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首页> 外文期刊>British Journal of Cancer >Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours
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Results of a phase II clinical trial of 6-mercaptopurine (6MP) and methotrexate in patients with BRCA-defective tumours

机译：BRCA缺陷肿瘤患者6-巯基嘌呤（6MP）和甲氨蝶呤的II期临床试验结果

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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/m ~(2) per day, and methotrexate 15–20?mg/m ~(2) 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). 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. Trial registration NCT01432145 http://www.ClinicalTrials.gov .
机译：背景技术具有BRCA1 / 2基因突变的肿瘤细胞表现出对铂和聚（ADP-核糖）聚合酶（PARP）抑制剂的敏感性增加。发现6-巯基嘌呤（6MP）在作为PARP抑制剂AG014699中，选择性地杀死异种移植模型中的BRCA缺陷细胞，即使在这些细胞获得对PARP抑制剂或顺铂的耐药性之后，也是如此。方法该第二阶段单臂试验研究了每天6mp 55-75〜（2）的活性，甲氨蝶呤每周在先进的乳房或铂卵巢中每周15-20毫克/ m〜（2）癌症患者患有BRCA1 / 2种系突变，患者在α≥1之前进行了进展。主要结果是客观反应，包括稳定的疾病（SD），作为临床效益率（CBR）的评估，在8周内通过Recist V1.1。二次结果包括整体存活（OS）和无进展生存（PFS）。结果总计，67名可评估患者招募; 55例卵巢和11名乳腺癌患者。总共21例患者有SD（31％），一个部分反应（1.5％）; CBR在8周内为33％。总共12/67名患者（18％）在16周内患有SD。总共有五个卵巢癌患者的SD超过200天。中位数OS为10.3个月（95％CI 6.9-14.5），中位数PFS 1.9个月（1.7-2.8）。结论这些患者中6MP和甲氨蝶呤的总体活性低;然而，有一小组患者似乎导致长期临床效益。试验登记NCT01432145 http://www.clinicaltrials.gov。

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