去铁胺显 (Deferoxamine) 与疾病晚期肝癌

StephenW

http://www.hivandhepatitis.com/hepatitis-b/3150-deferoxamine-shows-promise-for-advanced-liver-cancer
Hepatitis B                                                                                                                    Deferoxamine Shows Promise for Liver Cancer in People with Advanced Disease                    Category: Hepatitis B
Published on Friday, 12 August 2011 00:00                                                     Written by Liz Highleyman               

© Russell Kightley

Deferoxamine, a cancer drug that has an anti-proliferative effect on tumor cells, led to improvement of hepatocellular carcinoma (HCC) in 2 out of 10 patients with moderate-to-severe liver disease, according to a letter in the August 11, 2011, New England Journal of Medicine.
Takahiro Yamasaki and colleagues from Yamaguchi University Graduate School of Medicine in Ube, Japan, evaluated deferoxamine therapy in patients with advanced HCC and serious liver function impairment.
The researchers previously reported that deferoxamine (an iron chelator) can prevent liver injury and development of precancerous lesions in rats. The anti-proliferative effect of deferoxamine arrests the cell cycle and induces apoptosis, they noted as background. Sorafenib (Nexavar) was recently established as the standard of care for people with advanced HCC and preserved liver function (Child-Pugh class A), but its safety and efficacy for patients with Child-Pugh class B or C (moderate or severe) liver disease is unknown.
The present study included 10 participants (6 men and 4 women) with advanced HCC who did not respond to hepatic arterial infusion chemotherapy using standard anticancer drugs. The average age was 64 years. Of these patients, 7 had hepatitis C virus (HCV) infection, 2 had hepatitis B virus (HBV) infection, and 1 did not have either type of viral hepatitis.
At baseline, 1 patient had HCC tumor stage II, 2 patients had stage IVA, and 7 had stage IVB (according to Liver Cancer Study Group of Japan criteria). Looking at liver function, 3 had Child-Pugh class A (least severe liver disease), 5 had class B (moderate severity), and 2 had class C (most severe).
Participants received arterial infusions of deferoxamine at a dose of 10-80 mg per kilogram of body weight over 24 hours on alternate days, using an injection port. Deferoxamine was administered an average of 27 times (range 9-78 infusions).
Results

• 2 patients had a partial response, 3 maintained stable disease, and 5 experienced disease progression (according to Eastern Cooperative Oncology Group criteria).
• The overall response rate, therefore, was 20%.
• Levels of tumor-related biomarkers -- alpha-fetoprotein, alpha-fetoprotein L3, des-gamma-carboxyprothrombin, or all of these -- decreased in patients with a partial response.
• In 1 patient, "a massive hepatocellular tumor with lung metastases disappeared with deferoxamine treatment," the researchers wrote.
• The 1-year cumulative survival rate was 20%.
• 4 patients developed grade 2 or 3 (moderate or severe) interstitial pneumonia and 1 patient had grade 2 kidney dysfunction.
• No grade 4 (life-threatening) adverse events were observed.
  

Based on these findings, the report authors concluded, "Deferoxamine may warrant testing in patients with Child-Pugh class B or C hepatocellular carcinoma."
8/12/11
Reference
T Yamasaki, S Terai, and I Sakaida. Deferoxamine for Advanced Hepatocellular Carcinoma (Correspondence). New England Journal of Medicine 365(6): 576-578. August 11, 2011.




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StephenW

谷歌翻译不是100％准确，仅供参考使用。

去铁胺，抗癌药物对肿瘤细胞的抗增殖作用，导致肝细胞癌（HCC）的改善，据信在2011年8月11日，10中度至严重的肝脏疾病患者中有2 ，“新英格兰医学杂志。

山崎隆宏和他的同事从山口大学研究生医学院，日本宇部兴产评估去铁胺治疗中晚期肝癌和严重的肝功能损害的患者。

此前，研究人员报告说，去铁胺（铁螯合剂），可以防止肝损伤和大鼠癌前病变的发展。去铁胺逮捕细胞周期和诱导细胞凋亡的抗增殖作用，他们指出，作为背景。索拉非尼（多吉美）是最近成立的护理晚期肝癌的人，并保留肝功能（Child - Pugh分级A级）的标准，但其安全性和有效性为患者Child - Pugh分级B或C肝（中度或重度）病是未知之数。

本研究包括10例晚期肝癌的参与者（六男四女）谁没有回应肝动脉灌注化疗，使用标准的抗癌药物。平均年龄为64岁。在这些患者中，有7个丙型肝炎病毒（HCV）感染，2例乙型肝炎病毒（HBV）感染，并没有两种类型的病毒性肝炎。

基线，1例肝癌肿瘤的第二阶段的，有2例出现Ⅳa期，7期IVB部（根据日本标准的肝癌研究小组）。纵观肝功能，Child - Pugh分级（至少有严重的肝脏疾病），有5个B级（中度），和2个C类（最严重）。

与会者收到动脉输注去铁胺，剂量为10-80毫克每公斤体重超过24小时隔日使用注射口。去铁胺给药平均的27倍（范围9-78输注）。

结果

    2例患者有部分反应，保持病情稳定，和经验丰富的病情恶化（根据东部肿瘤协作组标准）。
    因此，整体回应率为20％。
    肿瘤相关的生物标志物的水平 - 甲胎蛋白，甲胎蛋白三级，DES-γ-  carboxyprothrombin， 或所有这些   -   减少部分反应的患者。
    1例患者，“一个巨大的肝癌肿瘤消失去铁胺治疗肺转移，”研究人员写道。
    1年累积生存率为20％。
    发展了2或3级（中度或重度）间质性肺炎和1例4例，2级肾功能不全。
    无4级（危及生命）的不良事件进行观察。

基于这些发现，该报告的作者得出结论，“去铁胺可能有必要与儿童Pugh分级B级或C肝癌患者进行测试。”

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