Oncology Section, Second Department of Internal Medicine, Hippokration Hospital, University of Athens School of Medicine, Athens, Greece.
Oncol Rep. 2012 Jan;27(1):216-24. doi: 10.3892/or.2011.1504. Epub 2011 Oct 13.
It is well known that low-dose metronomic chemotherapy has antiangiogenic activity. The aim of the present trial was to investigate the antiangiogenic properties of weekly docetaxel in patients with metastatic breast cancer. In total, 157 metastatic breast cancer patients received 35 mg/m2 docetaxel weekly as a recommended treatment. Blood samples were collected before the start of chemotherapy (baseline) and during treatment. Nitric oxide (NO) and vascular endothelial growth factor A (VEGF-A) plasma levels were measured at baseline and during treatment, while VEGF-A, endothelial nitric oxide synthase (eNOS) and thrombospondin-1 (THBS-1) peripheral blood mRNA levels were measured at baseline, in 127 patients and 39 female healthy controls. In general, the treatment was well-tolerated. Sixty-one patients (38%) achieved an objective response (4% complete and 34% partial response), while 52 (33%) had stable disease and 27 (17%) progressed. At a median follow-up of 33.5 months (range 2.8-45.0), 118 patients (74%) demonstrated disease progression and 94 (59%) had died. Median progression-free survival (PFS) was 8.8 months and median overall survival (OS) was 27.7 months. Median baseline level of plasma NO was significantly lower in patients than in healthy controls (p=0.010), while none of the plasma markers significantly changed upon docetaxel treatment. In addition, the median relative quantification value for THBS-1 mRNA was significantly higher (p<0.001) in patients as compared to healthy controls. NO plasma levels were positively associated with the number of organs involved (p=0.008). In multivariate analysis, low eNOS mRNA levels showed adverse prognostic significance for OS and high THBS-1 mRNA levels were found to be associated with shorter OS and PFS, independently from established clinical prognostic factors. Although an antiangiogenic activity of weekly docetaxel was not demonstrated in the present study, some interesting observations regarding the prognostic role of a number of blood angiogenic markers could be made.
众所周知，低剂量节拍化疗具有抗血管生成活性。本试验的目的是研究每周多西紫杉醇治疗转移性乳腺癌患者的抗血管生成特性。共有 157 名转移性乳腺癌患者接受每周 35mg/m2 多西紫杉醇的推荐治疗。在化疗开始前（基线）和治疗期间采集血样。在基线和治疗期间测量血浆中一氧化氮（NO）和血管内皮生长因子 A（VEGF-A）水平，而在基线时、127 名患者和 39 名女性健康对照者中测量 VEGF-A、内皮型一氧化氮合酶（eNOS）和血小板反应蛋白-1（THBS-1）外周血 mRNA 水平。一般来说，治疗耐受性良好。61 名患者（38%）获得客观缓解（4%完全缓解和 34%部分缓解），52 名患者（33%）病情稳定，27 名患者（17%）进展。在中位数为 33.5 个月（范围 2.8-45.0）的随访中，118 名患者（74%）出现疾病进展，94 名患者（59%）死亡。中位无进展生存期（PFS）为 8.8 个月，中位总生存期（OS）为 27.7 个月。基线时血浆 NO 水平显著低于健康对照组（p=0.010），而多西紫杉醇治疗后血浆标志物均无明显变化。此外，与健康对照组相比，THBS-1 mRNA 的中位数相对定量值显著升高（p<0.001）。NO 血浆水平与受累器官数量呈正相关（p=0.008）。多变量分析显示，低 eNOS mRNA 水平对 OS 具有不良预后意义，而高 THBS-1 mRNA 水平与 OS 和 PFS 缩短独立于既定的临床预后因素相关。尽管本研究未显示每周多西紫杉醇具有抗血管生成活性，但一些关于血液血管生成标志物预后作用的有趣观察结果值得注意。
