Improving responses in hepatomas with circadian-patterned hepatic artery infusions of recombinant interleukin-2.
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.
Kemeny
M M
MM
Department of Surgery, St. Vincent's Hospital and Medical Center, New York, NY 10011.
Alava
G
G
Oliver
J M
JM
D000818:Animals; D002940:Circadian Rhythm; D004334:Drug Administration Schedule; D006499:Hepatic Artery; D007155:Immunologic Factors / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D007261:Infusions, Intra-Arterial; D007376:Interleukin-2 / Q000008:administration & dosage / Q000627:therapeutic use* / Q000633:toxicity; D008114:Liver Neoplasms, Experimental / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use / Q000633:toxicity
D007155:Immunologic Factors; D007376:Interleukin-2; D011994:Recombinant Proteins