picibanil and Pleural-Effusion--Malignant

The patient was a 42-year-old woman. After 4 courses of capecitabine therapy for right chest wall recurrence of breast cancer, ER(+, 10-15%), PgR(-), HER2(-), she underwent pleurodesis using OK-432 for increased right pleural effusion. On the 12th day after pleurodesis diffuse infiltrative shadows in the right lung, and frosted shadows in both lungs, were observed, and she was diagnosed with drug-induced lung injury. About 3 weeks after administration of prednisolone 1 mg/ kg a tendency for improvement in lung injury was observed, but the patient died of breast cancer progression. Drug- induced lung injury by pleurodesis carries the risk of delaying resumption of chemotherapy. We report this case with a review of the literature.

Topics: Adult; Breast Neoplasms; Female; Humans; Lung Diseases, Interstitial; Lung Injury; Picibanil; Pleural Effusion; Pleural Effusion, Malignant; Pleurodesis

Topics: Cisplatin; Drainage; Humans; Instillation, Drug; Picibanil; Pleural Effusion, Malignant; Thorax

Symptomatic malignant pleural effusions should be treated systemic chemotherapy in chemo-sensitive tumors such as small cell lung cancer, breast cancer, lymphoma, or ovarian cancer. In other non-chemo-sensitive malignancies including non-small cell lung cancer, water-sealed tube drainage and pleurodesis is the standard treatment of choice in most of the cases. Drugs for instillation should be blomycin or OK-432 if commercially available. Instead of the former standard drug tetracycline, doxycycline has been frequently used. As we have no randomized trials, this drug awaits phase III trials. Talc slurry has been accepted and counted as one of the standard choices in the western countries, however, it usually needs general anesthesia and adverse effects are not negligible. As we have little experience on this modality, it should not be considered as a standard treatment. Other antitumor drugs instillation, thoraco-abdominal shunting, and pleuro-pneumonectomy should be considered experimental because of the lack of randomized trials. Symptomatic pericardial malignant effusion or cardiac tamponade is an oncologic emergency. We had better to treat the patient immediately by pericardiocentesis under the cardiac echographic guidance. It should be reserved to solve in randomized trials that the best method would be pericardiocentesis alone, percutaneous continuous drainage, pericardial fenestration, or pericardio-thoraco fenestration. Instillation of drug like doxycycline, OK-432, or bleomycin, lacks phase III comparison and it should be categorized as experimental.

Topics: Antineoplastic Agents; Bleomycin; Breast Neoplasms; Carcinoma, Small Cell; Drainage; Female; Humans; Lung Neoplasms; Pericardial Effusion; Picibanil; Pleural Effusion, Malignant; Randomized Controlled Trials as Topic

The current prospective randomized study was designed to evaluate the safety and efficacy of combined intrapleural cisplatin and OK-432 (picibanil) plus hyperthermotherapy in patients with malignant pleural effusion (MPE).. A total of 358 patients with MPE due to end-stage malignancies were enrolled and randomly divided into two groups, A and B: the intrapleural combination of cisplatin and OK-432 with hyperthermotherapy (n = 179) or without hyperthermotherapy (n = 179), respectively. Mild toxicities such as nausea, vomiting or anorexia, bone marrow depression, and pyrexia were similar in both groups.. Patients in Group A (with hyperthermotherapy) showed a significantly higher overall response (93.4%) compared to those in Group B (79.8%, χ(2) = 43.11, p < .05). The median survival time for patients in Group A and Group B were 8.9 and 6.2 months, respectively (p > .05). After treatment, the quality of life scores were significantly increased in both groups as compared to prior treatment (p < .05).. In conclusion, our study suggests that combined intrapleural cisplatin and OK-432 followed by hyperthermotherapy are more effective in the control of MPE and improve patients' quality of life.

Topics: Adult; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Female; Humans; Hyperthermia, Induced; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Prospective Studies; Quality of Life; Survival Analysis

To evaluate the efficacy and toxicity of three intrapleural therapy regimens consisting of bleomycin (BLM), OK-432 (a pulverized product of heat-killed Streptococcus pyogenes) or cisplatin plus etoposide (PE) for the management of malignant pleural effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1mg/kg (maximum 60mg/body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10KE/body), or the PE arm: cisplatin (80mg/m(2)) and etoposide (80mg/m(2)). Pleural response was evaluated every 4 weeks according to the study-specific criteria. All responders received systemic chemotherapy consisting of PE every 3-4 weeks for two or more courses. Pleural progression-free survival (PPFS) was defined as the time from randomization to the first observation of pleural progression or death due to any cause. The primary endpoint was the 4-week PPFS rate. Of 105 patients enrolled, 102 were assessed for response. The 4-week PPFS rate for the BLM arm was 68.6%, 75.8% for the OK-432 arm, and 70.6% for PE arm. Median survival time (MST) for the BLM arm was 32.1 weeks, 48.1 weeks for the OK-432 arm, and 45.7 weeks for the PE arm. However, the outcomes did not differ significantly between groups. Toxicity was tolerable in all arms except for one treatment-related death due to interstitial pneumonia induced by BLM. We will select intrapleural treatment using OK-432 in the management of MPE in NSCLC for further investigation because it had the highest 4-week PPFS rate.

Topics: Adult; Aged; Bleomycin; Carcinoma, Non-Small-Cell Lung; Cisplatin; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Survival Rate

To evaluate the efficacy of combined intrapleural therapy with cisplatin, an antineoplastic agent, and OK432, a sclerosing agent, in controlling malignant pleural effusions, when compared with monotherapy with either agent.. A total of 49 non-small cell lung cancer patients with malignant pleural effusion were randomly assigned to one of three groups: intrapleural cisplatin therapy (n = 17), intrapleural OK432 therapy (n = 17), or both (n = 15). They were compared in terms of success rate, duration of indwelling chest tube and adverse reactions.. Rates of pleural effusion recurrence within 180 days following cisplatin, OK432, or combination therapy were 64.7%, 52.9% and 13.3%, respectively, being significantly lower in the combination therapy group (P = 0.01). The mean duration of chest tube drainage was 8.4 days, 5.5 days and 12.9 days, respectively, being significantly longer in the combination therapy group (P < 0.001). All procedures were well tolerated.. Although chest tube drainage took longer because of the time required for multiple administration of the agents, intrapleural combination therapy with cisplatin and OK432 was more effective in controlling malignant pleural effusions due to non-small cell lung cancer than monotherapy with either agent.

