Linked Life Data

2786553

Source:http://linkedlifedata.com/resource/pubmed/id/2786553

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1989-7-20
pubmed:abstractText
Interleukin-2 (IL-2) and beta-interferon (beta-IFN) are cytokines with profound immunobiological effects on T-cell and natural killer (NK) cell activity; IL-2 also induces lymphokine-activated killer (LAK) cell cytotoxicity in humans. Both lymphokines induce antineoplastic activity against several refractory tumors. This Phase I study of 50 patients assessed the toxicities, maximally tolerated dose (MTD), effects on certain immune effector cells, pharmacokinetics of IL-2, and development of antibodies to the combination of subcutaneously administered IL-2 and intravenously administered beta-IFN. Fever was common. Indomethacin reduced the incidence and severity of fever and was necessary to prevent it from becoming dose-limiting. Hypotension occurred but never required pressors or produced complications. Constitutional symptoms, local skin toxicity at the site of IL-2 injection, generalized desquamation, eosinophilia, nausea, and vomiting were also observed. One patient had reversible renal dysfunction. Two patients experienced drug-related dyspnea without evidence of capillary leak syndrome; neither required intubation. Fluid retention and cardiotoxicity were not observed. The MTD was 5 x 10(6) U/m2 s.c. of IL-2 and 2 x 10(6) U/m2 i.v. of beta-IFN when given in combination. Enhancement of in vivo NK cell cytotoxicity and proliferation of T4+, T8+, and NK cells occurred. In vivo induction of LAK cell cytotoxicity was observed in three patients. Four patients developed nonneutralizing anti-IL-2 IgG antibodies, but none developed antibodies to beta-IFN. Peak IL-2 serum levels typically occurred 4 h following drug administration. Serum levels were within a factor of 3 of the peak level in the period studied, 1-6 h postinjection. No complete responses occurred. One patient with rectal cancer and one with transitional cell carcinoma each had a partial response, and 13 other patients (5 with renal cell, 4 with colorectal, and 4 other cancers) had stable disease. Induction of NK cell cytotoxicity was seen more commonly in patients with stable disease than in those with progressive disease. Combined administration of these agents is feasible with acceptable toxicity, and Phase II trials are warranted.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0732-6580
pubmed:author
pubmed:issnType
Print
pubmed:volume
8
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
122-39
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1989
pubmed:articleTitle
Phase I trial of recombinant interleukin-2 and recombinant beta-interferon in refractory neoplastic diseases.
pubmed:affiliation
Department of Medicine, SUNY Health Science Center, Syracuse 13210.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't