Splenic versus hepatic artery infusion of interleukin-2 in patients with liver metastases.

Abstract

In an attempt to improve the therapeutic index of recombinant interleukin-2 (rIL-2) by generating or activating lymphokine-activated killer (LAK) cells and tumor-infiltrating lymphocytes (TIL) regionally and/or in situ, we randomly assigned 28 patients with liver metastases to receive rIL-2 by continuous infusion for 5 days via either the splenic artery or the hepatic artery. Clinically significant and lasting tumor regression was observed only in two of 28 patients (7%), one in each of the two treatment arms. The maximum-tolerated daily dosage of rIL-2 was 3 x 10(6) U/m2; beyond this dosage, toxicity was excessive. Peripheral LAK cell activity measured in vitro and clinical tumor regression did not correlate. This observation, coupled with the equal distribution of regressions between the two treatment arms, raises the possibility that tumor regression, rare though it may be in response to rIL-2 administration, is largely mediated by TIL activation and not by LAK cell generation.