picibanil and Urinary-Bladder-Neoplasms

Topics: BCG Vaccine; Clinical Trials as Topic; Double-Blind Method; Hemocyanins; Humans; Immunotherapy; Interferons; Levamisole; Picibanil; Poly I-C; Prospective Studies; Random Allocation; Transfer Factor; Urinary Bladder Neoplasms

The prognosis of metastatic or relapsed renal cell carcinoma (RCC) or bladder cancer (BC) remains poor despite the introduction of immune checkpoint blockade agents. We aimed to investigate the safety and the feasibility of a vaccination with WT1 peptide-loaded dendritic cells (DCs) and OK-432 adjuvant combined with molecular targeted therapy or conventional chemotherapy. Five eligible patients with metastatic or relapsed RCC and five eligible patients with BC were enrolled. No severe adverse events related to a vaccination were observed. Seven patients with RCC or non-muscle invasive BC had durable stable disease and three other patients had disease progression after DC vaccination. DC vaccination augmented WT1 specific immunity and the reduction of regulatory T cells which might be related to clinical outcome. These results indicate that DC-based immunotherapy combined with a molecular targeted therapy or a conventional chemotherapy is safe and feasible for patients in advanced stage of RCC or BC.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Cancer Vaccines; Carcinoma, Renal Cell; Dendritic Cells; Disease Progression; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Molecular Targeted Therapy; Neoplasm Metastasis; Neoplasm Recurrence, Local; Picibanil; Treatment Outcome; Urinary Bladder Neoplasms; WT1 Proteins

To evaluate the effects of bladder instillation chemotherapy of anticancer agents with OK-432 intradermal injection (group A) in preventing postoperative recurrence of bladder carcinoma, a randomized controlled study with intravesical instillation chemotherapy of anticancer agents (group B) as the reference standard was performed. As the anticancer agents, pepleomycin (PEP) was usually used at a concentration of 30 mg/30 ml physiological saline. OK-432 injection dose was gradually increased from 0.5 KE to 5.0 KE and maintenance dose was decided by local skin reactions. There were no differences in the patient's background factors between group A (22 cases) and group B (17 cases). The no-recurrence rate of bladder carcinoma was similar in the two groups, but the no-recurrence rate for the virgin tumor or the stage T0 cases was higher in group B. On the other hand, the values for the recurrent cases or the stage T1,2 cases was higher in group A. The SU-PS skin reaction as an immunological response was significantly higher in group A. There were no severe side effects derived from anticancer bladder instillation or OK-432 injection.

Topics: Administration, Intravesical; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Bleomycin; Female; Humans; Injections, Intradermal; Male; Middle Aged; Multicenter Studies as Topic; Neoplasm Recurrence, Local; Neoplasm Staging; Peplomycin; Picibanil; Postoperative Complications; Random Allocation; Urinary Bladder Neoplasms

A streptococcal preparation, OK432 was evaluated as the adjuvant immunotherapeutic agent for superficial bladder tumors. Twenty-nine cases were treated with complete transurethral resection and then randomized prospectively into two groups. One group had adjuvant therapy of OK432 intradermal administration and another group had no adjuvant therapy. OK432 administration significantly reduced the recurrence rates as compared to the control group. Although further studies were required for its full significance, in a short-term study, OK432 intradermal administration produced a beneficial effect in reducing the recurrence rates.

Topics: Aged; Biological Products; Combined Modality Therapy; Drug Evaluation; Female; Humans; Injections, Intradermal; Male; Middle Aged; Neoplasm Recurrence, Local; Picibanil; Prospective Studies; Random Allocation; Urinary Bladder Neoplasms

OK-432, a lyophilized preparation of Streptococcus pyogenes, was cystoscopically injected into bladder cancer to destroy cancer cells and to prevent recurrences. Marked reactions occurred such as stromal edema, vascular dilation, cancer cell exfoliation, and polymorphonuclear cell infiltration, succeeded by monocyte and lymphocyte infiltration with occasional lymph follicle formation. Cancer cells were sometimes intermingled in microscopic necrotic foci. Foamy granuloma was another characteristic finding. The postoperative follow-up study showed a significantly low recurrence rate.

