Philip Philip A, Mahoney Michelle R, Allmer Cristine, Thomas James, Pitot Henry C, Kim George, Donehower Ross C, Fitch Tom, Picus Joel, Erlichman Charles
Karmanos Cancer Institute, Wayne State University, 4-HWCRC, 4100 John R St, Detroit, MI 48201, USA.
J Clin Oncol. 2006 Jul 1;24(19):3069-74. doi: 10.1200/JCO.2005.05.3579.
Epidermal growth factor receptor/human epidermal growth factor receptor 1 and ligand expression is common in biliary cancers (BILI) and may be associated with worse outcome. The primary objective of this study was to determine the proportion of patients with advanced BILI who were progression-free at 6 months.
Patients with either unresectable or metastatic disease were studied. Only one prior systemic or locoregional therapy was allowed. Erlotinib was administered continuously at a dose of 150 mg per day orally.
Forty-two patients with BILI were enrolled. The median age was 67 years (range, 33 to 82 years). Fifty-two percent of patients had Eastern Cooperative Oncology Group performance status of 1. Fifty-seven percent of patients had received prior chemotherapy for advanced BILI. HER1/EGFR expression by immunohistochemistry in tumor cells was detected in 29 (81%) of the 36 assessable patients. Seven of the patients (17%; 95% CI, 7% to 31%) were progression free at 6 months. Three patients had partial response by Response Evaluation Criteria in Solid Tumors Group classification of duration 4, 4, and 14 months, respectively. All responding patients had mild (grade 1/2) skin rash and two patients had positive tumoral HER1/EGFR expression. Three patients (7%) had toxicity-related dose reductions of erlotinib due to grade 2/3 skin rash.
Results suggest a therapeutic benefit for EGFR blockade with erlotinib in patients with biliary cancer. Additional studies with erlotinib as a single agent and in combination with other targeted agents are warranted in this disease.
表皮生长因子受体/人表皮生长因子受体1及其配体表达在胆管癌中常见，可能与较差的预后相关。本研究的主要目的是确定晚期胆管癌患者6个月时无进展的比例。
对不可切除或转移性疾病患者进行研究。仅允许接受过一种既往全身或局部区域治疗。厄洛替尼以每日150毫克的剂量持续口服给药。
42例胆管癌患者入组。中位年龄为67岁（范围33至82岁）。52%的患者东部肿瘤协作组体能状态评分为1。57%的患者曾接受过晚期胆管癌的化疗。在36例可评估患者中，29例（81%）肿瘤细胞免疫组化检测到HER1/EGFR表达。7例患者（17%；95%CI，7%至31%）在6个月时无进展。3例患者根据实体瘤疗效评价标准组分类分别有持续4、4和14个月的部分缓解。所有有反应的患者均有轻度（1/2级）皮疹，2例患者肿瘤HER1/EGFR表达阳性。3例患者（7%）因2/3级皮疹出现与毒性相关的厄洛替尼剂量减少。
结果提示厄洛替尼阻断EGFR对胆管癌患者有治疗益处。有必要对厄洛替尼作为单药及与其他靶向药物联合用于该病进行更多研究。