Topics: Aged; Analysis of Variance; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Prospective Studies; Survival Analysis

Malignant pleural effusion, a common complication seen in advanced lung cancer patients, is often treated with intrapleural administration of chemical agents. In Japan, OK-432, a biological response modifiers, which activates the cytotoxic activity of lymphocytes and boosts antitumor immunity, is among the most frequently used chemical agents. The purpose of this study was to determine, in a case-control study, whether or not the rate of lymphocytes in malignant pleural effusion (lymphocyte rate) influences the therapeutic efficacy of intrapleural OK-432.. We enrolled 20 lung cancer patients with malignant pleural effusion treated with intrapleural OK-432 who were admitted to our hospital between January 2000 and December 2004. Therapeutic efficacy was assessed from the response rate, duration of chest drainage after treatment with intrapleural OK-432, time to progression of malignant pleural effusion, and survival time.. Response rate in patients who had a high lymphocyte rate (the High lymphocyte rate group) was significantly higher than in patients who had a low lymphocyte rate (the Low lymphocyte rate group). Lymphocyte rate did not correlate with duration of chest drainage after treatment with intrapleural OK-432, time to progression of malignant pleural effusion, or survival time.. The lymphocyte rate in malignant pleural effusion influences the response rate to treatment by intrapleural OK-432. In the High lymphocyte rate group, intrapleural OK-432 for malignant pleural effusion was effective. We conclude that intrapleural OK-432 is useful for malignant pleural effusion patients with a high lymphocyte rate before treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Case-Control Studies; Disease Progression; Drainage; Female; Humans; Lung Neoplasms; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Picibanil; Pleural Cavity; Pleural Effusion, Malignant; Survival Rate

The current prospective randomized study was designed to compare the effects of intracavitary (i.c.) chemotherapy vs immunotherapy vs immunochemotherapy for malignant effusion. Between 1992 and 1995, a total of 42 patients with malignant effusion were registered, and 41 patients were eligible for statistical analysis. The primary diseases of the eligible patients included 27 gastric, four colorectal, four pancreatic, three lung, two liver and one oesophageal cancers. The patients with malignant effusion were randomly assigned into one of three i.c. therapeutic regimens: chemotherapy alone with weekly injection of anticancer agents (ACAs: cisplatin, mitomycin-C, adriamycin, etc.) (Group A, n = 13); immunotherapy alone with weekly injection of streptococcal preparation OK-432 (Group B, n = 14); or immunochemotherapy with ACAs and OK-432 (Group C, n = 14). The response of the effusion, patient survival and the kinetics of cytokines in the effusion were compared. There were no differences in the patients' backgrounds. The side-effects of the regimens included pain, anorexia, fever, leucopenia and anaemia and there were no differences in their incidence among the three groups. One patient died after cisplatin (CDDP) administration in Group A. Cytologic examination revealed that tumour cells in the effusion disappeared in 23% of Group A cases, 36% of Group B cases and 36% of Group C cases. The malignant effusion did not disappear in any of the Group A cases; however, the effusion disappeared in 29% of Group B cases and 43% of Group C cases (P = 0.03, Group A vs Group C). Furthermore, the 50% survival period was 1.6 months for Group A, 2.4 months for Group B and 3.5 months for Group C. The 6-month survival rate was 7% for Group A, 6% for Group B and 34% for Group C, and the 1-year survival rate was 0%, 0% and 17% respectively (P = 0.048, Group A vs Group C by the log-rank test). The analysis of the cytokine kinetics revealed a prominent increase in the level of interleukin-6 in the effusion in Group C. These results suggest that i.c. immunochemotherapy with OK-432 and ACAs may be more beneficial than i.c. chemotherapy alone or immunotherapy alone.

Topics: Adjuvants, Immunologic; Aged; Antineoplastic Combined Chemotherapy Protocols; Ascitic Fluid; Cisplatin; Combined Modality Therapy; Cytokines; Digestive System Neoplasms; Doxorubicin; Female; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Mitomycin; Patient Selection; Picibanil; Pleural Effusion, Malignant; Prospective Studies

Objective Pleurodesis is an effective therapy for malignant pleural effusion (MPE). While interstitial lung disease (ILD) has been regarded as a serious complication of pleurodesis, its clinicopathological characteristics have not been fully understood. This study was conducted to elucidate the incidence of ILD and the risk factors for ILD in patients who underwent pleurodesis to control MPE. Methods The medical records of patients who underwent pleurodesis in Aichi Medical University between March 2008 and February 2013, the period before the approval of talc in Japan, were retrospectively analyzed. Results A total of 84 patients underwent pleurodesis, all using OK-432. ILD occurred in 13 patients (15.5%). The development of ILD after pleurodesis was significantly associated with old age (odds ratio [OR]: 4.82, 95% confidence interval [CI]: 1.22-19.08) and epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) treatment (OR: 5.97, CI: 1.7-20.9). A multivariate analysis revealed that >67 years of age (p=0.01) and EGFR-TKI treatment (p=0.02) were significantly associated with the development of pleurodesis-related ILD. Among the patients who received both pleurodesis and EGFR-TKIs (n=23), 8 patients developed ILD. All of these patients were receiving EGFR-TKI therapy at the time of pleurodesis or within 30 days after pleurodesis. In contrast, no cases of ILD were observed among the patients who stopped EGFR-TKIs before pleurodesis or started EGFR-TKIs at more than 30 days after pleurodesis. Conclusion ILD seemed to be a frequent complication of pleurodesis in patients using OK-432, especially elderly patients and those who underwent pleurodesis while receiving EGFR-TKI therapy or who started EGFR-TKI therapy within 30 days after pleurodesis.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Female; Humans; Japan; Lung Diseases, Interstitial; Male; Middle Aged; Odds Ratio; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Retrospective Studies; Risk Factors