Topics: Aged; Aged, 80 and over; Biological Products; Clinical Trials as Topic; Female; Follow-Up Studies; Humans; Male; Middle Aged; Picibanil; Urinary Bladder Neoplasms

Seventy-eight patients with superficial bladder cancer were entered into a randomized study. A streptococcal preparation, OK-432, was injected into bladder cancers before transurethral resection and instilled into the bladder for 6 months after resection to reduce the recurrence. The control group were only transurethrally resected, as usual. The recurrence rate for patients with primary disease was 3.6 in 100 months for the OK-432 group and 9.1 in 100 months for the control group (P less than 0.05). In the control group, multiple, large, sessile, and high-grade tumors had high recurrence rates. But in the OK-432 group, overall recurrence rates were low in both high-risk and low-risk patients. Supplementary immunotherapy is especially effective and is recommended in high-risk patients.

Topics: Adjuvants, Immunologic; Aged; Biological Products; Carcinoma, Transitional Cell; Female; Humans; Immunotherapy; Male; Middle Aged; Neoplasm Recurrence, Local; Picibanil; Urinary Bladder Neoplasms

Topics: BCG Vaccine; Clinical Trials as Topic; Double-Blind Method; Hemocyanins; Humans; Immunotherapy; Interferons; Levamisole; Picibanil; Poly I-C; Prospective Studies; Random Allocation; Transfer Factor; Urinary Bladder Neoplasms

OK-432, a Streptococcus-derived anticancer immunotherapeutic agent, has been applied in clinic for many years and achieved great progress in various cancers. In the present study, we investigated its anticancer effect on bladder cancer through tumor associated macrophages (TAMs). MTS assay validated OK-432 could inhibit proliferation in both T24 and EJ bladder cell lines. OK-432 also induced apoptosis of bladder cancer cells in vitro. Consequently, we demonstrated that OK-432 could suppress the bladder cancer cells migration and invasion by altering the EMT-related factors. Furthermore, using SD rat model, we revealed that OK-432 inhibited tumor growth, suppressed PCNA expression and inhibited metastasis in vivo. Taken together, these findings strongly suggest that OK-432 inhibits cell proliferation and metastasis through inducing macrophages to secret cytokines in bladder cancer.

Topics: Animals; Antineoplastic Agents; Apoptosis; Blotting, Western; Cell Movement; Cell Proliferation; Female; Flow Cytometry; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Macrophages; Picibanil; Rats; Rats, Sprague-Dawley; Tumor Cells, Cultured; Urinary Bladder Neoplasms; Xenograft Model Antitumor Assays

We studied the effect of an inhibitor of nitric oxide (NO) synthesis, N(G)-monomethyl-L-arginine (L-NMMA), on the Bacillus Calmette-Guérin (BCG)-induced antitumor activity of murine peritoneal exudate cells (PEC) against murine bladder cancer cell line MBT-2 in vitro. L-NMMA enhanced BCG-induced cytotoxic activity of PEC, as well as interferon (IFN)-gamma and tumor necrosis factor (TNF)-alpha production. The L-NMMA-induced enhancement was due to the prolonged survival of BCG in macrophages, because no enhancement of cytotoxicity was observed and neither IFN-gamma nor TNF-alpha production was significantly enhanced by killed BCG. Anti-TNF-alpha antibody (Ab) and anti-IFN-gammaAb reduced the L-NMMA-induced enhancement of the cytotoxicity. The depletion of T cells from PEC reduced the production of both IFN-gamma and TNF-alpha, as well as the enhancement of cytotoxicity induced by viable BCG plus L-NMMA. These results suggest that L-NMMA has an enhancing effect on BCG-induced macrophage cytotoxicity and the enhancement is partially mediated by T cells and their soluble products. Accordingly, NO inhibitor should be a valuable adjunct to BCG immunotherapy for bladder cancer.

Topics: Animals; Antibodies; Antineoplastic Agents; BCG Vaccine; Cell Communication; Colony-Forming Units Assay; Enzyme Inhibitors; Interferon-gamma; Killer Cells, Natural; Macrophage Activation; Macrophages; Mice; Nitric Oxide; omega-N-Methylarginine; Picibanil; T-Lymphocytes; Thioglycolates; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha; Urinary Bladder Neoplasms

