Phase II study of XR 5000, an inhibitor of topoisomerases I and II, in advanced colorectal cancer

F. Caponigro, C. Dittrich, J. B. Sorensen, J. H M Schellens, F. Duffaud, L. Paz Ares, D. Lacombe, C. De Balincourt, P. Fumoleau

Research output: Contribution to journalArticlepeer-review

Abstract

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/m2 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.

Original languageEnglish
Pages (from-to)70-74
Number of pages5
JournalEuropean Journal of Cancer
Volume38
Issue number1
DOIs
Publication statusPublished - 2002

Keywords

  • Colorectal cancer
  • Phase II study
  • Topoisomerase
  • XR 5000

ASJC Scopus subject areas

  • Cancer Research
  • Hematology
  • Oncology

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