Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer.

2.50
Hdl Handle:
http://hdl.handle.net/10541/77879
Title:
Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer.
Authors:
Jones, P H; Christodoulos, K; Dobbs, N; Thavasu, P; Balkwill, Frances; Blann, A D; Caine, G J; Kumar, Shant; Kakkar, A J; Gompertz, N; Talbot, D C; Ganesan, T S; Harris, Adrian L
Abstract:
Marimastat, low molecular weight heparins and captopril have antiangiogenic activity in vitro and in animal models. We studied the safety and efficacy of the combination of these drugs in patients with advanced cancer. In all, 50 patients were enrolled. Captopril was given orally at a dose of 50 mg bd daily. Fragmin was administered as a daily subcutaneous injection of 200 units kg(-1) for the first 28 days and 5000 units thereafter. Marimastat was given at 10 mg bd orally. Serum, plasma and urinary angiogenic factors were measured at baseline and after 1 month of treatment. Inhibition of release of tumour necrosis factor alpha (TNF-alpha) from peripheral lymphocytes was used as a surrogate pharmacodynamic end point. There was one case of haemorrhagic stroke and one upper gastrointestinal haemorrhage. The commonest toxicity was myalgia. One of 10 patients with renal cancer had a partial response, and three patients had a prolonged period of stable disease. The treatment significantly inhibited phytohaemagglutinin (PHA)-stimulated TNF-alpha release from patient's lymphocytes. The combination of marimastat, fragmin and captopril is well tolerated and has in vivo activity. Inhibition of PHA-stimulated TNF-alpha release from lymphocytes is a surrogate pharmacodynamic marker of metalloprotease inhibition.
Affiliation:
Cancer Research UK Medical Oncology Unit, Churchill Hospital, Headington, Oxford OX3 7LJ, UK.
Citation:
Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer. 2004, 91 (1):30-6 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
5-Jul-2004
URI:
http://hdl.handle.net/10541/77879
DOI:
10.1038/sj.bjc.6601897
PubMed ID:
15162145
Type:
Article
Language:
en
ISSN:
0007-0920
Appears in Collections:
All Christie Publications

Full metadata record

DC FieldValue Language
dc.contributor.authorJones, P H-
dc.contributor.authorChristodoulos, K-
dc.contributor.authorDobbs, N-
dc.contributor.authorThavasu, P-
dc.contributor.authorBalkwill, Frances-
dc.contributor.authorBlann, A D-
dc.contributor.authorCaine, G J-
dc.contributor.authorKumar, Shant-
dc.contributor.authorKakkar, A J-
dc.contributor.authorGompertz, N-
dc.contributor.authorTalbot, D C-
dc.contributor.authorGanesan, T S-
dc.contributor.authorHarris, Adrian L-
dc.date.accessioned2009-08-19T14:41:54Z-
dc.date.available2009-08-19T14:41:54Z-
dc.date.issued2004-07-05-
dc.identifier.citationCombination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer. 2004, 91 (1):30-6 Br. J. Canceren
dc.identifier.issn0007-0920-
dc.identifier.pmid15162145-
dc.identifier.doi10.1038/sj.bjc.6601897-
dc.identifier.urihttp://hdl.handle.net/10541/77879-
dc.description.abstractMarimastat, low molecular weight heparins and captopril have antiangiogenic activity in vitro and in animal models. We studied the safety and efficacy of the combination of these drugs in patients with advanced cancer. In all, 50 patients were enrolled. Captopril was given orally at a dose of 50 mg bd daily. Fragmin was administered as a daily subcutaneous injection of 200 units kg(-1) for the first 28 days and 5000 units thereafter. Marimastat was given at 10 mg bd orally. Serum, plasma and urinary angiogenic factors were measured at baseline and after 1 month of treatment. Inhibition of release of tumour necrosis factor alpha (TNF-alpha) from peripheral lymphocytes was used as a surrogate pharmacodynamic end point. There was one case of haemorrhagic stroke and one upper gastrointestinal haemorrhage. The commonest toxicity was myalgia. One of 10 patients with renal cancer had a partial response, and three patients had a prolonged period of stable disease. The treatment significantly inhibited phytohaemagglutinin (PHA)-stimulated TNF-alpha release from patient's lymphocytes. The combination of marimastat, fragmin and captopril is well tolerated and has in vivo activity. Inhibition of PHA-stimulated TNF-alpha release from lymphocytes is a surrogate pharmacodynamic marker of metalloprotease inhibition.en
dc.language.isoenen
dc.subjectCanceren
dc.subjectTumour Necrosis Factor-alphaen
dc.subject.meshAdministration, Oral-
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAngiogenesis Inhibitors-
dc.subject.meshAngiotensin-Converting Enzyme Inhibitors-
dc.subject.meshBiological Markers-
dc.subject.meshCaptopril-
dc.subject.meshDalteparin-
dc.subject.meshDrug Therapy, Combination-
dc.subject.meshEnzyme Inhibitors-
dc.subject.meshFemale-
dc.subject.meshFibrinolytic Agents-
dc.subject.meshHumans-
dc.subject.meshHydroxamic Acids-
dc.subject.meshInjections, Subcutaneous-
dc.subject.meshLymphocytes-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasms-
dc.subject.meshPhytohemagglutinins-
dc.subject.meshTreatment Outcome-
dc.subject.meshTumor Necrosis Factor-alpha-
dc.titleCombination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer.en
dc.typeArticleen
dc.contributor.departmentCancer Research UK Medical Oncology Unit, Churchill Hospital, Headington, Oxford OX3 7LJ, UK.en
dc.identifier.journalBritish Journal of Canceren

Related articles on PubMed

All Items in Christie are protected by copyright, with all rights reserved, unless otherwise indicated.