Fatal complications from the intravesical instillation of bacillus Calmette-Guérin (BCG) for the treatment of superficial urinary bladder tumors have been reported. OK-432, an immunomodulating agent like BCG, may be an effective and safe agent for the treatment of urinary bladder tumors. We investigated the cytokine-mediated antitumor effect of OK-432 on established human bladder cancer cell lines (T24 and KK-47) in vitro. Peripheral blood mononuclear cells (PBMCs) from a healthy volunteer were cultured with OK-432 for various periods, and the culture supernatants were used as conditioned media. Cytokines in the culture supernatants were quantified. The antitumor effect of OK-432 was evaluated by colony-forming assays, using the conditioned media as the culture media. The colony survival of T24 and KK-47 cells was significantly inhibited by conditioned media from 24-h cultures of PBMCs incubated with OK-432 at concentrations of 0.05 and 0.1 Klinische Einheit (KE)/ml. Conditioned media from PBMCs cultivated with OK-432 for 7 days at 0.01 and 0.05 KE/ml also significantly inhibited the colony survival of both cell lines. Higher concentrations of interleukin-1 beta (IL-1 beta) and tumor necrosis factor alpha (TNF alpha) were detected in conditioned media cultivated with OK-432 for 24 h than in media from PBMCs alone. However, higher concentrations of interferon gamma (IFN gamma) were detected in conditioned media cultivated with OK-432 for 7 days. Approximately 90% of the inhibition of KK-47 cells by the 24-h conditioned media was neutralized by an anti-TNF monoclonal antibody. The inhibition of T24 cells was neutralized approximately 50% by the same antibody. The inhibition of T24 and KK-47 cells by 7-day conditioned media was completely neutralized by an anti-IFN gamma monoclonal antibody. The cultivation of PBMCs with OK-432 inhibited the production of granulocyte-colony-stimulating factor (G-CSF) by PBMCs. The inhibition may play a role in the mechanism of the antitumor effect of OK-432. Urinary bladder tumor cell lines have different sensitivities to cytokines. The cytokines induced by OK-432 vary with the concentration of OK-432 and the culture period. It is suggested that in intravesical instillation of OK-432 for treatment of urinary bladder tumor, the optimal dose and interval of instillation should be considered.

Topics: Antibodies, Monoclonal; Antineoplastic Agents; Carcinoma, Transitional Cell; Cell Division; Culture Media, Conditioned; Cytokines; Drug Interactions; Granulocyte Colony-Stimulating Factor; Humans; Leukocytes, Mononuclear; Picibanil; Time Factors; Tumor Cells, Cultured; Urinary Bladder Neoplasms

The streptococcal preparation OK-432 was tested for its ability to enhance the susceptibility of fresh urinary bladder tumor (UBT) cells to autologous peripheral blood lymphocytes (PBL) in patients with UBT. PBL treated with OK-432 at 0.1 Klinishe Einheit (KE)/ml for 18 hours killed the human T24-lined UBT cells and freshly separated autologous UBT cells more efficiently than untreated PBL. Treatment of K562 erythroleukemia cells with OK-432 at 0.1 KE/ml for 18 hours had no effect on their susceptibility to lysis by fresh PBL. In contrast, treatment of T24 and fresh autologous UBT cells with OK-432 resulted in an enhancement of their susceptibility to PBL. The susceptibility of autologous UBT cells to both large granular lymphocytes (LGL) and T-lymphocytes was also enhanced by treatment of tumor cells with OK-432. Binding of PBL to T24 and fresh autologous UBT cells was also augmented by treatment of the tumor cells with OK-432. The frequency of binding of OK-432 to fresh UBT cells was positively correlated with the increased target sensitivity to autologous PBL. The inhibition of RNA synthesis in fresh UBT cells by OK-432 was also associated with the elevated susceptibility to autologous PBL. These results indicate that OK-432 activates the autologous tumor killing system through stimulation of effector cells and elevation of target susceptibility to effector cells in patients with UBT, and suggest that the OK-432-augmented target sensitivity to PBL may be oriented specifically to UBT cells and local immunotherapy with OK-432 may be remarkably beneficial in the treatment of UBT.

Topics: Adult; Aged; Aged, 80 and over; Carcinoma, Transitional Cell; Chromium Radioisotopes; Cytotoxicity, Immunologic; Female; Humans; Killer Cells, Lymphokine-Activated; Lymphocytes; Male; Middle Aged; Picibanil; RNA, Neoplasm; Tumor Cells, Cultured; Urinary Bladder Neoplasms

Authors studied the effects of several biological response modifiers (BRMs) on bladder carcinoma. On carcinogenesis in BBN-induced bladder carcinoma rats, Schizophyllan (SPG) showed inhibition of body weight loss and thymus weight loss. Bladder weight increase was also inhibited. SPG prolonged cancer-bearing survival time, and postponed malignant changes of bladder mucosa. On thymocytes of SPG-treated cancer-bearing rats, rosette-forming thymocytes increased. In clinical study, SPG, OK-432, ubenimex and kampo medicine were used as BRMs. As a result, the number of suppressor-inducer T cells increased, and in cytotoxic T cells a slow fall was observed. On helper-inducer T cells, a slow rise and decrease were noticed in the SPG group, and the reverse tendency was seen in the ubenimex and OK-432 group.

