Source:http://linkedlifedata.com/resource/pubmed/id/10815886
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rdf:type | |
lifeskim:mentions |
umls-concept:C0024501,
umls-concept:C0025202,
umls-concept:C0030705,
umls-concept:C0085732,
umls-concept:C0123759,
umls-concept:C0205210,
umls-concept:C0205263,
umls-concept:C0278678,
umls-concept:C0332281,
umls-concept:C0348016,
umls-concept:C0721534,
umls-concept:C0871261,
umls-concept:C0920321,
umls-concept:C1704632,
umls-concept:C1706817,
umls-concept:C2911692
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pubmed:issue |
5
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pubmed:dateCreated |
2000-8-29
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pubmed:abstractText |
The aim of this study was to examine the tolerability, antitumor activity, and biological effects of a new schedule of i.v. recombinant human interleukin 12 (rhIL-12). Twenty-eight patients were enrolled in a Phase I trial in which rhIL-12 was administered twice weekly as an i.v. bolus for 6 weeks. Stable or responding patients were eligible to receive additional 6-week cycles until there was no evidence of disease or until tumor progression. Patient cohorts were treated with escalating doses of rhIL-12 (30-700 ng/kg). The maximum tolerated dose (MTD) was 500 ng/kg, with dose-limiting toxicities consisting of elevated hepatic transaminases and cytopenias. At the MTD (n = 14), there was one partial response occurring after 6 cycles of rhIL-12 in a patient with renal cell cancer. Two additional renal cell cancer patients treated at the MTD had prolonged disease stabilization, with one of these exhibiting tumor regression after 8 cycles of rhIL-12. IFN-gamma, IL-15, and IL-18 were induced in patients treated with rhIL-12. Whereas IFN-gamma and IL-15 induction were attenuated midway through the first cycle in patients with disease progression, those patients with tumor regression or prolonged disease stabilization were able to maintain IFN-gamma, IL-15, and IL-18 induction. The down-modulation of IFN-gamma induction during rhIL-12 treatment did not relate to IL-10 production or alterations in rhIL-12 bioavailability but was associated with an acquired defect in lymphocyte IFN-gamma production in response to IL-12, IL-2, or IL-15. This defect could be partially overcome in vitro through combined stimulation with IL-12 plus IL-2. These findings show that the chronic administration of twice-weekly i.v. rhIL-12 is well-tolerated, stimulates the production of IL-12 costimulatory cytokines and IFN-gamma, and can induce delayed tumor regression. Strategies aimed at maintaining IFN-gamma induction, such as the addition of IL-2, may further augment the response rate to this schedule of rhIL-12.
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pubmed:grant | |
pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-gamma,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-12,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-15,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-18,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
1078-0432
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
6
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1678-92
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:10815886-Adult,
pubmed-meshheading:10815886-Aged,
pubmed-meshheading:10815886-Arthralgia,
pubmed-meshheading:10815886-Carcinoma, Renal Cell,
pubmed-meshheading:10815886-Dose-Response Relationship, Drug,
pubmed-meshheading:10815886-Female,
pubmed-meshheading:10815886-Fever,
pubmed-meshheading:10815886-Hematologic Diseases,
pubmed-meshheading:10815886-Humans,
pubmed-meshheading:10815886-Hypotension,
pubmed-meshheading:10815886-Injections, Intravenous,
pubmed-meshheading:10815886-Interferon-gamma,
pubmed-meshheading:10815886-Interleukin-12,
pubmed-meshheading:10815886-Interleukin-15,
pubmed-meshheading:10815886-Interleukin-18,
pubmed-meshheading:10815886-Kidney Neoplasms,
pubmed-meshheading:10815886-Male,
pubmed-meshheading:10815886-Melanoma,
pubmed-meshheading:10815886-Middle Aged,
pubmed-meshheading:10815886-Mouth Mucosa,
pubmed-meshheading:10815886-Neoplasm Metastasis,
pubmed-meshheading:10815886-Recombinant Proteins,
pubmed-meshheading:10815886-Skin,
pubmed-meshheading:10815886-Stomatitis,
pubmed-meshheading:10815886-Time Factors
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pubmed:year |
2000
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pubmed:articleTitle |
Phase I trial of twice-weekly intravenous interleukin 12 in patients with metastatic renal cell cancer or malignant melanoma: ability to maintain IFN-gamma induction is associated with clinical response.
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pubmed:affiliation |
Beth Israel Deaconess Medical Center, Division of Hematology/Oncology, Boston, Massachusetts 02215, USA.
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pubmed:publicationType |
Journal Article,
Clinical Trial,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't,
Clinical Trial, Phase I
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