)-4'-0-tetrahydropyranyl adriamycin. Four of 6 anticancer drugs were decided as chemosensitive drugs. These results corresponded to the results of the antitumor effects on subcutaneously transplanted MBT-2 in vivo, moreover was correlated well with those of the conventional SDI test. Twenty of 22 cases, including 11 of 13 bladder cancer cases, 1 of 3 renal cancer cases, 2 of 3 testicular cancer cases and 1 of 1 adrenal cortical cancer cases, were evaluable in the clinical study of the CGM assay. Corresponding rates between the results of the CGM assay and those of the conventional SDI test performed simultaneously in 12 cases were excellent for each anticancer drug.. This CGM assay can serve as an effective tool for chemosensitivity testing because of its convenience and high evaluable rate.

Topics: Animals; Antineoplastic Agents; Bleomycin; Carcinoma, Renal Cell; Cisplatin; Collagen; Culture Media; Doxorubicin; Drug Screening Assays, Antitumor; Etoposide; Female; Humans; Kidney Neoplasms; Mice; Mice, Inbred C3H; Mitomycin; Urinary Bladder Neoplasms; Vinblastine

The effective and less side effect retention time of intravesical instillation therapy with Pirarubicin (THP) was investigated for the treatment of urinary bladder tumor. Fifty-seven cases of urinary bladder tumor were treated by intravesical instillation therapy with THP (20 mg/40 ml) a total of 6 times, with the first instillation at the time of surgery and the other 5 at a rate of three times a week thereafter. The retention time was 30 minutes, and it was allowed to last 10 or 60 minutes for comparison in some cases. Tumor and normal tissue were examined in the first instillation, and normal tissue in the sixth instillation. Infiltration to the bladder wall of THP was observed under fluorescence microscopy. Although the amount of tumor uptake was larger than normal tissue in the first instillation, no satisfactory infiltration was obtained. Repeated administration of THP with the retention time of 30 minutes enhanced the uptake and increased the infiltration in many cases, and side effects were scarcely noted. Retention time of 10 minutes was unsatisfactory, while the retention time of 60 minutes was discontinued in the early stage of treatment due to severe irritative bladder symptoms. Therefore, a retention time of 30 minutes is adequate in the case of repeated administration of THP in a short period.

Topics: Administration, Intravesical; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Urinary Bladder; Urinary Bladder Neoplasms

We studied the efficacy of glutathione in the prevention of CDDP-induced neurotoxicity. Nine patients with muscle-invasive bladder cancer were treated with intra-arterial THP and CDDP chemotherapy plus radiotherapy. Glutathione was given at a dose of 1,500 mg/m2 before CDDP administration and at a dose of 600 mg/body on days 2 to 4. The CR rate of 9 patients was 89%, and 2 of the 9 patients developed grade 1 neurotoxicity. These patients were then compared with 15 patients treated with the same regiment but without glutathione. The two groups did not differ in CR rate (89% vs 87%), but the incidence of neurotoxicity of patients with glutathione was significantly lower than that of patients without glutathione (22% vs 73%).

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Female; Glutathione; Humans; Male; Middle Aged; Nervous System Diseases; Sensation; Urinary Bladder Neoplasms

The object of this study is to evaluate the usefulness of the ATP sensitivity assay for appropriate selection of anticancer drugs for prophylactic bladder instillation therapy in patients with superficial bladder cancer.. The ATP assay was performed using the method reported previously. The anticancer drugs examined were ADM, MMC, THP-ADM and EPI. The 5-year rate of non-recurrence in group A (32 cases) which had been treated using the results of ATP assay, was compared with that of group B (37 cases), for which the ATP assay was not performed.. The most sensitive anticancer drug was THP-ADM. The 5-year rate of non-recurrence in group A (80.9%) was significantly higher than that in group B (39.4%) (p < 0.001). Tumor recurrences in group A was observed within 2 years post-operatively in all cases. When the ATP assay was re-performed in 3 cases with recurrent disease, altered antitumor sensitivity was observed.. These findings suggested that ATP assay was useful for choosing effective anti-cancer drugs for prophylactic instillation, especially for patients with primary or solitary tumor, grade 2 disease or tumor of a certain size (> or = 1 cm). It also appeared that the ATP assay should be performed for patients with primary superficial bladder cancer as a screening test for the selection of drugs for prophylactic instillation therapy.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Agents; Doxorubicin; Drug Screening Assays, Antitumor; Epirubicin; Female; Humans; Male; Middle Aged; Mitomycin; Neoplasm Recurrence, Local; Urinary Bladder Neoplasms