Topics: Adjuvants, Immunologic; Animals; Antibiotics, Antineoplastic; Antineoplastic Agents; Combined Modality Therapy; Drugs, Chinese Herbal; Female; Humans; Immunologic Factors; Leucine; Male; Picibanil; Rats; Rats, Inbred Strains; Sizofiran; Urinary Bladder Neoplasms

The anti-tumor effect of OK432 instilled into the bladder was evaluated in rat bladder tumors induced by N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN). In experiment I, the rate of the natural killer (NK) activity was determined with cells from spleen and mesenteric lymph nodes. Intravesical OK432 instillation enhanced NK activity; however, this activity was not dose-dependent and was not augmented by OK432 inoculation into the foot pad. In experiment 2, the therapeutic effect of intravesical OK432 instillation was examined in rat bladder tumors induced by BBN. OK432 was instilled weekly for six weeks. Rats given BBN for 10 weeks were divided into six groups: 1) control; 2) saline; 3) OK432 0.05 KE/ml; 4) OK432 0.05 KE/ml bladder instillation with 0.01 KE/ml foot pad inoculation; 5) OK432 0.05 KE/ml, every other week; and 6) OK432 0.5 KE/ml. Weekly OK432 instillation significantly reduced tumor weight and the incidence of tumor development; however, this inhibition was not dose-dependent and was not enhanced by OK432 inoculation into the foot pad. In rats given OK432 weekly, the augmentation of NK activity and increase in tissue infiltrating lymphocytes were significant. These results suggest that intravesical OK432 instillation is effective in the management of superficial bladder tumors. The study further emphasizes that the dose and method of administration are critical variables in determining the efficacy of immunotherapy.

Topics: Administration, Intravesical; Animals; Butylhydroxybutylnitrosamine; Female; Killer Cells, Natural; Picibanil; Rats; Rats, Inbred Strains; Urinary Bladder Neoplasms

The cross-antigenicity between streptococcus, Su strain (OK-432), and rat bladder cancer BC-47 was studied by the immunocytochemistry. Both anti-Su (OK-432) and anti-BC-47 reacted with both homo- and heterogenous antigens. The specificity of the PAP reactions using these sera was confirmed by absorption study of the first antibodies. But, OK-432 did not share with normal rat tissues. Furthermore, the presence of common antigens between OK-432 and animal tumors where OK-432 was effective was indicated by the PAP studies, but OK-432 did not share with tumors where OK-432 was ineffective. By the PAP studies using antigroup A streptococcus-specific C-polysaccharide and antigroup-specific sera, it was suggested that the determinant of the cross-antigenicity was group A-specific C-polysaccharide. The common antigens between OK-432 and human urogenital cancers were also identified by the PAP study. Then, local immunotherapy with OK-432 was carried out in 38 patients with superficial bladder tumor and the tumors were eliminated in 23.7%. In 77.8% of the complete response and in 10.3% of the no change, the tumor tissues demonstrated antigens common between OK-432 and tissues. From these results, it was concluded that common antigens which OK-432 shared with tumors could favorably augment host defense against human bladder tumors, the same as animal tumors.

Topics: Animals; Antigens, Bacterial; Antigens, Neoplasm; Biological Products; Carcinoma, Transitional Cell; Cross Reactions; Epitopes; Female; Humans; Immunoenzyme Techniques; Male; Mice; Middle Aged; Picibanil; Rats; Urinary Bladder Neoplasms

A 42-year-old man was admitted because of huge retrovesical mass. The organ from which the tumor originated was unknown. The biopsy specimen showed poorly differentiated adenocarcinoma. The tumor increased rapidly and could not be resected because of peritoneal dissemination. The mass fully occupied the abdominal space with marked dyspnea. Fortunately, a marked decrease in the tumor size was noted by neo-MFC without any side effect. Therefore, the patient could enjoy a daily life until he died suddenly of cardiac failure 8 months after first admission. Retrovesical tumor is usually discovered at advanced stage because of lack of symptoms. For recovery of good performance status combined chemotherapy with relatively mild side effect must be selected and administered for a long time.

