picibanil and Mesothelioma

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

In order to evaluate the incidence of an adverse event encountered when using a new therapeutic intervention, it is essential to know the background rate of this adverse event in the same patient population. Interstitial lung disease (ILD) often develops in Japanese patients receiving treatment with anti-neoplastic agents or other drugs. In our study, we estimated the background rate of ILD in patients with malignant mesothelioma (MM).. We conducted a retrospective cohort study of 328 Japanese patients diagnosed with MM during the period between 1996 and 2006.. After the diagnosis of MM had been made, 21 (15 new and 6 exacerbation) of the 328 patients developed ILD. The crude baseline rate of ILD was estimated to be 0.023 (95%CI, 0.009-0.054) per patient-year, and the baseline rate using the Poisson regression model was estimated to be 0.032 (95%CI, 0.017-0.059) per patient-year where major therapeutic interventions were incorporated in the model. The risk of ILD was increased by surgical excision (rate ratio, 8.87; 95%CI, 2.39-33.0), pleurodesis with picibanil (rate ratio, 5.14; 95%CI, 1.63-16.3), and systemic chemotherapy using vinorelbine (rate ratio, 5.95; 95%CI, 1.22-29.0).. Our results have implications for evaluating the safety outcomes of future studies in patients receiving treatment for MM. The development of ILD in such studies at an incidence rate higher than 0.02-0.03 per patient-year might indicate an excess occurrence as a result of a therapeutic intervention.

Topics: Adult; Aged; Aged, 80 and over; Antineoplastic Agents; Cohort Studies; Female; Humans; Incidence; Japan; Lung Diseases, Interstitial; Male; Mesothelioma; Middle Aged; Picibanil; Pleurodesis; Poisson Distribution; Regression Analysis; Retrospective Studies; Risk Factors; Vinblastine; Vinorelbine

A 71-year-old man was found to have right hydropneumothorax by chest X-ray film on a regular checkup. Thoracic drainage and bullectomy by thoracoscopy did not improve the pneumothorax, so pleurodesis with OK-432 was done. Pneumothorax recurred twice, requiring thoracic drainage and pleurodesis. Although pneumothorax was treated successfully, increased pleural effusion, pleural thickening and subcutaneal tumor at the thoracic drainage suture site developed. The concentration of hyaluronic acid in the pleural fluid was very high. The histological examination of the biopsied subcutaneous tumor showed mixed type malignant pleural mesothelioma. Chemotherapy with gemcitabine and vinorelbine could not control the progression.

Topics: Aged; Antineoplastic Agents; Disease Progression; Fatal Outcome; Humans; Male; Mesothelioma; Picibanil; Pleural Neoplasms; Pneumothorax; Radiography; Recurrence

A case of malignant mesothelioma of the peritoneum successfully treated with short-term intraperitoneal chemotherapy is reported. A 67-year-old woman underwent laparotomy for ascending colon cancer. During, laparotomy, numerous mucoid nodules were found on the peritoneal surface, even though the colonic tumor did not invade the serosa. Ileocecal resection (D1) with partial omentectomy was performed. Intraperitoneal infusion with cisplatin (200 mg) was started immediately after surgery and additional cisplatin (150 mg) was administered with OK-432 (30KE). The serum level of CA125 rapidly decreased after the chemotherapy, and was normalized 3 months postoperatively. The histological diagnosis of the peritoneal lesions was malignant mesothelioma of the peritoneum (diffuse type). The patient is living without any evidence of recurrence 10 months postoperatively. These results suggest that this short-term chemotherapy is worth trying in cases of malignant mesothelioma of the peritoneum.

Topics: Aged; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Cisplatin; Female; Humans; Infusions, Parenteral; Mesothelioma; Peritoneal Neoplasms; Picibanil