The patient was a 71-year-old woman. Two years ago right nephrectomy was performed by a general surgeon at the diagnosis of right renal cell carcinoma. However, the pathological report was transitional cell carcinoma (TCC) of the right renal pelvis, Grade II. She developed chronic renal failure and received hemodialysis once a week. The recurrence of bladder tumor was recognized and she was transferred to our hospital. Transurethral resection of bladder tumor (TUR-Bt) and right ureterectomy with a bladder cuff were performed. Also intravesical instillation of pirarubicin was done after the operation. No side effects or elevation of serum pirarubicin level were observed.

Topics: Administration, Intravesical; Aged; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Cystectomy; Doxorubicin; Female; Humans; Kidney Failure, Chronic; Renal Dialysis; Urinary Bladder Neoplasms

The effect in combination therapy of high energy under water shock waves (HESW) and anticancer drugs for subcutaneous murine bladder cancer (MBT-2) in C3H/He mice was examined. HESW were generated by piezoceramics and directed to the subcutaneous tumor under ultrasonographic guidance. The subcutaneous tumor was exposed to HESW alone (100 MPa, 1000 shots, 3 shots/sec) or in combination with pirarubicin (THP, 5 mg/kg, i.p.) or carboplatin (CBDCA, 40 mg/kg, i.p.). Remarkable bleeding in the tumor was seen immediately after the exposure of HESW, destroyed cancer cells appeared after one day and wider and clearly bordered tumor necrosis was observed after three days. In the HESW alone therapy, tumor growth of smaller tumors (< 10 mm3, n = 8) were suppressed more than that of larger tumors (10-35 mm3, n = 11). Tumor growth ratio on the 14th day (TGR 14) (tumor volume on the 14th day/tumor volume on the 1st day) was examined in larger tumors. TGR 14 were 152.2 +/- 146.6 (mean +/- S.D.) in the control (n = 20), 116.3 +/- 98.9 in HESW alone (n = 11), 75.5 +/- 110.7 in THP alone (n = 8), 90.7 +/- 61.6 in CBDCA alone (n = 6), 75.8 +/- 72.2 in THP + HESW (n = 9), 3.2 +/- 4.5 in CBDCA + HESW (n = 8) and 0.8 +/- 1.3 in CBDCA + HESW 2 cycles (n = 9). Evident suppression on tumor growth was more often seen in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.01). The cumulative survival rates were higher in CBDCA + HESW and CBDCA + HESW 2 cycles therapies than in the other therapies (p < 0.05). Tumor metastasis was seen only in the lungs of the dead mice after 19 days. Lung metastases were seen in 1/6 in the control, 0/5 in HESW alone, 1/5 in CBDCA alone, 0/6 in CBDCA + HESW and 1/5 in CBDCA + HESW 2 cycles therapy, respectively.

Topics: Animals; Antibiotics, Antineoplastic; Carboplatin; Combined Modality Therapy; Doxorubicin; Female; Mice; Mice, Inbred C3H; Neoplasm Transplantation; Ultrasonic Therapy; Urinary Bladder Neoplasms

Intravesical instillation of tetrahydropyranyl-adriamycin (THP) and cytosine arabinoside (CA) was performed on 42 patients with superficial bladder cancer after transurethral resection (TUR) for the purpose of prophylaxis of recurrence. The instillation was carried out with 30 mg of THP dissolved in 30 ml of distilled water and 200 mg of CA (total 40 ml). These drugs were instilled 7 times for the initial 2 weeks after TUR, and then 7 times every two weeks, 8 times every month, and 4 times every three months. Cases eligible for evaluation of efficacy were 38 out of 42 patients. The cumulative non-recurrence rate at one, two and three years were 94%, 84% and 75%, respectively. These high non-recurrence rates were demonstrated regardless of the size, number and pathological grade of the tumors. Severe bladder irritability was demonstrated in 8 (19%) of 42 patients, but generalized side effects were not seen in any case. The reformed regimen with 20 mg of THP in 30 ml of physiological saline solution was then performed on trial in several patients and there were no severe symptoms. THP combined with CA seems to be remarkably effective for the prophylaxis of recurrence, while a high concentration of THP in distilled water may lead to severe bladder irritability.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Cytarabine; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Neoplasm Recurrence, Local; Postoperative Care; Prognosis; Remission Induction; Urinary Bladder Neoplasms

