Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours
<br><strong>Background: </strong>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...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Journal article |
| Language: | English |
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Springer Nature
2019
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| _version_ | 1826283640605114368 |
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| author | Roberts, C Strauss, VY Kopijasz, S Gourley, C Hall, M Montes, A Abraham, J Clamp, A Kennedy, R Banerjee, S Folkes, LK Stratford, M Nicum, S |
| author_facet | Roberts, C Strauss, VY Kopijasz, S Gourley, C Hall, M Montes, A Abraham, J Clamp, A Kennedy, R Banerjee, S Folkes, LK Stratford, M Nicum, S |
| author_sort | Roberts, C |
| collection | OXFORD |
| description | <br><strong>Background: </strong>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.</br>
<br><strong>Methods: </strong>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 ≥1 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).</br>
<br><strong>Results: </strong>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).</br>
<br><strong>Conclusions: </strong>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.</br> |
| first_indexed | 2024-03-07T01:01:56Z |
| format | Journal article |
| id | oxford-uuid:8a04e4ec-fdfd-4848-8662-e74f94c9e800 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T01:01:56Z |
| publishDate | 2019 |
| publisher | Springer Nature |
| record_format | dspace |
| spelling | oxford-uuid:8a04e4ec-fdfd-4848-8662-e74f94c9e8002022-03-26T22:28:36ZResults of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumoursJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8a04e4ec-fdfd-4848-8662-e74f94c9e800EnglishSymplectic ElementsSpringer Nature2019Roberts, CStrauss, VYKopijasz, SGourley, CHall, MMontes, AAbraham, JClamp, AKennedy, RBanerjee, SFolkes, LKStratford, MNicum, S<br><strong>Background: </strong>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.</br> <br><strong>Methods: </strong>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 ≥1 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).</br> <br><strong>Results: </strong>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).</br> <br><strong>Conclusions: </strong>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.</br> |
| spellingShingle | Roberts, C Strauss, VY Kopijasz, S Gourley, C Hall, M Montes, A Abraham, J Clamp, A Kennedy, R Banerjee, S Folkes, LK Stratford, M Nicum, S Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours |
| title | Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours |
| title_full | Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours |
| title_fullStr | Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours |
| title_full_unstemmed | Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours |
| title_short | Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours |
| title_sort | results of a phase ii clinical trial of 6 mercaptopurine 6mp and methotrexate in patients with brca defective tumours |
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