Double epigenetic modulation of high-dose chemotherapy with azacitidine and vorinostat for patients with refractory or poor-risk relapsed lymphoma
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- 作者：Yago Nieto ; Benigno C. Valdez ; Peter F. Thall ; Roy B. Jones ; Wei Wei ; Alan Myers ; Chitra Hosing ; Sairah Ahmed ; Uday Popat ; Elizabeth J. Shpall ; Muzaffar Qazilbash ; Alison Gulbis ; Paolo Anderlini ; Nina Shah ; Qaiser Bashir ; Amin Alousi ; Yasuhiro Oki ; Michelle Fanale ; Bouthaina Dabaja ; Chelsea Pinnix ; Richard Champlin and Borje S. Andersson
- 刊名：Cancer
- 出版年：2016
- 出版时间：September 1, 2016
- 年：2016
- 卷：122
- 期：17
- 页码：2680-2688
- 全文大小：204K
- ISSN：1097-0142
文摘
More active high-dose chemotherapy (HDC) regimens are needed for refractory lymphomas. The authors previously combined infusional gemcitabine with busulfan and melphalan (Gem/Bu/Mel) pursuing DNA damage repair inhibition. Subsequently, they combined Gem/Bu/Mel with vorinostat, which facilitates chemotherapy access to DNA. The resulting regimen was safe and synergistic. However, vorinostat induced DNA methyltransferase up-regulation, which could be preclinically abrogated by azacitidine, increasing tumor-cell kill. Those observations led to a clinical combination of azacitidine with vorinostat/Gem/Bu/Mel.