培美曲塞联合吉非替尼治疗EGFR-TKI二线治疗失败非小细胞肺癌的疗效
The effect of pemetrexed combined with gefitinib in the treatment of advanced NSCLC with second-line treatment of EGFＲ-TKI
-
摘要: 目的:探讨培美曲塞联合吉非替尼继续治疗表皮生长因子受体-酪氨酸激酶抑制剂(EGFR-TKI)二线治疗失败的非小细胞肺癌(NSCLC)患者的疗效及安全性。方法:对接受EGFR-TKI(厄洛替尼/吉非替尼)二线治疗失败的Ⅲb/Ⅳ期28例NSCLC患者,以培美曲塞联合吉非替尼继续治疗:培美曲塞500 mg/m2d1,吉非替尼250 mg/d,21 d为1周期,治疗至进展。结果:中位随访时间12. 4个月,28例中有1例不可评价疗效,其余患者中完全缓解率为0. 0%、部分缓解37. 0%、疾病稳定44. 4%、疾病进展18. 5%;疾病控制率为81. 5%,总体有效率为37. 0%;中位无疾病进展时间和中位生存时间分别为7. 0个月和13. 6个月;1年无肿瘤进展生存率和1年生存率分别为33. 3%和55. 6%。Ⅲ度以上皮疹的发生率为14. 3%。结论:培美曲塞联合吉非替尼继续治疗EGFR-TKI二线治疗失败的NSCLC疗效良好,且耐受可。
-
关键词:
- 癌,非小细胞肺 /
- 吉非替尼 /
- 培美曲塞 /
- 表皮生长因子受体-酪氨酸激酶抑制剂
Abstract: Objective: To investigate the effects and safety of pemetrexed combined with gefitinib in the treatment of patients with advanced non-small-cell lung cancer( NSCLC) with second-line treatment of epidermal growth factor receptor-tyrosine kinase inhibitor ( EGFr-TKI) . Methods: Twenty-eight patients with stage Ⅲb /Ⅳ NSCLC treated with second-line treatment of EGFr-TKI( gefitinib /erlotinib) were treated with 500 mg /m2 of pemetrexed and 250 mg of gefitinib per day( 21 days each cycle) until these cases were improved. Results: The median follow-up time was 12. 4 months， except 1 case without evaluation， complete response in 0. 0%，partial response in 37. 0%， stabilization of the disease in 44. 4% and progression of disease in 18. 5% were found. The disease control and total effective rates were 81. 5% and 37. 0%， respectively. The time of median without disease progression and survival time were 7. 0 months and 13. 6 months， respectively. No tumor progression and survival rate of 1 year were 33. 3% and 55. 6%， respectively. The occurrence rate of skin rash with more grade Ⅲ was 14. 3%. Conclusions: The effects and tolerance of pemetrexed combined with gefitinib in the treatment of patients with advanced NSCLC with second-line treatment of EGFr-TKI are good. -
[1] Spira A，Etting DS. Multidisciplinary management of lung cancer[J]. N Engl J Med，2004，350(4) : 379 － 392. [2] 张力. 晚期非小细胞肺癌的二线治疗进展[J]. 中国肺癌杂志，2 008，11(1) : 4 － 9. [3] Kosaka T，Yatabe Y，Endoh H，et al. Analysis of epidermal growth factor receptor gene mutation in patients with non-small cell lung cancer and acquired resistance to gefitinib[J]. Clin Cancer Res，2006，12(19) : 5764 － 5769. [4] Chmielecki J，Foo J，Oxnard GR，et al. Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling[J]. Sci Transl Med，2011，3 (90) : 90ra59. [5] Engelman JA，Zejnullahu K，Mitsudomi T，et al. MET amplification leads to gefitinib resistance in lung cancer by activating ERBB3 signaling[J]. Science，2007，316(5827) : 1039 － 1043. [6] Yano S，Wang W，Li Q，et al. Hepatocyte growth factor induces gefitinib resistance of lung adenocarcinoma with epidermal growth factor receptor-activating mutations [J]. Cancer Res，2008，68(22) : 9479 － 9487. [7] Takezawa K，Okamoto I，Okamoto W，et al. Thymidylate synthase as a determinant of pemetrexed sensitivity in non-small cell lung cancer[J]. Br J Cancer，2011，104(10) : 1594 － 1601. [8] Adjei AA. Pharmacology and mechanism of action of pemetrexed [J]. Clin Lung Cancer，2004，5(Suppl 2) : S51 － S55. [9] Scagliotti GV，Parikh P，von Pawel J，et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naive patients with advanced-stage non-small-cell lung cancer[J]. J Clin Oncol，2008，26 (21 ) :3543 － 3551. [10] Peterson P，Simms L，Park K，et al. Is pemetrexed more effective in patients with non-squamous histology? A retrospective analysis of a phase III trial of pemetrexed vs docetaxel in previously treated patients with advanced non-small cell lung cancer(NSCLC) [J]. Eur J Cancer，2007，5(4) : 363 － 364. [11] Riely GJ，Kris MG，Zhao B，et al. Prospective assessment of discontinuation and reinitiation of erlotinib or gefitinib in patients with acquired resistance to erlotinib or gefitinib followed by the addition of everolimus[J]. Clin Cancer Res，2007，13 (17 ) :5150 － 5155. [12] Okabe T，Okamoto I，Tsukioka S，et al. Synergistic antitumor effect of S-1 and the epidermal growth factor receptor inhibitor gefitinib in non-small cell lung cancer cell lines: role of gefitinibinduced down-regulation of thymidylate synthase[J]. Mol Cancer Ther，2008，7(3) : 599 － 606. [13] Wu SG，Yang CH，Yu CJ，et al. Good response to pemetrexed in patients of lung adenocarcinoma with epidermal growth factor receptor(EGFR) mutations[J]. Lung Cancer，2011，72 (3 ) :333 － 339. [14] Douillard JY，Shepherd FA，Hirsh V，et al. Molecular predictors of outcome with gefitinib and docetaxel in previously treated nonsmall- cell lung cancer: data from the randomized phase Ⅲ INTEREST trial[J]. J Clin Oncol，2010，28(5) : 744 － 752. -
点击查看大图
计量
- 文章访问数: 2988
- HTML全文浏览量: 292
- PDF下载量: 113
- 被引次数: 0
下载:
