A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer

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dc.contributor.authorKhan, O.
dc.contributor.authorRanson, M.
dc.contributor.authorMichael, M.
dc.contributor.authorOlver, I.
dc.contributor.authorLevitt, N.
dc.contributor.authorMortimer, P.
dc.contributor.authorWatson, A.
dc.contributor.authorMargison, G.
dc.contributor.authorMidgley, R.
dc.contributor.authorMiddleton, M.
dc.date.issued2008
dc.description.abstractTo evaluate the tumour response to lomeguatrib and temozolomide (TMZ) administered for 5 consecutive days every 4 weeks in patients with metastatic colorectal carcinoma. Patients with stage IV metastatic colorectal carcinoma received lomeguatrib (40 mg) and TMZ (50–200 mg m−2) orally for 5 consecutive days every 4 weeks. Response was determined every two cycles. Pharmacokinetics of lomeguatrib and TMZ as well as their pharmacodynamic effects in peripheral blood mononuclear cells (PBMC) were determined. Nineteen patients received 49 cycles of treatments. Despite consistent depletion of O6-methylguanine-DNA methyltransferase in PBMC, none of the patients responded to treatment. Three patients had stable disease, one for the duration of the study, and no fall in carcinoembryonic antigen was observed in any patient. Median time to progression was 50 days. The commonest adverse effects were gastrointestinal and haematological and these were comparable to those of TMZ when given alone. This combination of lomeguatrib and TMZ is not efficacious in metastatic colorectal cancer. If further studies are to be performed, emerging data suggest that higher daily doses of lomeguatrib and a dosing period beyond that of TMZ should be evaluated.
dc.description.statementofresponsibilityO. A. Khan, M. Ranson, M. Michael, I. Olver, N. C. Levitt, P. Mortimer, A. J. Watson, G. P. Margison, R. Midgley and M. R. Middleton
dc.identifier.citationBritish Journal of Cancer, 2008; 98(10):1614-1618
dc.identifier.doi10.1038/sj.bjc.6604366
dc.identifier.issn0007-0920
dc.identifier.issn1532-1827
dc.identifier.orcidOlver, I. [0000-0001-5478-1576]
dc.identifier.urihttp://hdl.handle.net/2440/52549
dc.language.isoen
dc.publisherNature Publishing Group
dc.rights© 2008 Cancer Research UK
dc.source.urihttps://doi.org/10.1038/sj.bjc.6604366
dc.subjectO⁶-methylguanine-DNA methyltransferase
dc.subjectlomeguatrib
dc.subjecttemozolomide
dc.subjectcolorectal cancer
dc.subjectDNA repair
dc.titleA phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer
dc.typeJournal article
pubs.publication-statusPublished

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