Bendamustine治疗慢性淋巴细胞白血病和rituximab-refractory,懒惰的b细胞非霍奇金淋巴瘤。

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Dennie TW, Kolesar JM

Bendamustine治疗慢性淋巴细胞白血病和rituximab-refractory,懒惰的b细胞非霍奇金淋巴瘤。

其他。2009;31 Pt 2:2290 - 311。doi: 10.1016 / j.clinthera.2009.11.031。

PubMed ID
20110042 (在PubMed
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文摘

背景:Bendamustine与purine-like氮芥衍生物苯并咪唑环,可提高其临床疗效。Bendamustine通过美国食品和药物管理局(FDA)治疗慢性淋巴细胞白血病(CLL) 2008年3月治疗rituximab-refractory,懒惰的b细胞非霍奇金淋巴瘤(NHL) 2008年10月。目的:本文综述bendamustine的药理学和药效学特性,结合数据有效性和毒性试验调查使用bendamustine各种血液恶性肿瘤的治疗,包括慢性淋巴细胞白血病、NHL,多发性骨髓瘤(MM)。方法:MEDLINE和国际制药抽象(1970 - 2009年4月15日)搜索使用条款bendamustine bendamustin, Treanda, Ribomustin,有关- 105,imet - 3393和Cytostasan。引用相关的文章也回顾了其他来源和材料。美国血液学会的数据库(2004 - 2008)和美国临床肿瘤学会(1995 - 2008)是寻找相关的抽象。结果:Bendamustine氮芥衍生物与结构相似性苯丁酸氮芥和其他从氮芥类药物,以及苯并咪唑环,可以作为拮抗剂嘌呤和氨基酸。具有良好的口服生物利用度,但几乎只在静脉注射配方研究。它经历了广泛的初步的新陈代谢的细胞色素P450 1 a2活性代谢物gamma-hydroxy bendamustine N-desmethyl-bendamustine,但临床活动似乎主要是与母体化合物有关。t (1/2) bendamustine大约是40分钟。 While bendamustine has 2 moieties with possible antitumor effect, it is unclear to what extent the benzimidazole ring enhances the efficacy of the drug. Numerous studies including in vitro assays have reported, however, that bendamustine has little cross-resistance with other alkylating agents and remains active even in extensively pretreated patients. FDA approval for use in CLL was based on findings from a randomized, open-label, Phase III study comparing bendamustine with chlorambucil as single-agent therapy in treatmentnaive patients with CLL (Binet stage B or C). Bendamustine was administered intravenously at a dose of 100 mg/m2 on days 1 and 2, while chlorambucil was administered orally at 0.8 mg/kg daily, both over 4-week cycles for up to 6 cycles. At interim analysis (the data used for FDA approval), bendamustine was associated with a greater overall response (68% vs 39%; P < 0.001), median progression-free survival (21.7 vs 9.3 months; P < 0.001) and median duration of remission (18.9 vs 6.1 months; P < 0.001) compared with chlorambucil. FDA approval for rituximabrefractory, indolent B-cell NHL followed a Phase III, open-label, single-arm study evaluating bendamustine monotherapy in patients who did not respond to rituximab or had progressive disease within 6 months of rituximab therapy. Bendamustine 120 mg/m(2) was administered intravenously on days 1 and 2 of a 21-day cycle for up to 8 cycles. At interim analysis, the overall response rate was 84%, including 29% complete response. The median progression-free survival was 9.7 months. The efficacy of bendamustine has also been reported in the treatment of MM in clinical studies, and bendamustine has been approved in Europe for treating MM, NHL, CLL, breast cancer, and Hodgkin lymphoma. Dose-limiting toxicity is primarily hematologic. Treatment-associated infections have been reported in some studies; however, nonhematologic adverse events have rarely been dose limiting. The most common nonhematologic adverse events include fatigue, nausea, xerostomia, and pyrexia. CONCLUSIONS: Bendamustine is a mechlorethamine derivative with a purine-like benzimidazole ring, which may enhance its clinical efficacy. It has been approved in the United States for the treatment of CLL and rituximab-refractory, indolent B-cell NHL. It has been approved in Europe for use in other malignancies, and clinical studies have reported activity in MM.

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