Randomized phase II trial of three intrapleural therapy regimens for the management of malignant pleural effusion in previously untreated non-small cell lung cancer: JCOG 9515

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 pleura( effusion (MPE) in previously untreated non-small cell lung cancer. Eligible patients were randomized to the BLM arm: BLM 1 mg/kg (maximum 60 mg/ body), the OK-432 arm: OK-432 0.2 Klinische Einheit units (KE)/kg (maximum 10 KE/body), or the PE arm: cisplatin (80 mg/m(2)) and etoposide (80 mg/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. (c) 2007 Elsevier Ireland Ltd. All rights reserved.