The choice of an optimal sclerosant for pleurodesis for malignant pleural effusion remains controversial. This retrospective clinical study compared the efficacy and safety of two sclerosants; talc slurry (talc-s) and OK-432.. We compared the characteristics, 30/90-day success rates, and adverse events in patients with lung adenocarcinoma who underwent pleurodesis by using either OK-432 or talc-s. Propensity score matching was used to compare the two scelrosants.. Ninety-four patients (mean age=71.6±9.6 years) were included in this retrospective study, of whom 64 received OK-432 and 30 received talc-s. Seventy-three patients (77.6%) were initially diagnosed with clinical stage IV lung cancer, with a 28.7% epidermal growth factor receptor mutation frequency. The propensity score-matched cohort included 26 patients from each group. The 30-day success rates for OK-432 and talc-s were 80.7% and 76.9%, respectively (odds ratio: 1.26, 95% confidence interval: 0.33-4.77, p=0.73). Neither the overall incidence of adverse events nor the 90-day success rates differed significantly. Multivariate logistic regression revealed that the predictors of 30-day success were lower drainage volume on the previous day, particularly <250mL/day, the presence of full lung expansion, and pre-therapy with an epidermal growth factor receptor-tyrosine kinase inhibitor. The median post-pleurodesis survival time was 6.9 months, which was not significantly different between the study groups.. Propensity score-matched analyses showed that pleurodesis using OK-432 and talc-s demonstrated comparable efficacy and safety profiles in patients with lung adenocarcinoma. This indicated that OK-432 could be a viable alternative to talc-s in this procedure.

Topics: Adenocarcinoma; Aged; Female; Humans; Lung Neoplasms; Male; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Propensity Score; Regression Analysis; Sclerosing Solutions; Talc

Malignant pleural effusion is a common and devastating complication of metastatic breast cancer. This occurs in about 30% of patients with metastatic breast cancer during the clinical course, and chemical pleurodesis is sometimes performed to relieve dyspnea. However, the long-term outcome of pleurodesis and factors affecting successful pleurodesis have not been clarified.. The aim of this analysis is to evaluate the long-term outcome of pleurodesis and to identify risk factors associated with success.. Data on 75 patients who had undergone chemical pleurodesis with OK-432 for pleural effusion due to metastatic breast cancer were reviewed retrospectively. The primary outcomes were success rate and pleural progression-free survival (PPFS) rate.. The median duration of follow-up was 134 days (range 8-975 days). During this period, 22 patients re-accumulated pleural fluid. The overall success rate was 70.5%. The 4-, 8- and 12-week PPFS rates were 88.0, 84.0 and 78.7% respectively. Multivariate analysis identified three unfavorable factors that were independently associated with unsuccessful pleurodesis, including estrogen-receptor negative status, a 24-h drainage volume of more than 100 mL before extubation and NSAID use. The PPFS rate at median follow-up was 93.5% in the low-risk group (n = 41, 0 or 1 unfavorable factor) and 55.1% in the high-risk group (n = 34, 2 or 3 unfavorable factors). The difference between the PPFS curves of the two risk groups was statistically significant (P < 0.001).. Pleurodesis for metastatic breast cancer was efficacious in controlling malignant pleural effusion. Our simple new risk model warrants further studies.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Disease-Free Survival; Female; Humans; Middle Aged; Neoplasm Metastasis; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Retrospective Studies; Survival Rate; Treatment Outcome

The intrathoracic administration of OK-432, a lyophilized preparation of the heat- and penicillin-treated Su-strain of type 3, group A Streptococcus pyogenes, is performed in Japan for pleurodesis of malignant pleural effusion or pneumothorax. Persistent fever is often observed after pleurodesis. To elucidate whether procalcitonin (PCT) is useful for distinguishing between the side effects of OK-432 and infection, we measured the serum PCT levels before and after pleurodesis.. We performed a prospective study of 12 patients with refractory pleural effusion or pneumothorax who required pleurodesis using OK-432 between August 2011 and February 2012. The serum PCT and C-reactive protein (CRP) levels were measured on days 1 and 3.. Of the 12 patients, five had pneumothorax and seven had uncontrolled pleural effusion with carcinomatous pleurisy. The median serum levels of PCT and CRP increased from 0.055 to 1.59 ng/mL (p=0.0022) and from 1.52 to 16.82 mg/dL (p=0.0022), respectively. The fevers subsided without antibiotic administration.. The serum PCT level may not be useful for distinguishing fever caused by side effects of OK-432 from that caused by bacterial infection. The intrathoracic administration of OK-432 increased the serum levels of both PCT and CRP in the absence of any bacterial infection.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Bacterial Infections; C-Reactive Protein; Calcitonin; Calcitonin Gene-Related Peptide; Female; Fever; Humans; Male; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Pneumothorax; Prospective Studies; Protein Precursors

The combination treatment of non-specific immunomodulator Lentinan (LNT) and OK-432 is effective for controlling Th1/Th2 balance and inducing Th1 dominant status in cancer patients. According to this rationale, we tried an administration of LNT and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. In all 21 lesions of the 20 cases, 10 revealed a complete disappearance and 7 revealed diminution of the effusion. The efficacy of this treatment is 81%. All patients developed a clinical efficacy in 1 to 3 courses of this treatment, and 9 lesions developed clinical efficacy in only 1 course. None of patients developed toxic symptoms LNT, and 10 developed a low grade fever by OK-432. The combination of LNT and OK-432 is effective and for QOL conserving loco-regional treatment.

