Phase II trial of curcumin in patients with advanced pancreatic cancer
Phase II trial of curcumin in patients with advanced pancreatic cancer
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DOI：
10.1158/1078-0432.ccr-08-0024
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发表时间：
2008-07-15
影响因子：
11.5
通讯作者：
Kurzrock, Razelle
中科院分区：
文献类型：
--
作者：
Dhillon, Navneet;Aggarwal, Bharat B.;Kurzrock, Razelle
目的：胰腺癌几乎总是致命的，美国食品和药物管理局唯一批准的治疗方法，吉西他滨和厄洛替尼，在18个月内产生客观反应;有趣的是，另外一名患者出现了短暂但显著的肿瘤消退（73%），同时伴有显著的增加（4- 35倍）的血清细胞因子水平（IL-6、IL-8、IL-10和IL-1受体拮抗剂）。未观察到毒性。姜黄素下调患者外周血单核细胞中NF-κ B B、环氧合酶2和磷酸化信号转导子和转录激活子3的表达（其中大多数患者的基线水平显著高于健康志愿者）。而有相当大的患者间血浆姜黄素水平的变化，药物水平达到峰值在22至41 ng/mL，并保持相对恒定的前4 weeks.Conclusions：口服姜黄素是耐受性良好，尽管其吸收有限，在一些胰腺癌患者的生物活性。
Purpose: Pancreatic cancer is almost always lethal, and the only U.S. Food and Drug Administration - approved therapies for it, gemcitabine and erlotinib, produce objective responses in 18 months; interestingly, one additional patient had a brief, but marked, tumor regression (73%) accompanied by significant increases (4- to 35-fold) in serum cytokine levels (IL-6, IL-8, IL-10, and IL-1 receptor antagonists). No toxicities were observed. Curcumin down-regulated expression of NF-kappa B, cyclooxygenase-2, and phosphorylated signal transducer and activator of transcription 3 in peripheral blood mononuclear cells from patients (most of whom had baseline levels considerably higher than those found in healthy volunteers). Whereas there was considerable interpatient variation in plasma curcumin levels, drug levels peaked at 22 to 41 ng/mL and remained relatively constant over the first 4 weeks.Conclusions: Oral curcumin is well tolerated and, despite its limited absorption, has biological activity in some patients with pancreatic cancer.