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 w ith interleukin-2 (IL-2) for metastatic liver malignancies revealed ve ry 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 pharm acokinetics of anticancer drugs were examined in a rat model. Adult ra ts mere 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 measuremen t 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 fas hion 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. Th is effect may improve the delivery of anticancer drugs to the liver an d alleviate general toxicity by reducing the amount of circulating ant icancer agents.