目的观察吉非替尼或厄洛替尼常规剂量继发性耐药的晚期非小细胞肺癌（ NSCLC）患者接受高剂量相应表皮生长因子受体酪氨酸激酶抑制剂（ EGFR⁃TKI）脉冲治疗的疗效及安全性。方法收集2013年8月至2014年12月42例吉非替尼或厄洛替尼常规治疗1年后出现耐药的NSCLC患者，其中吉非替尼组29例，一次性给予相应4倍剂量的吉非替尼（1000 mg／次），4天为1个周期；厄洛替尼组13例，一次性给予相应3倍剂量的厄洛替尼（450 mg／次），3天为1个周期。治疗直至出现疾病进展或不可耐受的毒性反应。比较两种药物治疗的近期疗效和无进展生存期（ PFS）。结果42例初始接受吉非替尼或厄洛替尼治疗1年后出现疾病进展的患者中位PFS为30个月；其中，吉非替尼组为31个月，厄洛替尼组为24个月，两组差异无统计学意义（P＞0�05）。经高剂量EGFR⁃TKI脉冲治疗后，全组获PR 8例、SD 11例、PD 23例，有效率（RR）为19�0％，疾病控制率（ DCR）为45�2％，中位PFS为6个月。其中吉非替尼组获PR 6例、SD 9例、PD 14例，中位PFS为8个月；厄洛替尼组获PR 2例、SD 2例、PD 9例，中位PFS为6个月；两组比较差异均无统计学意义（ P＞0�05）。按EGFR外显子突变情况分组，Exon 19突变组获PR 4例、SD 6例、PD 17例，Exon 21突变组获PR 4例、SD 5例、PD 6例；两组中位PFS分别为6个月和7个月，差异无统计学意义（ P＞0�05）。毒副反应均为1～2级，主要表现为皮疹、乏力、纳差和皮肤干燥等，两组毒副反应发生率的差异无统计学意义（ P＞0�05）。结论对于吉非替尼或厄洛替尼常规剂量治疗后出现进展的晚期NSCLC患者，高剂量EGFR⁃TKI脉冲治疗能使部分患者再次获益，可能是一种安全有效的治疗方法。%Objective To observe the efficacy and safety of pulsatile administration of high⁃dose gefitinib or erlotinib for ad⁃vanced non⁃small cell lung cancer( NSCLC) patients with secondary drug resistance to standard dose of epidermal growth factor receptor tyrosine kinase inhibitor( EGFR⁃TKI) treatment. Methods Forty⁃two cases of NSCLC patients with drug resistance after 1⁃year con⁃ventional treatment of gefitinib or erlotinib were recruited in this study from August 2013 to December 2014. The gefitinib group, inclu⁃ding 29 cases, received one dose of 1000 mg gefitinib every four days. The erlotinib group, including 13 cases, received one dose of 450 mg erlotinib every three days. Treatments continued till disease progression or development of intolerable toxicity. The short⁃term ef⁃ficacy and progression⁃free survival( PFS) were compared between the two groups. Results The median PFS of the total 42 cases was 30 months, with 31 months in gefitinib group and 24 months in erlotinib group, respectively. No significant difference was observed in the two groups in PFS( P>0�05) . After the high⁃dose pulsatile administration, the total group had 8 cases of PR, 11 cases of SD and 23 case of PD. Meanwhile, the response rate( RR) was 19�0%, the disease control rate( DCR) was 45�2%,the median PFS was 6 months. Gefitinib group had 6 cases of PR, 9 cases of SD and 14 cases of PD. The erlotinib group had 2 cases of PR, 2 cases of SD and 9 cases of PD. The median PFS of gefitinib and erlotinib group was 8 months and 6 months, respectively, with no significant differ⁃ ence( P>0�05) . All cases were divided to 2 groups based on the mutation of EGFR exon. Exon 19 mutation group had 4 cases of PR, 6 cases of SD and 17 cases of PD. Exon 21 mutation group had 4 cases of PR, 5 cases of SD and 6 cases of PD. The median PFS of two groups were 6 months and 7 months, respectively, with no significant difference(P>0�05). Adverse reactions were all in grade 1⁃2, such as rash, fatigue, anorexia and dry skin were observed. The incidence had no difference between the two groups( P>0�05) . Con⁃clusion For advanced NSCLC patients who have previously undergone a standard dose treatment of gefitinib or erlotinib, high⁃dose EGFR⁃TKI pulsatile treatment is a safe and efficient choice, which can improve prognosis of a portion of the patients.
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