小分子酪氨酸激酶抑制剂和培美曲塞二钠互为二三线治疗晚期肺腺癌的临床研究

Comparison of the efficacy of second line EGFR TKIs followed by third line pemetrexed or the reverse sequence in the treatment of advanced lung adenocarcinoma

目的比较晚期肺腺癌患者采用表皮生长因子酪氨酸激酶抑制剂（EGFR-TKIs）和培美曲塞互为二、三线治疗是否存在优先顺序。方法回顾性分析标准一线治疗失败的83例晚期肺腺癌患者的临床资料，并分为A组（45例）和B组（38例）。A组患者在接受EGFR-TKIs二线治疗失败后接受培美曲塞三线治疗，B组患者在接受培美曲塞二线治疗失败后接受EGFR-TKIs三线治疗。结果A组和B组患者二线治疗后的PFS分别为8．05个月（95％C15．90-10．20个月）和4．20个月（95％CI3．33-5．06个月，P=0．001），吸烟和不吸烟患者二线治疗后的PFS分别为3．69个月（95％CU5．00-7．59个月）和7．12个月（95％C15．51-8．38个月，P=0．007），男性患者和女性患者二线治疗后的PFS分别为5．56个月（95％C14．02-7．10个月）和6．85个月（95％CI4．98-7．58个月，P=0．279）。A组和B组患者三线治疗后的PFS分别为6．88个月（95％CI5．07-8．69个月）和7．60个月（95％CI5．59-9．12个月，P=0．899），吸烟和不吸烟患者三线治疗后的PFS分别为4．95个月（95％C12．83-7．05个月）和8．49个月（95％C16．27-10．76个月，P=0．050），男性患者与女性患者三线治疗后的PFS分别为5．96个月（95％C14．02-7．91个月）和8．38个月（95％CI5．68-11．07个月，P：0．176）。A组和B组患者的MST分别为23．60个月（95％C119．23-28．00个月）和15．58个月（95％CI11．85-19．32个月，P=0．021），吸烟和不吸烟患者的MST分别为11．99个月（95％CI8．55-15．49个月）和23．18个月（95％CI19．33-27．02个月，P=0．001），男性患者与女性患者的MST分别为17．40个月（95％CI13．19-21．61个月）和22．74个月（95％CI18．29-27．19个月，P=0．111）。结论一线治疗失败的晚期肺腺癌患者，EGFR-TKIs二线治疗失败后选择培美曲塞三线治疗较培美曲塞二线治疗失败后选择EGFR-TKIs治疗更能延长患者的PFS和MST，且更为合理。吸烟为肺腺癌预后的独立危险因素（P=0．012）。

Objective To compare the efficacy of second-line EGFR-TKIs followed by third-line pemetrexed with second-line pemetrexed followed by third-line EGFR-TKIs in patients with advanced lung adenocarcinoma. Methods From March 2007 to August 2008, 83 patients with advanced lung adenocarcinoma who failed standard first-line chemotherapy were included in this study. The patients who received EGFR-TKIs as second-line therapy followed by third-line pemetrexed were designated as group A （n = 45）. The patients who received pemetrexed as second-line therapy followed by third-line EGFR-TKIs were designated as group B （ n = 38）. PFS and MST were estimated with Kaplan-Meier analysis and the difference between groups were compared with Log-rank test. Results The progression-free survival （PFS） after second-line therapy in the groups A and B was 8.05 months （95% CI, 5.90 to 10.20） and 4.20 months （95% CI, 3.33 to 5.06）, respectively （P =0. 001 ）. The PFS after second-line therapy in smokers and non-smokers was 3.69 months （95% CI, 5. O0 to 7.59） and 7. 12 months （95% CI. 5.51 to 8.38）,respectively （P =0.007）. The PFS of male and female patients was 5.56 months （95% CI, 4.02 to 7.10） and 6.85 months （95% CI, 4.98 to 7.58）, respectively （P =0. 279）. The PFS after third-line therapy in groups A and B was 6.88 months （95% CI, 5.07 to 8.69） and 7.60 months （95% CI, 5.59 to 9.12） respectively, （ P = 0. 899）. The PFS after third-line therapy in smokers and non-smokers was 4.95 months （ 95 % CI, 2.83 to 7.05 ） and 8.49 months （95 % CI, 6.27 to 10.76 ）, respectively （ P = 0. 050）. The PFS after third-line therapy in male and female patients was 5.96 months （95% CI, 4.02 to 7.91 ） amd 8.38 months （95% CI, 5.68 toll. 07）, respectively （P =0. 176）. The MST in groups A and B was 23.60 months （95%CI, 19.23 to 28.00） and 15.58 months （95% CI, 11.85 to 19.32）, respectively （P = 0.021）. The MST in smokers and non-smokers was 11.99 months （95% CI, 8.55 to 15.49） and 23.18 months （95% CI, 19.33 to 27.02）, respectively （P = 0.001 ）. The MST in male and female patients was 17.40 months （95 % CI, 13.19 to 21.61 ） and 22.74 months （95 % CI, 18.29 to 27.19）, respectively （P = 0.111 ）. Conclusions Second line EGFR TKIs followed by third line pemetrexed regimen improves the PFS and MST compared with the regimen second line pemetrexed followed by third line EGFR TKIs in patients with advanced lung adenocarcinoma. Smoking status is an independent prognostic factor. Survival is not influenced by ~ender. Prosoective clinical trials are needed to confirm these findinas.