IL-2 perfusion to the liver augments the hepatic extraction rate of accompanying anticancer drugs.
A pilot study we conducted on hepatic infusion chemotherapy combined with interleukin-2 (IL-2) for metastatic liver malignancies revealed very encouraging results indicating that this treatment modality is more effective than either of the anticancer drugs used alone. To clarify the mechanisms underlying the synergism of these modalities, the pharmacokinetics of anticancer drugs were examined in a rat model. Adult rats were given 5-fluorouracil (5-FU) or mitomycin C (MMC) combined with various doses of IL-2 up to 7500 JRU/kg per minute for the measurement of hepatic extraction rates (HER). The HER of 5-FU was significantly increased (P < 0.01) in combination with IL-2 in a dose-dependent fashion while that of MMC also showed a tendency to increase. Thus, it is conceivable that the increase of vascular permeability caused by IL-2 results in augmentation of the HER of associated anticancer drugs. This effect may improve the delivery of anticancer drugs to the liver and alleviate general toxicity by reducing the amount of circulating anticancer agents.
Okuno
K
K
First Department of Surgery, Kinki University School of Medicine, Osaka, Japan.
Kobayashi
S
S
Jinnai
H
H
Lee
Y S
YS
Shigeoka
H
H
Yasutomi
M
M
D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D005472:Fluorouracil / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007261:Infusions, Intra-Arterial; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000493:pharmacokinetics; D008099:Liver / Q000378:metabolism*; D016685:Mitomycin / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D007376:Interleukin-2; D016685:Mitomycin; D005472:Fluorouracil