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Experimental and clinical evaluation of cisplatin-containing microspheres as intraperitoneal chemotherapy for ovarian
T Sugiyama1, S Kumagai, T Nishida
1Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan.
Background:
We aimed to evaluate the in vitro and in vivo effects of poly [L-lactic acid] microsphere containing cisplatin (CDDP-MS) for intraperitoneal (i.p.) 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 i.p. 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 i.p. administration of CDDP-MS increased the dose intensity of cisplatin and appeared to be safe and effective for the treatment of ovarian cancer.