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[Efficacy of intravesical bacillus Calmette-Guerin for carcinoma in situ of bladder].

Three months after an initial 6-week course ofintravesical bacillus Calmette-Guerin (BCG) given between January 1990 and March 2005, 94 (90%) out of 104 patients with carcinoma in situ (CIS) of the bladder achieved a complete response (CR). The 5- and 10-year recurrence-free rates were 67 and 60%, respectively (median follow-up 42 months). Three months after a second course ofintravesical BCG given to 23 patients who failed the initial induction course for CIS was evaluated. Of these, 96% achieved a CR, and the 5- and 10-year recurrence-free rates were 56 and 28%,respectively (median follow-up 23 months). Only one patient who received a second course of BCG therapy showed disease progression. Two of the 4 patients with BCG-refractory CIS of the bladder achieved CR after intravesical gemcitabine therapy and maintained a tumor-free status beyond 6 months. Five of the 16 patients showing disease progression had upper urinary tract cancer, 4 had recurrent or muscle invasive bladder cancer, 6 had prostatic involvement of CIS, and one patient had urethral recurrence. Three of the 16 patients died. Bladder preservation was achieved in 97 of the 104 patients, although 7 patients ultimately underwent radical cystectomy and urinary diversion for aggressive disease. In conclusion, some patients may be managed safely by repeated endoscopic resection and intravesical therapy with cystectomy postponed until objective evidence of progression exists.

Adjuvants, Immunologic↗

Short schedule intravesical mitomycin preceding transurethral resection for recurrent Ta-T1, G1-G2 bladder cancer.

AIMS AND BACKGROUND: Intravesical instillations commonly follow resection, when all visible lesions have been removed, making impossible any direct assessment of efficacy. The study was conceived to evaluate the ablative effect on the tumor and the efficacy in reducing the risk of recurrence of short schedule intravesical chemotherapy administered before endoscopic resection. STUDY DESIGN: Four weekly intravesical instillations of mitomycin C followed by transurethral resection (TUR) were administered to 31 patients with recurrent small volume superficial bladder cancer. RESULTS: At TUR no evidence of disease was found in 22 patients (70.9%) and residual disease in the remaining 9 (29.1%). At a median follow-up of 15 months (range, 3-33) 16 of 31 patients (51.6%) had recurrence of disease. The treatment was well tolerated. CONCLUSIONS: Short-schedule intravesical chemotherapy can completely ablate small volume recurrent superficial bladder cancer in a relevant number of patients but is probably not sufficient to obtain long-term prophylaxis.

Administration, Intravesical↗

Toxicity of local, continuous and cyclic, high-dose bladder perfusion with recombinant and natural interleukin-2 in advanced cancer of the urinary bladder.

We evaluated the toxicity of high-dose local interleukin-2 (IL-2) in 18 patients not eligible for standard treatment of advanced transitional cell bladder carcinoma. Seven received continuous high-dose local natural IL-2 via pump system in the bladder for up to 420 days. 11 received cyclic high-dose local natural IL-2 or recombinant IL-2 for up to 420 days. Treatment was well tolerated and, considering the low rate of toxicity, could be offered in an outpatient setting. Except for local contrast-media hypersensitivity, no serious side-effects were observed. This study provides a basis for the non-toxic use of local IL-2 in future studies to evaluate effectiveness of the treatment or prophylaxis of patients with superficial bladder cancer in order to prevent recurrences.

Administration, Intravesical↗

Does isoniazid reduce side effects of intravesical bacillus Calmette-Guerin therapy in superficial bladder cancer? Interim results of European Organization for Research and Treatment of Cancer Protocol 30911.

PURPOSE: We analyzed the influence of the tuberculostatic agent isoniazid on the incidence and severity of adverse effects of intravesical bacillus Calmette-Guerin (BCG) therapy in patients with superficial bladder cancer. MATERIALS AND METHODS: In a prospective randomized multicenter study the side effects of intravesical instillations with Tice strain BCG with and without isoniazid were compared in patients with stages pTa and pT1 bladder tumors. Isoniazid was given orally at a dose of 300 mg. daily at every instillation in an attempt to decrease the side effects of BCG. RESULTS: No differences in local or systemic adverse reactions after intravesical immune therapy with BCG could be observed between patients treated with or without prophylactic isoniazid therapy. However, analysis of liver function tests after BCG with isoniazid showed slightly more liver toxicity compared to BCG alone. CONCLUSIONS: Prophylactic administration of isoniazid during BCG instillations provides no decrease in any known side effect of BCG. In contrast, transient liver function disturbances are encountered slightly more frequently when isoniazid is administered. The use of prophylactic isoniazid in patients treated with BCG is not recommended.

