A phase I trial of flavopiridol in relapsed multiple myeloma.
A phase I trial of flavopiridol in relapsed multiple myeloma.
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黄叶替醇在复发多发性骨髓瘤中进行的I期试验。
DOI：
10.1007/s00280-013-2347-y
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发表时间：
2014-02
影响因子：
3
通讯作者：
Byrd, John C.
中科院分区：
文献类型：
--
作者：
Hofmeister, Craig C.;Poi, Ming;Bowers, Mindy A.;Zhao, Weiqiang;Phelps, Mitch A.;Benson, Don M.;Kraut, Eric H.;Farag, Sherif;Efebera, Yvonne A.;Sexton, Jennifer;Lin, Thomas S.;Grever, Michael;Byrd, John C.
关键词：
黄吡醇主要是一种细胞周期蛋白依赖性激酶(CDK)-9抑制剂，我们进行了一项剂量递增试验，以确定最大耐受剂量、安全性，并产生药代动力学谱。在至少两次治疗后诊断为骨髓瘤复发的患者被包括在内。黄匹吡醇作为大剂量给药，然后每周连续输注，共4周，以6周为周期。15例患者采用三种剂量水平（30mg /m2丸，30mg /m2 CIV至50mg /m2丸，50mg /m2 CIV）治疗。细胞减少明显，转氨酶升高（3例患者为4级，4例患者为3级，3例患者为2级），但都是短暂的。腹泻（6例为3级，5例为2级）未导致住院。虽然一名t（4;14）患者的单克隆蛋白下降超过50%，但没有持续，但没有证实部分反应。药代动力学性质与先前的出版物相似，细胞周期蛋白D1和视网膜母细胞瘤的免疫组织化学染色不能预测反应。黄匹吡醇作为单药，通过丸剂和输注引起明显的腹泻、细胞减少和转氨酶升高，但在复发性骨髓瘤中仅取得边际反应（ClinicalTrials.gov标识号NCT00112723）。
Flavopiridol is primarily a cyclin-dependent kinase (CDK)-9 inhibitor and we performed a dose escalation trial to determine the maximum tolerated dose, safety, and generate a pharmacokinetic profile. Patients with a diagnosis of relapsed myeloma after at least two prior treatments were included. Flavopiridol was administered as a bolus then continuous infusion weekly for 4 weeks in a 6 week cycle. Fifteen patients were treated at three dose levels (30 mg/m2 bolus, 30 mg/m2 CIV to 50 mg/m2 bolus, 50 mg/m2 CIV). Cytopenias were significant and elevated transaminases (grade 4 in 3 patients, grade 3 in 4 patients, and grade 2 in 3 patients) were noted but were transient. Diarrhea (grade 3 in 6 patients, grade 2 in 5 patients) did not lead to hospital admission. There were no confirmed partial responses although one patient with t(4;14) had a decrease in his monoclonal protein greater than 50% percent that did not persist. Pharmacokinetic properties were similar to prior publications and immunohistochemical staining for cyclin D1 and phospho-retinoblastoma did not predict response. Flavopiridol as a single agent given by bolus then infusion caused significant diarrhea, cytopenias, and transaminase elevation but only achieved marginal responses in relapsed myeloma (ClinicalTrials.gov identifier NCT00112723).
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影响因子：
64.8
作者：
Shaffer, Arthur L.;Emre, N. C. Tolga;Staudt, Louis M.
通讯作者：
Staudt, Louis M.
影响因子：
11.5
作者：
Tan, AR;Yang, XW;Swain, SM
通讯作者：
Swain, SM
影响因子：
20.3
作者：
Byrd, John C.;Lin, Thomas S.;Grever, Michael R.
通讯作者：
Grever, Michael R.
影响因子：
20.3
作者：
Bergsagel, PL;Kuehl, WM;Shaughnessy, J
通讯作者：
Shaughnessy, J
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.