A PHASE-II STUDY IN ADVANCED BREAST-CANCER - ZD1694 (TOMUDEX) A NOVELDIRECT AND SPECIFIC THYMIDYLATE SYNTHASE INHIBITOR

ZD1694 ('Tomudex'), a novel, direct and specific thymidylate synthase (Ts) inhibitor, was developed in a collaborative research programme be tween 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 (eith er as adjuvant cytotoxic or hormonal therapy or hormone therapy for ad vanced disease); 39% had received prior adjuvant cytotoxic chemotherap y. All patients had measurable disease and 50% had liver metastases. I n all 43 patients were evaluable for response. Of these patients 26% a chieved complete (CR) or partial response (PR) (95% Cl 14-42%). A resp onse rate of 44% was seen in liver metastases. Two patients achieved C R of 265 and 301 days' duration respectively, one in locoregional dise ase, and one in liver metastases. The most common grade 3/4 adverse ev ents were nausea and vomiting (11%), diarrhoea (11%) and leucopenia (2 0%). 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, comparabl e with that reported for other anti-metabolites, with acceptable toler ability.