Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2

M. Margaret Kemeny, Galo Alava, Jorge M. Oliver

Research output: Contribution to journalArticlepeer-review

11 Scopus citations

Abstract

Previous studies on continuous hepatic artery infusions of recombinant interleukin-2 (IL-2) have shown that in a nontumor-bearing animal a continuous infusion given in a circadian "day cycled" pattern was much less toxic and could be given with 10 times higher doses of IL-2 than if the constant pattern of infusion was used. In the present study, circadian-patterned continuous hepatic artery infusions of IL-2 were used in hepatoma-bearing rats. Doses of 10 mg/m2/day could be tolerated when IL-2 was given in a "day cycle" rhythm. Control animals were given 1 mg/m2/day of constant infusion IL-2, which was the highest hepatic artery infusion dose tolerated at a constant rate without mortality in nontumor-bearing animals. Animals treated with the constant infusions of IL-2 had a 37.5% mortality rate and a 25% objective response rate in measurable tumor size. Animals receiving the "day cycle" had no mortality and a 100% objective response rate. The conclusion was that "day cycled" circadian-patterned continuous hepatic artery infusions of IL-2 could be given with much lower toxicity and much improved tumor response rates than constant continuous infusions.

Original languageEnglish
Pages (from-to)219-223
Number of pages5
JournalJournal of Immunotherapy
Volume12
Issue number4
DOIs
StatePublished - Nov 1992
Externally publishedYes

Keywords

  • Circadian-patterned chemotherapy
  • Hepatic artery infusion
  • Hepatocellular carcinoma
  • Interleukin-2

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