Lacouture M E, Melosky B L
SERIES Clinic, Department of Dermatology and Robert H Lurie Comprehensive Cancer Center, Northwestern University Feinberg School of Medicine, Chicago, IL, USA.
Skin Therapy Lett. 2007 Jul-Aug;12(6):1-5.
The epidermal growth factor receptor (EGFR) is often overexpressed or dysregulated in solid tumors. Targeting the EGFR-mediated signaling pathway has become routine practice in the treatment of lung, pancreatic, head and neck, and colon carcinomas. Available agents with selected activity towards the EGFR include low molecular weight tyrosine kinase inhibitors, e.g., erlotinib (Tarceva, Genentech BioOncology/ OSI Pharmaceuticals/ F. Hoffmann-La Roche) and monoclonal antibodies, such as cetuximab (Erbitux, Bristol-Myers Squibb/ ImClone Systems/ Merck) and panitumumab (Vectibix, Amgen). Their use is anticipated to increase for treating other solid tumors that are dependent on this pathway for growth and proliferation. Health Canada and the US FDA have approved erlotinib for the treatment of advanced non-small cell lung carcinoma (NSCLC). It has also been approved in the US for use against pancreatic cancer in combination with gemcitabine (Gemzar, Eli Lilly). Cetuximab and most recently panitumumab (Vectibix, Amgen/ Abgenix) were approved by the US FDA for metastatic colorectal carcinoma. Cetuximab is also approved in the US for head and neck squamous cell carcinoma. The safety profile for this class of drugs is unique, with virtually no hematological toxicity, but frequent cutaneous and gastrointestinal side-effects. Although there is a dearth of randomized trials addressing treatment of the dermatological side-effects, some basic principles of management have been agreed upon and can likely improve patient compliance and decrease inappropriate dose reduction, which may negatively influence the antitumor effect.
表皮生长因子受体（EGFR）在实体瘤中常过度表达或失调。靶向EGFR介导的信号通路已成为治疗肺癌、胰腺癌、头颈癌和结肠癌的常规方法。对EGFR具有特定活性的现有药物包括低分子量酪氨酸激酶抑制剂，如厄洛替尼（特罗凯，基因泰克生物肿瘤学公司/OSI制药公司/F.霍夫曼-罗氏公司），以及单克隆抗体，如西妥昔单抗（爱必妥，百时美施贵宝公司/ImClone系统公司/默克公司）和帕尼单抗（维克替比，安进公司）。预计它们在治疗依赖该信号通路生长和增殖的其他实体瘤方面的应用将会增加。加拿大卫生部和美国食品药品监督管理局已批准厄洛替尼用于治疗晚期非小细胞肺癌（NSCLC）。在美国，它还被批准与吉西他滨（健择，礼来公司）联合用于治疗胰腺癌。西妥昔单抗以及最近的帕尼单抗（维克替比，安进公司/Abgenix公司）已被美国食品药品监督管理局批准用于转移性结直肠癌。西妥昔单抗在美国也被批准用于治疗头颈鳞状细胞癌。这类药物的安全性特征独特，几乎没有血液学毒性，但常有皮肤和胃肠道副作用。尽管针对皮肤副作用治疗的随机试验较少，但已就一些基本管理原则达成共识，这些原则可能会提高患者的依从性，并减少不适当的剂量减少，而剂量减少可能会对抗肿瘤效果产生负面影响。