From 1983 to 1988, 20 patients (group A: 3 stage T1, 4 stage T2 and 13 stage T3-4 tumors) with bladder cancer were treated with single injection of CDDP (150-200 mg/body), and 28 patients (group B: 4 stage T1, 9 stage T2 and 15 stage T3-4 tumors) were treated twice with injection of CDDP (100 mg/m2) and THP-ADM (40 mg/m2) mixture from the internal iliac artery. As a rule, one half of the agents was equally given for the both sides, while 75% dose was given to the tumor side to the case with unilateral localized tumors. Then total or partial cystectomy was followed. When residual invasive cancer was pathologically present in operative specimens, patients underwent three to six courses of adjuvant chemotherapy including CDDP. Clinical response rate (CR+PR) to the intra-arterial chemotherapy in group A and B were 39% and 62%, respectively. Pathological response rate (grade 3 and grade 4 by Oboshi and Shimozato classification) were 17% in both group. After total cystectomy, the 2-year cancer specific survival rates of 17 patients in group A and 22 patients in group B were 75% and 59%, respectively. The 2-year cancer specific survival rates of 8 patients in group A and 10 patients in group B with pT3b were 63% and 54%, respectively. No cancer death occurred thereafter in the patients of group A during another three years. The 3-year cancer specific survival rate of 9 patients after partial cystectomy (3 in group A, 6 in group B) was 86%.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Cystectomy; Doxorubicin; Female; Humans; Iliac Artery; Injections, Intra-Arterial; Male; Middle Aged; Urinary Bladder Neoplasms

The patient was a 70-year-old male with invasive bladder cancer. We performed intermittent arterial infusion (ITI) combined with alteration of blood flow in the bladder wall using the contralateral arterial embolization. As for anti-tumor agents, cisplatin (CDDP) 10mg and pirarubic in (THP) 10 mg were selected, and were injected every week for 11 times. Complete response (CR) was noted by cystoscopy and biopsied specimen. In our conclusion. ITI was useful for the treatment of bladder cancer.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Chemoembolization, Therapeutic; Cisplatin; Doxorubicin; Drug Administration Schedule; Humans; Infusion Pumps, Implantable; Infusions, Intra-Arterial; Male; Neoplasm Invasiveness; Regional Blood Flow; Remission Induction; Urinary Bladder Neoplasms

Tissue concentration of THP-ADM was analysed after the administration of THP-ADM with or without exposure of high energy underwater shock waves (SW) to rabbit bladder VX2 cancer. THP-ADM was administered intravenously (2 mg/kg) or into the urinary bladder (10 mg/body). After the administration of THP-ADM, SW was exposed (6,000-10,000 shots) to VX2 bladder cancer or normal bladder tissue. One hour later, THP-ADM tissue concentration was measured by high performance liquid chromatography method. In intra-venous group, THP-ADM concentration of cancer tissue was significantly lower (p < 0.02) in SW group than that of non-SW group. In bladder instillation group, THP-ADM concentration of normal bladder tissue was significantly higher (p < 0.02) in SW group than that of non-SW group and the average concentration of cancer tissue was higher about three times in SW group than that of non-SW group.

Topics: Administration, Intravesical; Animals; Antibiotics, Antineoplastic; Chromatography, High Pressure Liquid; Combined Modality Therapy; Doxorubicin; Male; Rabbits; Ultrasonic Therapy; Urinary Bladder; Urinary Bladder Neoplasms

Bilateral sciatic nerve paralysis developed in two patients with invasive bladder cancer following intraarterial infusion of cisplatin (CDDP) and 4'-0-tetrahydropyranyladriamycin (THP) as preoperative adjuvant chemotherapy. Balloon catheters were selectively inserted into both internal iliac arteries, and CDDP 100 mg/m2 and THP 40 mg/m2 were administered under balloon occlusion. Pain of lower extremities developed soon after infusion and was gradually followed by paralysis. One patient recovered from paralysis partially after 4 months, but the other patient didn't recover. The use of balloon catheters resulted in an excessive concentration of chemotherapeutic agents with the adverse action on the sciatic nerves.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Paralysis; Peripheral Nervous System Diseases; Sciatic Nerve; Urinary Bladder Neoplasms

