picibanil and Carcinoma--Non-Small-Cell-Lung

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

We conducted a phase II study of OK-432 intrapleural administration followed by systemic chemotherapy using cisplatin with gemcitabine to determine their combined effects on non-small cell lung cancer (NSCLC) with pleuritis carcinomatosa. Between December 1999 and October 2001, 15 patients were registered in the study. Fourteen patients had an Eastern Cooperative Oncology Group performance status (PS) of 1, and one patient had a PS of 2. Ten patients had adenocarcinoma, one had squamous cell carcinoma, and four had malignant mesothelioma. Patients underwent thoracocentesis and received an OK-432 intrapleural injection. They were then treated every three weeks with chemotherapy consisting of 80 mg/m2 cisplatin on day 1 and 1000 mg/m2 gemcitabine on days 1 and 8. Thirteen patients received two or more courses of chemotherapy. Grade 3 or 4 neutropenia, anemia and thrombocytopenia occurred in five, two and three patients, respectively. Non-hematological toxicities were mild, except for one patient who experienced a grade 3 elevation of transaminase and two patients who experienced grade 3 nausea. Of the 15 patients, one achieved partial response (PR), 13 a stable disease (SD) rating, and one a progressive disease (PD) rating, and the overall response rate was 6.7%. The median survival time was 13.5 months and the one-year survival rate was 60.0%. In conclusion, OK-432 intrapleural administration followed by cisplatin and gemcitabine systemic chemotherapy did not reduce patients' tumors but did prolong their survival time. A large-scale phase II study of the efficacy of this combination therapy is required.

Topics: Adenocarcinoma; Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Cisplatin; Deoxycytidine; Female; Gemcitabine; Humans; Lung Neoplasms; Male; Mesothelioma; Middle Aged; Picibanil; Pleural Neoplasms; Survival Rate; Treatment Outcome

The efficacy of postoperative adjuvant chemo- and chemoimmunotherapy in non-small cell lung cancer was evaluated in a multicentric prospective randomized study. From September 1987 to June 1990, resected lung cancer patients were randomly stratified into three groups. Group A received 2 courses of chemotherapy with CDDP and VDS following operation. Group B was administered UFT daily for 1 year after 2 courses of CDDP. Group C received intrapleural administration of OK-432 after lung resection, then UFT and OK-432 once every 2 weeks for 1 year. Out of 94 cases, analyses were carried out on 87 of eligible cases. The five-year survival rate was 56.8% in stage I (43 cases), 73.3% in stage II (12 cases), 18.8% in stage IIIA (24 cases), 50% in stage IIIB (2 cases) and 33.3% in stage IV (6 cases). The five-year survival rate in group A was 32.2%, 55.2% in group B and 53.9% in group C, and no statistical difference was recognized between 3 groups. But in the cases of noncurative resection, the 5-year survival rate was significantly low in group A compared with Group B or C. Similarly, the cases with low-grade TP (<6.0 g/dl) or low response of PPD skin reaction (< 12mm) showed a significantly low 5-year survival rate only in group A. From these results, it was suspected that aggressive chemotherapy provides no benefit for postoperative lung cancer patients with advanced disease.

Topics: Adult; Aged; Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Chemotherapy, Adjuvant; Cisplatin; Combined Modality Therapy; Drug Combinations; Female; Humans; Japan; Lung Neoplasms; Male; Middle Aged; Picibanil; Prospective Studies; Survival Rate; Tegafur; Uracil; Vindesine

A prospective randomized study to compare the effectiveness of pleurodesis by two new sclerosing agents: OK-432 and mitomycin C were conducted in 53 patients with malignant pleural effusion caused by lung cancer. None of the patients received concomitant systemic chemotherapy or radiation therapy during the study. After complete drainage of pleural fluid, the patients were allocated randomly to receive 10 Klinische Einheit units of OK-432 or 8 mg of mitomycin C by intrapleural injection at weekly intervals. The treatment was terminated if the pleural effusion disappeared or the patients had received four consecutive procedures. There were 26 patients who received pleurodesis with OK-432 and 27, with mitomycin C. Patient characteristics in the two treatment groups (age, sex, histologic type, performance status, and prior treatment before pleurodesis) were compatible. These results showed that pleurodesis with OK-432 achieved a higher complete response rate (73%) than that of mitomycin C (41%). The rates of objective treatment response (complete response plus partial response) were comparable in both groups (88% for OK-432 and 67% for mitomycin C). The average number of intrapleural injections needed to achieve complete response was fewer in the OK-432 group (1.9 +/- 0.9) than in mitomycin C group (2.8 +/- 0.9). There was no significant difference in the median survival of the patients who received pleurodesis with OK-432 (5.8 months) or mitomycin C (5.1 months). However, the effusion-free period in the OK-432 group was significantly longer than that in the mitomycin C group (7.0 months versus 1.5 months). Patients who underwent OK-432 pleurodesis had a higher complication rate (80%) than did those in the mitomycin C group (30%). Transient febrile reaction was the most common reaction encountered. The immunologic study in OK-432 group showed an increase in peripheral leukocyte count and decrease in the OKT4/OKT8 ratio. The mitomycin C group had a mild reduction in peripheral blood leukocyte count and no significant change in the OKT4/OKT8 ratio. It was concluded that pleurodesis with OK-432 is an effective alternative treatment for malignant effusion in patients with lung cancer.

