Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours
| Autor: | Sylwia Kopijasz, Corran Roberts, Victoria Y Strauss, Shibani Nicum, Andrew R Clamp, Marcia Hall, Richard D. Kennedy, Ana Montes, Charlie Gourley, Jacinta Abraham, Michael R.L. Stratford, Susana Banerjee, Lisa K. Folkes |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
Adult
Oncology medicine.medical_specialty Cancer Research Cancer therapy medicine.medical_treatment Breast Neoplasms Gene mutation Article 03 medical and health sciences 0302 clinical medicine Breast cancer SDG 3 - Good Health and Well-being Internal medicine Antineoplastic Combined Chemotherapy Protocols Humans Medicine Aged 030304 developmental biology BRCA2 Protein Ovarian Neoplasms Salvage Therapy Cisplatin 0303 health sciences Chemotherapy BRCA1 Protein Mercaptopurine business.industry Middle Aged medicine.disease Progression-Free Survival Cancer therapeutic resistance Methotrexate Drug Resistance Neoplasm 030220 oncology & carcinogenesis PARP inhibitor Female Neoplasm Recurrence Local business Ovarian cancer medicine.drug |
| Zdroj: | Roberts, C, Strauss, V Y, Kopijasz, S, Gourley, C, Hall, M, Montes, A, Abraham, J, Clamp, A, Kennedy, R, Banerjee, S, Folkes, L K, Stratford, M & Nicum, S 2020, ' Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours ', British Journal of Cancer, vol. 122, no. 4, pp. 483-490 . https://doi.org/10.1038/s41416-019-0674-4, https://doi.org/10.1038/s41416-019-0674-4 Roberts, C, Strauss, V Y, Kopijasz, S, Gourley, C, Hall, M, Montes, A, Abraham, J, Clamp, A, Kennedy, R, Banerjee, S, Folkes, L K, Stratford, M & Nicum, S 2020, ' Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours ', British Journal of Cancer, vol. 122, no. 4, pp. 483-490 . https://doi.org/10.1038/s41416-019-0674-4 British Journal of Cancer |
| Popis: | BackgroundTumour 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.MethodsThis 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).ResultsIn 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).ConclusionsThe 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. |
| Databáze: | OpenAIRE |
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