Adjuvants, Immunologic↗

[Results of clinical study with epirubicin hydrochloride injectable solution for superficial bladder cancer. IMI28 Injectable Solution Study Group for Superficial Bladder Cancer].

A 7-center cooperative clinical study with a new formulation of epirubicin hydrochloride injectable solution (Epirubicin-RTU) was conducted in patients with superficial bladder carcinoma. Epirubicin-RTU at the dose of 60 mg/30 ml was administered by intravesical instillation once daily for three (3) consecutive days and a 4-day drug-free interval followed; then the above intravesical instillation of Epirubicin-RTU was repeated for three consecutive days. All 20 registered cases were eligible, and 18 cases completed the whole course of the study. In 18 completers, CR was observed in 12 cases and PR was observed in one (1) case, for an efficacy rate of 72.2%. The primary adverse reaction was bladder irritation including pollakiuria 85.0% (17/20), miction pain 85.0% (17/20), and hematuria 80.0% (16/20), which were all reversible and tolerable. In urinalysis, urinary sediment showed leukocytes and erythrocytes, and proteinuria was observed. All were reversible. From the above results, this new formulation of Epirubicin-RTU was considered useful for the treatment of superficial bladder carcinoma.

Administration, Intravesical↗

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin for prophylaxis of recurrence of superficial bladder cancer: a preliminary report.

The effects of intravesical chemoimmunotherapy with epirubicin and bacillus Calmette-Guérin (BCG) for prophylaxis of recurrence of superficial bladder cancer (pTa, pT1) were investigated in 29 patients aged a median of 70 years between January of 1991 and May of 1993. The patients received intravesical instillation of 40 mg epirubicin immediately after transurethral resection (TUR) of the bladder cancer. At 1 week after TUR, 80 mg Tokyo-strain BCG was instilled into the bladder once a week for 6 weeks. Thereafter, the patients were followed by cystoscopy and urinary cytology at 3-month intervals until recurrence was detected. Of the 29 patients, 28 had no evidence of disease over a mean follow-up period of 20 months. The 1 case of recurrence occurred at 3 months after TUR and that patient died of cancer progression. The simple recurrence rate was 3.5% after therapy. According to the person-years method, the number of recurrent tumors per 100 patient-months was 0.17. The cumulative nonrecurrence rate determined for all cases was 96.5% at 30 months. Adverse reactions, including urinary frequency, urgency, and miction pain, among others, were observed in 27 patients (93%). Only 1 patient was withdrawn from the treatment because of severe bladder-irritation symptoms due to the BCG instillation. The intravesical chemoimmunotherapy with epirubicin and BCG seemed to be effective for prophylaxis of recurrence of superficial bladder cancer.

Administration, Intravesical↗

Intravesical gemcitabine therapy for superficial transitional cell carcinoma: results of a Phase II prospective multicenter study.

OBJECTIVES: To determine the tolerability and efficacy after 1 year of weekly intravesical gemcitabine therapy in patients with intermediate-risk and high-risk superficial transitional cell carcinoma. METHODS: A total of 116 patients with intermediate-risk and high-risk bladder cancer who had undergone transurethral resection were treated with one cycle (once a week for 6 weeks) of gemcitabine 2000 mg. Local and systemic tolerability and efficacy were evaluated. RESULTS: In terms of the tolerability of gemcitabine, 14 patients (12.0%) reported urgency, 6 (5.1%) dizziness and slight fever (less than 38 degrees C), 1 (0.8%) severe abdominal pain, with ulcerative lesions of the bladder mucosa at cystoscopy, and 1 (0.8%) parosmia. The remaining 94 patients (81.3%) did not report any local side effects during the treatment period. In terms of efficacy, recurrence developed in 29 patients (25.4%) a mean of 7 months after transurethral resection; 85 patients (74.6%) were disease free after 12 months. The univariate analysis showed a greater level of efficacy in patients with a first occurrence (P = 0.0408), patients who had had no previous treatment (P = 0.0368), and patients with Stage pTa superficial transitional cell carcinoma (P = 0.0018). The multivariate analysis did not reveal any significant data. No significant differences were found between the intermediate-risk and high-risk patients in tolerability or efficacy. No recurrence developed in 18 (75%) of 24 intermediate-risk bacille Calmette-Guérin-refractory or 7 (43.7%) of 16 high-risk bacille Calmette-Guérin-refractory patients. CONCLUSIONS: The results of our study have confirmed the good tolerability and 1 year efficacy of intravesical gemcitabine. The treatment schedule proposed resulted in high patient compliance, and the results can be compared with the results of studies using other intravesical treatments.

