不同抗癌方案对晚期肝细胞癌患者血管生成生物标志物的影响。
Impact of different anticancer regimens on biomarkers of angiogenesis in patients with advanced hepatocellular cancer.
作者信息
Treiber G, Wex T, Malfertheiner P
机构信息
Department of Gastroenterology and Hepatology, University Hospital of Magdeburg, Magdeburg, Germany.
出版信息
J Cancer Res Clin Oncol. 2009 Feb;135(2):271-81. doi: 10.1007/s00432-008-0443-x. Epub 2008 Jul 19.
OBJECTIVE
Advanced hepatocellular cancer (HCC) is a highly vascularised tumor with limited treatment options. We wanted to evaluate the impact of different treatments on systemic biomarkers linked to angiogenesis.
METHODS
Two subsequent prospective, randomised, phase-I/II trials in patients with advanced HCC were performed. A total of 38 patients was randomised to a total of 4 regimens consisting of 3 cycles of 4 weeks each: Trial 1 included group 1 receiving octreotide 30 mg im on day 1, and group 2 octreotide 30 mg on day 1 plus Imatinib 400 mg po daily; Trial 2 included group 3 with oxaliplatin on day 1 (60 mg-90 mg/m(2)), and group 4 with oxaliplatin on day 1, 8, 15 (20 mg-30 mg/m(2)) in combination with octreotide 30 mg on day 1 plus imatinib 400 mg po daily. Primary outcome measure was the relative changes in plasma biomarkers over time.
RESULTS
Time-to-progression and overall survival was not different between the the two study trials. Within group 1-4, the mean relative increase from baseline to week 12 of treatment was 17, 18, 37, and 2% for s-E-selectin; -1, 90, 10, and -9% for VEGF-A; 18, 84, 141, and 74% for PDGF-BB, and 111, 142, 30, and 7% for serum AFP, respectively.
CONCLUSIONS
The increase of plasma levels for s-E-selectin and PDGF-BB seen in patients receiving chemotherapy alone may reflect activation of angiogenesis. In contrast, low-dose metronomic chemotherapy in combination with anti-angiogenic drugs seems to correlate with the least increase in biomarkers. Imatinib-octreotide temporarily leads to a decrease in PDGF-BB, whereas octreotide alone had no effect on PDGF-BB plasma levels.
目的
晚期肝细胞癌（HCC）是一种血管高度丰富的肿瘤，治疗选择有限。我们想评估不同治疗方法对与血管生成相关的全身生物标志物的影响。
方法
对晚期HCC患者进行了两项连续的前瞻性、随机、I/II期试验。共有38名患者被随机分为4种治疗方案，每种方案包括3个周期，每个周期4周：试验1包括第1组，在第1天接受30mg奥曲肽皮下注射；第2组在第1天接受30mg奥曲肽加400mg伊马替尼口服；试验2包括第3组，在第1天接受奥沙利铂（60mg - 90mg/m²）；第4组在第1、8、15天接受奥沙利铂（20mg - 30mg/m²），并在第1天联合30mg奥曲肽加400mg伊马替尼口服。主要观察指标是血浆生物标志物随时间的相对变化。
结果
两项研究试验之间的疾病进展时间和总生存期没有差异。在第1 - 4组中，从基线到治疗第12周，可溶性E选择素（s-E-selectin）平均相对增加分别为17%、18%、37%和2%；血管内皮生长因子A（VEGF-A）分别为-1%、90%、10%和-9%；血小板衍生生长因子BB（PDGF-BB）分别为18%、84%、141%和74%；血清甲胎蛋白（AFP）分别为111%、142%、30%和7%。
结论
单独接受化疗的患者中观察到的s-E-selectin和PDGF-BB血浆水平升高可能反映血管生成的激活。相比之下，低剂量节拍化疗联合抗血管生成药物似乎与生物标志物的最少增加相关。伊马替尼 - 奥曲肽可使PDGF-BB暂时降低，而单独使用奥曲肽对PDGF-BB血浆水平无影响。
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