Document 0354
 DOCN  M9550354
 TI    Phase I trial of escalating doses of interleukin-1 beta in combination
       with a fixed dose of interleukin-2.
 DT    9505
 AU    Triozzi PL; Kim JA; Martin EW; Young DC; Benzies T; Villasmil PM; Ohio
       State University Comprehensive Cancer Center, Columbus.
 SO    J Clin Oncol. 1995 Feb;13(2):482-9. Unique Identifier : AIDSLINE
       MED/95147037
 AB    PURPOSE: Interleukin-1 (IL-1) and IL-2 have synergistic antitumor and
       myelostimulatory activities. We investigated the clinical and biologic
       effects of IL-1/IL-2 therapy. PATIENTS AND METHODS: Twenty patients with
       metastatic cancer, divided into five cohorts, were treated with
       escalating doses of IL-1 beta (0.005 to 0.2 micrograms/kg/d)
       administered as a 30-minute intravenous (IV) infusion on days 1 to 4,
       combined with a fixed dose of IL-2 (0.1 mg/m2/d) administered by
       continuous IV infusion on days 1 to 4. The 4-day cycles were repeated
       weekly for up to 8 weeks in the absence of toxicity and/or progressive
       disease. RESULTS: Patients tolerated up to 0.2 microgram/kg/d of IL-1
       beta in combination with IL-2 without severe adverse effects.
       Peripheral-blood CD4-to-CD8 ratios and lymphokine-activated killer (LAK)
       activity were higher at the lower doses (0.005 to 0.05 microgram/kg/d)
       of IL-1 beta and higher than that of a cohort of patients treated with
       IL-2 alone. WBC counts, primarily neutrophils, increased significantly
       with higher doses of IL-1 beta (0.1 to 0.2 microgram/kg/d). Platelet
       counts were not significantly altered. Increases in serum IL-6,
       interferon gamma (IFN-gamma), and soluble IL-2 receptor levels were
       observed, but did not vary with IL-1 beta dose. Tumor regressions were
       observed in patients with colorectal cancer, melanoma, and renal cell
       carcinoma. CONCLUSION: IL-1 beta cancer be administered in combination
       with IL-2 with acceptable toxicity. Our results suggest that the
       addition of even low-dose IL-1 beta to IL-2 may be associated with
       potentially beneficial biologic activity; higher doses of IL-1 beta (0.1
       to 0.2 microgram/kg/d) may add potentially beneficial hematologic
       activity.
 DE    Adjuvants, Immunologic/BLOOD  Adult  Aged  Carcinoma, Renal
       Cell/IMMUNOLOGY/*THERAPY  Colorectal Neoplasms/IMMUNOLOGY/*THERAPY
       Comparative Study  CD4-CD8 Ratio  Female  Human  Infusions, Intravenous
       Interleukin-1/*ADMINISTRATION & DOSAGE/TOXICITY
       Interleukin-2/*ADMINISTRATION & DOSAGE/TOXICITY  Kidney
       Neoplasms/IMMUNOLOGY/*THERAPY  Leukocyte Count  Male
       Melanoma/IMMUNOLOGY/*THERAPY  Middle Age  Neoplasm Metastasis
       Neutrophils  Peptides/BLOOD  Support, Non-U.S. Gov't  Support, U.S.
       Gov't, P.H.S.  Time Factors  CLINICAL TRIAL  CLINICAL TRIAL, PHASE I
       JOURNAL ARTICLE

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