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Lomeguatrib, an O(6)-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.

Original publication

DOI

10.1038/sj.bjc.6605016

Type

Journal article

Journal

Br J Cancer

Publication Date

21/04/2009

Volume

100

Pages

1245 - 1249

Keywords

Aged, Aged, 80 and over, Anemia, Antineoplastic Agents, Child, Dacarbazine, Dose-Response Relationship, Drug, Female, Humans, Melanoma, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Neutropenia, Patient Selection, Purines, Skin Neoplasms, Temozolomide, Thrombocytopenia