|
楼主 |
发表于 2008-4-7 08:10:12
|
显示全部楼层
来自: 美国
第一期试验: 口服talactoferrin alfa 治疗难治性实体瘤<br/><br/>Teresa G. Hayes1, 2 Contact Information, Gerald F. Falchook1, Gauri R. Varadhachary1, Dori P. Smith1, Lisa D. Davis1, Hari M. Dhingra1, Benjamin P. Hayes1 and Atul Varadhachary1<br/>(1)      Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas, USA<br/>(2)      VA 111H, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd., Houston, TX 77030, USA<br/><br/>简要背景:<br/>乳铁蛋白是一种铁结合糖蛋白,作为一种蛋白质产物,首次发现于母乳的乳腺上皮细胞中。其免疫调节功能,包括活化的NK细胞和淋巴因子激活的杀伤细胞,<br/>并增强中性粒细胞和巨噬细胞的细胞毒作用。<br/>研究目的:<br/>talactoferrin alfa( talactoferrin ; tlf ) 在动物模型中已显示出大有希望的抗癌活性。本研究的目的是在人类,以及 药代动力学和药效学,评价安全性和耐受性。<br/>方法:<br/>10例成人患者,具有常规化疗失败后已进展的晚期实体肿瘤,口服talactoferrin alfa,剂量由1.5至9克/日,用 服药2周,<br/>停药2周时间安排。,从   药物毒性,肿瘤的生长速度, talactoferrin药动学和细胞因子的标志物,对患者进行了评价。<br/>结果:<br/>talactoferrin很很好的耐受性。没有血液,肝,肾毒性的报道。一个有病人二级腹泻,并有没有三级或4不良反应。继口服,在相当程度上<br/>talactoferrin被undetectable流通中,但统计上的显着增加,在循环白细胞介素-18<br/>,药效学指标talactoferrin活动进行了观察。在上述 8例中,用 胸片评估, 5 人( 63 %<br/>)在开始治疗后两个月,按照recist准则,病情 稳定,(其中包括1名病人有少量的响应)。七名病人(( 88 % )<br/>,的肿瘤生长速度减少了。其中三名非小细胞肺癌( NSCLC )患者成活率,在    开始talactoferrin治疗后,至少一年<br/>结论:<br/>talactoferrin是一种很有前途的,耐受性良好新的代理人选进行评估应进一步治疗难治性转移性癌。 <br/><br/>hase I trial of oral talactoferrin alfa in refractory solid tumors<br/><br/>Teresa G. Hayes1, 2 Contact Information, Gerald F. Falchook1, Gauri R. Varadhachary1, Dori P. Smith1, Lisa D. Davis1, Hari M. Dhingra1, Benjamin P. Hayes1 and Atul Varadhachary1<br/>(1)      Michael E. DeBakey VA Medical Center and Baylor College of Medicine, Houston, Texas, USA<br/>(2)      VA 111H, Michael E. DeBakey VA Medical Center, 2002 Holcombe Blvd., Houston, TX 77030, USA<br/><br/>ublished online: 20 September 2005<br/>Summary  Background: Lactoferrin is an iron-binding glycoprotein first identified in breast milk as a protein product of mammary epithelial cells. Its immunomodulatory functions include activation of NK and lymphokine-activated killer cells and enhancement of PMN and macrophage cytotoxicity. Studies in animal models have shown promising anti-cancer activity. The purpose of the present study was to evaluate the safety and tolerability of talactoferrin alfa (talactoferrin; TLF) in humans, as well as pharmacokinetics and pharmacodynamics. Methods: Ten adult patients with progressive advanced solid tumors who had failed conventional chemotherapy were administered oral TLF at doses from 1.5 to 9 g/day, using a 2 weeks on, 2 weeks off schedule. Patients were evaluated for drug toxicity, tumor growth rate, talactoferrin pharmacokinetics and cytokine markers. Results: Talactoferrin was very well tolerated. No hematological, hepatic, or renal toxicities were reported. A single patient had Grade 2 diarrhea, and there were no Grade 3 or 4 toxicities. Following oral administration, significant levels of talactoferrin were undetectable in circulation, but a statistically significant increase in circulating IL-18, a pharmacodynamic indicator of talactoferrin activity, was observed. Of the eight patients who were radiologically evaluable, five (63%) had stable disease by RECIST criteria two months after start of therapy, including one patient with a minor response. Seven patients (88%) had a decrease in their tumor growth rate. The three patients with non-small cell lung cancer (NSCLC) all survived for at least one year following the start of talactoferrin monotherapy. Conclusions: Talactoferrin is a promising, well-tolerated new agent that should be evaluated further in patients with refractory metastatic cancer.<br/><br/>Key Words  talactoferrin - nonsmall cell lung cancer - refractory cancer<br/>Research supported by Agennix, Inc., Houston, Texas.<br/>resented previously in part: Proc. ASCO, Vol. 22, Abstract 947, 2003 and Proc. ASCO, Vol. 23, Abstract 3140, 2004.<br/><br/> <br/>
[此贴子已经被作者于2008-4-11 7:04:48编辑过] |
|