Dragovich Tomislav, McCoy Sheryl, Fenoglio-Preiser Cecilia M, Wang Jiang, Benedetti Jacqueline K, Baker Amanda F, Hackett Christopher B, Urba Susan G, Zaner Ken S, Blanke Charles D, Abbruzzese James L
University of Arizona Cancer Center, Tucson, AZ 85724, USA.
J Clin Oncol. 2006 Oct 20;24(30):4922-7. doi: 10.1200/JCO.2006.07.1316.
A phase II trial of the oral epidermal growth factor receptor (EGFR) inhibitor erlotinib in patients with gastroesophageal adenocarcinomas stratified according to primary tumor location into two groups: gastroesophageal junction (GEJ)/cardia and distal gastric adenocarcinomas.
Patients with a histologically proven diagnosis of adenocarcinoma of the GEJ or stomach (ST) that was unresectable or metastatic; presence of measurable disease; no prior chemotherapy for advanced or metastatic cancer; Zubrod performance status (PS) of 0 to 1; and adequate renal, hepatic, and hematologic function were treated with erlotinib 150 mg/d orally. Patient characteristics were median age, GEJ-63 years, ST-64 years; sex, GEJ-84% male and 16% female, ST-60 male and 40 female; Zubrod PS, GEJ-25 had a PS of 0 and 18 had a PS 1, ST-13 had a PS of 0 and 12 had a PS of 1.
Percentage of common toxicities were skin rash, 86% and 72%; fatigue, 51% and 44%; and AST/ALT elevation, 28% and 28%, respectively for GEJ and ST. There has been one confirmed complete response, three confirmed partial responses (PRs) and one unconfirmed PR for an overall response probability of 9% confirmed (95% CI, 3% to 22%), all occurring in GEJ stratum. No responses were observed in ST stratum. The median survival was 6.7 months in GEJ and 3.5 months in ST stratum. Neither intratumoral EGFR, transforming growth factor-alpha or phosphorylated Akt kinase expression nor plasma proteomic analyses were predictive of clinical outcome. No somatic mutations of the EGFR exons 18, 19, or 21 were detected and there was no gross amplification of EGFR by fluorescence in situ hybridization.
Erlotinib is active in patients with GEJ adenocarcinomas, but appears inactive in gastric cancers. The molecular correlates examined were not predictive of the patient therapeutic response.
进行一项口服表皮生长因子受体（EGFR）抑制剂厄洛替尼用于胃食管腺癌患者的II期试验，根据原发肿瘤位置将患者分为两组：胃食管交界（GEJ）/贲门癌和远端胃癌。
组织学确诊为GEJ或胃（ST）腺癌且无法切除或已转移的患者；存在可测量病灶；既往未接受过晚期或转移性癌症的化疗；Zubrod体能状态（PS）为0至1；肾、肝和血液学功能良好的患者，口服厄洛替尼150mg/d进行治疗。患者特征为：中位年龄，GEJ组63岁，ST组64岁；性别，GEJ组84%为男性，16%为女性，ST组60%为男性，40%为女性；Zubrod PS，GEJ组25例PS为0，18例PS为1，ST组13例PS为0，12例PS为1。
常见毒性发生率分别为，GEJ组和ST组的皮疹为86%和72%；疲劳为51%和44%；AST/ALT升高为28%和28%。有1例确认的完全缓解，3例确认的部分缓解（PR）和1例未确认的PR，确认的总缓解率为9%（95%CI，3%至22%），均发生在GEJ亚组。ST亚组未观察到缓解。GEJ组的中位生存期为6.7个月，ST组为3.5个月。肿瘤内EGFR、转化生长因子-α或磷酸化Akt激酶表达以及血浆蛋白质组分析均不能预测临床结局。未检测到EGFR外显子18、19或21的体细胞突变，荧光原位杂交未发现EGFR的明显扩增。
厄洛替尼对GEJ腺癌患者有效，但对胃癌似乎无效。所检测的分子关联因素不能预测患者的治疗反应。
