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 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;


CONCLUSIONS
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.
Sugiyama
T
T
Department of Obstetrics and Gynecology, Kurume University School of Medicine, Japan.
Kumagai
S
S
Nishida
T
T
Ushijima
K
K
Matsuo
T
T
Yakushiji
M
M
Hyon
S H
SH
Ikada
Y
Y
D000328:Adult; D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D001202:Ascitic Fluid / Q000737:chemistry; D002945:Cisplatin / Q000008:administration & dosage* / Q000032:analysis / Q000493:pharmacokinetics* / Q000633:toxicity; D016503:Drug Delivery Systems / Q000379:methods*; D005069:Evaluation Studies as Topic; D005260:Female; D006801:Humans; D007274:Injections, Intraperitoneal; D008863:Microspheres; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D002945:Cisplatin