The efficacy of anti neoplastic agents for chest catheter pleurodesis remains controversial, and little is known regarding the optimal treatment protocol. Of the various anti neoplastic agents, bleomycin and cisplatin are preferred for intrapleural therapy in Japan, and a wide variation among institutions is evident in agent doses and medication methods for pleurodesis. In many reported trials of anti neoplastic pleurodesis, problems exist such as disease heterogeneity, small sample size and differences in response criteria, and randomized control trials (RCTs) are needed to establish evidence. The JCOG 9515 trial randomly assigned patients to either the bleomycin (BLM) arm, the OK-432 arm, or the cisplatin+etoposide (PE) arm. Among them, OK-432 was demonstrated to be more effective than BLM or PE in terms of pleural progression-free survival. Intrapleural combination therapy (chemotherapy plus biological response modifiers) appeared to be superior to either alone, and further randomized studies are warranted.