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 language | English |
|---|---|
| Pages (from-to) | 836-840 |
| Number of pages | 5 |
| Journal | Cancer Research |
| Volume | 51 |
| Issue number | 3 |
| State | Published - Feb 1 1991 |
| Externally published | Yes |
Fingerprint
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
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 journal › Article
}
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 -