Linked Life Data

7804528

Source:http://linkedlifedata.com/resource/pubmed/id/7804528

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1995-2-2
pubmed:abstractText
R24, a murine monoclonal antibody, has been shown to mediate complement- and antibody-dependent cellular cytotoxicity (ADCC) of melanoma tumor targets. We conducted a Phase Ib clinical trial using granulocyte-macrophage colony-stimulating factor (GM-CSF) and R24 in 20 patients with metastatic melanoma. The purpose of this study was to test the hypothesis that treatment with GM-CSF could up-regulate monocyte and granulocyte ADCC and that the combination of GM-CSF plus R24, which mediates ADCC, would lead to enhanced anti-tumor activity in patients with melanoma. GM-CSF was administered by subcutaneous injection daily for 21 days at a dose of 150 micrograms/m2/day. R24 was administered by continuous intravenous infusion on days 8-15 at three dose levels: 0, 10, and 50 mg/m2/day. All 20 patients received one cycle of treatment only. Immune parameters measured were monocyte and granulocyte direct cytotoxicity and ADCC. All patients were evaluable for toxicity. Fifteen patients were evaluable for immune response. Treatment with GM-CSF alone was well tolerated. Toxicity from the combination of GM-CSF plus R24 included diffuse urticaria, nausea and vomiting, hypertension, and hypotension. Hypotension was the dose-limiting toxicity. Two patients on the 50-mg/m2/day dose level of R24 achieved a partial response lasting 2+ and 5+ months. Treatment with GM-CSF led to a statistically significant enhancement of monocyte and granulocyte direct cytotoxicity and ADCC. The maximally tolerated dose of R24 given at this schedule combined with GM-CSF is < 50 mg/m2/day. We conclude that GM-CSF given by subcutaneous injection at 150 micrograms/m2 x 21 days can enhance effector cell ADCC and direct cytotoxicity and that the combination of GM-CSF and R24 can be therapeutic.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
1067-5582
pubmed:author
pubmed:issnType
Print
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
132-41
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1994
pubmed:articleTitle
Phase Ib trial of granulocyte-macrophage colony-stimulating factor combined with murine monoclonal antibody R24 in patients with metastatic melanoma.
pubmed:affiliation
Kaplan Cancer Center, Division of Medical Oncology, New York University Medical Center NY 10016.
pubmed:publicationType
Journal Article, Clinical Trial, Research Support, U.S. Gov't, P.H.S., Clinical Trial, Phase I