Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer.
Authors
Jones, P HChristodoulos, 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
Affiliation
Cancer Research UK Medical Oncology Unit, Churchill Hospital, Headington, Oxford OX3 7LJ, UK.Issue Date
2004-07-05
Metadata
Show full item recordAbstract
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.Citation
Combination antiangiogenesis therapy with marimastat, captopril and fragmin in patients with advanced cancer. 2004, 91 (1):30-6 Br. J. CancerJournal
British Journal of CancerDOI
10.1038/sj.bjc.6601897PubMed ID
15162145Type
ArticleLanguage
enISSN
0007-0920ae974a485f413a2113503eed53cd6c53
10.1038/sj.bjc.6601897