A 67-year-old man was admitted with the chief complaint of macroscopic hematuria in May 1990. Endoscopic examination showed a bladder tumor at the right lateral wall. Biopsy proved Grade 3 transitional cell carcinoma. Transurethral ultrasonogram, CT scan and MRI revealed T2-T3a invasive bladder cancer. Preoperative chemotherapy by balloon occluded arterial infusion using CDDP 75 mg, etoposide 100 mg and pirarubicin 50mg was performed. Repeat endoscopy after chemotherapy revealed significant necrotic change of tumor. Radical cystectomy and pelvic node dissection with ileal conduit urinary diversion were performed in August 1990. Significant necrosis of bladder wall was observed and no cancer cells were recognized in the cystectomy specimen. The patient is alive at this writing with no evidence of disease for 2 years.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Chemotherapy, Adjuvant; Cisplatin; Doxorubicin; Etoposide; Humans; Infusions, Intra-Arterial; Male; Preoperative Care; Remission Induction; Urinary Bladder; Urinary Bladder Neoplasms

The case was a 63-year-old male with the chief complaint of hematuria. A local doctor made the diagnosis of a bladder tumor (egg-sized) on the basis of the results of ultrasonography. CT-scan and cystoscopy. He was thus referred to our Department for treatment. Histopathological study of the biopsied tumor specimen revealed that the tumor was a squamous cell carcinoma. The bilateral internal iliac arteries were occluded for 48 hours, and 100 mg of CDDP and 40 mg of THP were arterially infused. After 7 days, hematuria disappeared, as did the tumor 5 weeks after treatment. No malignancy was noted from histological examination of a biopsy specimen obtained from the cured cancer region using a cystoscope. Since then, there was no recurrence for 12 months. Thus, this approach is thought to be an effective treatment for primary bladder cancer.

Topics: Antineoplastic Combined Chemotherapy Protocols; Catheterization; Cisplatin; Doxorubicin; Humans; Iliac Artery; Infusions, Intra-Arterial; Male; Middle Aged; Remission Induction; Urinary Bladder Neoplasms

From our experimental study, an instillation of THP for 5 minutes was attempted in 23 patients with superficial bladder tumors. THP (30 mg dissolved in 50 ml of distilled water) was instilled into the bladder 6 times every 48 hours. Of 23 patients, 9 (39%) showed complete disappearance of the bladder tumors, while partial disappearance (more than 50% tumor reduction) was observed in 3 cases (13%). Therefore the overall response rate was 52%. Neither urinary frequency nor hematuria was observed in all the cases, while painful urination was observed in 3 cases (13%). This newly designed bladder instillation therapy was effective against superficial bladder tumors with low incidence of local side effects.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Treatment Outcome; Urinary Bladder Neoplasms

From January, 1987 through January, 1990, partial cystectomy was performed for 4 (18%) of 22 patients with invasive bladder cancer who had received neoadjuvant intra-arterial chemotherapy. The criteria of patient selection for partial cystectomy were: 1) invasive bladder cancer showing good response (greater than or equal to PR) to neoadjuvant chemotherapy, 2) solitary or localized tumor that can be eradicated by segmental resection, and 3) tumor of stage T3 or less. As a rule, cisplatinum (100 mg/m2) and THP-adriamycin (40 mg/m2) were administered selectively to the internal iliac artery by one-shot infusion. Concurrently, sodium thiosulfate (10 g/m2), a neutralizing agent against cisplatinum, was administered intravenously. All four patients had achieved clinical complete responses by one or two courses of intra-arterial chemotherapy, and then underwent partial cystectomy with pelvic lymphadenectomy. Pathological examination revealed pTONO in two patients, and the remains were pT3aNO and pT3bN1. After the mean follow-up of 24 months, three of them are alive with no evidence of disease, and also with normal bladder and sexual functions. However, one with pT3bN1 tumor underwent total cystectomy 5 months later for local recurrence (pT4b) and had died of cancer 18 months later. Neoadjuvant intra-arterial chemotherapy followed by partial cystectomy should be the most applicable conservative therapy with high radicality for invasive bladder cancer, when: 1) the patient has localized invasive cancer showing good response (greater than or equal to PR) to neoadjuvant chemotherapy, 2) the tumor is stage T3a or less and without findings of tentacular invasion (INF gamma) by pre-operative biopsy, and 3) pre-operative multiple biopsy is performed as deeply as possible along the prearranged incision line.

