Mg Of Mitomycin C Research Articles

No clinical benefit from sequential combination of mitomycin C plus bacillus Calmette-Guérin (BCG) than BCG alone in the adjuvant treatment of high risk non muscle invasive bladder cancer: result of a planned interim analysis of a prospective randomized trial.

The aim of this study was to evaluate whether the sequential use of Mitomycin C (MMC) and Bacillus Calmette-Guérin (BCG) is superior to BCG alone in reducing the risk of disease recurrence in patients with non-muscle invasive bladder cancer (NMIBC) with high risk of progression. Prospective randomized trial was conducted from March 2021 to March 2023 and included 72 patients with high risk NMIBC. Trial registration number: NCT03790384; EUDRACT Number: 2017-004540-37. Thirty-one patients underwent to BCG alone and forty-one to MMC plus BCG during the induction course. The BCG schedule comprised six weekly instillation of 81 mg Connaught strain BCG as the induction course, followed by a further three-monthly instillation at three, six and twelve months, as the maintenance course. Forty mg of MMC were administered the day prior to each weekly BCG instillation in BCG plus MMC arm. A planned interim analysis was carried out in June 2023, at the end of the 12mo follow-up period. Six out of thirteen 6/31(19.3%) and 10/41 (24.4%) patients experienced recurrence in BCG and BCG plus MMC group (P=0.611), respectively. BCG plus MMC did not improve Disease Free Interval (HR: 1.23 95% CI:0.46-3.50; P=0.640). Patients receiving sequential treatment experienced similar AEs (P>0.05) and more urinary symptoms (P<0.05). This interim pre-planned analysis suggested absence of clinical advantages in terms of disease recurrence rate when MMC is administered one day prior to BCG during induction course.

Conductive hyperthermic chemotherapy versus electromotive drug administration of mitomycin C as intravesical adjuvant treatment of patients with intermediate or high-risk non-muscle invasive bladder cancer

BackgroundDevices that increase the penetration of intravesical chemotherapeutic agents have been developed as alternatives to the use of bacillus Calmette–Guérin, in short supply at a time of increasing global incidence of non-muscle invasive bladder cancer (NMIBC).We performed a prospective observational study to compare 2 of these devices in the treatment of patients with high- and intermediate-risk NMIBC. The primary endpoint was the recurrence-free rate. Secondary endpoints were the rate of progression and adverse events. MethodsAfter undergoing transurethral bladder resection, 98 patients were selected to receive 1 of 2 treatments: hyperthermic intravesical chemotherapy (HIVEC) treatment with 40 mg of mitomycin C (MMC) using Combat BRS System V2.0 at 43 ± 0.5°C and 200 ml/min for 60 minutes (56 patients) or electromotive drug administration (EMDA) with 40 mg of MMC at 20 mA for 30 minutes (42 patients). The treatment schemes were similar: 6 weekly instillations as induction and 6-monthly instillations as maintenance. The recurrence rates were evaluated at 6 and 12 months and the progression rates at 12 months. ResultsThe recurrence-free rate at 12 months was 91,1% in the HIVEC group and 88.1% in the EMDA group (P ≥ 0.05). After the 12-month follow-up, only 1 progression occurred in each treatment group. In terms of adverse events, no significant differences were found between the treatments. ConclusionsHIVEC and EMDA techniques are comparable in terms of recurrence, progression and adverse events at 12 months in the treatment of patients with high- and intermediate-risk NMIBC.

Mitomycin C allergy after passive and device-assisted hyperthermia for non-muscle invasive bladder cancer treatment: A retrospective cohort from a high-volume center.

