Asahina H, Yamazaki K, Kinoshita I, Sukoh N, Harada M, Yokouchi H, Ishida T, Ogura S, Kojima T, Okamoto Y, Fujita Y, Dosaka-Akita H, Isobe H, Nishimura M
First Department of Medicine, Hokkaido University School of Medicine, North 15, West 7, Kita-ku, Sapporo 060-8638, Japan.
Br J Cancer. 2006 Oct 23;95(8):998-1004. doi: 10.1038/sj.bjc.6603393.
Retrospective analysis has shown that activating mutations in exons 18-21 of the epidermal growth factor receptor (EGFR) gene are a predictor of response to gefitinib. We conducted a phase II trial to evaluate the efficacy and safety of gefitinib as first-line therapy for advanced non-small cell lung cancer (NSCLC) with EGFR mutations. Patients with stage IIIB or IV chemotherapy-naïve NSCLC with EGFR mutation were treated with 250 mg gefitinib daily. For mutational analysis, DNA was extracted from paraffin-embedded tissues and EGFR mutations were analysed by direct sequence of PCR products. Twenty (24%) of the 82 patients analysed had EGFR mutations (deletions in or near E746-A750, n=16; L858R, n=4). Sixteen patients were enrolled and treated with gefitinib. Twelve patients had objective response and response rate was 75% (95% CI, 48-93%). After a median follow-up of 12.7 months (range, 3.1-16.8 months), 10 patients demonstrated disease progression, with median progression-free survival of 8.9 months (95% CI, 6.7-11.1 months). The median overall survival time has not yet been reached. Most of the toxicities were mild. This study showed that gefitinib is very active and well tolerated as first-line therapy for advanced NSCLC with EGFR mutations.
回顾性分析表明，表皮生长因子受体（EGFR）基因外显子18 - 21的激活突变是吉非替尼治疗反应的预测指标。我们开展了一项II期试验，以评估吉非替尼作为一线治疗药物用于治疗具有EGFR突变的晚期非小细胞肺癌（NSCLC）的疗效和安全性。对未经化疗的IIIB期或IV期且具有EGFR突变的NSCLC患者，给予每日250 mg吉非替尼治疗。对于突变分析，从石蜡包埋组织中提取DNA，并通过PCR产物直接测序分析EGFR突变。在分析的82例患者中，有20例（24%）存在EGFR突变（E746 - A750区域内或附近的缺失，n = 16；L858R，n = 4）。16例患者入组并接受吉非替尼治疗。12例患者获得客观缓解，缓解率为75%（95% CI，48 - 93%）。中位随访12.7个月（范围3.1 - 16.8个月）后，10例患者疾病进展，中位无进展生存期为8.9个月（95% CI，6.7 - 11.1个月）。总生存时间的中位数尚未达到。大多数毒性反应较轻。本研究表明，吉非替尼作为具有EGFR突变的晚期NSCLC的一线治疗药物，活性很高且耐受性良好。
