A phase II study in advanced breast cancer: ZD1694 ('Tomudex') a novel direct and specific thymidylate synthase inhibitor

I. Smith, A. Jones, M. Spielmann, M. Namer, M. D. Green, J. Bonneterre, H. E. Wander, T. Hatschek, N. Wilking, J. Zalcberg, J. Spiers, L. Seymour

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42 Scopus citations


ZD1694 ('Tomudex') a novel, direct and specific thymidylate synthase (TS) inhibitor, was developed in a collaborative research programme between Zeneca Pharmaceuticals and the Institute of Cancer Research (UK) and entered clinical trials in 1991; phase II studies began in 1992, using 3.0 mg m-2 every 3 weeks as a short 15 min infusion. Forty-six patients entered a phase II study of ZD1694 in advanced breast cancer. A total of 74% of patients had received prior systemic therapy (either as adjuvant cytotoxic or hormonal therapy or hormone therapy for advanced disease); 39% had received prior adjuvant cytotoxic chemotherapy. All patients had measurable disease and 50% had liver metastases. In all 43 patients were evaluable for response. Of these patients 26% achieved complete (CR) or partial response (PR) (95% Cl 14-42%). A response rate of 44% was seen in liver metastases. Two patients achieved CR of 265 and 301 days' duration respectively, one in locoregional disease, and one in liver metastases. The most common grade 3/4 adverse events were nausea and vomiting (11%), diarrhoea (11%) and leucopenia (20%). Grade 3/4, self-limited and reversible increases in transaminases were seen in 22% of patients. ZD1694 has useful single agent activity in patients with hormone-refractory advanced breast cancer, comparable with that reported for other anti-metabolites, with acceptable tolerability.

Original languageEnglish
Pages (from-to)479-481
Number of pages3
JournalBritish Journal of Cancer
Issue number3
StatePublished - 1 Jan 1996
Externally publishedYes


  • 'Tomudex'
  • Breast cancer
  • Thymidylate synthase inhibitor
  • ZD1694

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


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