Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0149871 (deep vein thrombosis)
 12,364 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

XR 5000 is one of a series of tricyclic carboxamide-based cytotoxic agents. It binds to DNA by intercalation and stimulates DNA cleavage by inhibition of both topoisomerase I and II, thus possibly overcoming the resistance resulting from downregulation of either enzyme. Twenty patients with advanced or metastatic colorectal cancer, unpretreated for metastatic disease, received XR 5000 at the dose of 3010 mg/m(2) in a 120-h central intravenous (i.v.) infusion every 3 weeks. Response was evaluated every two cycles. No complete (CR) or partial responses (PR) were observed in eligible patients (response rate, 0 of 19, 0%; 95% confidence interval (CI): 0-18%). 5 patients had stable disease, which lasted from 79 to 157 days. Haematological toxicity was low, since only one grade 4 neutropenia and two grade 3 anaemia were observed. Other treatment-related grade 3-4 toxicities were: deep venous thrombosis (2 cases), liver toxicity, diarrhoea, anorexia, dyspnoea, chest pain, infection (1 case each). Despite the good toxicity profile, these results do not support further trials with XR 5000 in metastatic colorectal cancer.
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PMID:Phase II study of XR 5000, an inhibitor of topoisomerases I and II, in advanced colorectal cancer. 1175 Aug 42

XR5000 is a tricyclic carboxamide-based cytotoxic agent that binds to DNA by intercalation and stimulates DNA cleavage by inhibition of both topoisomerase I and II. The aim of this study was to evaluate the antitumoral activity and safety profile of XR5000 given as second-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). Patients received XR5000 at the dose of 3010 mg/m(2) as a 120-h central venous infusion every 3 weeks. The 15 patients (median age 56 years, range 48-71 years) enrolled had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 (3 patients), 1 (11 patients) or 2 (1 patient). A total of 32 cycles of XR5000 (median 2, range 1-6) were given to 14 patients. No objective response (assessed according to World Health Organization (WHO) criteria) was documented in the 12 evaluable patients by an external review panel; in 4 out of the 12 patients disease stabilisation was recorded. The following toxicities graded according to the Common Toxicity Criteria (CTC) version 2.0. were observed: one grade 3 and two grade 4 granulocytopenia, one grade 3 and one grade 4 thrombocytopenia, one grade 3 deep venous thrombosis, one grade 3 fatigue, and grade 3 undocumented epileptic seizures which led to death in 2 patients. With only 4 out of 12 patients reaching stable disease when using this dose and regimen, further evaluation of XR5000 in advanced NSCLC is not justified.
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PMID:Phase II study of XR 5000 (DACA), an inhibitor of topoisomerase I and II, administered as a 120-h infusion in patients with non-small cell lung cancer. 1256 85