Intraperitoneal administration of interleukin-2 in patients with cancer.

Abstract

We have administered 11 to 64 doses of recombinant interleukin-2 (IL-2) ranging from 10,000 to 300,000 U/kg, given three times daily as a bolus infusion through an indwelling Tenckhoff catheter, to seven patients with melanoma, ovarian carcinoma, or colorectal carcinoma. The total IL-2 dose ranged from 800 to 3800 X 10(3) U/kg. Side effects included fever, chills, nausea, vomiting, diarrhea, and major weight gain presumedly related to a capillary leak syndrome. Total weight gain ranged from 5.1 to 17.4 kg and was associated with the development of both peripheral edema and ascites. Marked eosinophilia was noted. Serum IL-2 levels were maintained at 10 to 35 U/mL for up to eight hours following intraperitoneal administration of IL-2. Increases from less than 10(4) cells/mL of a 2-L peritoneal wash to more than 10(6) cells/mL were noted in peritoneal exudate cell yields. Lysis of the natural killer target K562 increased from undetectable levels to as high as 125 lytic units per 10(6) cells. Proliferative capacity to IL-2 increased as much as 30-fold in peritoneal exudate cell yields. In addition, 70% to 80% of the mononuclear cells were T cells (Leu 4+) with intraperitoneal phenotype treatment. A single patient with pulmonary and hepatic metastases showed marked decrease in these lesions with intraperitoneal IL-2 treatment. The other patients treated intraperitoneally with IL-2 did not have significant (greater than 50%) reduction in tumor volume. These findings indicate that the intraperitoneal route of IL-2 administration may allow the in vivo development and expansion of lymphoid cells with antitumor activities.

• Authors: M T Lotze, M C Custer, S A Rosenberg
• Journal: Archives of surgery (Chicago, Ill. : 1960) (Arch Surg) Vol. 121 Issue 12 Pg. 1373-9 (Dec 1986) ISSN: 0004-0010 [Print] United States
• PMID: 3491595 (Publication Type: Journal Article)

Chemical References

• Interleukin-2
• RNA, Messenger
• Recombinant Proteins

Topics

• Biological Assay
• Cell Division (drug effects)
• Cytotoxicity, Immunologic (drug effects)
• Flow Cytometry
• Humans
• Injections, Intraperitoneal
• Interleukin-2 (adverse effects, metabolism, therapeutic use)
• Monitoring, Physiologic
• Neoplasms (immunology, therapy)
• Peritoneal Cavity (cytology)
• Phenotype
• RNA, Messenger (metabolism)
• Recombinant Proteins (therapeutic use)