Efficacy of intrapleural administration of amrubicin, a novel anthracycline derivative, for disseminated pleural tumor model

Abstract

2126 Background: Malignant pleural effusion caused by disseminated pleural tumors is a common and critical issue in patients with advanced malignancies. Pleurodesis is usually performed for the control, but it sometimes fails to control or cause some complications. In some clinical studies, intrapleural administration of chemotherapeutic agents such as doxorubicin was tested, but the efficacy has not been established. Recently, amrubicin (AMR), a novel anthracycline derivative, has been developed, and the present experimental study was conducted to examine the efficacy of intrapleural AMR administration in disseminated pleural-tumor models. Methods: Two human non-small cell carcinoma cell (NSCLC) lines (A549, adenocarcinoma; H1299, large cell carcinoma) and one pleural mesothelioma cell line (H211) were used. BALBc Nu/Nu mice were injected with 5,000,000 tumor cells into the pleural space. When disseminated pleural tumors were established, we started repeated intrapleural administration of AMR (5mg/kg/day, once a week for 8 weeks); the optimal schedule and dose, which caused no significant body weight-loss, was determined in preliminary experiments. Results: Repeated intrapleural administration of AMR significantly prolonged survivals in all three cell-line models (Table). In H211-disseminated model, the efficacy of intrapleural administration was also compared with that of intravenous administration, which revealed the superiority of intrapleural administration (MST, 97days vs 55days; p=0.074). Conclusions: Repeated intrapleural administration of AMR was effective in in vivo disseminated pleural tumor models, and we are now planning a phase I-II clinical study of repeated intrapleural administration of AMR. No significant financial relationships to disclose.