Mitomycin C (MMC) is one of the most frequently utilized intravesical chemotherapy drugs for the management of non-muscle-invasive bladder cancer (NMIBC). Allergic reactions (Type 4 delayed hypersensitivity) are seldomly reported in the literature but not so infrequent in daily practice, its incidence has been increasing with the use of device-assisted hyperthermia. This study aims to identify the incidence, risk factors, and clinical characteristics of patients with allergic reactions to MMC. Single-center retrospective cohort from June 2014 to August 2018. Patients with intermediate or high-risk NMIBC were included. Patients received passive MMC (4 weekly and eleven monthly instillations of 40mg of MMC) or Chemohyperthermia (CHT) with MMC (6 weekly and 6-monthly instillations, heated at 43°C [+/- 0.5°C] using Combat BRS). We included 258 patients (MMC = 157, CHT = 101) and found 7 (4.4%) suspected and 4 confirmed (2.4%) allergies in the passive MMC group and 11 suspected (10.9%) and 7 confirmed (6.9%) in the CHT group. The mean number of instillations received before developing the allergy was 6 in the passive MMC and 5 in the CHT group. Seven out of 18 suspected allergy cases were pseudo-allergic reactions with negative allergy tests. Early postoperative MMC instillation was associated with an increased risk of allergy (OR 2.47 [CI 1.39-4.36], P = 0.001), while neither history of atopy nor history of other medications allergy was found to increase the risk. MMC allergy risk is increased with the use of device-assisted hyperthermia with an incidence of 2.4% for passive MMC and 6.9% for CHT. History of prior allergies does not seem to increase the risk of developing MMC allergy. In this series 38% of suspected cases were found to be pseudo-allergic reactions, highlighting the need to confirm the diagnosis before definitively stopping the treatment.

Low grade transitional cell carcinoma of the urethra successfully treated with only intraurethral instillation of Mitomycin-C

Urethral cancer is very rare disease, accounting for less than 0.5% of incidences of malignancies. Data on its management are scarce due to the rare nature of the cases. We present a 34-year-old man, who presented to our hospital with a month history of hematuria. He had no lower urinary tract symptoms and no significant risk factors for urothelial cancer. He was evaluated and found to have lesions in the posterior urethra on urethrocytoscopy, biopsy of which revealed a low-grade urothelial cancer. He was counselled and had 6 courses of intraurethral instillation of 40mg of Mitomycin-C diluited in 50mL of saline held in the urethra with penile clamp for 30 minutes. The hematuria stopped after the second course, a repeat urethrocystoscopy 6 months after the completion of the chemotherapy, showed resolution of the lesion and repeat biopsy showed no evidence of malignancy. However, the patient developed short segment partial penile urethral stricture that was treated with dilatation. In conclusion, low-grade urothelial cancer of the urethra can be successfully cured with Intraurethral instillation of Mitomycin-C, without prior transurethral resection.

Conflicting Data on the Incidence of Leukopenia and Neutropenia After Heated Intraperitoneal Chemotherapy with Mitomycin C.

During heated intraperitoneal chemotherapy (HIPEC), neutropenia rates of 20 to 40% have been reported when mitomycin C (MMC) is dosed by weight or body surface area (BSA). This study investigated the authors' HIPEC experience using a fixed 40-mg dose of MMC, per consensus guidelines, and analyzed predictors for severe leukopenia and neutropenia. Patients who underwent MMC-HIPEC from 2007 to 2016 at a single tertiary care center were retrospectively reviewed. Among 314 MMC-HIPEC cases, 72 patients in the early era of the authors' program received routine prophylactic postoperative granulocyte-colony-stimulating factor (GCSF). This early cohort had five severe leukopenic reactions and one neutropenic reaction. In the subsequent 242 cases without GCSF prophylaxis, severe leukopenia developed in 16 patients (7%), with neutropenia occurring in 11 (4.5%) of these cases. A history of prior systemic chemotherapy was noted in 9 (56%) of the 16 leukopenic patients compared with 112 (46%) of the patients who had no leukopenia (nonsignificant difference). The median nadir of leukopenia was 5days (range 1-11days). Of the 11 neutropenic patients, 6 received therapeutic GCSF, and 5 recovered without intervention. The 30-day postoperative mortality of the patients with leukopenia was 0%. In this study, the incidence of neutropenia after HIPEC with 40mg of MMC was markedly lower than reported in the literature for doses adjusted by BSA or weight. The authors report that GCSF is not necessary for routine prophylaxis of all MMC-HIPEC patients. The findings suggest that a fixed 40-mg dose of MMC allows HIPEC to be performed with less risk of immunosuppression.

