[The pharmacokinetics of intraperitoneal (IP) carboplatin (CBDCA) and dose-up study of intravenous (IV) cyclophosphamide (CPM) in combination with IP CBCDA for advanced ovarian cancer patients].
The pharmacokinetics of IP CBDCA was compared with IV CBDCA and a dose-up study of IV CPM was performed in combination with 400 mg/m2 IP CBDCA for advanced ovarian cancer patients. The maximum concentration of free platinum (F-Pt) in serum following IP CBDCA administration was approximately 1/3 that of F-Pt following IV CBDCA. F-Pt in serum remained more than 90% of total platinum following IP CBDCA until 12 hours after administration. The t1/2 of F-Pt in serum after IP CBDCA administration was two times longer when compared with t1/2 following IV CBDCA, showing the slow peritoneal clearance of CBDCA. The area under curve (AUC) following IP CBDCA was approximately 67% of AUC following IV CBDCA. Cumulative urinary secretion (CUS) of platinum following IP CBDCA was 37% of CUS after IV CBDCA. The maximum tolerable dose of IV CPM in combination with 400 mg/m2 IP CBDCA was 550-600 mg/m2. The dose limiting factor of this combination therapy was leukocytopenia. Thrombocytopenia was mild in this study. Combination of 400 mg/m2 IP CBDCA and 550-600 mg/m2 seemed to be a tolerable and repeatable therapy for most patients with advanced ovarian carcinoma. Since thrombocytopenia was mild and the pharmacokinetics showed the smaller AUC of free platinum in serum following IP CBDCA, a dose-up study for IP CBDCA should be considered.
Fujiwara
K
K
Department of Obstetrics and Gynecology, Kawasaki Medical School, Kurashiki, Japan.
Yamauchi
H
H
Sawada
S
S
Koike
H
H
Mohri
H
H
Ohishi
Y
Y
Kohno
I
I
D000230:Adenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D000328:Adult; D000368:Aged; D016190:Carboplatin / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D003520:Cyclophosphamide / Q000008:administration & dosage*; D003536:Cystadenocarcinoma / Q000188:drug therapy / Q000378:metabolism; D004334:Drug Administration Schedule; D005260:Female; D006801:Humans; D015918:Infusion Pumps, Implantable; D007262:Infusions, Intravenous; D007263:Infusions, Parenteral; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy* / Q000378:metabolism
D003520:Cyclophosphamide; D016190:Carboplatin