Administration, Intravesical↗

Corticosteroid-associated fatal mycobacterial sepsis occurring 3 years after instillation of intravesical bacillus Calmette-Guerin.

A case is reported of systemic Mycobacterium bovis infection that occurred 3 years after uneventful instillation of intravesical bacillus Calmette-Guerin (BCG) and after several months of oral prednisone therapy. The literature on delayed BCG infection and the systemic persistence of BCG after intravesical instillation is reviewed. We propose that rarely a reservoir of dormant M. bovis may become established after intravesical therapy. Reactivation infection may later develop in a manner that parallels the natural history of secondary tuberculosis.

Administration, Intravesical↗

Instillation of anesthetic gel is no longer necessary in the era of flexible cystoscopy: a crossover study.

BACKGROUND AND PURPOSE: Whether urethral injection of anesthetic and lubricating gel prior to outpatient flexible cystoscopy is worthwhile with regard to pain tolerance has been investigated only in a parallel randomized study. A crossover study was thus designed for further elucidation. PATIENTS AND METHODS: Each of 33 male patients underwent three flexible cystoscopic examinations with intraurethral instillation of 11 mL of cold anesthetic gel (group 1), plain lubricating gel (group 2), or no gel (group 3). In every examination, 2% lidocaine gel was applied to the cystoscope. Although the cystoscopy was performed by two urologic surgeons, each patient underwent the three consecutive examinations with the same urologist. All the patients separately recorded pain levels during gel instillation, cystoscope insertion, and intravesical observation on a 100-mm visual analog scale after every cystoscopy. RESULTS: From the median scores, the degree of pain resulting from gel injection was 77.0% and 98.0% of those for cystoscope insertion and intravesical observation, respectively. For each group stratified by anesthetic method, there was no significant difference in the pain score during either cystoscope insertion or intravesical observation. CONCLUSION: The pain caused by intraurethral gel instillation is significant compared with that from cystoscope insertion and intravesical observation. Anesthetic gel instillation appears to have no significant advantage over anesthesia-free flexible cystoscopic examinations.

Administration, Intravesical↗

Intravesical capsaicin and resiniferatoxin therapy: spicing up the ways to treat the overactive bladder.

PURPOSE: Pharmacological treatment of the overactive bladder relies on partially blocking the efferent parasympathetic innervation to the detrusor with anticholinergic drugs. However, often these drugs have troublesome side effects and doses are insufficient to restore continence in patients with detrusor instability. We present the background, basic and clinical research with intravesical instillation of capsaicin and resiniferatoxin as treatments for the overactive bladder. MATERIALS AND METHODS: Capsaicin, the main pungent ingredient in hot peppers of the genus Capsicum, is a specific neurotoxin that desensitizes C fiber afferent neurons which may be responsible for signals that trigger detrusor overactivity. RESULTS: In the last 6 years studies have demonstrated encouraging improvement in lower urinary tract symptoms with minimal long-term complications. Most of these studies have also demonstrated that the acute pain and irritation associated with capsaicin are major deterrents to widespread use. Therefore, resiniferatoxin, an ultra-potent analogue of capsaicin which appears to have similar efficacy but less acute side effects, may be more useful. CONCLUSIONS: Intravesical capsaicin and resiniferatoxin are novel and promising treatments for the overactive bladder, with profound basic and clinical implications.

Administration, Intravesical↗

Effect of intravesical treatment of transitional cell carcinoma with bacillus Calmette-Guerin and mitomycin C on urinary survivin levels and outcome.