Intravesical mitomycin C combined with hyperthermia for patients with T1G3 transitional cell carcinoma of the bladder

Objectives Non-muscle invasive bladder cancer (NMIBC) classified as T1G3 represents one of the most challenging issues in urologic oncology. Although it is still considered a lesion amenable for conservative management, the risk for recurrence and progression remains high. The aim of this study was to define both recurrence and progression rate in patients with T1G3 UCC treated by complete transurethral resection (TURT) and adjuvant thermochemotherapy approach. Materials and methods We retrospectively evaluated the clinical data of patients with T1G3 NMIBC who underwent TURT followed by thermochemotherapy (TCT) treatment. Data recorded included age, gender, previous resections, previous intravesical treatment, time to tumor recurrence, and progression. TCT was given once weekly for 6 consecutive weeks, followed by 6 maintenance sessions at 4 to 6 weeks intervals. During each treatment session, 40 mg of mitomycin C (MMC) was instilled into the bladder in combination with bladder wall hyperthermia of 42 ± 2°C for 60 minutes. Follow-up cystoscopy and urinary cytology were performed every 3 months for the first 2 years and than biannually. Results A total of 56 T1G3 patients were treated with adjuvant TCT treatment at 7 urologic centers. Mean age was 68 years (range 35–91), 10 were females and 46 were males. Twenty-six patients failed on at least 1 previous intravesical treatment. Five patients who dropped out due to adverse events before reaching the first outcome evaluation cystoscopy were referred to another intravesical therapy, and were therefore excluded from the current analysis. A total 51 patients were available for analysis. Median follow-up time of tumor-free patients was 18 months (average 20, range 2–49 months). Seventeen patients (33.3%) had tumor recurrence and 4 of them progressed to muscle invasive disease. The median time to recurrence was 9 months (average 11, range 2–31 months). The Kaplan-Meier estimated recurrence rate for this group is: 42.9% at 2 years, 51.0% at 4 years. Conclusions TCT can be an effective adjuvant treatment option after TURT to prevent recurrence in patients with T1G3 NMIBC. Progression rate after this treatment was low (7.9%). TCT treatment was documented to be effective also in those who failed previous intravesical BCG. Treatment was confirmed to be safe and well tolerated.

表在性膀胱癌に対する Mitomycin-Cおよび Pirarubicin の5年間にわたる膀胱内注入療法の再発予防効果

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.

Hemicolectomy With Concomitant Heated Intraperitoneal Chemotherapy: A Case Study

The use of heated intraperitoneal chemotherapy is an emerging new adjunct in the treatment of adenocarcinoma of the colon. However, documentation regarding perfusion circuitry and techniques associated with this therapy remain largely undescribed. After consultation with the surgical service team, a custom designed circuit was constructed for this procedure. Institutional approval and informed consent were obtained for surgical debulking and heated intraperitoneal chemotherapy for a 58-year old female. After surgical resection, a right hemicolectomy was performed and pathological specimens obtained. A modified custom circuit using a roller pump was first primed with 3 liters of Dianeal® PD-2 and recirculated until temperature of 41°C was obtained. The circuit was then connected to the patient for infusion of perfusate via Blake drains placed in the deep pelvis. Two additional drains were placed in the subdiaphragmatic space for return. Perfusate containing 30 mg of Mitomycin-C was circulated at 600–800 mL/min for 60 min at 41°C. An additional 10 mg of Mitomycin-C was then administered through the circuit for an additional hour under similar conditions. Upon completion, a washout procedure was performed with 2 additional liters of Dianeal® PD-2. The patient tolerated the procedure well and was discharged postoperative day 7. We describe the successful use of a perfusion-administered heated intraperitoneal chemotherapy regimen as an integral part of successful treatment of adenocarcinoma of the colon.

Intraocular pressure reduction after subconjunctival mitomycin-C in absolute glaucomatous eyes

This study investigated the intraocular pressure (IOP) lowering effect of subconjunctival injection of mitomycin-C in human eyes blinded by glaucoma. Twenty eyes received injection of 1 mg of mitomycin-C and were followed up for 2 months. A statistically significant decline in IOP was observed until day 30 in all patients. The IOP-lowering effect of 1 mg of subconjunctivally injected mitomycin in patients with intractable glaucoma appears to be temporary.

