晚期肺腺癌EGFR-TKIs对后续培美曲赛化疗的影响

背景与目的培美曲赛和表皮生长因子受体-酪氨酸激酶抑制剂(epidermal growth factor receptor-tyrosine kinase inhibitors,EGFR-TKIs)对于有EGFR基因突变的非小细胞肺癌(non-small cell lung cancer,NSCLC)患者能获得比野生型更好的疗效。本研究旨在通过临床观察肺腺癌患者EGFR-TKIs进展后后续培美曲赛化疗的疗效和毒副反应,分析EGFR-TKIs对后续培美曲赛化疗的影响。方法收集III期和IV期肺腺癌患者,根据有无EGFR-TKIs治疗史分为靶向治疗组和非靶向治疗组。所有患者接受培美曲赛(500 mg/m2),均为二线及二线以上治疗。按照RECIST(Response Evaluation Criteria in Solid Tumors)1.0标准评价培美曲赛疗效,NCI-CTC(National Cancer InstituteCommon Toxicity Criteria)4.0标准评价毒副反应。研究终点为疾病控制率(disease control rate,DCR)、无进展生存期(progression free survival,PFS)和总生存期(overall survival,OS)。结果靶向治疗组57例和非靶向治疗组56例患者,DCR分别为77.2%和67.9%(P=0.367),中位PFS为5.95个月和3.55个月(P=0.535),中位OS为10.10个月和8.24个月(P=0.432),靶向治疗组优于非靶向治疗组,但两组差异无统计学意义。常见毒性反应为I度-II度血液学毒性和胃肠道反应。靶向治疗组有2例患者因不能耐受的毒副反应而中断培美曲赛治疗,非靶向治疗组无因毒副反应而停药者。靶向治疗组和非靶向治疗组各有1例患者因IV度骨髓抑制而减量;分别有5例和9例患者因主观因素治疗延迟,但无严重毒副反应。结论 EGFR-TKIs后续培美曲赛化疗的DCR、PFS和OS有改善趋势,但两组差异无统计学意义;培美曲赛序贯应用具有良好的安全性,可以作为EGFR-TKIs进展后的挽救性治疗。

Effects of EGFT-TKIs on Sequential Pemetrexed for Advanced Pulmonary Adenocarcinoma

Background and objective Pemetrexed and epidermal growth factor receptor(EGFR)-tyrosine kinase inhibitors(TKIs) were used in patients with EGFR mutation to determine their effects.This study analyzed the influence of EGFR-TKIs on pemetrexed by observing the clinical efficacy and toxicity of pemetrexed following responses to EGFR-TKIs.Methods Pulmonary adenocarcinoma patients were divided into EGFR-TKIs and no-EGFR-TKI groups according to the targeted therapy.All patients received pemetrexed(500 mg/m2) as second(or higher)-line treatment.The Response Evaluation Criteria in Solid Tumors(version 1.0) were used to evaluate the response to pemetrexed.Adverse events were classified based on version 4.0 of the National Cancer Institute Common Toxicity Criteria.Results There were 57 patients in the EGFR-TKIs group and 56 in the no-EGFR-TKIs group.The disease control rates(DCRs) were 77.2% and 67.9%(P=0.367).The progression free survival(PFS) periods were 5.95 and 3.55 months(P=0.535).The overall survival(OS) periods were 10.10 and 8.24 months(P=0.432).However,these values were not statistically significant.The common toxicities of pemetrexed were hematologic and gastrointestinal(grades I and II).Two patients in the EGFR-TKIs group discontinued pemetrexed because of severe toxicities,which were not observed in the no-EGFR-TKIs group.Both groups had one patient who reduced dosage because of myelosuppression(grade IV).There were five and nine patients in the EGFR-TKIs and no-EGFR-TKIs groups,respectively,who delayed therapy not because of severe toxicities but due to subjective factors.Conclusion The DCRs,PFS periods,and OS periods of the patients administered with pemetrexed following EGFR-TKIs were better than those of the EGFR-TKIs group,but the differences were not statistically significant.Therefore,sequential pemetrexed administration caused negligible toxicities and can be used in adenocarcinoma therapy following responses to EGFR-TKIs.