Topics: Adjuvants, Immunologic; Adult; Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Female; Humans; Injections; Injections, Intraperitoneal; Lentinan; Male; Middle Aged; Picibanil; Pleural Cavity; Pleural Effusion, Malignant; Treatment Outcome

Effects of low-dose anti-CD25 antibody on targeting regulatory T (Treg) cells in vitro and in vivo were investigated. Human-mouse chimeric anti-CD25 monoclonal antibody basiliximab was administered into the effusion cavity, followed by locoregional immunotherapy using OK-432 on day 7. Peripheral blood mononuclear cells and effusion lymphocytes (ELs) were collected before and after the basiliximab administration and subjected to further investigations. Surface phenotypes, IFN-gamma production, cytotoxic activity and foxp3 expression of ELs were assessed by flow cytometry, ELISA, 51Cr-releasing assay, and RT-PCR analysis, respectively. We observed that a low concentration of 0.01 microg/ml basiliximab effectively targeted CD4+CD25(bri) Treg cells while preserving CD4+CD25(dim) activated T cells in vitro. This concentration of basiliximab significantly augmented interferon (IFN)-gamma production of ELs when interleukin (IL)-2 was added on day 0 or on day 1 after basiliximab. In the clinical study, intracavitary administration of basiliximab on day 0 followed by OK-432 on day 7 was as safe, well-tolerated, and effective as using OK-432 alone, and a low-dose of 0.002-0.005 mg/kg basiliximab could target CD4+CD25(bri) cells for at least 3 days while relatively preserving CD4+CD25(dim) cells. Foxp3 expression of ELs was not changed definitely by the intracavitary basiliximab. These results suggest that low-dose basiliximab can target Treg cells in vitro and in vivo, and subsequently augment the activation of ELs. Locoregional immunotherapy of malignant effusion using the Treg cell-conditioning regimen with low-dose basiliximab followed by OK-432 administration on day 0 or on day 1 should be evaluated for clinical efficacy in the next phase II trial.

Topics: Adult; Aged; Aged, 80 and over; Antibodies, Monoclonal; Ascites; Basiliximab; Dose-Response Relationship, Drug; Female; Humans; Interferon-gamma; Interleukin-2; Interleukin-2 Receptor alpha Subunit; Lymphocyte Activation; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Recombinant Fusion Proteins; T-Lymphocytes, Regulatory

Percutaneous balloon pericardiotomy and intrapericardial instillation seemed to be less invasive and effective treatments for refractory pericardial effusion. A 65-year-old man who suffered from refractory pericardial effusion associated with gastric cancer and had been hospitalized three times for pericardiocentesis, complained of dyspnea at rest and visited our emergency room. Echocardiography showed a large amount of pericardial effusion all around the heart and signs of cardiac tamponade. Percutaneous balloon pericardiotomy was performed and pericardial effusion turned to pleural effusion. We performed left thoracocentesis. One week later, massive pericardial effusion localized only around the right heart appeared, and pericardiocentesis was performed again. After another month, pericardial effusion around right heart appeared again and intrapericardial instillation with OK-432 (Picibanil) was tried. After the procedure, the pericardial effusion did not increase, and he has had few symptoms for 2 months as an outpatient.

Topics: Aged; Antineoplastic Agents; Cardiac Tamponade; Echocardiography; Humans; Male; Pericardial Effusion; Pericardiectomy; Picibanil; Pleural Effusion, Malignant; Stomach Neoplasms

We report a case of cerebral arterial air embolism that was followed by a brain computed tomographic scan and magnetic resonance imaging during the first week after onset. A 73-year-old man was admitted for treatment of pleural dissemination that was a recurrence after right lower bilectomy for advanced lung cancer. Thirty minutes after an anti-drug administration through the chest drainage tube, he lost consciousness shortly after coughing. A bubble in the inferior sagittal sinus was observed on the day of the stroke, which then disappeared within 24 hours. It seems that the anti-cancer agent evoked inflammation at the visceral pleura and the subject inhaled massive air flow into the systemic circulation.

Topics: Aged; Antineoplastic Combined Chemotherapy Protocols; Brain Edema; Brain Ischemia; Bronchial Fistula; Carcinoma, Squamous Cell; Cerebral Infarction; Chest Tubes; Cisplatin; Coma; Combined Modality Therapy; Cough; Disease Progression; Embolism, Air; Fatal Outcome; Fistula; Hemiplegia; Humans; Injections; Intracranial Embolism; Lung Neoplasms; Lymph Node Excision; Male; Picibanil; Pleura; Pleural Cavity; Pleural Effusion, Malignant; Pneumonectomy; Postoperative Complications; Pulmonary Veins

We investigated the effectiveness and complications of intrathoracic infusion with a combination of cisplatin, OK-432, and minocycline for malignant pleural effusion. All patients were hospitalized with chest tube drainage of pleural effusion until the daily drainage volume was less than 100 ml. Twenty-five mg of minocycline, 1 to 3 KE of OK-432, and 5 to 10 mg of cisplatin were instilled into the pleural space. The administration was repeated until drainage effusion disappeared. Therapeutic effect was evaluated according to the following criteria: (1) excellent, no fluid reaccumulation for at least 4 weeks as determined by chest radiogram and clinical evaluation; (2) effective, fluid reaccumulation less than 50% of original effusion with no need of thoracentesis for symptomatic relief within 4 weeks after treatment; and (3) failure, reaccumulation of more than 50% of the original effusion requiring thoracentesis to relieve symptoms within 4 weeks of treatment. Twelve patients with malignant effusion received the combination treatment; 11 patients had primary lung cancer and one had metastatic lung tumor from cancer of the rectum. In all cases, the histology or cytology revealed adenocarcinoma. Eleven of the 12 patients had an excellent response with relief of clinical symptoms. The remaining case failed to show any improvement. Complications such as local pain, fever, nausea, and vomiting were mild and transient. We conclude that combination administration of low-dose minocycline, OK-432, and cisplatin into the thoracic cavity for malignant effusion is an effective alternative treatment with the potential for improvement of the general condition and reduced morbidity.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Combined Modality Therapy; Dose-Response Relationship, Drug; Drainage; Drug Administration Schedule; Female; Humans; Infusions, Intralesional; Lung Neoplasms; Male; Middle Aged; Minocycline; Picibanil; Pleural Effusion, Malignant; Thoracic Cavity