Isolated hypoxic perfusion with mitomycin C in patients with advanced pancreatic cancer

Chemotherapy as a palliative therapy option for patients with advanced pancreatic cancer remains disappointing. Some authors have recently claimed high response rates and a prolongation of median survival after regional chemotherapy. Isolated perfusion may result in the highest drug concentrations within the target tissue without causing systemic side-effects. An established, commercially available system of isolated hypoxic perfusion (IHP) was therefore evaluated in patients with unresectable or recurrent pancreatic cancer. IHP was performed in 17 patients with unresectable pancreatic cancer. Five women and 12 men with a median age of 61 years were treated. A 20-min isolated hypoxic perfusion was performed after 40 mg of mitomycin C (MMC) had been instilled into the running perfusion system over 5 min. Tumour response was evaluated by CT-scan 6 weeks after IHP. Twenty perfusions were carried out in 17 patients. Within 10 min of perfusion, the perfusate's PO2 decreased to 13% of the baseline value. Five minutes after the infusion of MMC a local concentration of 15.2 mg/litre was observed. Toxicity-related deaths did not occur. Nausea and vomiting (NCI> or =II: 12 episodes) were the most frequently observed toxicities after IHP. In five patients (29%) a deep vein thrombosis occurred. None of the treated patients responded to the regimen used in this trial. The median survival time after IHP was 4.2 months (range 1.3-21). The overall rate of side-effects and complications after IHP was high. In spite of some hopeful reports on this treatment in recent years, IHP did not show any benefit in terms of tumour response or median survival. On the basis of these experiences, this procedure should no longer be used as treatment for patients with unresectable or recurrent pancreatic cancer.

Long-term follow-up of an EORTC randomized prospective trial comparing intravesical bacille calmette-guérin–RIVM and mitomycin c in superficial bladder cancer

Objectives. To determine long-term efficacy of intravesical mitomycin C (MMC) versus bacille Calmette-Guérin (BCG) in patients with superficial bladder cancer with regard to recurrences and progression. Methods. Patients with superficial bladder cancer (pTa, pT1, pTis) were treated with intravesical MMC (30 mg, weekly for 4 weeks, and thereafter monthly for 5 months) or BCG (weekly for 6 weeks). Results. Three hundred forty-four patients were eligible (171 in the BCG group, 173 in the MMC group). The median follow-up was 7.2 years. Toxicity was not significantly different between the two treatment groups. Efficacy of the two treatment policies was similar with regard to tumor recurrence. With regard to progression to invasive disease, MMC was more effective than BCG in patients without carcinoma in situ (CIS) ( P = 0.006). Conclusions. We can confirm the conclusions of other studies that intravesical treatment with 30 mg of MMC remains an effective treatment option that can also be used in high-risk patients. Like others, we could not confirm that a 6-week course of BCG is more effective in the prevention of tumor progression. Of the 33 patients with tumor progression after intravesical therapy, 20 died of bladder cancer, confirming that tumor progression after intravesical therapy carries a poor prognosis. In this study the difference in toxicity between BCG and MMC was not significant. When comparing studies with MMC and BCG, differences in treatment schedule and/or patient selection should be kept in mind.

Intraperitoneal hyperthermic perfusion with mitomycin C for colorectal cancer with peritoneal metastases.

Intraperitoneal (i.p.) metastases pose a special problem for surgical treatment because of their multiplicity and microscopic size. This study was designed to examine the feasibility and safety of i.p. hyperthermic perfusion (IPHP) with mitomycin C (MMC) for treating recurrent colorectal cancer. Fifteen patients with metastatic colon cancer were treated. All patients underwent cytoreductive procedures leaving only residual i.p. metastases < 1 cm in diameter. All patients had received prior systemic chemotherapy, but their disease had progressed. Intraperitoneal chemotherapy was administered through three large catheters (28 French) using a closed system of two pumps, a heat exchanger, and two filters. After the patient's abdominal temperature reached 41 degrees C, 45-60 mg of MMC was circulated intraperitoneally for 1 h. The majority of patients had various anastomoses: small bowel (n = 11), large bowel (n = 5), and urologic (n = 5). No anastomotic complications occurred in any of the patients. One patient experienced severe systemic MMC toxicity, which caused cytopenia and respiratory depression. In all patients the carcinoembryonic antigen (CEA) level decreased after surgery and IPHP. Median follow-up was 10 months, and recurrence was defined as an elevation in CEA level. Disease recurred in three patients within 5 months, and disease recurred in seven other patients over the next 3 months; one patient remains clinically free of disease after 8 months. Our data suggest that IPHP is a safe palliative method of treatment for patients with peritoneal carcinomatosis. The median patient response duration of 6 months may warrant consideration of a repeat IPHP procedure at that time.

