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    Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours

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    Authors
    Roberts, C
    Strauss, VY
    Kopijasz, S
    Gourley, C
    Hall, M
    Montes, A
    Abraham, J
    Clamp, Andrew R
    Kennedy, R
    Banerjee, S
    Folkes, LK
    Stratford, M
    Nicum, S
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    Affiliation
    Centre for Statistics in Medicine, Nuffield Department of Orthopaedics, Rheumatology and Musculoskeletal Sciences, University of Oxford, Oxford, UK
    Issue Date
    2019
    
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    Abstract
    BACKGROUND: 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.
    Citation
    Roberts 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.
    Journal
    British Journal of Cancer
    URI
    http://hdl.handle.net/10541/622661
    DOI
    10.1038/s41416-019-0674-4
    PubMed ID
    31813938
    Additional Links
    https://dx.doi.org/10.1038/s41416-019-0674-4
    Type
    Article
    Language
    en
    ae974a485f413a2113503eed53cd6c53
    10.1038/s41416-019-0674-4
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