Malignant pleural effusion is typical of complications in advanced lung cancer patients, most of whom complain of dyspnea. The standard treatment for symptomatic pleural effusion is intrapleural administration of a chemical agent. In Japan, OK-432, a streptococcal preparation, and cisplatin (CDDP) have been among the most frequently used chemical agents. There have been very few reports on the efficacy of chemical agents for malignant pleural effusion. We compared therapeutic efficacy and toxicity of intrapleural OK-432 with CDDP in a case-control study. The subjects consisted of 32 lung cancer patients with malignant pleural effusion who were admitted to our hospital between January 2000 and June 2004. The therapeutic efficacy was assessed from duration of chest drainage after intrapleural administration, response rate, time to progression of malignant pleural effusion, and survival time. No statistically significant difference was observed for therapeutic efficacy. Although the OK-432-treated group had only grade 1 fever, chest pain, nausea, the CDDP-treated group had a grade 2 increase in creatinine and grade 3 nausea. Intrapleural OK-432 seemed to be better tolerated in the treatment of malignant pleural effusion than intrapleural CDDP.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Case-Control Studies; Cisplatin; Disease Progression; Drainage; Female; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Cavity; Pleural Effusion, Malignant

LTN and OK-432 combined therapy is effective for controlling Th1/Th2 balance. We tried a repetitive administration of LTN and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. Of all 11 lesions of the 10 cases, 7 revealed complete remission and 1 revealed partial response. The level of IL-12 (p70) and IFN-gamma in ascites of two gastric cancer patients after the second administration of LTN and OK-432 was much higher than those after the first administration, whereas the level of IL-10 was not suppressed strongly. In 8 lesions that we could confirm complete remission or partial response, 7 lesions were improved after two or three administrations of LTN and OK-432. In conclusion, a repetitive intracavital administration of LTN and OK-432 is effective for malignant effusion.

Topics: Aged; Antineoplastic Agents; Ascitic Fluid; Female; Humans; Interferon-gamma; Interleukin-10; Interleukin-12; Lentinan; Male; Middle Aged; Peritoneal Cavity; Picibanil; Pleural Cavity; Pleural Effusion, Malignant

We report two patients of recurrent breast cancer with carcinomatous pleurisy well controlled pleural effusion. One patient is a 49-year-old woman. She underwent radical mastectomy for right breast cancer in September 1993. She suffered from multiple liver metastases in June 2000, so CEF therapy contained hepatic arterial infusion chemotherapy and extended right lobectomy of the liver were performed in December 2001. Right pleural effusion was detected in December 2003, then, pleurodesis was carried out with OK-432 after thoracic drainage. After pleurodesis, a weekly paclitaxel therapy was started and she was taking the regimen continuously. Another patient is a 55-year-old woman. She underwent radical mastectomy for left breast cancer in September 1999. Local recurrent lesions on the left chest and left pleural effusion were found in May 2003. After thoracic drainage, infectious pleurisy was complicated, so the drainage tube was removed after the therapy for preventing infection. After pleurodesis, CE therapy followed by peroral chemo-endocrine therapy was performed. Both of the two patients are receiving outpatient treatment without recurrent pleural effusion as of July 2005.

Topics: Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Drainage; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Picibanil; Pleural Effusion, Malignant; Pleurisy

Malignant pleural effusion develops frequently in patients with advanced lung cancer. Chemical pleurodesis is the most effective palliative treatment for these patients. The efficacy of pleurodesis using both OK-432, a preparation of Streptococcus pyogenes, and doxorubicin for 20 patients with cytology-proven malignant pleural effusion associated with lung cancer was evaluated. After complete removal of pleural effusion, OK-432 and 30 mg of doxorubicin were injected via an inserted chest tube. Treatment was terminated when the volume of daily drainage reached <200 mL. If the daily volume remained >200 mL, an additional OK-432 was administered every 3 days. In total, 16 patients (80%) revealed a complete response, two patients (10%) revealed a partial response, and no response was seen in two patients. Eighteen patients with complete or partial responses did not show subsequent reaccumulation of pleural effusion after pleurodesis. The chest tube remained in place for an average of 6.4 days, draining a mean of 2,854 mL. The main side-effects were fever and pain that were easily treated with nonsteroidal anti-inflammatory drugs. Pleurodesis using both OK-432 and doxorubicin showed high efficacy for controlling malignant pleural effusions caused by lung cancer.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Dose-Response Relationship, Drug; Doxorubicin; Drug Administration Schedule; Female; Follow-Up Studies; Humans; Injections, Intralesional; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Pleurodesis; Prospective Studies; Remission Induction; Risk Assessment; Tomography, X-Ray Computed; Treatment Outcome

Since 1984, we have had 151 breast cancer patients with cytologically-confirmed malignant pleural effusions by local transfer of autologous effusion lymphocytes cultured with a conditioned medium containing T-cell growth factor after intrapleural preadministration of a streptococcal preparation, OK-432. Among the 81 patients given this therapy more than 5 years ago, 12 patients have survived 5 or more years, and 4 of these 12 have survived 10 (<) years. Patients surviving 5 (<) years had longer (32-204 months) disease-free periods, except for one patient with stage IV disease. Estrogen receptor was positive in 5 patients, negative in 1 patient, and unknown in 6 patients. Moreover, preceding or concomitant metastases in these patients were not life-threatening (6 chest-wall, 2 lymph-node, 4 lung, 3 bone metastases). In conclusion, effective therapy (effusion disappeared in all patients) and good control of concomitant metastases resulted in long-term survival of patients who had intrinsically better prognostic factors.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Female; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Middle Aged; Picibanil; Pleural Effusion, Malignant; Survival Rate

It is very important to control the Th2-dominant condition in cancer patients while they are undergoing immunotherapy. OK-432 powerfully guides Th1 cytokine, but sometimes it can not eliminate the Th2 dominant state in cancer patients, which is needed to induce Th2 cytokine. Premedication with combined LTN and OK-432 is an effective therapy for controlling the Th1/Th2 balance. We tried administering LTN and OK-432 in the pleural or peritoneal cavity for patients with malignant effusion. Of all 9 lesions of the 8 cases, 6 showed complete remission and 1 showed partial response. The level of IL-12 (p70) and IFN-gamma in the pleural effusion or ascites of the combination group was higher than the OK-432 only group. In conclusion, LTN and OK-432 combined therapy appears to be an effective local treatment.

