Faculty Collaboration Database

Phase I study of a combination of recombinant interferon-alpha and recombinant interferon-gamma in cancer patients. J Clin Oncol 1986 Nov;4(11):1677-83

Date

11/01/1986

Pubmed ID

3095504

DOI

10.1200/JCO.1986.4.11.1677

Scopus ID

2-s2.0-0023039353 (requires institutional sign-in at Scopus site)   44 Citations

Abstract

Combinations of interferon-alpha and interferon-gamma demonstrate synergistic antiviral and anti-proliferative activity in vitro. Therefore, we initiated a clinical study of combination interferon therapy in humans. Eighteen patients with metastatic solid tumors received daily intramuscular (IM) injections of recombinant interferon-alpha-A (IFN alfa-2a, Roferon-A; Hoffman-LaRoche, Nutley, NJ) and recombinant IFN-gamma (rIFN-gamma) for 6 weeks. The dose levels were 0.5, 1.0, 2.0, and 5.0 X 10(6) U/m2/d of each interferon. A minimum of two patients were entered sequentially at each dose level. Fever, chills, fatigue, and a greater than or equal to 50% drop in granulocyte counts were observed at all doses. Severity of symptoms corresponded to increasing dose levels. In contrast to the tachyphylaxis to these symptoms that usually develops in patients treated with the individual interferons, many patients on this study experienced persistent fever and worsening fatigue over 6 weeks. The maximum tolerated dose was 1 X 10(6) U/m2/d of each interferon. One patient with renal-cell carcinoma achieved a partial remission (duration, 3 months). Enzyme-linked immunoassay analysis in all four patients for whom complete data were available revealed that peak blood levels of IFN alfa-2a on day 22 were about tenfold higher than on day 1. Because of the possibility of cumulative toxicity, the recommended starting dose for further studies is 0.5 X 10(6) U/m2/d of each interferon, with escalation to 1.0 X 10(6) U/m2/d after 1 month if tolerance is acceptable. Phase II investigations to explore the antitumor efficacy of this regimen are planned.

Author List

Kurzrock R, Rosenblum MG, Quesada JR, Sherwin SA, Itri LM, Gutterman JU

Author

Razelle Kurzrock MD Center Associate Director, Professor in the Medicine department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Adult
Aged
Antibodies
Antineoplastic Combined Chemotherapy Protocols
Central Nervous System Diseases
DNA, Recombinant
Dose-Response Relationship, Drug
Drug Evaluation
Enzyme-Linked Immunosorbent Assay
Female
Gastrointestinal Diseases
Hematologic Diseases
Humans
Interferon Type I
Interferon-gamma
Kinetics
Male
Middle Aged
Neoplasms
Research Design