Gene Modulatory Effects, Pharmacokinetics, and Clinical Tolerance of Interferon‐α1b: A Second Member of the Interferon‐α Family

Interferon‐α1 (IFN‐α1), which may have a primary role in innate immunity, differs significantly in amino‐acid sequence from IFN‐α2, the only recombinant IFN‐α with substantial clinical evaluation. Patients with metastatic malignancies received daily subcutaneous doses of 1.5–270 μg/m2 of recombinant IFN‐α1b. Gene modulation, pharmacokinetics, tolerability, and disease response were determined. Significant (Pgrade 1 weight loss. Three patients at the highest dose developed grade 3 fatigue after ⩾3 months, which required dose reduction or discontinuation. Patient acceptability of fatigue defined a dose for initiation of Phase II trials, 270 μg/m2. Six patients (five with renal cell carcinoma) had progression‐free survival for >1 year, including two who had partial responses. IFN‐α1b resulted in potent stimulation of IFN‐regulated genes and tumor regressions in renal cell carcinoma. Unique gene modulatory effects, when coupled with the moderate severity of side effects and a potentially central role in innate immunity, provide rationale for further clinical evaluation of IFN‐α1 in virus infections and cancer. Clinical Pharmacology & Therapeutics (2007) 81, 354–361. doi:10.1038/sj.clpt.6100081