Phase I dose-escalation and pharmacokinetic study of a novel folate analogue AG2034

Donald Bissett, H. L. McLeod, B. Sheedy, M. Collier, Y. Pithavala, M. Pitsiladis, J. Cassidy, L. Paradiso

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    24 Citations (Scopus)


    The novel folate analogue AG2034, which was designed as an inhibitor of GARFT (glycinamide ribonucleotide formyltransferase), was evaluated in this phase I study under the auspices of The Cancer Research Campaign. UK. AG2034 blacks de nova purine synthesis through inhibition of GARFT. A total of 28 patients with histologically proven intractable cancers were enrolled. AG2034 was administered as a short intravenous infusion once every 3 weeks. 8 dose levels ranging from 1-11 mg/m(2) were evaluated with patients receiving up to 6 cycles. Dose-limiting toxicities in the form of mucositis, diarrhoea and vomiting were observed at doses of 6 mg/m2 and above. Significant levels of thrombocytopenia, neutropenia and anaemia were also recorded. Other sporadic toxicities included fatigue and myalgia. The MTD with this schedule of AG2034 was 5 mg/m(2). Most side effects occurred more frequently with cumulative dosing. In keeping with this, pharmacokinetic analysis revealed evidence of drug accumulation. The AG2034 AUG,,, increased by a median of 184% (range 20-389%) from cycle 1 to 3 in all 10 patients examined. No objective antitumour responses were observed in the study. (C) 2001 Cancer Research Campaign.

    Original languageEnglish
    Pages (from-to)308-312
    Number of pages4
    JournalBritish Journal of Cancer
    Issue number3
    Publication statusPublished - 2001


    • folate analogue
    • AG2034
    • GARFT inhibitor


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