Topics: Adenocarcinoma; Adult; Antineoplastic Combined Chemotherapy Protocols; Cyclophosphamide; Humans; Male; Mitomycin; Mitomycins; Neoplasm Staging; Picibanil; Tegafur; Urinary Bladder Neoplasms

The role of natural killer (NK) cells in bladder tumors was assessed from the aspect of local and systemic immune responses. The NK cell activity was measured in a 4-hour 51Cr-release assay. The NK activity in patients with bladder tumor was lower, though not significantly, than that in normal individuals. In patients with bladder tumor, the NK activity was significantly lower in invasive tumors and lymph node metastases. Moreover, the NK activity was lower in those who died (n = 4) than it was in survivors (n = 21). In an in vitro experiment, OK432 significantly augmented the NK activity in peripheral blood lymphocytes (PBL), however, this augmentation was not always OK432 dose-dependent. The augmented NK activity induced by OK432 occurred even in patients with invasive tumors. On the other hand, the spontaneous NK activity in tissue-infiltrating lymphocytes (TIL) and lymph node lymphocytes (LNL) was significantly lower than that in PBL. In these three groups, the NK activity was significantly increased by OK432, this rate of increase was highest in TIL, followed by LNL and PBL. Further studies are required to elucidate the role of NK cells in bladder tumor, from the aspect of local and systemic immune responses.

Topics: Aged; Cells, Cultured; Cytotoxicity Tests, Immunologic; Female; Flow Cytometry; Humans; Killer Cells, Natural; Lymphocytes; Macrophages; Male; Middle Aged; Picibanil; Urinary Bladder Neoplasms

In 38 patients with superficial bladder, local immunotherapy with streptococcal preparation OK-432 has been performed. We investigated whether OK-432 was an effective biological response modifier (BRM) against bladder tumors or not, and the relationship between the common antigens which OK-432 shared with the tumors, and antitumor effects of OK-432. In six out of 28 patients treated by intravesical instillation, and three out of 10 cases treated by intratumor injection, tumors were eliminated endoscopically. In the other patients, the tumors did not change. The PAP study using an anti-OK-432 antibody, showed a positive reaction in 66.7% of the instillation cases and in 40.0% in the injection cases. In 66.7% of the patients with the common antigens treated by the instillation and in 75.0% of patients with the antigens treated by the injection, tumors were eliminated. However, the PAP study showed a positive reaction in 9.1% of the no-change cases treated by the instillation and in 14.3% out of the no-change cases treated by the injection. We concluded that OK-432 was a favorable BRM for topical immunotherapy against bladder tumor and the presence of the common antigens between OK-432 and tumor may enhance the immune response of patients and promote tumor regression.

Topics: Administration, Intravesical; Adult; Biological Products; Cross Reactions; Female; Humans; Immunotherapy; Male; Middle Aged; Picibanil; Urinary Bladder Neoplasms

Prognosis on evaluable 86 patients with primary bladder tumor seen during the 10 years up to 1985 was evaluated in relation to treatment mode and tumor stage. The majority of patients underwent multimodal therapies including surgery, chemotherapy and immunotherapy with picibanil (OK432). Transurethral resection of the tumor was performed as an initial surgical treatment in 49 patients, 9 of whom ultimately underwent total cystectomy. After leaving hospital, these patients were kept on immunotherapy with OK432 and topical chemotherapy with bladder instillation of mitomycin C or adriamycin (ADM) with or without systemic administration of Tegefur as long as possible. The overall actual 5-year survival rate for the patients treated by initial transurethral resection was 80%. Recurrence rate for these 49 patients was 35%. Total cystectomy with urinary diversion was performed in 37 patients who had been placed postoperatively on systemic administration of Tegafur and immunotherapy with OK 432 as long as possible. The overall actual 5-year survival rate for the patients treated with total cystectomy was 54%. The patients with pT2 and lower stage tumor had an actual 5 year survival rate of 72%, while the patients with pT3 and higher stage tumors had a survival of 10%. The high recurrence rate in the patients with superficial tumor and the low actual survival rate of the patients with pT3 and higher stage remain a problem in the treatment of bladder tumor. In recent trials, bacillus Calmette-Gúerin instillation therapy has been initiated to lower the recurrence rate in superficial tumor and we have had a satisfactory 4-year result.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Combined Modality Therapy; Doxorubicin; Female; Fluorouracil; Humans; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Prognosis; Tegafur; Uracil; Urinary Bladder Neoplasms

Topics: Adjuvants, Immunologic; Humans; Interleukin-2; Picibanil; T-Lymphocytes; Urinary Bladder Neoplasms

The effects of 12 weeks of intravesical instillation of bleomycin, cisplatinum and picibanyl on development of urinary bladder tumors and preneoplastic lesions were examined in rats pretreated with N-butyl-N-(4-hydroxybutyl)-nitrosamine (BBN) for four weeks. Upon sacrifice at week 36, histopathological examination revealed a significantly reduced incidence of PN hyperplasia and a tendency for decreased papilloma generation in rats given cisplatinum. However, the other treatments were not associated with any effect on carcinogen-induced lesion development. The results demonstrate that cisplatinum has a potential for postinitiation inhibition of rat bladder carcinogenesis.

