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Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours
Roberts, C Strauss, VY Kopijasz, S Gourley, C Hall, M Montes, A Abraham, J Clamp, Andrew R Kennedy, R Banerjee, S
Roberts, C
Strauss, VY
Kopijasz, S
Gourley, C
Hall, M
Montes, A
Abraham, J
Clamp, Andrew R
Kennedy, R
Banerjee, S
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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.
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Date
2019
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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.