The effect of mitomycin C on daily sperm production potential and other spermatogenic parameters in mice.

Thirty CD-1 male mice were randomly allocated to one of three groups and treated daily for five consecutive days via intraperitoneal (IP) injections. Treatments consisted of: 1) control (vehicle), consisting of 0.2 ml dose of phosphate buffered saline, 2) 1.0 mg of Mitomycin C (MC) per kg body weight, and 3) 2.0 mg of MC per kg body weight. All animals were sacrificed 35 days post-initiation of the experiment. Mice administered the higher dose of MC died within the first 19 days after the first injection. Significant differences (P less than 0.001) were observed between the two remaining groups in daily sperm production potential, sperm count per high power field, percent motility and progressive motility. Histological preparation of testicular parenchymal tissue revealed a high degree of seminiferous epithelial destruction and increased vacuolization associated with treatment of MC. These data indicate that MC causes severe pathological changes to spermatogonial cells within the seminiferous tubules, which in turn, induce spermatogenic dysfunctions noted in all parameters measured in this study.

Modified pelvic vascular bed isolation chemotherapy: Theoretical basis, surgical procedure, and two clinical case reports

Recently, the surgical procedure of pelvic vascular bed isolation chemotherapy (PVI) was modified to avoid gluteal muscle necrosis. The modified technic was used to treat two cases of advanced, unresectable, severely hemorrhagic, and obstinately radioresistant cervical cancer during 1977 in our department. Local evidence of macroscopic, cytological, and histological malignancy was completely eradicated with the modified technic using the respective dose of 60 and 66 mg of mitomycin C (MMC), and also no macroscopic evidence of malignancy was found in the specimens surgically excised 4 to 5 weeks after the chemotherapy. However, histological examination detected definite malignancy in one specimen, and suspicious malignancy in the other. They have been surviving without evidence of malignancy during the past 17 and 18 months, respectively. The result of our recent study to establish the theoretical basis for PVI and its modified technic is also presented.

Intraperitoneal free cancer cells and their viability in gastric cancer.

Free cancer cells in the peritoneal cavity of 100 patients with gastric cancer were examined by means of Douglas lavage, and their viability was estimated by 3H-thymidine uptake with autoradiographical technic. Furthermore, the effect of mitomycin-C on the viability of free cancer cells in the peritoneal cavity was studied. The appearance of intraperitoneal free cancer cells was dependent on the degree of invasion of cancer to the gastric serosa; that is, free cancer cells were not found in cases without serosal invasion, but were found in 48% with serosal invasion. The viability of free cancer cells in the peritoneal cavity was relatively high, but could be suppressed remarkably by intraperitoneal administration of 10 mg of mitomycin-C.

Preoperative infusion of mitomycin-C in the bronchial artery in squamous cell carcinoma of the lung.

Bronchial angiography was performed in 9 patients with squamous cell carcinoma of the lung. The tumor-feeding vessel was identified and infused with 10 mg of mitomycin-C (MMC) diluted in saline. At operation after 28 to 48 days complete remission of the tumor had occurred in 2 patients, almost complete in one, partial remission in 2 and a marked regression in 2. In 2 patients no change was noted. No side effects except moderate malaise and slight fever occurred.

Bronchial artery infusion of mitomycin-C in advanced bronchogenic carcinoma.

Bronchial angiography was performed in 17 patients with advanced non-oat cell bronchogenic carcinoma. The patients were treated 1 to 5 times with infusions of 10 mg of mitomycin-C (MMC) into the tumor-feeding bronchial artery. All but 2 patients received in addition small doses of vincristine (intravenously) and bleomycin (intramuscularly) or only bleomycin to potentiate the effect of MMC. No major side effects occurred and the systemic toxicity was insignificant. An objective tumor reponse was encountered in 11/17 patients. Intraarterial chemotherapy is strictly local and therefore effective especially in patients with limited or locally advanced disease. In patients with more extensive disease an adjunctive therapy of a more regional or systemic modality must be given.

Local injection of antitumor agents in the gastric wall for treatment of nodal metastases of gastric carcinoma.

