Mitsudomi Tetsuya, Kosaka Takayuki, Endoh Hideki, Horio Yoshitsugu, Hida Toyoaki, Mori Shoichi, Hatooka Shunzo, Shinoda Masayuki, Takahashi Takashi, Yatabe Yasushi
Department of Thoracic Surgery, Aichi Cancer Center Hospital, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan.
J Clin Oncol. 2005 Apr 10;23(11):2513-20. doi: 10.1200/JCO.2005.00.992. Epub 2005 Feb 28.
To evaluate the relationship between mutations of the epidermal growth factor receptor (EGFR) gene and the effectiveness of gefitinib treatment in patients with recurrent lung cancer after pulmonary resection.
We sequenced exons 18-21 of the EGFR gene using total RNA extracted from 59 patients with lung cancer who were treated with gefitinib for recurrent lung cancer. Gefitinib effectiveness was evaluated by both imaging studies and change in serum carcinoembryonic antigen (CEA) levels.
EGFR mutations were found in 33 patients (56%). Of these mutations, 17 were deletions around codons 746-750 and 15 were point mutations (12 at codon 858, three at other codons), and one was an insertion. EGFR mutations were significantly more prevalent in females, adenocarcinoma, and never-smokers. Gefitinib treatment resulted in tumor shrinkage and/or CEA decrease to less than half of the baseline level in 26 patients, tumor growth and/or CEA elevation in 24 patients, and gefitinib effect was not assessable in nine patients. Female, never-smoking patients with adenocarcinoma tended to respond better to gefitinib treatment. Gefitinib was effective in 24 of 29 patients with EGFR mutations, compared with two of 21 patients without mutations (P < .0001). Of note, del746-750 might be superior to L858R mutations for prediction of gefitinib response. Patients with EGFR mutations survived for a longer period than those without the mutations after initiation of gefitinib treatment (P = .0053).
EGFR mutations were a good predictor of clinical benefit of gefitinib in this setting.
评估表皮生长因子受体（EGFR）基因突变与吉非替尼治疗肺切除术后复发性肺癌患者疗效之间的关系。
我们使用从59例接受吉非替尼治疗复发性肺癌的肺癌患者中提取的总RNA对EGFR基因的第18 - 21外显子进行测序。通过影像学研究和血清癌胚抗原（CEA）水平变化评估吉非替尼疗效。
33例患者（56%）检测到EGFR基因突变。其中，17例为746 - 750密码子周围的缺失，15例为点突变（12例位于858密码子，3例位于其他密码子），1例为插入突变。EGFR基因突变在女性、腺癌和从不吸烟者中显著更常见。吉非替尼治疗使26例患者肿瘤缩小和/或CEA降至基线水平的一半以下，24例患者肿瘤生长和/或CEA升高，9例患者的吉非替尼疗效无法评估。女性、从不吸烟的腺癌患者对吉非替尼治疗的反应往往更好。29例EGFR基因突变患者中有24例吉非替尼治疗有效，而21例未突变患者中仅有2例有效（P < .0001）。值得注意的是，del746 - 750在预测吉非替尼反应方面可能优于L858R突变。开始吉非替尼治疗后，EGFR基因突变患者的生存期比未突变患者更长（P = .0053）。
在这种情况下，EGFR基因突变是吉非替尼临床获益的良好预测指标。