Topics: Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Breast Neoplasms; Female; Humans; Immunotherapy; Interferon-gamma; Interleukin-10; Interleukin-12; Lentinan; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Stomach Neoplasms

Tumor infiltrating lymphocytes (TILs) are candidates for adoptive cellular immunotherapy. Here we report on a patient whose TILs presented unusual lymphocyte antigens. Pleural effusions were collected from a 47-year-old man with recurrent cholangio cell carcinoma and malignant effusion. Effusion-associated lymphocytes (EALs) were separated by Ficoll-Hypaque gradient, and the EAL phenotype was determined by flow cytometry. The percentage of positive cells was determined for each lymphocyte-related differentiation antigen. The percentages of CD3+, CD19+, and CD16+ lymphocyte subpopulations among EALs were 20%, 7%, and 3%, respectively. Nearly 70% of EALs were CD3-/CD19-/CD56-/CD16- cells. The phenotypes of peripheral blood lymphocytes (PBLs) collected simultaneously from the patient's peripheral blood were CD3+ (52%), CD19+ (20%), and CD16+ (20%). When EALs were cultured in medium without pleural effusion, T cell-related antigens, but not B cell- or natural killer (NK) cell-related antigens, were newly expressed on EALs, and this expression reached a plateau after 48 h in culture. The proportions of CD3+, CD19+, and CD16+ cells were 69%, 7%, and 3%, respectively. However, when EALs were cultured in medium with pleural effusion, increased expression of T cell-related antigens was not observed; the proportions of CD3+, CD19+, and CD16+ cells were 16%, 6%, and 1%, respectively. Neither total cell numbers nor cellular viability of EALs changed significantly after in-vitro culture, suggesting that significant proliferation or death of EALs did not occur during the culture period. Co-culture of the patient's PBLs with autologous pleural effusion for 96 h did not alter the expression of lymphocyte-related antigens on the PBLs. These results indicate that expression of T cell-related antigens, but not B cell- or NK cell-related antigens, on EALs was blocked temporarily by the malignant pleural effusion. This is the first report concerning the existence of a large quantity of unclassified lymphocytes in which the T cell-related antigens were reversibly masked in the malignant pleural effusion.

Topics: Antigens, CD19; CD3 Complex; Cholangiocarcinoma; Humans; Immunotherapy, Adoptive; In Vitro Techniques; Interferon-gamma; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Neoplasm Recurrence, Local; Picibanil; Pleural Effusion, Malignant; Receptors, IgG; T-Lymphocytes

Locoregional administration using OK-432 was evaluated in treating malignant effusion. Positive clinical responses were seen in 19 (52%) of 36 gastric cancer patients, and in 9 (90%) of 10 colon cancer patients (p < 0.05), indicating its clinical benefit in treating malignant effusion of colon cancer. Fever elevation was observed in 43 (93%) patients and local pain occurred with 9 (20%) of 46 administrations. Immunological analysis for responder patients with rectal cancer revealed that OK-432 induced autologous tumor-reactive CD 3+ CD 4+ TCRV beta 20+ killer lymphocytes. The TCR gene analysis permitted us to clone a V beta 20 CDR 3 sequence, by which positive bands were shown in 3 (75%) of 4 responders and negative bands in 3 (100%) of 3 non-responders. It is suggested that cross-antigenicity exists between OK-432 and colon cancer, and that genetic analysis using the TCRCDR 3 sequence makes it possible to predict responder patients to OK-432 immunotherapy.

Topics: Adult; Aged; Antineoplastic Agents; Ascitic Fluid; ATP-Binding Cassette Transporters; Colorectal Neoplasms; Complementarity Determining Regions; Female; Humans; Immunotherapy; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Receptors, Antigen, T-Cell; Reverse Transcriptase Polymerase Chain Reaction; Stomach Neoplasms

Eleven patients with massive effusion due to pleuritis carcinomatosa were treated by tube drainage, followed by instillation of OK-432 and minocycline for pleurodesis. Pleural immunological and chemical reactions of adhesion were strongly induced by the use of these adhesive agents. As a result, pleural effusion was diminished in all patients without recurrence, allowing the drainage tubes to be successfully removed. As severe adverse effects following this course of therapy, high fever was observed in all patients, and acute renal failure in one. Blood chemical data from the patients revealed an increase in the number of granulocytes with a high level of interleukin-6 one day after instillation. These findings suggested that the symptoms of general inflammation were induced by local pleural inflammation. The median survival period was 253.7 days for 5 patients who were sufficiently fit to be discharged from our hospital. This was better than the historical average for the patients with uncontrolled pleural effusion. In conclusion, it was possible to control malignant pleural effusion and achieve longer survival periods through the optimal management of tube drainage and instillation of adhesion-inducing agents.

Topics: Aged; Aged, 80 and over; Anti-Bacterial Agents; Antineoplastic Agents; Drug Therapy, Combination; Female; Humans; Lung Neoplasms; Male; Middle Aged; Minocycline; Picibanil; Pleura; Pleural Effusion, Malignant

Autologous effusion lymphocytes cultured for 9-13 days with condition medium containing T cell growth factor were transferred after intrapleural administration with a streptococcal preparation, OK-432, for 84 breast cancer patients with cytologically-confirmed malignant pleural effusion. Effusion disappeared in 54 and decreased in 19 patients, while in 11 the treatment was ineffective (87% response). A positive cytology changed to negative in 52 of 55 (95%) of the patients tested, while in 29 patients, effusion sample could not be obtained after treatment. A multivariate analysis of prognostic factors showed a significantly poorer prognosis in patients with the following concomitant metastases: liver metastasis, lung metastasis with lymphangitis carcinomatosa, and simultaneous bilateral effusions. Median survival time (MST) of all patients was 9 months (5-year survival: 18%). However, MST of the patients with limited disease (patients without liver metastasis, lymphangitis, or bilateral effusion) was 23 months (5-year survival: 28%). Ten patients survived more than 5 years (3 survived over 10 years) after the treatment among 46 patients with follow-up periods of > 5 years.