Topics: Aged; Antineoplastic Agents; Cisplatin; Combined Modality Therapy; Cystectomy; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Urinary Bladder Neoplasms

Focused high-energy shock waves (6,000 to 10,000 shots) were targeted under ultrasound guidance onto implanted urinary bladder cancer in rabbits to elucidate its effect. Although only focal necrosis of the tumor was seen following 6,000 to 10,000 shots daily for 3 days or following chemotherapy (THP-adriamycin) alone, almost total tumor necrosis was observed following a combined shock-wave therapy for one day and THP-adriamycin administration, demonstrating an additive and/or synergetic effect on rabbit urinary bladder cancer.

Topics: Animals; Combined Modality Therapy; Doxorubicin; Male; Rabbits; Ultrasonic Therapy; Urinary Bladder Neoplasms

We examined the effect of dimethylsulfoxide (DMSO) on the absorption of a chemotherapeutic drug instilled into the bladder. Female Wistar rats with bladder tumors underwent intravesical instillation of normal saline (S group) or 50% DMSO (D group) prior to the administration of pirarubicin (tetrahydropyranyl-Adriamycin). The absorption of pirarubicin was estimated histologically by observing its fluorescence. In the S group, fluorescence of pirarubicin was observed only in the epithelial layer of normal or hyperplastic regions and in the cells of superficial layers of the tumor. In the D group fluorescence was observed in the entire bladder wall of normal or hyperplastic regions and extended to deeper regions of the tumors than in the S group. These findings indicate enhancement of the absorption of pirarubicin by pretreatment with DMSO.

Topics: Absorption; Animals; Dimethyl Sulfoxide; Doxorubicin; Female; Microscopy, Fluorescence; Rats; Rats, Inbred Strains; Urinary Bladder; Urinary Bladder Neoplasms

The efficacy and safety of Pirarubicin (THP), administered by intravesical instillation, have been studied in recurrent multiple superficial bladder cancer patients and patients who tested positive by urine cytology but lacked protuberant legions (CIS). The average age and range of the 19 patients (M 15, F4) studied were 63.3 (37-84). Twelve patients had protuberant, multiple cancer and 7 patients had CIS. Sixteen of the cases were recurrent disease. Twenty mg THP, delufed in 40 ml of 5% glucose solution were instilled for 2 hours once or twice a week. Each patients received 8 treatments. One week after the last treatment, the therapeutic result was evaluated on the bases of cystoscopy and urine cytology. Before and after administration, CBC and biochemical blood tests were run. Nine of the 12 patients (75%) with multiple recurrent tumor and all the 7 patients with CIS showed complete response. The total outcome for CR was 84.2% in this study. Intravesical instillation with THP did not cause any serious side effects.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antibiotics, Antineoplastic; Carcinoma, Transitional Cell; Doxorubicin; Female; Humans; Male; Middle Aged; Urinary Bladder Neoplasms

Eight patients with bladder cancer and two patients with prostate cancer were given intra-arterial infusion chemotherapy using the reservoir system. The tip of the catheter was inserted through the femoral artery to the common iliac artery and we compressed both femoral arteries during infusion. Five patients with locally advanced bladder cancer and two patients with prostate cancer were evaluated for the clinical and pathological efficacy of the treatment. Clinically, the efficacy of four of the five patients with bladder cancer was CR or PR and pathologically (according to Shimosato's criteria), the efficacy was two in IVb or III, and three in IIb. Clinically, the efficacy in two patients with prostate cancer was CR or PR, and pathologically the efficacy was IVb or IIb. Three patients had complications of the reservoir system. These results suggest that good therapeutic efficacy and an improved quality of life can be obtained by intra-arterial chemotherapy using the reservoir system.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Doxorubicin; Epirubicin; Etoposide; Female; Humans; Infusion Pumps; Infusions, Intra-Arterial; Male; Middle Aged; Prognosis; Prostatic Neoplasms; Urinary Bladder Neoplasms

