Investigational New Drugs

, Volume 21, Issue 3, pp 347–352

Phase II study of XR5000 (DACA), an inhibitor of topoisomerase I and II, administered as a 120-h infusion in patients with advanced ovarian cancer*

  • Christian Dittrich
  • Veronique Dieras
  • Pierre Kerbrat
  • Cornelis Punt
  • Roberto Sorio
  • Francesco Caponigro
  • Xavier Paoletti
  • Christine de Balincourt
  • Denis Lacombe
  • Pierre Fumoleau
Article

DOI: 10.1023/A:1025476813365

Cite this article as:
Dittrich, C., Dieras, V., Kerbrat, P. et al. Invest New Drugs (2003) 21: 347. doi:10.1023/A:1025476813365

Abstract

Background. 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 the present study was to evaluate the antitumoral activity and safety profile of XR5000 given as second-line chemotherapy in patients with ovarian cancer who had relapsed within 1 year after first-line chemotherapy with taxanes and platinum for advanced disease. Patients and methods. Patients received XR5000 at the dose of 3010 mg/m2 through a 120-h central venous infusion every 3 weeks. Toxicity was graded according to the Common Toxicity Criteria (CTC), version 2.0. An independent panel assessed response every two cycles according to the World Health Organization (WHO) criteria. Gehan's rule was used for sample size determination. Results. Sixteen patients were enrolled; one patient was ineligible because of prior melphalan single agent treatment. Eastern Cooperative Oncology Group (ECOG) performance status was 0 (eight patients), 1 (five patients), or 2 (two patients). The 15 eligible patients received 43 cycles of XR5000 (median 2, range 1–8). Hematological toxicity was mild with only one grade 3 anemia in one patient. Other drug-related toxicities never exceeded grade 3 and included fatigue (four patients), thrombosis (one patient), nausea (one patient), stomatitis (one patient) as well as dyspnea/cough (one patient). One patient who had refused further therapy and controls after the first cycle was not assessable for response evaluation. No objective responses were observed. Four patients experienced stable disease and 10 patients progressive disease. The median time to progression was 42 days (CI 95% 40; 54). Conclusions. The complete lack of any objective response does not justify further evaluation of XR5000 in patients with advanced ovarian cancer using this dose and schedule, although the therapy was generally well tolerated.

ovarian cancer phase II topoisomerase I and II XR5000 

Copyright information

© Kluwer Academic Publishers 2003

Authors and Affiliations

  • Christian Dittrich
    • 1
  • Veronique Dieras
    • 2
  • Pierre Kerbrat
    • 3
  • Cornelis Punt
    • 4
  • Roberto Sorio
    • 5
  • Francesco Caponigro
    • 6
  • Xavier Paoletti
    • 7
  • Christine de Balincourt
    • 7
  • Denis Lacombe
    • 7
  • Pierre Fumoleau
    • 8
  1. 1.Kaiser Franz Josef-SpitalLudwig Boltzmann-Institute for Applied Cancer Research (LBI-ACR VIEnna)ViennaAustria
  2. 2.Institut CurieParisFrance
  3. 3.Centre Eugene MarquisRennesFrance
  4. 4.St Radboud University HospitalNijmegenThe Netherlands
  5. 5.Centro di Riferimento OncologicoAvianoItaly
  6. 6.Istituto Nazionale per lo Studio E la Cura dei TumoriNapoliItaly
  7. 7.EORTC Data CenterBrusselsBelgium
  8. 8.Centre René GauducheauNantesFrance

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