Topics: Administration, Intravesical; Animals; Antineoplastic Combined Chemotherapy Protocols; Biological Products; Bleomycin; Butylhydroxybutylnitrosamine; Cisplatin; Drug Evaluation, Preclinical; Drug Interactions; Epithelium; Female; Nitrosamines; Picibanil; Precancerous Conditions; Rats; Rats, Inbred F344; Time Factors; Urinary Bladder; Urinary Bladder Neoplasms

Topics: Animals; Antigens, Neoplasm; Antineoplastic Agents; Biological Products; Cross Reactions; Humans; Immunoenzyme Techniques; Mice; Picibanil; Rats; Streptococcus; Urinary Bladder Neoplasms

Thermotherapy combined with tegafur (FT-207) and Picibanil was performed in 13 patients with cancer of the urinary bladder. The thermotherapy was performed using a closed circulation type of thermotherapeutic apparatus manufactured for this experiment, by way of a 3-way catheter. The flow rate of the perfusate was 150 ml/min at a constant temperature of 43 degrees C. The temperature was monitored at the inlet and outlet catheter of the urethral meatus. The thermotherapy was performed for a 6-hour period once a week. A tegafur 3000-mg suppository was given 2 hours before the thermotherapy, and Picibanil was added to the perfusate at the time of thermotherapy. No anesthesia was used. Complete disappearance of the tumor was observed in 1 case. The concentrations of tegafur in the serum, tumor and bladder wall were measured simultaneously. The levels obtained at two hours after rectal administration of the tegafur 3000-mg suppository were 19.420 mcg/ml for FT-207 and 0.025 mcg/ml for 5-FU in the serum, 13.170 mcg/g for FT-207 and 0.140 mcg/g for 5-FU in the bladder tumor, and 20.447 mcg/g for FT-207 and 0.252 mcg/g for 5-FU in the bladder wall. Eruption was observed in 1 case. No other side effects were noted.

Topics: Adult; Aged; Biological Products; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Fluorouracil; Humans; Hyperthermia, Induced; Male; Middle Aged; Picibanil; Suppositories; Tegafur; Urinary Bladder; Urinary Bladder Neoplasms

Four patients with urinary bladder carcinoma were treated by combination therapy which consisted of hyperthermia vesical irrigation of two anticancer drugs (peplomycin and picibanil), intravesical instillation of those drugs and radiation. Following the therapeutic method we planned, 40 mg of peplomycin and 10 KE of picibanil in 1,500 ml of sterile distilled water was irrigated at 42 to 43 degrees C into the bladder for 3 hours; 40 mg of peplomycin and 10 KE of picibanil in 40 ml of sterile distilled water was instilled into the bladder; and, the focus was irradiated with 60Co to a focal dose of 200 rad 30 minutes later. This pattern of treatment was repeated once a week, 3 to 5 times in total. On the days this pattern was not taken, 5 KE of picibanil in 20 ml of sterile distilled water was instilled into the bladder cavity. Complete response was observed in one patient and partial response in 3 patients. The side effect was temporary irritable bladder symptom.

Topics: Aged; Antibiotics, Antineoplastic; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Carcinoma, Transitional Cell; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Male; Middle Aged; Peplomycin; Picibanil; Radiotherapy Dosage; Urinary Bladder Neoplasms

A total of 24 patients with urothelial cancer were treated with a combination chemotherapy consisting of vincristine (1 mg, i.v., day 1), bleomycin (15 mg, or peplomycin, 10 mg, i.m. day 2), mitomycin-C (4 mg, i.v. day 3), tegafur (600-750 mg, p.o., every day) and OK-432 (2-4 KE, i.m., day 1, 3, 5). This one-week course was repeated for an average of 4.6 courses. Of these cases, 13 patients with early stage treated as adjuvant chemotherapy after radical operation showed strong suppressive effects against tumor recurrence or metastasis except 3 cases. However, in advanced cancer this regimen was less effective. Therefore, we modified this regimen: VCR 2mg and PEP, 10 mg on days 2, 4 and 6. This modified regimen was given to two patients and one showed partial response and I-A according to Karnofsky's criteria. Mild side effects such as slight leukopenia, fever up, gastrointestinal symptoms or alopecia were observed. These results suggest that this regimen could be used as an adjuvant chemotherapy after radical operation of urothelial malignancy for the purpose of protecting tumor recurrence or metastasis.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Bleomycin; Combined Modality Therapy; Female; Humans; Kidney Neoplasms; Male; Middle Aged; Mitomycin; Mitomycins; Picibanil; Tegafur; Ureteral Neoplasms; Urinary Bladder Neoplasms; Urologic Neoplasms; Vincristine