With the aim of obtaining effective concentration of antitumor agents in the regional lymph nodes of the stomach, 1) local injection of antitumor agent, 2) ligation of the gastric veins and 3) combined use of dextran sulphate (DS) and urokinase (UK) were performed, and it was examined whether these methods were useful for treatment and prevention of metastases from the view point of tissue level of the agents in the lymph nodes. The subjects examined were 120 cases of gastric Cancer, in which concentration-dependent antitumor agents such as Mitomycin C (MMC) or Cyclophosphamide (CPA) were injected into the gastric wall adjacent to the carcinoma just after laparotomy. After extirpation of the regional lymph nodes and resection of the stomach, the concentration of antitumor agents was measured. The concentration of agents in the regional lymph nodes after local injection of 500 mg of CPA was approximately two times higher in both direct and indirect values than those after intravenous injection. By a local injection of 10 mg of MMC, effective concentration of MMC was detected in the groups 1 and 2 regional lymph nodes of the stomach as well as at the surgical margins of resection. Although the concentration of agents in the lymph nodes containing metastatic carcinoma was lower than that in the normal nodes, ligation of the efferent gastric veins caused 1.5-2.5 times increase in concentration. Moreover, combined use of DS and UK with antitumor agents before the surgical operation increased the tissue level of antitumor agents regardless of metastases in the lymph nodes.

Picibanil (溶連菌製剤) の近交系ACI/Nラット移植膀胱腫瘍に対する免疫反応について

Transitional cell carcinomas (BC-47, BC-35 and BC-50) were produced in urinary bladder of ACI/N rats by oral administration of N-butyl-N-butanol (4) nitrosamine (BBN). The cells of these carcinomas can multiply successively in vitro and these cultured cells are always iso-transplantable into the urinary bladder of ACI/N rats. BC-47 is a high antigenic transitional cell carcinoma accompanied with squamous cell metaplasia, BC-35 is a moderate antigenic and BC-50 is a low antigenic. PICIBANIL is a biological preparation obtained from a low virulent mutant of lancefield's type III, group A Streptococcus pyogenes. PICIBANIL attacks directly the tumor cells and also potenciates the defence mechanism of the host.In vitro study.Effects of PICIBANIL and Mitomycin C (MMC) for BC-47 cells were tested in cell culture by the method of colony inhibition assay. Complete inhibition of cell growth was seen in PICIBANIL at a concentration of 1000μg/3ml. No inhibition was seen at a concentration of 200μg/3ml and below. This concentration was higher than the concentration of PICIBANIL in the bladder wall of rats, when 0.5mg of the agent was injected intraperitoneally. Complete inhibition of BC-47 cells was seen in MMC at a concentration of 10μg/3ml, and no inhibition was seen at a concentration of 0.01μg/3 ml and below.In vivo study.Ten days after implantation of various cancer cells (2×108) into the urinary bladder of ACI/N rats, when the growth of carcinomas was confirmed macroscopically, the first injection was done as follows. In case of BC-47, BC-35 and BC-50, 0.5mg of PICIBANIL alone and in case of BC-47, 0.5mg of PICIBANIL combined with 1.0mg of β-methasone and 0.1mg of MMC were injected intraperitoneally. These injections were repeated 5 times at one day interval.Complete regression of all high antigenic BC-47 carcinomas were seen with PICIBANIL therapy alone, but this effect of PICIBANIL was cancelled by combination of β-methasone due to the immunosuppressive effect of this steroid.The effect of MMC for BC-47 was a strong inhibition of tumor growth of the bladder wall, but no complete regression was seen. Histologically, a remarkable lymphocytic infiltration and appearance of foreign body giant cells phogocytizing horny materials were seen in the bladder carcinoma from BC-47, treated with PICIBANIL. And then tumor cells disappeared completely.However, such immunologic reactions were not seen in the same carcinoma when it was treated with PICIBANIL combined with β-methasone. Similarly, BC-35 and BC-50 did not show immunologic reactions even if they were treated with PICIBANIL alone. In BC-47 carcinomas treated with MMC, destroyed tumor cell were observed in histologically.It was thus supposed that the mechanism of the therapeutic effect of PICIBANIL was an acceleration immunologic reaction of the system. On the contrary, that of MMC was a direct destruction of tumor cells.