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

2.50
Hdl Handle:
http://hdl.handle.net/10541/66160
Title:
A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer.
Authors:
Khan, O A; Ranson, Malcolm R; Michael, M; Olver, I; Levitt, N C; Mortimer, Peter; Watson, Amanda J; Margison, Geoffrey P; Midgley, R; Middleton, Mark R
Abstract:
To 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 O(6)-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.
Affiliation:
CR UK Medical Oncology Unit, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.
Citation:
A phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer. 2008, 98 (10):1614-8 Br. J. Cancer
Journal:
British Journal of Cancer
Issue Date:
20-May-2008
URI:
http://hdl.handle.net/10541/66160
DOI:
10.1038/sj.bjc.6604366
PubMed ID:
18475294
Type:
Article
Language:
en
ISSN:
1532-1827
Appears in Collections:
All Paterson Institute for Cancer Research; Carcinogenesis Group; Medical Oncology

Full metadata record

DC FieldValue Language
dc.contributor.authorKhan, O A-
dc.contributor.authorRanson, Malcolm R-
dc.contributor.authorMichael, M-
dc.contributor.authorOlver, I-
dc.contributor.authorLevitt, N C-
dc.contributor.authorMortimer, Peter-
dc.contributor.authorWatson, Amanda J-
dc.contributor.authorMargison, Geoffrey P-
dc.contributor.authorMidgley, R-
dc.contributor.authorMiddleton, Mark R-
dc.date.accessioned2009-04-24T09:24:38Z-
dc.date.available2009-04-24T09:24:38Z-
dc.date.issued2008-05-20-
dc.identifier.citationA phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer. 2008, 98 (10):1614-8 Br. J. Canceren
dc.identifier.issn1532-1827-
dc.identifier.pmid18475294-
dc.identifier.doi10.1038/sj.bjc.6604366-
dc.identifier.urihttp://hdl.handle.net/10541/66160-
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 O(6)-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.en
dc.language.isoenen
dc.subjectColorectal Canceren
dc.subjectDNA Repairen
dc.subjectClinical Trialen
dc.subject.meshAdult-
dc.subject.meshAged-
dc.subject.meshAged, 80 and over-
dc.subject.meshAntineoplastic Combined Chemotherapy Protocols-
dc.subject.meshColorectal Neoplasms-
dc.subject.meshDacarbazine-
dc.subject.meshDisease Progression-
dc.subject.meshFemale-
dc.subject.meshHumans-
dc.subject.meshMale-
dc.subject.meshMiddle Aged-
dc.subject.meshNeoplasm Staging-
dc.subject.meshPurines-
dc.subject.meshTreatment Failure-
dc.titleA phase II trial of lomeguatrib and temozolomide in metastatic colorectal cancer.en
dc.typeArticleen
dc.contributor.departmentCR UK Medical Oncology Unit, Churchill Hospital, Old Road, Oxford OX3 7LJ, UK.en
dc.identifier.journalBritish Journal of Canceren

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