TREATMENT OF MALIGNANT PLEURAL EFFUSIONS WITH DOXORUBICIN HYDROCHLORIDE-CONTAINING POLY(L-LACTIC ACID) MICROSPHERES

For the treatment of malignant pleural effusions, we prepared doxorubicin hydrochloride (Adriamycin)-containing poly(L-lactic acid) microspheres (ADR-MS). In vitro, 50 percent and 100 percent release times of ADR from ADR-MS were 6.3 and 20 days, respectively. After intrapleural administration of ADR-MS for seven patients at an ADR dose of 40 mg, ADR was detected in the effusions for more than two weeks; however, ADR concentrations in serum were very small, consistent with minimal transpleural absorption of ADR. These results indicated the slow release of ADR into the pleural cavity. Furthermore, the amount of drained ADR was less than a few percent of the administered dose. In some cases, malignant cells in the effusion disappeared after the treatment. No complications related to the procedure occurred, and the patients developed no systemic symptoms. One patient died after four months, and the other six patients are alive after 21 to 31 months without reaccumulation of the effusion. The local administration of ADR-MS produces a localized high and systemic low concentration of ADR, which could potentially improve the patient's quality of life.