Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.
Low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors: a phase I/II report.
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DOI：
10.1155/2014/371087
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发表时间：
2014
影响因子：
4.1
通讯作者：
Han W
中科院分区：
文献类型：
--
作者：
Fan H;Lu X;Wang X;Liu Y;Guo B;Zhang Y;Zhang W;Nie J;Feng K;Chen M;Zhang Y;Wang Y;Shi F;Fu X;Zhu H;Han W
异常DNA甲基化是肿瘤发生和发展的主要驱动因素之一。甲基化调节的可逆性使其成为新型抗癌疗法的一个有吸引力的靶点。临床研究表明，大剂量地西他滨（一种低甲基化药物）对难治性晚期肿瘤患者有一定的临床益处；然而，它们是剧毒的。低剂量地西他滨将毒性降至最低，同时可能改善DNA低甲基化的靶向效应。基于这些机制，低剂量地西他滨联合化疗免疫治疗可能是难治性晚期肿瘤患者的一种新的治疗选择。我们提出了以低剂量地西他滨为基础的化疗免疫治疗难治性晚期实体瘤的方案。在我们的试验中观察到一个有利的不良事件概况，主要是发现这些不良事件大多数为1-2级。此外，我们的队列活动乐观，临床获益率高达60%，中位PFS较先前治疗的PFS延长。我们还发现PFS与既往治疗和临床反应之间存在显著相关性。以低剂量DAC地西他滨为基础的化学免疫治疗可能是一种有希望提高难治性晚期实体瘤患者特异性和效率的方案。该试验已在ClinicalTrials.gov数据库中注册（标识符NCT01799083）。
Aberrant DNA methylation is one of the main drivers of tumor initiation and progression. The reversibility of methylation modulation makes it an attractive target for novel anticancer therapies. Clinical studies have demonstrated that high-dose decitabine, a hypomethylating agent, results in some clinical benefits in patients with refractory advanced tumors; however, they are extremely toxic. Low doses of decitabine minimize toxicity while potentially improving the targeted effects of DNA hypomethylation. Based on these mechanisms, low-dose decitabine combined with chemoimmunotherapy may be a new treatment option for patients with refractory advanced tumors. We proposed the regimen of low-dose decitabine-based chemoimmunotherapy for patients with refractory advanced solid tumors. A favorable adverse event profile was observed in our trial that was highlighted by the finding that most of these adverse events were grades 1-2. Besides, the activity of our cohort was optimistic and the clinical benefit rate was up to 60%, and the median PFS was prolonged compared with PFS to previous treatment. We also identified a significant correlation between the PFS to previous treatment and clinical response. The low-dose DAC decitabine-based chemoimmunotherapy might be a promising protocol for improving the specificity and efficiency of patients with refractory advanced solid tumors. This trial is registered in the ClinicalTrials.gov database (identifier NCT01799083).
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影响因子：
11.5
作者：
Fonsatti, Ester;Nicolay, Hugues J. M.;Maio, Michele
通讯作者：
Maio, Michele
影响因子：
10.5
作者：
Berger, Shelley L.;Kouzarides, Tony;Shilatifard, Ali
通讯作者：
Shilatifard, Ali
影响因子：
6.4
作者：
Hirata, Hiroshi;Hinoda, Yuji;Dahiya, Rajvir
通讯作者：
Dahiya, Rajvir
影响因子：
11.2
作者：
Lundqvist, Andreas;Abrams, Scott I.;Childs, Richard
通讯作者：
Childs, Richard
影响因子：
45.3
作者：
Samlowski, WE;Leachman, SA;Karpf, AR
通讯作者：
Karpf, AR