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A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma.

Journal Article


Abstract


  • 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.

Publication Date


  • 2009

Citation


  • Kefford, R. F., Thomas, N. P. B., Corrie, P. G., Palmer, C., Abdi, E., Kotasek, D., . . . Middleton, M. R. (2009). A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma.. British journal of cancer, 100(8), 1245-1249. doi:10.1038/sj.bjc.6605016

Web Of Science Accession Number


Start Page


  • 1245

End Page


  • 1249

Volume


  • 100

Issue


  • 8

Abstract


  • 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.

Publication Date


  • 2009

Citation


  • Kefford, R. F., Thomas, N. P. B., Corrie, P. G., Palmer, C., Abdi, E., Kotasek, D., . . . Middleton, M. R. (2009). A phase I study of extended dosing with lomeguatrib with temozolomide in patients with advanced melanoma.. British journal of cancer, 100(8), 1245-1249. doi:10.1038/sj.bjc.6605016

Web Of Science Accession Number


Start Page


  • 1245

End Page


  • 1249

Volume


  • 100

Issue


  • 8