Topics: Adenocarcinoma; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Immunity, Cellular; Lung Neoplasms; Male; Middle Aged; Mitomycin; Neoplasm Staging; Picibanil; Pleural Effusion; Prospective Studies; Tissue Adhesions

It is not clear whether postoperative inflammation affects the prognosis of malignant disease.. We retrospectively reviewed the patients with non-small-cell lung cancer who underwent a complete resection at the National Kyushu Cancer Center from 1989 to 1996. For the treatment of prolonged air leakage after a pulmonary lobectomy, 25 patients received an intrapleural injection of OK-432, a lyophilized preparation of the heat- and penicillin-treated Su-strain of the Streptococcus pyogenes group A3. All patients were males who were older than 50 years of age. As a control, we selected 164 male patients who were older than 50 years of age and not given OK-432 during the same period.. The administration of OK-432 in most patients was performed on the 4th day after the operation. Pleural drainage could be terminated in a mean of 5.5 days after the intrapleural administration of OK-432. In the control group, the serum C-reactive protein (CRP) level reached a peak on day 4 after the operation and returned to almost a normal level on day 14 after the operation. In the OK-432 group, the peak CRP level, which was significantly higher than that in the control group, was observed on day 7 after the operation and the elevated CRP level was maintained until 28 days after the operation. The mean level of CRP in the OK-432 group was significantly higher than that in the control on days 7, 14, and 28 after the operation. No significant difference was observed in the disease-free survivals between the two groups.. Based on the above findings, postoperative prolonged inflammation does not seem to affect the progression of subclinically residual tumor cells.

Topics: Aged; Aged, 80 and over; Antineoplastic Agents; Carcinoma, Non-Small-Cell Lung; Disease-Free Survival; Humans; Inflammation; Injections; Lung Neoplasms; Male; Middle Aged; Picibanil; Postoperative Period; Prognosis; Retrospective Studies

The effect of intrapleural injection of OK-432, a streptococcal preparation, for management of carcinomatous pleural effusion was investigated in patients with non-small cell lung cancer (NSCLC). Ten patients, including 5 men and 5 women with performance status 2-3(ECOG) and average age of 66.4 years, received OK-432 for different times after the tumor burden in effusion was relieved with adequate drainage. The response rate was 100% in terms of decreased reaccumulation of pleural fluid, improvement of general status, and disappearance of tumor cells in the fluid. The adverse effects of this treatment were mild-including fever, chills, chest pain and nausea-and all were tolerable to patients. Median survival time was 4.5 months after treatment. This preliminary report indicates that intrapleural injection of OK-432 is an effective alternate method for management of carcinomatous pleural effusion to improve the quality of life for terminally ill cancer patients.

Topics: Adenocarcinoma; Adult; Aged; Aged, 80 and over; Carcinoma, Non-Small-Cell Lung; Female; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil; Pleural Effusion; Time Factors

A 61-year-old woman was admitted to our hospital because of hoarseness and abnormal shadow on chest X-ray. We diagnosed this patient as large cell carcinoma of the right upper lobe of the lung; T3N3M1 Stage IV. She was treated with OK-432, CDDP and CQ. On the 6th day after 2nd cycle chemotherapy, she was confused, and we diagnosed her as a case of hyperosmolar nonketotic coma (HNC) on the 7th day. Unfortunately, she died on the 8th day, after 20 hours of treatment for HNC. She suffered from chronic dehydration due to trouble with left recurrent nerve palsy. Although continuous intravenous hyperalimentation was used, she had severe HNC. HNC might be one complication in chemotherapy for patients with malignancy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Carbazilquinone; Carcinoma, Non-Small-Cell Lung; Cisplatin; Female; Humans; Hyperglycemic Hyperosmolar Nonketotic Coma; Infusions, Intravenous; Lung Neoplasms; Middle Aged; Parenteral Nutrition, Total; Picibanil

Topics: Antineoplastic Combined Chemotherapy Protocols; Carcinoma, Non-Small-Cell Lung; Cisplatin; Cytotoxicity, Immunologic; Humans; Killer Cells, Natural; Lung Neoplasms; Nimustine; Picibanil; Vindesine

A combination of OK-432 and high-dose Carboquone (12-22 mg/m2) was administered to 17 patients with unresectable non-small cell lung cancer. The response rate was 42.9% (CR-1, PR-5) among 14 patients in whom measurement of tumor diameter was possible. With regard to hematologic adverse effects, 13 patients had a WBC count of less than 3,000, and 6 patients had a platelet count of less than 50,000. Duration of WBC nadir was not longer than 3 days, and there were no cases of infectious complication or bleeding tendency. Other side effects were all transient.

Topics: Adenocarcinoma; Aged; Antineoplastic Combined Chemotherapy Protocols; Carbazilquinone; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Female; Humans; Lung Neoplasms; Male; Middle Aged; Picibanil