Repetitive Weekly Cycles of Interleukin 2: Effect of Outpatient Treatment with a Lower Dose of Interleukin 2 on Non-Major Histocompatibility Complex-restricted Killer Activity

D. Goldstrein, J. A. Sosman, J. A. Hank, G. Weil-Hillman, K. H. Moore, A. Borchert, R. Bechhofei, B. Store], P. C. Kohler, D. Levitt, P. M. Sondel*

*Corresponding author for this work

Research output: Contribution to journalArticle

23 Scopus citations

Abstract

Fifteen patients with advanced malignancy who had failed conventional therapy were entered into a protocol consisting of 1 inpatient mo of repetitive weekly cycles of interleukin 2 (IL-2) at 3 × 106 units/m2/day by constant infusion for the first 4 days of each week. This was followed by IL-2 administered on an outpatient basis at the same schedule but at a dose of 1 × 106 units/m2/day for the next 1 to 6 mo. Nine patients had renal carcinoma, four had melanoma, and two had lymphoma. Thirteen patients completed the induction month, and ten patients completed >1 mo of outpatient therapy. Only one patient had therapy discontinued because of toxicity due to IL-2. No major toxicities occurred during outpatient therapy. After 1 mo of IL-2 at 3 × 106 units/m2/day, profound changes similar to those previously documented were seen in peripheral blood lymphocyte (PBL) counts (4.7-fold increase), lymphokine-activated killer activity (16-fold increase), and the percentage of PBL with natural killer-associated markers including a 3.6-fold increase in the percentage of PBL expressing the Leu 19 (NKH-I) marker, a 3.7-fold increase in Leu 11 (FcIgGR), and a 3.0-fold increase in Leu 17 (OKTIO). These indicators of IL-2 effect all remained elevated relative to the baseline at the end of 1 and 2 mo of outpatient therapy at the lower dose. However, lymphokine-activated killer activity and Leu 17 percentage were significantly reduced relative to the effect of the higher induction dose. PBL taken from patients while receiving maintenance therapy showed strong and rapid responses to IL-2 in vitro, confirming the in vivo effects of prolonged IL-2 treatment. Nevertheless, there were no complete or partial antitumor responses seen. This study demonstrates that an immunologically active dose of IL-2 can be given long term as outpatient therapy with tolerable toxicity and results in highly IL-2-responsive “primed” lymphokine-activated killer cells.

Original languageEnglish (US)
Pages (from-to)6832-6839
Number of pages8
JournalCancer Research
Volume49
Issue number23
StatePublished - Dec 1 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Goldstrein, D., Sosman, J. A., Hank, J. A., Weil-Hillman, G., Moore, K. H., Borchert, A., Bechhofei, R., Store], B., Kohler, P. C., Levitt, D., & Sondel, P. M. (1989). Repetitive Weekly Cycles of Interleukin 2: Effect of Outpatient Treatment with a Lower Dose of Interleukin 2 on Non-Major Histocompatibility Complex-restricted Killer Activity. Cancer Research, 49(23), 6832-6839.