转移性乳腺癌的节拍化疗：对血管内皮生长因子的影响

Metronomic chemotherapy in metastatic breast cancer: impact on VEGF.

作者信息

El-Arab Lobna R Ezz, Swellam Menha, El Mahdy Manal M

机构信息

Radiation Oncology and Nuclear Medicine, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

出版信息

J Egypt Natl Canc Inst. 2012 Mar;24(1):15-22. doi: 10.1016/j.jnci.2011.12.002. Epub 2012 Jan 17.

DOI:10.1016/j.jnci.2011.12.002

PMID:23587228

Abstract

BACKGROUND

Anticancer chemotherapy is thought to be effective by means of direct cytotoxicity on tumor cells. Alternative mechanisms of efficacy have been ascribed to several common anticancer agents; including cyclophosphamide (CTX) and capecitabine (Cap) when given at lower doses for prolonged period (metronomic chemotherapy) postulating an antiangiogenic activity as well.

AIM OF WORK

To evaluate the action and tolerability of metronomic chemotherapy (MC) and its impact on serum vascular endothelial growth factor (VEGF) levels in metastatic breast cancer (MBC) patients.

PATIENTS AND METHODS

In this study we evaluated the clinical efficacy and tolerability of low dose, capecitabine (500mg twice daily) together with oral cyclophosphamide (CTX) (a dose of 50mg once daily) in patients with metastatic breast cancer. Vascular endothelial growth factor (VEGF), an angiogenic marker, was measured in the serum samples; at base line, and after 2 and 6months of therapy.

RESULTS

Sixty patients were evaluable. One achieved complete response (CR), 12 partial responses (PR), and 21 stable diseases (SD), while 26 were with progressive disease (PD). The overall response rate was 21.7% with overall disease control (CR, PR, and SD) 56.7%. The median time to progression was 7±2.59months and overall survival 16±8.02months. Toxicity was mild, Palmar-plantar erythrodythesia was the most common side effect and was observed in 22 patients (37%), leucopenia (G1+2) was the most common hematological toxicity, and it was reported in 27% of the cases. The median VEGF level was significantly declined after 2 and 6months of therapy compared to the base line among the patients with disease control (CR, PR, and SD). In multivariate logistic regression analysis, patients with post-menopausal, positive hormonal receptors, negative HER-2/Neu, and one metastatic site, were statistically significant and have a better disease control rate.

CONCLUSIONS

MC induced drop in VEGF, and was effective, minimally toxic regimen for the treatment of metastatic breast cancer patients.

摘要

背景

抗癌化疗被认为是通过对肿瘤细胞的直接细胞毒性发挥作用。几种常见抗癌药物的疗效还有其他作用机制；包括环磷酰胺（CTX）和卡培他滨（Cap），当低剂量长时间给药时（节拍化疗），也假定具有抗血管生成活性。

工作目的

评估节拍化疗（MC）对转移性乳腺癌（MBC）患者的作用、耐受性及其对血清血管内皮生长因子（VEGF）水平的影响。

患者与方法

在本研究中，我们评估了低剂量卡培他滨（每日两次，每次500mg）联合口服环磷酰胺（CTX）（每日一次，剂量50mg）对转移性乳腺癌患者的临床疗效和耐受性。在基线、治疗2个月和6个月后，检测血清样本中的血管内皮生长因子（VEGF），这是一种血管生成标志物。

结果

60例患者可评估。1例达到完全缓解（CR），12例部分缓解（PR），21例病情稳定（SD），26例病情进展（PD）。总缓解率为21.7%，疾病总体控制率（CR、PR和SD）为56.7%。中位疾病进展时间为7±2.59个月，总生存期为16±8.02个月。毒性较轻，手足红斑是最常见的副作用，22例患者（37%）出现该症状，白细胞减少（1级+2级）是最常见的血液学毒性，27%的病例报告有此情况。与基线相比，疾病得到控制（CR、PR和SD）的患者在治疗2个月和6个月后，VEGF的中位水平显著下降。在多因素逻辑回归分析中，绝经后、激素受体阳性、HER-2/Neu阴性且有一个转移部位的患者具有统计学意义，疾病控制率更高。