Thermotherapy combined with Tegafur and Picibanil was performed in 32 patients with cancer of the urinary bladder. The thermotherapy was performed with a closed circulation type of thermotherapeutic apparatus manufactured for trial, using a 3-way catheter. The flow quantity of the perfusate was 150 ml/min at a constant temperature of 43 degrees C. The temperature was monitored at the inlet and outlet catheter at the urethral meatus. The thermotherapy was performed for 6 hours once a week. Tegafur and Picibanil were added to the perfusate at the time of thermotherapy. No anesthesia was used. Complete disappearance of tumor occurred in 9 cases. The concentration of Tegafur in the serum, tumor and bladder wall was simultaneously measured. The serum levels after two hours of thermotherapy with 16 gm of dissolved Tegafur showed that FT-207 was 28.837 mcg/ml and 5-FU, 0.028 mcg/ml. After 4 hours the FT-207 was 36.464 mcg/ml and 5-FU, 0.040 mcg/ml. By the 6th hour FT-207 was 39.430 mcg/ml and 5-FU, 0.049 mcg/ml. After 24 hours FT-207 was 11.242 mcg/ml and 5-FU, 0.013 mcg/ml in the serum, while FT-207 was 8.205 mcg/g and 5-FU, 0.274 mcg/g in the bladder tumor, and FT-207 was 17.029 mcg/g and 5-FU, 0.157 mcg/g in the bladder wall. Nausea was observed in 1 case in which a large quantity of Tegafur was absorbed. No other side effects were noted.

Topics: Aged; Biological Products; Combined Modality Therapy; Drug Therapy, Combination; Female; Fluorouracil; Humans; Hyperthermia, Induced; Male; Middle Aged; Picibanil; Tegafur; Urinary Bladder; Urinary Bladder Neoplasms

The relapse rate of bladder cancer (transitional cell Ca) is said to be about 45%-80% even after tumor resection. Multidisciplinary treatment was designed and studied to prevent such recurrence. This treatment was designed to have three steps: induction, consolidation, and maintenance therapy. Following surgical tumor removal, OK-432 and Adriamycin (ADM) were administered as consolidation therapy, followed by administration of PSK and carboquone (CQ) in small amounts as maintenance therapy continuously for about 3 years, and the course was observed. In both consolidation and maintenance groups various non-specific immunoparameters were superior in groups receiving combined immunotherapeutic agents. Thus, the use of immunotherapeutic agents in combination with chemotherapeutic agents was considered to be effective. The 3-year recurrence rate was only 8% in the multidisciplinary treatment group, while that in the non-multidisciplinary treatment group was 61%. This approach, especially with chemoimmunotherapy (ADM and OK-432) as a consolidation therapeutic mode, is therefore considered to be useful for the prevention of recurrence.

Topics: Adjuvants, Immunologic; Aged; Alopecia; Biological Products; Carbazilquinone; Carcinoembryonic Antigen; Carcinoma, Transitional Cell; Combined Modality Therapy; Doxorubicin; Female; Follow-Up Studies; Humans; Immunity, Cellular; Immunoglobulin G; Male; Middle Aged; Neoplasm Recurrence, Local; Picibanil; Proteoglycans; T-Lymphocytes; Urinary Bladder Neoplasms

Eighty-eight cases of urinary bladder tumor were treated in our Department from 1976 to 1978. The effect of so-called immunopotentiators (OK-432, Levamisole and PSK) was studied in 23 patients. The following results were obtained. Pretreatment intracutaneous response to PHA was significantly lower in the high stage and high grade group than in the low stage and low grade group (P less than 0.025). However, there was no correlation between the effect of immunotherapy and PHA skin reaction. Of the immunoglobulins, only IgM was significantly lower in the high grade group than in the low grade group (P less than 0.025). The one-year survival rate for the patients in the high stage group was higher receiving immunotherapy than those not treated. This suggests that immunotherapy may be useful for prolonging the survival time of patients with advanced bladder carcinoma.

