Intracavitary treatment of malignant ascitic carcinomatosis with oily anticancer agents in rats.
The anticancer effects and pharmacokinetics of intraperitoneal (ip) injection were determined for doxorubicin (DOX) dissolved in a lymphographic oily contrast medium, Lipiodol Ultrafluid (Lipiodol) (DOX/Lipiodol), using AH 130 ascitic tumor in rats. A high percentage (50%) of long-term survivors (cure) was observed with only a single ip injection of the DOX/Lipiodol on the seventh day after tumor inoculation, by which time the tumor ascites accumulated to a level similar to that seen clinically. The cure rate of this lipid formulation was much better than that for DOX dissolved in saline (DOX/saline) (17%). An immunopotentiating agent, Picibanil, given in 1 KE (clinical unit) or 5 KE doses was no better than the saline group, indicating that the above effect was not a result of immunopotentiation by Lipiodol. The severity of toxic side effects of DOX was also reduced by lipid solubilization. Pharmacokinetic study showed that DOX/saline was absorbed rapidly into the blood stream from the peritoneal cavity, whereas DOX/Lipiodol was retained in the ascites at a higher concentration for a much longer time. Thus the present results suggest that lipid formulations of anticancer agents have augmented therapeutic efficacy by intracavitary injection. The lipid formulations show increased stability in and prolonged slow release from the lipid milieu. Thus this therapeutic tactic of using oily anticancer agents appears to be promising for the control of pleural and peritoneal carcinomatoses.
Kimura
M
M
First Department of Surgery, Kumamoto University School of Medicine, Japan.
Konno
T
T
Oda
T
T
Maeda
H
H
Miyauchi
Y
Y
D000818:Animals; D001201:Ascites / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D006528:Carcinoma, Hepatocellular / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D004317:Doxorubicin / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004337:Drug Carriers; D004354:Drug Screening Assays, Antitumor; D004355:Drug Stability; D007274:Injections, Intraperitoneal; D007459:Iodized Oil; D008297:Male; D051381:Rats
D004337:Drug Carriers; D007459:Iodized Oil; D004317:Doxorubicin