第一阶段试验的bcl - 2反义(G3139)和每周多烯紫杉醇在晚期乳腺癌患者和其他实体肿瘤。

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马歇尔J,陈H,杨D, Figueira M, Bouker KB,凌Y,利普曼M, Frankel SR,海耶斯DF

第一阶段试验的bcl - 2反义(G3139)和每周多烯紫杉醇在晚期乳腺癌患者和其他实体肿瘤。

安8月杂志。2004;15 (8):1274 - 83。

PubMed ID

15277270 (在PubMed

]

文摘

目的:bcl - 2蛋白的表达抵抗各种凋亡信号。G3139 [oblimersen钠(Genasense)]是一个phosphorothioate反义oligodeoxynucleotide bcl - 2 mRNA的目标,会使bcl - 2蛋白翻译,和增强的抗肿瘤效应开始剂量紫杉醇(泰素帝)。患者和方法:我们进行了第一阶段试验来确定最大耐受剂量(MTD)和联合治疗的安全性和G3139每周先进Bcl-2-positive实体瘤病人中2例。群三到六患者注册升级剂量的G3139和固定剂量的多烯紫杉醇每周使用两个时间表。在第一部分,G3139是由连续注入21天(D1-22)和多西他赛(35毫克/平方米)每周8天,15 - 22所示。在第二部分,G3139是由连续输注前5天第一个周剂量的多西他赛,和前48 h第二和第三周多烯紫杉醇剂量。两个时间表,循环重复每4周。结果:22例了。13部分我安排患者治疗剂量的G3139升级从1到4毫克/公斤/天。9名患者的第二部分计划短G3139注入G3139剂量的5 - 9毫克/公斤/天。 Hematologic toxicities were mild, except for one case of persistent grade 3 thrombocytopenia in part I. The most common adverse events were cumulative fatigue and transaminase elevation, which prevented further dose escalation beyond 4 mg/kg/day for 21 days with the part I schedule. In part II of the study, using the abbreviated G3139 schedule, even the highest daily doses were tolerated without dose-limiting toxicity or the need for dose modification. Objective tumor response was observed in two patients with breast cancer, including one whose cancer previously progressed on trastuzumab plus paclitaxel. Four patients had stable disease. Pharmacokinetic results for G3139 were similar to those of other trials. CONCLUSIONS: G3139 in combination with standard-dose weekly docetaxel was well tolerated. The shortened and intermittent G3139 infusion had less cumulative toxicities and still allowed similar total G3139 delivery as the longer infusion. Further studies should examine the molecular effect of the regimen, as well as clinical activities in malignancies for which taxanes are indicated.

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药物靶点

药物	目标	类	生物	药理作用	行动
多烯紫杉醇	bcl - 2细胞凋亡调节器	蛋白质	人类	未知的	不可用	细节