Topics: Adjuvants, Immunologic; Aged; Antibiotics, Antineoplastic; Biological Products; Carcinoma, Squamous Cell; Carcinoma, Transitional Cell; Female; Humans; Levamisole; Male; Middle Aged; Phytohemagglutinins; Picibanil; Prognosis; Proteoglycans; Skin Tests; Urinary Bladder Neoplasms

Topics: Biological Products; Doxorubicin; Female; Humans; Male; Neoplasm Recurrence, Local; Picibanil; Proteoglycans; Urinary Bladder Neoplasms

The characteristics of the cytotoxic cells induced by ip injections of an immunoadjuvant, OK-432 (Picibanil), into ACI/N rats bearing syngeneic bladder cancer, BC47, were examined. The cytostatic activity, but not the cytolytic activity, of peritoneal macrophages was augmented when either normal or cancer-bearing rats were treated with OK-432. In contrast, the plastic nonadherent cells of the peritoneal exudate cells from OK-432-treated cancer bearing rats, but not lymph node cells or spleen cells, killed all ACI/N rat bladder cancers tested as well as ACI/N rat hepatoma cells and Meth-A mouse sarcoma cells. The plastic nonadherent cells from OK-432-treated normal rats also killed hepatoma cells and Meth-A cells, but not bladder cancer cells. The cytolytic cells that were induced in cancer-bearing rats by OK-432 treatment and showed cytolytic activity specific for bladder cancer were found to be sensitive to anti-rat thymocyte serum and complement, nylon-adherent, and Fc receptor-negative. The cells that showed nonselective cytolytic activity were nylon-adherent and insensitive to anti-rat thymocyte serum and complement.

Topics: Animals; Biological Products; Cell Adhesion; Cell Line; Cytotoxicity, Immunologic; DNA Replication; Male; Mice; Mice, Inbred BALB C; Neoplasms, Experimental; Picibanil; Rats; Rats, Inbred ACI; Sarcoma, Experimental; Urinary Bladder Neoplasms

We evaluated the immunostimulative activity of a Streptococcus pyogenes preparation (OK432) in 50 patients with urogenital carcinoma. Differential lymphocyte blastogenic response to mitogens and quantitation of the lymphocyte subpopulation bearing Fc receptor sites were the two immunoparameters used in this study to assess the status of the cancer-bearing host. Using these immunoparameters, we observed a pattern whereby a substantial deviation from unity in the mitogen reactive ratio and an increase in the number of IgGFcR+T cells were correlated with malignant progression; administration of the immunopotentiator OK432 had a marked effect on immunoparameters reflected by our assays, with a trend toward return to normal values with progression of immunotherapy.

Topics: Adult; Aged; Biological Products; Doxorubicin; Female; Humans; Lymphocyte Activation; Male; Middle Aged; Picibanil; Receptors, Fc; T-Lymphocytes; Urinary Bladder Neoplasms; Urogenital Neoplasms

Topics: Adult; Aged; Biological Products; Carcinoma, Transitional Cell; Female; Humans; Injections; Male; Middle Aged; Picibanil; Urinary Bladder Neoplasms

When 21 patients with bladder cancer (transitional cell carcinoma) were given local and systemic injections of a streptococcal preparation, OK-432, tumor regression was observed in 3 cases (14.3%). The marked infiltration of lymphocytes observed on histological examination of regressed tumors suggested that a host-mediated action was involved in the antitumor effect of OK-432.

Topics: Biological Products; Carcinoma, Transitional Cell; Female; Humans; Male; Middle Aged; Picibanil; Urinary Bladder Neoplasms

The effect of azathiopurine and OK-432 on bladder carcinogenesis in rats was evaluated using the carcinogens, N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) and N-[4-(5-nitro-2-furyl)-2-thiazolyl]formamide (FANFT). Azathiopurine did not affect FANFT bladder carcinogenesis in any treatment. By contrast, when azathiopurine was fed simultaneously with BBN there was a significant increase in the incidence of bladder tumors, although it had no effect if administered before or after BBN. Short-term administration (8 weeks) of OK-432 subcutaneously before, during, or after BBN did not affect bladder carcinogenesis, but if OK-432 was begun after BBN and continued until the end of the experiment, the incidence of BBN-induced bladder tumor was significantly reduced. No bladder lesions were observed in control rats or in rats receiving only azathiopurine or OK-432.

Topics: Animals; Azathioprine; Biological Products; Butylhydroxybutylnitrosamine; Drug Synergism; Immunosuppressive Agents; Male; Neoplasms, Experimental; Papilloma; Picibanil; Rats; Urinary Bladder Neoplasms