A chemosensitivity test was carried out on superficial bladder cancers using the trypan blue dye exclusion assay for the purpose of screening chemosensitive drugs for intravesical chemotherapy. Transplantable murine bladder tumor cells (MBT-2) were incubated, in vitro, in the presence of adriamycin (4, 40, 400, 1000 micrograms/ml) as well as verapamil (3, 30, 100, 500 micrograms/ml) at 5% CO2, 37 degrees C for two hours. After cellular viabilities were calculated, MBT-2 cells were inoculated into the hind limbs of mice. The cellular viability was correlated well with the ratio of tumor appearance, tumor growth inhibition and prolongation of survival, and was dose dependent in the adriamycin treated groups. On the other hand, a reduction of cellular viability, tumor growth inhibition and prolongation of survival were seen in the high dose verapamil (100, 500 micrograms/ml) treated groups. Human superficial bladder cancer cells were incubated in the presence of adriamycin, 4'-0-tetrahydropyranyladriamycin, mitomycin C and pepleomycin (1000 micrograms/ml) and/or verapamil (500 micrograms/ml). The reduction rates of cellular viability markedly varied with the kind of anticancer drugs. A reduction of cellular viability of human tumor cells as well as MBT-2 cells was seen in the verapamil treated groups. This rapid and handy assay seems to be useful for the purpose of screening chemosensitive drugs for intravesical chemotherapy.

Topics: Administration, Intravesical; Animals; Antineoplastic Agents; Carcinoma, Transitional Cell; Doxorubicin; Drug Screening Assays, Antitumor; Mice; Mitomycin; Mitomycins; Neoplasm Transplantation; Trypan Blue; Urinary Bladder Neoplasms; Verapamil

Absorption of tetrahydropyranyl adriamycin (THP) administered immediately after transurethral resection of bladder carcinoma (TUR-Bt) has not been reported. In this study, we have examined the absorption of THP and the systemic toxicity in the early post-TUR period. Of 21 patients with bladder carcinoma, 10 had a solitary tumor and 11 multiple tumors. Twenty mg THP in 40 ml of sterile water was intravesically administered on days 1, 3, 5, 7, 14 and 28, and then every 4th week. The THP solution was retained for 2 hours. The blood THP concentration was measured 30 minutes and 2 hours after the intravesical administration on days 1, 7 and 28. No systemic side effects were observed. Thirteen of the 38 (34%) samples contained a detectable level (more than 1 ng/ml) of THP on the post-TUR-Bt on day 1, 8, of 42 (19%) on day 7, and 3 of 18 (17%) on day 28. Altogether, 24 of the 98 (24%) samples contained more than 1 ng/ml THP. The highest blood THP level was 23 ng/ml on day 1. The differences between frequency of detection of blood THP in the samples at 30 minutes and 2 hours were not statistically significant. The difference between average concentration of blood THP of patients with solitary and multiple tumors also was not significant. These results indicate that intravesical THP administration starting within 24 hours after TUR-Bt can not result in significant systemic absorption of THP, and the systemic toxicity can be avoided.

Topics: Absorption; Administration, Intravesical; Aged; Combined Modality Therapy; Doxorubicin; Female; Humans; Male; Middle Aged; Postoperative Period; Urinary Bladder Neoplasms

The treatment with hyperthermia in combination with radiation and intravesical pirarubicin (THP-ADM) was preliminary investigated in 5 patients with urinary bladder carcinoma in situ. Following intravesical administration of 30 mg THP-ADM, external irradiation of 3.0 Gy was delivered to the urinary bladder. Immediately then, hyperthermia using Thermotron RF-8 was performed for 50 min (intravesical temperature: 42-43 degrees C for 35 min). After five courses of the treatment, complete response has been maintained for 6, 8, and 9 months in 3 patients. However, in a patient with complete response, urinary cytology became positive in the 6th month after the treatment. In the remaining patient treatment was interrupted after only 3 courses due to urinary irritation, urinary cytology didn't become negative. The side effects of the combined treatment were limited to the transient symptoms of bladder irritation in all patients and thermal burn in 2 patients. These preliminary results suggest that this combined treatment may represent an effective conservative therapy for patients with urinary bladder carcinoma in situ.

Topics: Administration, Intravesical; Aged; Carcinoma in Situ; Carcinoma, Transitional Cell; Combined Modality Therapy; Doxorubicin; Humans; Hyperthermia, Induced; Male; Middle Aged; Remission Induction; Urinary Bladder Neoplasms