Topics: Adult; Aged; Antineoplastic Agents; Breast Neoplasms; Female; Humans; Immunotherapy, Adoptive; Lymphocytes, Tumor-Infiltrating; Middle Aged; Multivariate Analysis; Picibanil; Pleural Effusion, Malignant; Prognosis; Retrospective Studies; Survival Analysis

Docetaxel is an anti-tumor agent which promotes the congregation and stabilization of microtubules, there by preventing cell division. It is reported to have anti-tumor activity against breast or non-small cell lung carcinomas which have been resistant to other anti-tumor agents. On the other hand, it causes peripheral edema and effusion in the pleural or peritoneal cavities. Thus, pleural or peritoneal effusions, which require drainage have been considered to be contraindications for the administration of docetaxel. OK-432 is an agent which causes adhesion by evoking a local inflammatory reaction. We experienced two cases of recurrent breast carcinoma with malignant pleural effusion. We successfully managed their pleural effusion with the intrapleural administration of OK-432. Thereafter, we safely administered docetaxel, and obtained good outcomes. The present paper also discussed the synergistic action between these agents.

Topics: Adenocarcinoma; Antineoplastic Agents; Antineoplastic Agents, Phytogenic; Breast Neoplasms; Docetaxel; Drug Administration Schedule; Female; Humans; Middle Aged; Neoplasm Recurrence, Local; Paclitaxel; Picibanil; Pleura; Pleural Effusion, Malignant; Taxoids

The intracavitary injection of OK-432, a streptococcal preparation, has been shown to be an effective immunotherapy for patients with malignant effusion. We found that this therapy increases surface expression of intercellular adhesion molecule-1 (ICAM-1) on tumor cells, and that the degree of increased ICAM-1 was correlated with therapeutic effects. In the present study, we investigated the ability of OK-432-induced inflammatory cytokines, such as interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), and interleukin-1 beta (IL-1 beta), to enhance ICAM-1 expression. We treated 17 patients who had a malignant effusion with OK-432. At 24 hr after OK-432 injection, ICAM-1 levels on tumor cells were increased significantly in responders except in one case (n=9), whereas no change was evident in nonresponders except in two cases (n=8). Induced maximum levels of IFN-gamma in responders were significantly higher than those in nonresponders. In contrast, there was no significant difference in the induced TNF-alpha or IL-1 beta levels between the two groups. Two types of cultured tumor cells derived from responder patients were successfully established from the 17 different tumor cells in effusion. We performed an in vitro study using these cultured tumor cells. Treatment of the two cultured tumor cells with recombinant IFN-gamma, but not recombinant TNF-alpha or IL-1 beta, significantly increased their ICAM-1 expression to a clinically detectable level. Direct treatment of the tumor cells with cell-free effusion samples obtained from the same patients 24 hr after the therapy successfully increased ICAM-1 expression and this action was blocked completely only by a pretreatment with anti-IFN-gamma mAb. Our results suggests that in this therapy IFN-gamma plays a crucial role in enhancing ICAM-1 expression by tumor cells and that induced IFN-gamma levels may be a useful marker for evaluation of the therapeutic effect.

Topics: Aged; Antineoplastic Agents; Ascitic Fluid; Cell Membrane; Cytokines; Humans; Injections; Intercellular Adhesion Molecule-1; Interferon-gamma; Interleukin-1; Male; Picibanil; Pleural Effusion, Malignant; Tumor Cells, Cultured; Tumor Necrosis Factor-alpha

T-cell receptor (TCR) gene rearrangements were analyzed in tumor-infiltrating lymphocytes (TIL) using the reverse transcription-polymerase chain reaction (RT-PCR) to determine whether oligoclonal expression of TCRV beta occurs in TIL, and if so, whether it is involved in the clinical response and mechanisms of locoregional immunotherapy using a streptococcal preparation, OK432. Patients with malignant effusion of various origins were treated with intrapleural administration of OK432, and clinical responses were assessed by cytological and chest X-ray examinations. Pleural exudate cells (PEC), obtained before and after the administration of OK432 (designated as pre- and OK432-PEC, respectively), were subjected to TCR analysis. Both pre-PEC and OK432-PEC showed highly diverse expressions of TCRV beta gene usage in either type of PEC. The frequency of TCRV beta 20 gene expression in OK432-PEC was significantly higher than in pre-PEC. Moreover, the over-expression of the TCRV beta 20 gene usage was also induced in the peripheral blood lymphocytes and pre-PEC of patients by in vitro OK432 stimulation, but not in the PBL of one healthy volunteer. Single-strand conformational polymorphism (SSCP) analysis revealed the clonotypes of these TCRV beta 20 genes. Autologous tumor-specific killing activity could be detected in OK432-PEC and was significantly reduced by treatment with a TCRV beta 20-specific monoclonal antibody. These findings suggest that the rearrangement of TCRV beta 20 gene usage may be involved in the autologous tumor-specific action of malignant effusions in the treatment with OK432.

Topics: Aged; Antineoplastic Agents; Blotting, Southern; Female; Genes, T-Cell Receptor beta; Humans; Immunotherapy; Injections; Male; Middle Aged; Phenotype; Picibanil; Pleura; Pleural Effusion, Malignant; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; RNA Probes; T-Lymphocytes, Cytotoxic

We analyzed the T cell receptor (TCR) V beta repertoire of lymphocytes obtained from patients with malignant effusion treated by locoregional immunotherapy. Polymerase chain reaction using a panel of V beta subfamily specific oligonucleotide primers(V beta 1-20) was employed after reverse transcription of mRNA isolated from the locoregional cells. No major oligoclonality of TCR repertoire was observed in effusion lymphocytes before the treatment. The expression level of V beta 13.1 repertoire was significantly higher in effusion lymphocytes than in peripheral blood lymphocytes before treatment. V beta 20 gene expression increased significantly after locoregional administration of OK-432. It is suggested that TCR V beta 13.1 may be responsible for effusion lymphocytes and TCR V beta 20 for OK-432-related antigenic stimulus.

