Linked Life Data

17339865

Source:http://linkedlifedata.com/resource/pubmed/id/17339865

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-3-6
pubmed:abstractText
Interferon-alpha1 (IFN-alpha1), which may have a primary role in innate immunity, differs significantly in amino-acid sequence from IFN-alpha2, the only recombinant IFN-alpha with substantial clinical evaluation. Patients with metastatic malignancies received daily subcutaneous doses of 1.5-270 mug/m(2) of recombinant IFN-alpha1b. Gene modulation, pharmacokinetics, tolerability, and disease response were determined. Significant (P<0.01) dose and gene-dependent increases of 2-10 fold occurred in IFN-stimulated genes, including four (tumor necrosis factor-related apoptosis-inducing ligand, cig 5, p56, GEM) never previously identified as increased in patients; significant increases (P<0.01) resulted at the lowest dose (1.5 microg/m(2); 1.5 x 10(4) human antiviral units/m(2)). Increases (P<0.01) were sustainable for >4 weeks. Peak levels of IFN-alpha1b were at 3 h; an increase of approximately eightfold in both C(max) and AUC occurred between 15 microg/m(2) and 270 microg/m(2). Chronic toxicities of anorexia, weight loss, and fatigue were relatively uncommon. Eighteen patients were treated for >8 weeks; none experienced >grade 1 weight loss. Three patients at the highest dose developed grade 3 fatigue after > or =3 months, which required dose reduction or discontinuation. Patient acceptability of fatigue defined a dose for initiation of Phase II trials, 270 microg/m(2). Six patients (five with renal cell carcinoma) had progression-free survival for >1 year, including two who had partial responses. IFN-alpha1b 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-alpha1 in virus infections and cancer.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0009-9236
pubmed:author
pubmed:issnType
Print
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
354-61
pubmed:dateRevised
2008-5-6
pubmed:meshHeading
pubmed-meshheading:17339865-Adult, pubmed-meshheading:17339865-Aged, pubmed-meshheading:17339865-Antineoplastic Agents, pubmed-meshheading:17339865-Body Temperature, pubmed-meshheading:17339865-Cohort Studies, pubmed-meshheading:17339865-Cytokines, pubmed-meshheading:17339865-Dose-Response Relationship, Drug, pubmed-meshheading:17339865-Female, pubmed-meshheading:17339865-Gene Expression, pubmed-meshheading:17339865-Humans, pubmed-meshheading:17339865-Interferon-alpha, pubmed-meshheading:17339865-Male, pubmed-meshheading:17339865-Middle Aged, pubmed-meshheading:17339865-Neoplasms, pubmed-meshheading:17339865-Neopterin, pubmed-meshheading:17339865-Pharmacogenetics, pubmed-meshheading:17339865-Survival Analysis, pubmed-meshheading:17339865-TNF-Related Apoptosis-Inducing Ligand, pubmed-meshheading:17339865-Ubiquitins, pubmed-meshheading:17339865-beta 2-Microglobulin
pubmed:year
2007
pubmed:articleTitle
Gene modulatory effects, pharmacokinetics, and clinical tolerance of interferon-alpha1b: a second member of the interferon-alpha family.
pubmed:affiliation
Taussig Cancer Center, Center for Hematology and Oncology Molecular Therapeutics, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA.
pubmed:publicationType
Journal Article, Clinical Trial, Phase I, Research Support, N.I.H., Extramural