We will test a new approach to management of malignant pleural effusions (MPE) based on chemotherapy using intrapleural administration of AD 32 rather than pleurodesis. There are about 100,000 cases p.a. of MPE in the US, and it causes significant morbidity in patients with advanced malignancies. MPE is currently treated primarily with chemical pleurodesis, a procedure that obliterates the pleural cavity with adherence of the lung to the chest wall, and consequently compromises respiratory functioning. AD 32 is a lipophilic anthracycline analog that has shown a good safety profile, minimal local toxicity and evidence of antitumor activity in clinical studies for intracavitary therapy of superficial bladder and ovarian cancer. Compared to other chemotherapeutic drugs, AD 32 has superior tissue penetration properties and very little sclerosing activity. Thus if AD 32 proves active in treatment of MPE, this activity is likely to be due to an antitumor effect that does not permanently damage normal pleural tissue and may spare respiratory function. In the absence of a good animal model for pleural effusions, we will sponsor a Phase I safety and tolerance study of intrapleural AD 32 in patients with MPE.National Cancer Institute (NCI)