Topics: Adult; Aged; Antineoplastic Agents; Female; Humans; Immunotherapy; Male; Middle Aged; Picibanil; Pleural Effusion, Malignant; Polymerase Chain Reaction; Receptors, Antigen, T-Cell, alpha-beta

We investigated the changes in cellular components and neutrophil chemotactic factors in pleural fluid from 19 lung cancer patients who received intrapleural injection of OK-432 to treat malignant pleurisy. Not only neutrophil chemotactic activity (NCA) but also neutrophil count and percentage were increased significantly at 6 hours after OK-432 injection. The neutrophil count was significantly correlated with NCA level. The levels of C5a and IL-8 in pleural fluid were increased significantly after OK-432 injection. The increased IL-8 level was associated with a increase of both NCA and neutrophil count. OK-432 treatment also induced a marked increase of IL-1 beta and IL-6 in pleural fluid. Thus, intrapleural injection of OK-432 induced production of neutrophil chemotactic factors (IL-8 and C5a) and cytokines (IL-1 beta and IL-6), which eventually attracted neutrophils into the pleural space. These observations suggest that neutrophil migration mediated by these factors and cytokines may contribute to the sclerosing effects of OK-432 treatment.

Topics: Adult; Aged; Chemotactic Factors; Complement C5a; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Leukocyte Count; Lung Neoplasms; Male; Middle Aged; Neutrophils; Picibanil; Pleural Effusion, Malignant

The intracavitary injection of OK-432 has been shown to be an effective immunotherapy for patients with malignant effusion. We investigated the contribution of intercellular adhesion molecule-1 (ICAM-1) on the surface of tumor cells to its therapeutic effect. We treated 13 patients with malignant effusion with OK-432. Tumor cells were freshly isolated from effusion samples obtained before and 24 hr after initiation of the therapy. Surface expression of ICAM-1 was analyzed by flow cytometry and its relation to the therapeutic effect was analyzed. An objective clinical response was observed in 7 (53.8%) of 13 patients. Following OK-432 injection, ICAM-1 levels showed an average of 5.73-fold increase in clinical responders (7 patients), whereas no increase in nonresponders (6 patients). ICAM-1 expression more than doubled after therapy in 7 patients, 6 of whom showed a clinical response. Survival was significantly prolonged in these patients compared with that in the 6 patients in whom ICAM-1 levels did not double after therapy. Only 1 of the 6 patients in whom ICAM-1 levels did not double showed a clinical response. Pretherapeutic ICAM-1 expression was not significantly correlated with the subsequent clinical effect. OK-432 injection was associated with an increase in surface expression of ICAM-1 on tumor cells. This increased ICAM-1 expression was positively correlated with therapeutic effect, suggesting that ICAM-1 expression on tumor cells may be a useful marker for evaluation of efficacy of OK-432 therapy.

Topics: Aged; Biomarkers, Tumor; Cell Adhesion Molecules; Female; Humans; Injections; Intercellular Adhesion Molecule-1; Male; Middle Aged; Picibanil; Pleura; Pleural Effusion, Malignant

When OK-432, a well-known streptococcal preparation for an anti-tumour drug, was administered into the pleural cavity of patients with malignant pleurisy, a rapid and prominent leukocytosis, predominantly consisting of neutrophils, was observed in the cavity. Neutrophil infiltration usually peaked 6-9 h after OK-432 administration, and levelled down after 24 h. Prior to the neutrophil accumulation, transient but marked elevation of various inflammatory cytokine levels including IL-1 beta, TNF-alpha, IL-8 and G-CSF was observed. In particular, IL-8 levels increased more than 10-fold, while GM-CSF did not change significantly. A good correlation between IL-8 levels and neutrophil chemotactic response was observed particularly during 0-3 h. Specific neutralization or removal of IL-8 by antibody column abrogated half of the neutrophil chemotaxis, while neutralization of C5a removed around 40%. Sequential removal of IL-8 and C5a abrogated totally 80% of chemotaxis, confirming that these two factors are mostly responsible for the neutrophil chemotaxis in the pleural fluids. These results have suggested that rapid neutrophil infiltration induced by OK-432 in vivo is ascribable largely to IL-8 and in part to C5a.

Topics: Adult; Aged; Chemotactic Factors; Chemotaxis, Leukocyte; Chromatography, Agarose; Complement C5a; Cytokines; Humans; Interleukin-1; Interleukin-8; Male; Middle Aged; Neutralization Tests; Neutrophils; Picibanil; Pleural Effusion, Malignant; Tumor Necrosis Factor-alpha

We developed a local AIT using PEL cultured with TCGF combined with preadministration of OK-432. Twenty-six patients of breast cancer with pleural effusion have been treated with this therapy since 1983. PEL expanded and tumor cells collapsed by day 9 in culture with TCGF. Cultured PEL possessed significantly higher cytotoxic activity against autologous tumor cells than PBL cultured in the same condition (p less than 0.05), but there was no difference between their cytotoxic activities against K562. The proliferation rate of PEL obtained after intrapleural administration of OK-432 was higher than that obtained before OK-432 (p less than 0.01). Moreover, the cytotoxic activities against both autologous tumor and K562 of cultured PEL obtained after OK-432 administration was significantly (p less than 0.05) higher than those cultured PEL obtained before. Cultured PEL (1 x 10(8)-6 x 10(9)) were transferred into the pleural cavity after the intrapleural administration of OK-432 (1-5 KE). The volume of pleural effusion increased temporarily after the administration of OK-432 but significantly (p less than 0.01) decreased after AIT. Tumor cells disappeared cytologically in 22 patients at the last puncture of pleural effusion. Pleural effusion disappeared completely in 19 of 26 patients and decreased by more than 50% in volume in 6 patients. Performance status improved in 22 patients. The response rate for OK-432-combined AIT in the present study was 96%. The survival period of the patients treated by OK-432-combined AIT in this trial was significantly (p less than 0.002) prolonged compared to that of the patients receiving chemotherapy alone.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adult; Aged; Breast Neoplasms; Cell Division; Cells, Cultured; Drug Administration Routes; Female; Humans; Immunotherapy, Adoptive; Interleukin-2; Lymphocytes; Lymphocytes, Tumor-Infiltrating; Middle Aged; Picibanil; Pleura; Pleural Effusion, Malignant