Intrapleural paclitaxel for malignant pleural effusion from ovarian and breast cancer: a phase II study with pharmacokinetic analysis.

Introduction: Malignant pleural effusion (MPE) is a frequent complication in many types of tumors diminishing the patient's ability to perform activities. Despite various studies on talc treatment, some doubts about its safety and effectiveness remain, so the search for a more ideal intrapleural agent continues. We analyzed the effectiveness and safety of intrapleural paclitaxel in ovarian and breast cancer patients.

Patients And Methods: The primary endpoint was overall response rate (ORR); secondary objectives included time to progression (TTP), overall survival (OS) and safety of intrapleural paclitaxel. Pharmacokinetics of the drug was also analyzed. After drainage of pleural effusion and lung re-expansion, paclitaxel 120 mg/m(2) diluted in normal saline was infused through a preinserted catheter which was immediately closed and reopened 24 h later. Blood and pleural fluid samples were collected 1, 4 and 24 h after the end of paclitaxel instillation. When MPE was less than 200 ml/24 h the catheter was removed. Chest radiographs were performed at the beginning of intrapleural paclitaxel, at 1 and 2 months later or with clinical deterioration.

Results: We enrolled 18 patients with recurrent MPE: 11 with ovarian cancer and 7 with breast cancer. ORR was 77.8% at 1 month and 88.8%. at 2 months. Median TTP was 5.5 months (CI 95% 0.9-10.1) and median OS was 8.9 months (CI 95% 0.1-17.6). Patients achieving a complete response obtained a statistically significant longer survival than did patients with partial response or progressive disease. Chest pain, fever, and dyspnea were the most frequent side effects. Intrapleural paclitaxel concentrations were very high (mean ± SD = 478 ± 187 mg/l) and declined slowly (mean 24 h reduction ~30%). Detectable but low taxol plasma levels were found in most patients (mean ± SD = 0.045 ± 0.073 mg/l).

Conclusion: Intrapleural paclitaxel is a safe and effective palliative treatment for MPE from breast and ovarian cancers and may be integrated with systemic chemotherapy.