1. ¹Department of Medicine, Westmead Hospital, Westmead, New South Wales 2145, Australia
2. ²Department of Medical Oncology, Churchill Hospital, University of Oxford, Old Road, Oxford OX3 7LJ, UK
3. ³Oncology Centre, Addenbrooke's Hospital, Hills Road, Cambridge CB2 2QQ, UK
4. ⁴Medical Oncology Unit, Tweed Hospital, Powell Street, Tweed Heads, New South Wales 2485, Australia
5. ⁵Ashford Cancer Centre, 55 Anzac Highway, Ashford, South Australia 5035, Australia
6. ⁶Sydney Melanoma Unit, Royal Prince Alfred Hospital, Missenden Road, Camperdown, New South Wales 2050, Australia
7. ⁷Department of Medical Oncology, Christie Hospital, Wilmslow Road, Manchester M20 4BX, UK
8. ⁸Kudos Pharmaceuticals, 410 Cambridge Science Park, Milton Road, Cambridge CB4 0PE, UK
9. ⁹Cancer Research UK Carcinogenesis Group, Paterson Institute for Cancer Research, Wilmslow Road, Manchester M20 9BX, UK

Correspondence: Professor MR Middleton, E-mail: mark.middleton@medonc.ox.ac.uk

Received 11 September 2008; Revised 2 March 2009; Accepted 6 March 2009; Published online 31 March 2009.

Abstract

Lomeguatrib, an O⁶-methylguanine-DNA methyltransferase inactivator, was evaluated in an extended dosing regimen with temozolomide, designed according to pharmacodynamic data from previous studies. Patients with unresectable stage 3 or 4 cutaneous or unknown primary melanoma metastases were treated with lomeguatrib 40 mg, b.i.d. for 10 or 14 days and temozolomide 75–100 mg m^-2 on days 1–5. Drugs were administered orally with cycles repeated every 28 days, for up to six cycles. A total of 32 patients were recruited to the study. Lomeguatrib for 10 days with temozolomide 75 mg m^-2 was established as the optimal extended lomeguatrib dosing schedule, with haematological toxicity being dose limiting. There were two partial responses to treatment giving an overall response rate of 6.25%. Extending lomeguatrib administration beyond that of temozolomide requires a reduced dose of the latter agent. Only limited clinical activity was seen, suggesting no advantage for this regimen over conventional temozolomide administration in the treatment of melanoma.