PURPOSE: Urine survivin is a predictive/prognostic molecular marker that detects transitional cell carcinoma (TCC) with high specificity and sensitivity. The presence of urine survivin in patients with TCC who receive intravesical instillation of bacillus Calmette-Guerin or mitomycin C may predict recurrence. MATERIALS AND METHODS: Urine from 25 subjects receiving 27 intravesical treatments of bacillus Calmette-Guerin or mitomycin C for TCC were collected prior to, during and after treatment. Urinary survivin levels were compared with outcome, as assessed by cytology and cystoscopy with or without biopsy 1 month and up to 12 months after the completion of treatment. RESULTS: Pretreatment survivin levels were higher in subjects in whom TCC recurred following treatment compared with those who achieved remission. Survivin levels increased several-fold during treatment with the highest survivin levels measured in subjects with recurrence. Median posttreatment values of survivin were zero in those who achieved remission and 1.0 ng/ml urine in subjects in whom TCC recurred. CONCLUSIONS: The presence of urinary survivin 1 month after the completion of treatment predicts TCC recurrence with 100% sensitivity and 78% specificity. Specificity to predict TCC recurrence increases to 92% after 1 year. No TCC recurred for 1 year in 12 of the 14 subjects with a posttreatment survivin level of 0.1 ng or less per ml urine. Three of the 4 subjects who were survivin positive but in remission 1 month after the completion of treatment had recurrent TCC within 1 year. Subjects who have urinary survivin after the completion of intravesical instillation have a high likelihood of TCC recurrence.

Adjuvants, Immunologic↗

Phase I pharmacokinetic study of a single intravesical instillation of gemcitabine administered immediately after transurethral resection plus multiple random biopsies in patients with superficial bladder cancer.

PURPOSE: In this phase I study we determined the pharmacokinetic and toxicity profiles of a single intravesical instillation of gemcitabine administered immediately after complete transurethral resection (TUR) plus multiple random biopsies. MATERIALS AND METHODS: Ten patients with superficial bladder cancer clinically staged as Ta/T1 with no carcinoma in situ were included. A single dose of gemcitabine was administered intra-vesically immediately after TUR plus 6 random biopsies. Five patients received 1,500 mg and 5 received 2,000 mg diluted in 100 ml saline. Retention time in the bladder was 60 minutes. Concentrations of gemcitabine and dFdU (2',2'-difluoro-2'-deoxyuridine) were determined by high pressure liquid chromatography assay. RESULTS: Treatment was clinically well tolerated in all patients. Two patients in the 1,500 mg group had minimal hipogastric discomfort and 1 in the 2,000 mg group had grade 1 bladder spasms. There was no remarkable systemic toxicity on hematology or biochemistry at any dose level on day 12 or 30. One patient per dose level showed tumor recurrence on 3-month repeat cystourethroscopy. Mean maximum gemcitabine concentration was 1.8 microg/ml and the mean last AUC was 158 microg/ml*minute. There was large interpatient variability but no significant differences between the 2 dose levels. CONCLUSIONS: Single intravesical instillation of gemcitabine immediately after TUR and multiple random biopsies for superficial bladder cancer are a safe and well tolerated treatment. The favorable toxicity and pharmacokinetic profiles of intravesical gemcitabine support future phase II studies with this agent.

Administration, Intravesical↗

Adjuvant intravesical mitoxantrone versus recombinant interferon-alpha after transurethral resection of superficial bladder cancer: a randomized prospective study.

OBJECTIVE: To determine the efficacy and safety of two different doses of intravesical mitoxantrone and of recombinant interferon-alpha (IFNalpha-2b), instilled after transurethral resection (TUR) of superficial transitional cell carcinoma (TCC) of the bladder. MATERIAL AND METHODS: 208 patients (mean age 62.05 years) with primary or recurrent superficial (TaG1, T1G1, T1G2) bladder cancer were randomly allocated into four groups, after TUR of all visible tumors. Group A (45 patients) received no further therapy; group B (56 patients) received 10 mg of mitoxantrone (6 weekly and 20 fortnightly instillations), group C (54 patients) 20 mg of mitoxantrone (3 fortnightly and 10 monthly instillations) and group D (53 patients) received 100 MU of IFNalpha-2b (8 weekly, 8 fortnightly and 6 monthly instillations). RESULTS: During the follow-up (mean 21.09 months), 29 (64.44%) patients in group A had recurrence, compared with 19 (33.92%) in group B, 17 (31.48%) in group C and 15 (28.3%) patients in group D (p < 0.005). Furthermore, the differences in simple recurrence rates were statistically more significant (p < 0.05), when group A was compared with the three other groups in the terms of T1G2, recurrent and multiple neoplasms. Twenty-nine patients (10, 7, 8, and 4 in groups A-D) experienced tumor progression, and the differences between the four groups were not statistically significant (p > 0.05). The mean recurrence time was 9.03 months in group A, 13.74 in group B, 14.24 in group C and 17.4 months in group D (p < 0.001), and the recurrence rate per 100 patient-months was 4.39, 1.57, 1.48 and 1.06, respectively (p < 0.05). Toxicity (grade 1-3) was recorded in 23.21% in group B, in 31.48% in group C and in 9.43% in group D (p < 0.01). CONCLUSION: The two doses of mitoxantrone resulted in similar efficacy for the prevention of superficial bladder cancer recurrences, with the dose of 10 mg of mitoxantrone being related to fewer side effects. In comparison with mitoxantrone, the adjuvant intravesical immunotherapy with 100 MU of IFNalpha-2b showed a better combination of efficacy and safety.