Rats with bladder tumor induced by BBN were treated by intravesical instillation of 0.8 mg of (2"R)-4'-O-tetrahydropyranyladriamycin (THP) (9 rats) or adriamycin (ADM) (8 rats) dissolved in 0.2 ml of distilled water. Thirty minutes later, the bladder was removed surgically. Rats without the tumor received the same treatment of THP (8 rats) or ADM (9 rats). THP and ADM infiltrations to the normal bladder tissue and the tumor were estimated by the use of the photonic microscope system, since both drugs were known to emit characteristic fluorescence. It was found that infiltration of THP to the tumor tissue was more prominent in amounts and deeper than that of ADM, while smaller amounts of THP infiltrated into the normal mucosa compared to ADM. The fact might explain the clinical finding that THP instilled intravesically in half a concentration of ADM showed the same effect on the tumor as ADM. Subsequently, tissue concentrations of THP and ADM were estimated by high performance liquid chromatography. Either THP or ADM was instilled intravesically for 30 minutes to 6 rats with bladder tumor. Similarly, either THP or ADM was instilled in 5 rats without the tumors. Contrary to the result of the photonic microscope system, the tissue concentration of THP was not different from that of ADM not only in the tumor tissues but also in the normal bladder ones. Furthermore, the tissue concentration of both drugs in the normal bladder was higher than that in the bladder tumor.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Administration, Intravesical; Animals; Butylhydroxybutylnitrosamine; Chromatography, High Pressure Liquid; Doxorubicin; Rats; Rats, Inbred ACI; Tissue Distribution; Urinary Bladder; Urinary Bladder Neoplasms

An intravesical chemotherapeutic agent must be capable of being rapidly absorbed by the tumor cells and expressing its activity while undergoing little systemic absorption. A comparative investigation was conducted on (2''R)-4'-O-tetrahydropyranyl-doxorubicin (Adriamycin) (THP) and Adriamycin (ADM) from the above viewpoint using cultured MBT-2 and T-24 cell lines. From in vitro experimental systems, it is surmized that THP is taken up by bladder tumor cells more rapidly than ADM is, and that THP is thus able to exert its effect on the bladder tumor within a shorter time than that required by ADM. This pharmacokinetic advantage of THP was proved in an in vivo experimental system; that is, bladder tumor tissue which was established by implanting MBT-2 cells into the mouse (C3H/He) bladder was found to contain THP in a concentration approximately 1.9 times higher than the concentration of ADM. The amount of systemic absorption from the bladder was small in the case of both THP and ADM. THP should be useful as a new agent for intravesical chemotherapy.

Topics: Administration, Topical; Animals; Carcinoma, Transitional Cell; Doxorubicin; Drug Screening Assays, Antitumor; Female; Mice; Mice, Inbred C3H; Neoplasms, Experimental; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Twenty milligrams of (2"R)-4'-O-tetrahydropyranyladriamycin (THP) was administered intravenously to 14 patients with renal cell carcinoma and 11 with urinary bladder tumor at the start of surgery. Heparinized peripheral blood samples were collected at regular intervals and separated into plasma and blood cell fractions by centrifugation for the estimation of the THP concentration. The THP concentrations in the surgical specimens were also studied. In the tissue of renal cell carcinoma, the nuclear fraction was obtained by fractionation in order to estimate the THP concentration. The THP concentrations of the plasma and blood cell fractions in both renal cell carcinoma and urinary bladder tumor gradually decreased with the lapse of time after administration. In renal cell carcinoma, grade 3 tumors revealed lower tissue and nuclear concentrations of THP than those of grade 1 and 2 tumors. Likewise, the tissue and nuclear concentrations of high-stage tumors were lower than those of low-stage tumors. On the other hand, in urinary bladder tumors, the THP concentrations in the tumors were found to be higher than those in normal urinary mucosa and muscle.

Topics: Carcinoma, Renal Cell; Combined Modality Therapy; Doxorubicin; Humans; Infusions, Intravenous; Kidney Neoplasms; Urinary Bladder Neoplasms

The effect of (2"R)-4'-0-tetrahydropyranyladriamycin (THP), a derivative of adriamycin (ADM) on bladder tumors was evaluated by intravesical instillation. Twenty-one patients with bladder tumors were treated with THP instillation into the bladder. THP (20-30 mg dissolved in 20-40 ml of distilled water) was instilled into the bladder daily for 3 consecutive days as a course. The patients received 2 to 5 courses in total. Of 21 patients, 4 showed complete disappearance of the bladder tumors, while partial response (50% tumor reduction) was observed in 6 cases. Therefore, the overall response rate was 48%. However, with regard to the 16 patients with superficial bladder tumors (Ta, T1) an overall response rate of 63% was noted. The main side effect of THP instillation was temporary bladder irritability, which was seen in 57% of all the patients. No cases revealed systemic side effects. The same antitumor effect was obtained at a lower concentration of THP in the intravesical chemotherapy, compared with that of ADM. It was concluded that THP is a useful drug for the intravesical chemotherapy of bladder tumors.

