Phase I trial of natural human interferon β in metastatic malignancy

Ronald M. Bukowski, James S. Sergi, William J. Sharfman, G. Thomas Budd, Siva Murthy, Barbara Barna, Sharon V. Medendorp, B. Yen-Lieberman, Vicki Gibson, Laurie Bauer, Rafael Valenzuela

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

A phase I trial of natural human β-interferon (nHuIFN-β) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-β was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 × 106 units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P < 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIKN-β (P < 0.01). Pharmacokinetic data demonstrated a short α half-life of 12.1 ± 2.5 (SE) min and a β half-life of 129.7 ± 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-β. In conclusion, toxicity of nHuIFN-β given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-β resemble those reported with rHuIFN-βser.

Original languageEnglish
Pages (from-to)836-840
Number of pages5
JournalCancer Research
Volume51
Issue number3
StatePublished - Feb 1 1991
Externally publishedYes

Fingerprint

Interferons
Neoplasms
Half-Life
Pharmacokinetics
Chills
Maximum Tolerated Dose
Population Growth
Leukopenia
Arthralgia
HLA-DR Antigens
Neutralizing Antibodies
Nausea
Fatigue
Fever
T-Lymphocytes
Kidney
Liver
Serum

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Bukowski, R. M., Sergi, J. S., Sharfman, W. J., Budd, G. T., Murthy, S., Barna, B., ... Valenzuela, R. (1991). Phase I trial of natural human interferon β in metastatic malignancy. Cancer Research, 51(3), 836-840.

Phase I trial of natural human interferon β in metastatic malignancy. / Bukowski, Ronald M.; Sergi, James S.; Sharfman, William J.; Budd, G. Thomas; Murthy, Siva; Barna, Barbara; Medendorp, Sharon V.; Yen-Lieberman, B.; Gibson, Vicki; Bauer, Laurie; Valenzuela, Rafael.

In: Cancer Research, Vol. 51, No. 3, 01.02.1991, p. 836-840.

Research output: Contribution to journalArticle

Bukowski, RM, Sergi, JS, Sharfman, WJ, Budd, GT, Murthy, S, Barna, B, Medendorp, SV, Yen-Lieberman, B, Gibson, V, Bauer, L & Valenzuela, R 1991, 'Phase I trial of natural human interferon β in metastatic malignancy', Cancer Research, vol. 51, no. 3, pp. 836-840.
Bukowski RM, Sergi JS, Sharfman WJ, Budd GT, Murthy S, Barna B et al. Phase I trial of natural human interferon β in metastatic malignancy. Cancer Research. 1991 Feb 1;51(3):836-840.
Bukowski, Ronald M. ; Sergi, James S. ; Sharfman, William J. ; Budd, G. Thomas ; Murthy, Siva ; Barna, Barbara ; Medendorp, Sharon V. ; Yen-Lieberman, B. ; Gibson, Vicki ; Bauer, Laurie ; Valenzuela, Rafael. / Phase I trial of natural human interferon β in metastatic malignancy. In: Cancer Research. 1991 ; Vol. 51, No. 3. pp. 836-840.
@article{4001c2c976394584a4b60106c7a1f3aa,
title = "Phase I trial of natural human interferon β in metastatic malignancy",
abstract = "A phase I trial of natural human β-interferon (nHuIFN-β) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-β was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 × 106 units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P < 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIKN-β (P < 0.01). Pharmacokinetic data demonstrated a short α half-life of 12.1 ± 2.5 (SE) min and a β half-life of 129.7 ± 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-β. In conclusion, toxicity of nHuIFN-β given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-β resemble those reported with rHuIFN-βser.",
author = "Bukowski, {Ronald M.} and Sergi, {James S.} and Sharfman, {William J.} and Budd, {G. Thomas} and Siva Murthy and Barbara Barna and Medendorp, {Sharon V.} and B. Yen-Lieberman and Vicki Gibson and Laurie Bauer and Rafael Valenzuela",
year = "1991",
month = "2",
day = "1",
language = "English",
volume = "51",
pages = "836--840",
journal = "Journal of Cancer Research",
issn = "0099-7013",
publisher = "American Association for Cancer Research Inc.",
number = "3",

}

TY - JOUR

T1 - Phase I trial of natural human interferon β in metastatic malignancy

AU - Bukowski, Ronald M.

AU - Sergi, James S.

AU - Sharfman, William J.

AU - Budd, G. Thomas

AU - Murthy, Siva

AU - Barna, Barbara

AU - Medendorp, Sharon V.

AU - Yen-Lieberman, B.

AU - Gibson, Vicki

AU - Bauer, Laurie

AU - Valenzuela, Rafael

PY - 1991/2/1

Y1 - 1991/2/1

N2 - A phase I trial of natural human β-interferon (nHuIFN-β) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-β was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 × 106 units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P < 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIKN-β (P < 0.01). Pharmacokinetic data demonstrated a short α half-life of 12.1 ± 2.5 (SE) min and a β half-life of 129.7 ± 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-β. In conclusion, toxicity of nHuIFN-β given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-β resemble those reported with rHuIFN-βser.

AB - A phase I trial of natural human β-interferon (nHuIFN-β) was initiated to evaluate its biological activity, maximum tolerated dose, and toxicity in patients with refractory malignancies. nHuIFN-β was administered to successive groups of 4-6 patients as an i.v. bolus on days 1 and 4, for 4 consecutive weeks. Dose levels were 0.1, 1.0, 10, 30, 60, 100, and 200 × 106 units/m2. Thirty-five patients were entered, and 34 patients were evaluable for toxicity, immunomodulatory, and antitumor effects. Toxicity was mild to moderate and included fever and chills, fatigue, arthralgias, nausea, transient renal and hepatic dysfunction, and leukopenia. No dose-limiting toxicity was observed, and no responses were seen. Significant immunological changes included the following: an increase in natural killer activity on day 5 when compared to pretreatment values (P < 0.01) and an increase in activated T-cells (CD3+/HLA-DR+) with increasing doses of nHuIKN-β (P < 0.01). Pharmacokinetic data demonstrated a short α half-life of 12.1 ± 2.5 (SE) min and a β half-life of 129.7 ± 14.7 min. Neutralizing serum antibodies were detected in 2 of 27 patients receiving nHuIFN-β. In conclusion, toxicity of nHuIFN-β given twice weekly was moderate, and further dose escalation is possible. The immunological changes and pharmacokinetic behavior of nHuIFN-β resemble those reported with rHuIFN-βser.

UR - http://www.scopus.com/inward/record.url?scp=0025975991&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0025975991&partnerID=8YFLogxK

M3 - Article

C2 - 1988123

AN - SCOPUS:0025975991

VL - 51

SP - 836

EP - 840

JO - Journal of Cancer Research

JF - Journal of Cancer Research

SN - 0099-7013

IS - 3

ER -