Administration, Intravesical↗

Urodynamic results of intravesical heparin therapy for women with frequency urgency syndrome and interstitial cystitis.

BACKGROUND AND PURPOSE: Although intravesical heparin instillation is effective in relieving symptoms in patients with frequency urgency syndrome and interstitial cystitis (IC), its efficacy has not been evaluated by urodynamic study. We used urodynamic studies to evaluate the efficacy of heparin instillation in patients with frequency urgency syndrome and IC. METHODS: Forty women (mean age, 59.6 yr) with severe frequency, urgency, and suprapubic pain at full bladder were enrolled in this study. Patients underwent videourodynamic study with the potassium chloride (KCl) test. All patients had a positive KCl test and were treated with intravesical heparin 25,000 units twice a week for 3 months. Results of urodynamic study and voiding symptom changes assessed by the International Prostate Symptom Score at the end of treatment were compared with baseline data. RESULTS: Twenty-nine patients had symptom score improvement of more than 50%, and eight had symptom score improvement of less than 50% but improved nocturia. Significant improvement in symptom score (9.0 +/- 4.0 vs 19.5 +/- 4.6, p < 0.001) and nocturia (2.3 +/- 1.1 vs 5.7 +/- 2.0, p < 0.001) were noted after treatment. Urodynamic study at the end of treatment revealed significant improvements in the first sensation of filling (146 +/- 55.4 vs 96 +/- 46.4 mL, p = 0.001) and cystometric capacity (304 +/- 84.8 vs 262 +/- 89.8 mL, p = 0.002). Posttreatment KCl test was negative in 20 patients, improved in 13, and unchanged in seven. Among the 10 patients with cystoscopically proven IC, eight had symptomatic improvement and four had a negative KCl test after treatment. CONCLUSIONS: IC and frequency urgency syndrome may be caused by increased urothelial permeability. The results of this study show that intravesical heparin can relieve bladder symptoms in a significant proportion of patients, and this may be associated with the restoration of mucosal integrity.

Administration, Intravesical↗

[Treatment of Bacillus Calmette-Guerin refractory superficial bladder cancer: further intravesical therapy].

We here report our clinical experience with salvage therapy for patients with bacillus Calmette-Guerin (BCG)-refractory superficial bladder cancer and discuss current approaches to the disease, especially focusing on bladder preservation. First, we evaluated the efficacy of an initial 6-week course of intravesical BCG in 93 patients with carcinoma in situ (CIS) of the bladder. Of these, 91% achieved a complete response (CR) at the evaluation at 3 months. The 2- and 5-year recurrence-free rates were 71 and 67%, respectively (mean follow-up 39 months). These results support the intravesical BCG as a first-line therapy for CIS. Next, we assessed the efficacy of a second course of intravesical BCG for 16 patients who failed the initial induction course for CIS. Of these, 94% achieved CR at the evaluation at 3-month, and the 2- and 5-year recurrence-free rates were 62 and 46%, respectively (mean follow-up 28 months). None of the patients who received a second course had disease progression. Thus, a second course of BCG therapy seems to be a reasonable option for CIS patients failing the initial course. We also report our initial experience with intravesical gemcitabine therapy for 3 patients with BCG-refractory CIS of the bladder and 1 patient with recurrent multiple tumors. Gemcitabine (1500 mg in 100 ml saline) was given in the bladder for 1 hour twice weekly for a total of 12 treatments. The treatment was associated with minimal bladder irritation and systemic absorption, and was well tolerated except in a 90-year-old man who discontinued therapy because of grade 2 toxicity. Two patients achieved CR and maintained a tumor-free status beyond 14 months, suggesting that the intravesical gemcitabine is a promising salvage therapy for BCG-refractory superficial bladder cancer.

