EXPERIMENTAL AND CLINICAL-EVALUATION OF CISPLATIN-CONTAINING MICROSPHERES AS INTRAPERITONEAL CHEMOTHERAPY FOR OVARIAN-CANCER

Background. We aimed to evaluate the in vitro and in vivo effects of p oly [L-lactic acid] microspheres containing cisplatin (CDDP-MS) for in traperitoneal (ip) chemotherapy for ovarian cancer. Methods: We initia lly examined the in vitro and in vivo profile of cisplatin release fro m the CDDP-MS, then this drug delivery system was evaluated in 15 pati ents. Results: The in vitro study showed that cisplatin was released c onstantly over a 3-week period. Rats in the CDDP-MS group had a signif icantly lower peak serum concentration of platinum compared with rats in the aqueous cisplatin solution (CDDP-S) group; the serum concentrat ion of platinum showed a gradual decline. The ascitic fluid concentrat ion of platinum also gradually decreased in the CDDP-MS group. We trea ted 15 patients with recurrent ovarian cancer with CDDP-MS containing 200 mg of cisplatin (n=5) or CDDP-S containing 100 mg of cisplatin (n= 10) administered ip. The peak serum and ascites concentrations of plat inum were lower immediately after administration of CDDP-MS than after administration of CDDP-S, but increased over time in the CDDP-MS grou p reflecting the slow-release effect of CDDP-MS. Grade 1 to 2 leukopen ia and/or neutropenia occurred in 2 of 5 patients. No thrombocytopenia or renal or neurologic toxicity was observed;Conclusion: These findin gs indicate that the ip administration of CDDP-MS increased the dose i ntensity of cisplatin and appeared to be safe and effective for the tr eatment of ovarian cancer.