Experimental and clinical evaluation of cisplatin-containing microspheres as intraperitoneal chemotherapy for ovarian cancer
Sugiyama, T.; Kumagai, S.; Nishida, T.; Ushijima, K.; Matsuo, T.; Yakushiji, M.; Hyon, S.H.; Ikada, Y.
Anticancer Research 18(4b): 2837-2842
1998
ISSN/ISBN: 0250-7005 PMID: 9713471 Document Number: 492325
Background: We aimed to evaluate the in vitro and in vivo effects of poly (L-lactic acid) microspheres containing cisplatin (CDDP-MS) for intraperitoneal (ip) chemotherapy for ovarian cancer. Methods: We initially examined the in vitro and in vivo profile of cisplatin release from the CDDP-MS, then this drug delivery system was evaluated in 15 patients. Results: The in vitro study showed that cisplatin was released constantly over a 3-week period Rats in the CDDP-MS group had a significantly lower peak serum concentration of platinum compared with rats in the aqueous cisplatin solution (CDDP-S) group; the serum concentration of platinum showed a gradual decline. The ascitic fluid concentration of platinum also gradually decreased in the CDDP-MS group. We treated 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 platinum were lower immediately after administration of CDDP-MS than after administration of CDDP-S, but increased over time in the CDDP-MS group, reflecting the slow-release effect of CDDP-MS. Grade 1 to 2 leukopenia and/or neutropenia occurred in 2 of 5 patients. No thrombocytopenia or renal or neurologic toxicity was observed; Conclusion: These findings indicate that the ip administration of CDDP-MS increased the dose intensity of cisplatin and appeared to be safe and effective for the treatment of ovarian cancer.