Adjuvants, Immunologic↗

Population pharmacokinetic modeling and Monte Carlo simulation of varying doses of intravenous metronidazole.

Population pharmacokinetic modeling and Monte Carlo simulation (MCS) are approaches used to determine probability of target attainment (PTA) of antimicrobial therapy. The objectives of this study were 1) to determine a population pharmacokinetic model (PPM) using metronidazole and hydroxy-metronidazole concentrations from healthy subjects and critically ill patients, and 2) to determine the probability of attaining the pharmacodynamic target area under the plasma concentration (AUC)/MIC ratio >or=70 against 218 clinical isolates of Bacteroides fragilis using MCS. Eighteen healthy subjects were randomized to 3 dosages of intravenous metronidazole (500 mg every 8 h, 1000 mg day(-1), 1500 mg day(-1)) in an open-label 3-way crossover fashion. Serial blood samples were collected over 25.5 h on the 3rd day of each study period. An additional of 8 critically ill patients received intravenous metronidazole 500 mg every 8 h. Serial blood samples were collected over 8 h after the 2nd day of dosing. Plasma metronidazole and hydroxy-metronidazole concentrations were analyzed using a high-performance liquid chromatographic assay. The 834 plasma concentrations from 62 data sets were simultaneously modeled with Non-Parametric Adaptive Grid population modeling program. A 4-compartment model with a metabolite and zero-order infusion into the central compartment was used. The mean parameter vector and covariance matrix from PPM were inserted into the simulation module of ADAPT II. A 10,000-subject MCS was performed to determine the probability of PTA for a total drug AUC to MIC ratio >or=70 against 218 isolates of B. fragilis (MIC range, 0.125-2.0 mg L(-1)). Mean parameter values were CL(non-OH), 3.08 L h(-1); Vc, 35.4 L; K(OH), 0.04 h(-1); CL(OH), 2.78 L h(-1); and V(OH), 9.66 L. The regression values of the observed versus predicted concentrations (r2) of metronidazole and hydroxy-metronidazole were 0.972 and 0.980, respectively. The PTA for metronidazole 1500 mg day(-1) or 500 mg every 8 h (taken together) and 1000 mg day(-1) were 99.9% and 99.8%, respectively, over the reported MIC distribution range. For an MIC of 4 mg L(-1), the predicted PTA decreased to 80.0% and 28.5%, respectively. A PPM was determined by comodeling metronidazole and hydroxy-metronidazole concentrations from healthy subjects and critically ill patients. Based on this model, attainment of the target pharmacodynamic parameter (AUC/MIC ratio >or=70) against B. fragilis isolates is >99% when MICs are <2 mg L(-1), irrespective of the dosing interval of 24 h.

Administration, Intravesical↗

Immunotherapy of bladder cancer.

Intravesical therapy has been used in the management of superficial transitional cell carcinoma (TCC) of the urinary bladder (i.e., Ta, Tl, and carcinoma in situ) with specific objectives which include treating existing/residual tumor, preventing recurrence of tumor, preventing disease progression, and prolonging survival. The initial clinical stage and grade remain the main determinant factors in survival irrespective of the treatment. Presently, bacillus Calmette-Guerin (BCG) immunotherapy remains the most effective treatment and prophylaxis for TCC (Ta, Tl, CIS) and has positive outcomes on tumor recurrence rate, disease progression, and prolongation of survival. Prostatic urethral mucosal involvement with bladder cancer can be effectively treated with BCG intravesical immunotherapy-it has demonstrated a reduction in tumor recurrence rates, but has had no positive impact on disease progression or prolongation of survival. Interferons, keyhole-limpet hemocyanin (KLH), bropirimine, and PHOTOFRIN-photodynamic therapy (PDT) are under investigation in the management of TCC and early results are encouraging. This comprehensive review highlights recent developments in intravesical therapy of bladder cancer and summarizes the mechanisms of action of BCG, and the important role of intravesical BCG immunotherapy and other immunotherapeutic agents in the therapy and prophylaxis of superficial TCC of the urinary bladder.

Adjuvants, Immunologic↗