Topics: Aged; Doxorubicin; Drug Administration Schedule; Female; Humans; Male; Middle Aged; Urinary Bladder; Urinary Bladder Neoplasms

A combination of 50 to 80 mg. per m.2 cis-platinum and 30 to 50 mg. per m.2 doxorubicin or 30 to 50 mg. per m.2 tetrahydropyranyl-doxorubicin instead of doxorubicin was infused into the bilateral internal iliac artery for the treatment of 20 patients with T3 or T4 advanced bladder cancer. Angiotensin II was administered together with these chemotherapeutic agents by means of an infusion pump at a rate of 1.5 to 2.0 micrograms. per minute for 20 minutes for both sides. Among the 20 patients complete (9) and partial (8) responses were obtained after only 1 or 2 courses of this intra-arterial treatment. Histological examination showed severe tumor destruction with no viable cells in 6 and no tumor in 4 of the 15 evaluable cases. Selective enhancement of regional blood flow in the tumor region after intra-arterial infusion of angiotensin II was observed by continuous target arterial 81mkrypton infusion. Intra-arterial chemotherapy with combined angiotensin II may be clinically useful for treatment of primary or metastatic bladder carcinoma.

Topics: Adult; Aged; Angiotensin II; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Transitional Cell; Cisplatin; Doxorubicin; Female; Humans; Infusions, Intra-Arterial; Male; Middle Aged; Regional Blood Flow; Urinary Bladder Neoplasms

A Phase II clinical trial of a new anthracycline, (2''R)-4'-0-tetrahydropyranyladriamycin (THP), was performed in 137 patients with urological malignancies. Out of them, 111 patients were evaluated for tumor responses and 125 patients were evaluated for adverse effects. In cases of intravenous administration, overall response rate was 18.5% (22.2% for bladder cancer, 30.0% for tumors of the renal pelvis and ureter, and 6.7% for prostatic cancer). In the case of intra-arterial administration, overall response rate was 42.9% (50.0% for bladder cancer). For 50 patients with superficial bladder cancer intravesical chemotherapy with THP was performed. Sixteen patients showed complete disappearance of the tumor, 2 patients showed more than 90% tumor regression and 12 patients showed more than 50% tumor regression, respectively. Overall response rate was 60%. Cardiotoxicity was minimal. Alopecia was noted in a total of 16 patients, but this was minimal. Leukocytopenia was the major adverse effect among patients undergoing systemic THP administration. In conclusion, THP was most effective against transitional cell carcinoma of the urinary tract.

Topics: Adult; Aged; Alopecia; Anorexia; Carcinoma, Transitional Cell; Doxorubicin; Drug Administration Schedule; Drug Evaluation; Female; Humans; Infusions, Parenteral; Kidney Neoplasms; Leukopenia; Male; Middle Aged; Urinary Bladder Neoplasms; Urologic Neoplasms

Each of 5 patients with renal cell carcinoma and urinary bladder tumor who were operated on at the department of urology, Hamamatsu University School of Medicine and its affiliated hospitals, received 20 mg of 4'-O-tetrahydropyranyladriamycin (THP) intravenously at the beginning of surgery. Heparinized peripheral blood samples were collected at regular intervals and separated in plasma and blood cell fractions by centrifugation for the estimation of THP. The THP concentration of the surgical specimen was also studied. In renal cell carcinoma, the surgical specimen was divided into cytoplasm and nuclear fractions, and the THP concentration in each fraction was measured. The THP concentration gradually decreased in the plasma and blood cell fractions with passage of time after the administration in both renal cell carcinoma and urinary bladder tumor. In renal cell carcinoma, although the tumor revealed a lower concentration of THP compared with the normal renal cortex and medulla, the nuclear fraction of the tumor showed a higher concentration than those of the normal renal cortex and medulla. In contrast to renal cell carcinoma, the THP concentration of the urinary bladder tumor was found to be higher than those of the normal urinary bladder mucosa and muscle.

Topics: Carcinoma, Renal Cell; Chromatography, High Pressure Liquid; Doxorubicin; Humans; Injections, Intravenous; Kidney Neoplasms; Tissue Distribution; Urinary Bladder Neoplasms