シスプラチン・マイクロスフェアーを用いた癌性胸膜炎の治療

Abstract

Microspheres were prepared using a polymer consisting of glycolic acid-L-lactic acid copolymer (PGLA) with a molecular weight of 27, 000 and cisplatin (CDDP) for local therapy of pleuritis carcinomatosa. The CDDP-containing PGLA microspheres(CDDP-MS) were about 100 μm in diameter with a CDDP content of 5%, and all the CDDP was released in vitro within about 3 weeks. For administration, a drain was inserted into the thoracic cavity of the patients, and CDDP-MS, equivalent to 100 mg CDDP, were infused into the pleural cavity with 100 ml of physiologic saline, followed by clamping of the drain. The clamp was removed after 24 h. All the pleural effusion was recovered thereafter, and CDDP was assayed periodically in the effusion and serum. As a control, CDDP solution was administered into the pleural cavity. After administration of CDDP-MS, CDDP was detectable in serum until 5 days and in the effusion until 8 days, at the time of extubation. The concentration of CDDP in serum was lower than that in the CDDP solution. The total amount of drained CDDP was about 1, 000 μg, or about 1% of the total dose. In contrast, after treatment with CDDP solution, 3.4% of the CDDP dose was drained. Upon removal of the drain, the cytology of the pleural effusion was changed from Class V to Class III. No side effects of CDDP-MS were noted, but nausea and vomiting were observed after treatment with the CDDP solution. Since CDDP-MS release non-protein-binding CDDP, they would be expected to produce a prolonged antitumor effect at the tumor cell implantation site, are therefore considered to be useful for the treatment of malignant pleural effusions.