Recombinant human interferon-β (rHuIFN-β) and radiation therapy for inoperable non-small cell lung cancer

Roger W. Byhardt, Louis Vaickus, Patricia L. Witt, Alex Y. Chang, Timothy McAuliffe, J. Frank Wilson, Colleen A. Lawton, James Breitmeyer, Mary Ellen Alger, Ernest C. Borden

Research output: Contribution to journalArticlepeer-review

Abstract

Fifteen patients with stage II, IIIA, and IIIB non-small cell lung cancer (NSCLC) received subcutaneous (s.c.) recombinant, glycosylated, human interferon-β1a (Rebif; rHuIFN-β1a) on each day of conventionally fractionated radiation therapy (RT) given in 2.0 Gy fractions to 60 Gy in 6 weeks. The rHuIFN-β1a was generated in CHO cells by recombinant DNA technology and is identical to natural IFN-β produced by fibroblasts in primary sequence and glycosylation. Cohorts of three patients each were treated with escalating doses of rHuIFN-β1a: 1.5, 3, 6, 12, and 24 MIU/m2 per treatment day. Acute toxicity was assessed according to modified WHO criteria; late toxicity was graded using RTOG late toxicity criteria. The maximum tolerated dose (MTD) of rHuIFN-β1a was defined as the dose level immediately below that in which dose-limiting toxicity occurred in ≤ two of six patients. Immunomodulatory effects and antigenicity of rHuUFN-β1a were assessed by 2-5A synthetase, β2-microglobulin, and neopterin levels and by measurement of anti-rHuIFN-β antibodies, respectively. Fourteen of fifteen patients experienced grades 1-3 acute (early) toxicity (≤90 days), which was primarily gastrointestinal: dysphagia/esophagitis (14/15), nausea/vomiting (12/15), anorexia (7/15), and liver transaminasemia (6/15). One of three patients treated with 24 MIU/m2 per treatment day (total rHuIFN-β1a dose 672 MIU) died of complications secondary to pneumonia, sepsis, adult respiratory distress syndrome (ARDS), and radiation pneumonitis. Twelve patients were evaluable for late toxicity (>90 days). Maximum toxicity was grade 0 in five patients, grade 1 in four patients, and grade 5 in one patient (radiation pneumonitis). Clinical responses from the combination were 1/15 CR, 6/15 PR, 6/15 stable disease, and 1/15 progressive disease. The MTD of rHuIFN-β1a has been estimated at 12 MIU/m2 per treatment day when given daily during conventional RT to 60 Gy in 6 weeks. Biologic response by rHuIFN-β1a alone was reflected by significant and dose-related increases in 2-5A synthetase, β2-microglobulin, and neopterin. Radiation therapy alone had no effect on these immune response parameters and did not diminish their augmentation by rHuIFN-β1a. There was no association of biologic modulation with clinical response or survival.

Original languageEnglish (US)
Pages (from-to)891-902
Number of pages12
JournalJournal of Interferon and Cytokine Research
Volume16
Issue number11
DOIs
StatePublished - Nov 1996
Externally publishedYes

ASJC Scopus subject areas

  • Immunology
  • Cell Biology
  • Virology

Fingerprint Dive into the research topics of 'Recombinant human interferon-β (rHuIFN-β) and radiation therapy for inoperable non-small cell lung cancer'. Together they form a unique fingerprint.

Cite this