P2.02-024 Phase I and II Trial of Intrapleural Paclitaxel Injection for Non-Small-Cell Lung Cancer Patients with Malignant Pleural Effusions

Abstract

The presence of malignant pleural effusion (MPE) frequently indicates locally advanced non-small cell lung cancer (NSCLC). The conventional management of MPE involves pleurodesis using a sclerosant substance. The Perng et al. reported injection into chest cavity using paclitaxel for 18 MPE cases. In this report overall response rate was 92.9%. No disease progression was noted among evaluable patients. Therefore we focused on Paclitaxel which had antitumor effect and a pleural effusion control, and planned clinical trials phase I and II for the treatment of MPE. The primary objective of this study was to evaluate the efficacy of paclitaxel pleurodesis, the side effects and systemic antitumor effect. Patients were enrolled cytologically proven malignant pleural effusion of NSCLC. Radiotherapy and systemic chemotherapy were also not allowed within 4 weeks. After adequate drainage and assurance of lung re-expansion, paclitaxel diluted in normal saline was infused through a double lumen catheter. The starting dose was 100 mg/m2 with dose escalation schedule of 125, 150, and 175mg/m2. The catheter was clamped for 24 hrs. Chest drainage was continued until daily drainage was under 200 ml, and the tube was removed. To measure paclitaxel concentration, serum and pleural fluid samples were collected 0.5, 1, 3, 6, 24, 72hrs after the end of drug instillation. The treatment response of malignant effusion was evaluated according to the following criteria: complete response (CR), no fluid reaccumulation for at least 4 weeks as determined by CT scan; partial response (PR), recurrence of effusion to less than 50% of the original effusion volume within 4 weeks after treatment; failure, recurrence of effusion greater than 50% of the original volume, patients were symptomatic and need for thoracentesis to relieve symptoms within 4 weeks. The criteria for main tumor lesion response to intrapleural paclitaxel treatment were in accordance with Response Evaluation Criteria in Solid Tumors (Revised RECIST guideline version 1.1). From April 2009 to November 2012, 12 patients were enrolled. There were minimal local and systemic toxicities. The serum level of PXL of the cases with the effect of treatment was significantly higher than these of the cases without the effect. Over all response rate was 67%. No disease progression was noted among evaluable patients. We decided to plan a late phase II study of the therapy with 175 mg/m2, because it was not dosage-dependent even if it was a low dose and serum level-dependent.