表皮生长因子受体血清（sEGFR）水平能否预测表皮生长因子受体（EGFR）阳性的晚期结直肠癌患者接受吉非替尼治疗后的反应？

Epidermal growth factor receptor serum (sEGFR) level may predict response in patients with EGFR-positive advanced colorectal cancer treated with gefitinib?

作者信息

Zampino M G, Magni E, Santoro L, Zorzino L, Dell'Orto P, Sonzogni A, Fazio N, Monfardini L, Chiappa A, Biffi R, de Braud F

机构信息

Department of Medicine, Medical Care Unit, European Institute of Oncology, Milan, Italy.

出版信息

Cancer Chemother Pharmacol. 2008 Dec;63(1):139-48. doi: 10.1007/s00280-008-0722-x. Epub 2008 Mar 8.

DOI:10.1007/s00280-008-0722-x

PMID:18327586

Abstract

PURPOSE

Epidermal growth factor receptor-overexpression reported in colorectal cancer, justifies therapeutic use of EGFR-inhibitors. We have recently conducted a phase II study in 57 patients with EGFR-positive advanced colorectal cancer (ACC) who received gefitinib-FOLFOX6 followed by gefitinib-single agent as maintenance. Main biological objective was to assess sEGFR as surrogate marker of tyrosine kinase inhibition and as predictor of response.

METHODS

sEGFR, evaluated by quantitative ELISA, was investigated as predictive factor both taking into account the basal value only, and its whole pattern over time. sEGFR was collected at baseline and at every 2-months assessment in 42 cases. Thirty-three patients reported CR/PR as best objective response (BOR), while nine showed SD/PD.

RESULTS

Retrospectively, on average, the sEGFR values reported by both responders (CR/PR) and not responders (SD/PD) were already different at baseline (49.4 +/- 6.2 and 42.4 +/- 8.4 ng/ml respectively). This difference was statistically significant (p = 0.042). Although sEGFR trend over time confirmed the basal difference (p = 0.032), this result should be taken with caution, due to the small number of patients reporting EGFR values besides the basal one.

CONCLUSIONS

Higher sEGFR at baseline was associated to BOR and may be considered a significant predictor of outcome in patients with ACC.

摘要

目的

结直肠癌中报道的表皮生长因子受体过表达证明了表皮生长因子受体抑制剂的治疗用途。我们最近对57例表皮生长因子受体阳性的晚期结直肠癌（ACC）患者进行了一项II期研究，这些患者接受吉非替尼-奥沙利铂/亚叶酸钙方案（FOLFOX6）治疗，随后以吉非替尼单药作为维持治疗。主要生物学目标是评估可溶性表皮生长因子受体（sEGFR）作为酪氨酸激酶抑制的替代标志物和反应预测指标。

方法

通过定量酶联免疫吸附测定（ELISA）评估的sEGFR，既作为预测因子单独考虑其基础值，也考虑其随时间的整体变化模式进行研究。在42例患者中于基线和每2个月评估时收集sEGFR。33例患者报告完全缓解/部分缓解（CR/PR）为最佳客观反应（BOR），而9例显示疾病稳定/疾病进展（SD/PD）。

结果

回顾性分析，平均而言，反应者（CR/PR）和无反应者（SD/PD）报告的sEGFR值在基线时就已不同（分别为49.4±6.2和42.4±8.4 ng/ml）。这种差异具有统计学意义（p = 0.042）。尽管sEGFR随时间的变化趋势证实了基础差异（p = 0.032），但由于除基础值外报告EGFR值的患者数量较少，该结果应谨慎看待。