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dc.contributor.authorRoberts, C
dc.contributor.authorStrauss, VY
dc.contributor.authorKopijasz, S
dc.contributor.authorGourley, C
dc.contributor.authorHall, M
dc.contributor.authorMontes, A
dc.contributor.authorAbraham, J
dc.contributor.authorClamp, Andrew R
dc.contributor.authorKennedy, R
dc.contributor.authorBanerjee, S
dc.contributor.authorFolkes, LK
dc.contributor.authorStratford, M
dc.contributor.authorNicum, S
dc.date.accessioned2020-01-29T15:17:47Z
dc.date.available2020-01-29T15:17:47Z
dc.date.issued2019en
dc.identifier.citationRoberts C, Strauss VY, Kopijasz S, Gourley C, Hall M, Montes A, et al. Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours. Br J Cancer. 2019:10.en
dc.identifier.pmid31813938en
dc.identifier.doi10.1038/s41416-019-0674-4en
dc.identifier.urihttp://hdl.handle.net/10541/622661
dc.description.abstractBACKGROUND: Tumour cells with BRCA1/2 gene mutations demonstrate increased sensitivity to platinum and poly (ADP-ribose) polymerase (PARP) inhibitors. 6-mercaptopurine (6MP) was found to selectively kill BRCA-defective cells in a xenograft model as effectively as the PARP inhibitor AG014699, even after these cells acquired resistance to a PARP inhibitor or cisplatin. METHODS: This phase II single-arm trial investigated the activity of 6MP 55-75?mg/m2 per day, and methotrexate 15-20?mg/m2 per week in advanced breast or platinum-resistant ovarian cancer patients with a BRCA1/2 germline mutation, who had progressed after?³1 previous line of chemotherapy. The primary outcome was objective response including stable disease (SD) as an assessment of clinical benefit rate (CBR), at 8 weeks, by RECIST v1.1. Secondary outcomes included overall survival (OS) and progression-free survival (PFS). RESULTS: In total, 67 evaluable patients were recruited; 55 ovarian and 11 breast cancer patients. In total, 21 patients had SD (31%), one had a partial response (1.5%); CBR was 33% at 8 weeks. In total, 12/67 patients (18%) had SD at 16 weeks. In total, five ovarian cancer patients had SD for over 200 days. Median OS was 10.3 months (95% CI 6.9-14.5), median PFS 1.9 months (1.7-2.8). CONCLUSIONS: The overall activity of 6MP and methotrexate in these patients was low; however, there was a small group of patients who appeared to derive longer-term clinical benefit.en
dc.language.isoenen
dc.relation.urlhttps://dx.doi.org/10.1038/s41416-019-0674-4en
dc.titleResults of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumoursen
dc.typeArticleen
dc.contributor.departmentCentre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UKen
dc.identifier.journalBritish Journal of Canceren
dc.description.noteen]
refterms.dateFOA2020-02-03T15:14:29Z


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