Kim Kyu-Sik, Jeong Ju-Yeon, Kim Young-Chul, Na Kook-Joo, Kim Yun-Hyeon, Ahn Sung-Ja, Baek Sun-Mi, Park Chang-Soo, Park Chang-Min, Kim Yu-Il, Lim Sung-Chul, Park Kyung-Ok
Lung and Esophageal Cancer Clinic, Chonnam National University Hwasun Hospital, 160 Ilsim-ri, Hwasun, Jeollanam-do, 519-809 South Korea.
Clin Cancer Res. 2005 Mar 15;11(6):2244-51. doi: 10.1158/1078-0432.CCR-04-2081.
Gefitinib, an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor, has a response rate of 10% to 20% in refractory non-small cell lung carcinoma. Although female gender, adenocarcinoma, and never having smoked are possible markers of a favorable response, mutations of the EGFR gene have also been reported to be highly significant predictors of response. Seventy patients with relapsed non-small cell lung carcinoma were enrolled in the Expanded Access Program. After the drug became available commercially, 28 more patients were treated with gefitinib. Response evaluations were feasible in 80 patients. Twenty-seven tumor specimens (8 responders and 19 nonresponders) were available for the sequence analysis of the EGFR gene. The response rate was 25% (20/80) and the disease control rate (remission + stable disease) was 47.5% (38/80). The response rate was significantly higher for adenocarcinoma (41.0%) versus non-adenocarcinoma (9.8%, P = 0.001), in those who never smoked (58.8%) versus smokers (15.9%, P < 0.001), and in females (42.1%) versus males (19.7%, P = 0.049). A deletion or mutation of the EGFR gene was found in six of eight responders. Remission was noted in all patients with a mutation, whereas the response rate was 9.5% (2/21) in patients without a mutation (P < 0.001). The predictors of response showed significant correlations with survival and time to progression. In a multivariate logistic analysis, the independent predictors of response were smoking history and adenocarcinoma. Given that 9.5% of smokers and 6.7% of those with non-adenocarcinoma showed a mutation of the EGFR gene, the genetic profile may replace those variables as an independent predictor of a response.
吉非替尼是一种表皮生长因子受体（EGFR）酪氨酸激酶抑制剂，在难治性非小细胞肺癌中的缓解率为10%至20%。虽然女性、腺癌和从不吸烟可能是缓解的有利标志，但EGFR基因突变也被报道为缓解的高度显著预测指标。70例复发的非小细胞肺癌患者参加了扩大可及项目。该药物上市后，又有28例患者接受了吉非替尼治疗。80例患者可行疗效评估。27份肿瘤标本（8例缓解者和19例未缓解者）可用于EGFR基因序列分析。缓解率为25%（20/80），疾病控制率（缓解+疾病稳定）为47.5%（38/80）。腺癌患者的缓解率（41.0%）显著高于非腺癌患者（9.8%，P = 0.001），从不吸烟者（58.8%）高于吸烟者（15.9%，P < 0.001），女性患者（42.1%）高于男性患者（19.7%，P = 0.049）。8例缓解者中有6例发现EGFR基因缺失或突变。所有有突变的患者均出现缓解，而无突变患者的缓解率为9.5%（2/21）（P < 0.001）。缓解预测指标与生存和疾病进展时间显著相关。在多因素逻辑分析中，缓解的独立预测指标是吸烟史和腺癌。鉴于9.5%的吸烟者和6.7%的非腺癌患者存在EGFR基因突变，基因特征可能会取代这些变量成为缓解的独立预测指标。
