Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma.
Phase 2 trial of the histone deacetylase inhibitor romidepsin for the treatment of refractory multiple myeloma.
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DOI：
10.1002/cncr.25584
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发表时间：
2011-01-15
期刊：
影响因子：
6.2
通讯作者：
Sparano, Joseph A.
中科院分区：
文献类型：
--
作者：
Niesvizky, Ruben;Ely, Scott;Mark, Tomer;Aggarwal, Sangeeta;Gabrilove, Janice L.;Wright, John J.;Chen-Kiang, Selina;Sparano, Joseph A.
表观遗传失调是癌症的标志，包括多发性骨髓瘤。组蛋白去乙酰化酶（HDAC）抑制剂通过抑制乙酰基从组蛋白上的氨基尾部的去除来诱导DNA超乙酰化，从而使浓缩的染色质展开，有利于沉默基因（包括肿瘤抑制基因）的转录。罗米地辛是HDAC抑制剂，其对多发性骨髓瘤细胞系表现出抗增殖和凋亡作用。我们在标准治疗难治性多发性骨髓瘤患者中进行了罗米地辛的2期试验。治疗包括罗米地辛（13 mg/m2），每28天在第1、8和15天IV输注4小时。13例患者接受了中位2个周期的治疗（范围1-7个周期）。尽管没有患者出现客观缓解，但12例分泌性骨髓瘤患者中有4例显示M蛋白稳定的证据，其他几例患者出现骨痛改善和高钙血症消退。我们的结论是，罗米地辛，作为一个单一的代理，是不太可能与30%或更高的反应率与难治性骨髓瘤患者，虽然有一些临床证据表明与治疗的生物效应。
Epigenetic dysregulation is a hallmark of cancer, including multiple myeloma. Inhibitors of histone deacetylases (HDAC) induce DNA hyperacetylation by inhibiting removal of acetyl groups from amino tails on histone proteins, thereby uncoiling condensed chromatin favoring transcription of silenced genes, including tumor suppressor genes. Romidepsin is an HDAC inhibitor which exhibits antiproliferative and apoptotic effects against multiple myeloma cell lines. We performed a phase 2 trial of romidepsin in patients with multiple myeloma who were refractory to standard therapy. Treatment consisted of romidepsin (13 mg/m2) given as a 4 hour IV infusion on days 1, 8, and 15 every 28 days. Thirteen patients received a median of 2 cycles of therapy (range 1–7 cycles). Although no patients had an objective response, 4 of 12 patients with secretory myeloma exhibited evidence of M-protein stabilization, and several other patients experienced improvement in bone pain and resolution of hypercalcemia. We conclude that romidepsin, as a single agent, is unlikely to be associated with response rate of 30% or higher in patients with refractory myeloma, although there was some clinical evidence suggesting a biological effect associated with therapy.
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影响因子：
20.3
作者：
Catley, Laurence;Weisberg, Ellen;Anderson, Kenneth C.
通讯作者：
Anderson, Kenneth C.
影响因子：
45.3
作者：
Piekarz, Richard L.;Frye, Robin;Bates, Susan E.
通讯作者：
Bates, Susan E.
影响因子：
20.3
作者：
Mitsiades, N;Mitsiades, CS;Anderson, KC
通讯作者：
Anderson, KC
Vorinostat与Bortezomib结合的I阶段研究，用于复发和难治性多发性骨髓瘤。
影响因子：
11.5
作者：
Badros, Ashraf;Burger, Angelika M.;Philip, Sunita;Niesvizky, Ruben;Kolla, Sarah S.;Goloubeva, Olga;Harris, Carolynn;Zwiebel, James;Wright, John J.;Espinoza-Delgado, Igor;Baer, Maria R.;Holleran, Julianne L.;Egorin, Merrill J.;Grant, Steven
通讯作者：
Grant, Steven
影响因子：
11.4
作者：
Durie, B. G. M.;Harousseau, J-L;Rajkumar, S. V.
通讯作者：
Rajkumar, S. V.