Phase I trial of escalating doses of interleukin-1 beta in combination with a fixed dose of interleukin-2.
OBJECTIVE
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.


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.


CONCLUSIONS
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.
Triozzi
P L
PL
Ohio State University Comprehensive Cancer Center, Columbus.
Kim
J A
JA
Martin
E W
EW
Young
D C
DC
Benzies
T
T
Villasmil
P M
PM
D000276:Adjuvants, Immunologic / Q000097:blood; D000328:Adult; D000368:Aged; D016516:CD4-CD8 Ratio; D002292:Carcinoma, Renal Cell / Q000276:immunology / Q000628:therapy*; D015179:Colorectal Neoplasms / Q000276:immunology / Q000628:therapy*; D005260:Female; D006801:Humans; D007262:Infusions, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage* / Q000633:toxicity; D007376:Interleukin-2 / Q000008:administration & dosage* / Q000633:toxicity; D007680:Kidney Neoplasms / Q000276:immunology / Q000628:therapy*; D007958:Leukocyte Count; D008297:Male; D008545:Melanoma / Q000276:immunology / Q000628:therapy*; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009504:Neutrophils; D010455:Peptides / Q000097:blood; D013997:Time Factors
D000276:Adjuvants, Immunologic; D007375:Interleukin-1; D007376:Interleukin-2; D010455:Peptides; C041640:poly(lysyl-(leucyl-poly-alanine))