FOLFOXIRI联合Kras基因靶向治疗方案对晚期结直肠癌预后的影响
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摘要
目的研究FOLFOXIRI联合Kras基因靶向治疗方案对晚期结直肠癌(CRC)患者预后的影响。方法纳入2013年4月至2015年4月本院80例晚期CRC患者作为研究对象,采用随机数字表法将患者分为两组,每组40例。对照组行常规FOLFOXIRI化疗方案,观察组患者进行Kras基因测序,并在常规FOLFOXIRI化疗基础上根据Kras基因检测结果进行靶向治疗。比较两组近期化疗效果,记录化疗期间毒副反应发生情况,随访记录两组患者化疗后3年生存情况。结果观察组17例发生Kras突变,发生率42. 50%,化疗后肿瘤疾病控制率显著高于对照组,差异有统计学意义(P <0. 05)。两组化疗期间消化道反应、中心粒细胞减少、皮疹、贫血、血小板减少及神经系统症状严重程度比较,差异无统计学意义(P> 0. 05)。两组化疗后3年总生存率差异无统计学意义(Log rank x~2=0. 679,P=0. 410)。观察组化疗后3年无进展生存率显著高于对照组,差异有统计学意义(Log rank x~2=5. 267,P=0. 022)。结论 FOLFOXIRI化疗联合Kras基因靶向治疗方案用于晚期CRC患者可显著改善治疗效果,延长无进展生存期,且具有较高的安全性。
Objective To study effect of FOLFOXIRI combined with Kras gene targeting therapy on prognosis of advanced colorectal cancer( CRC). Methods 80 patients with advanced CRC in our hospital from April 2013 to April 2015 were as the research objects and were divided into two groups by random number table method, 40 cases in each group. The control group received conventional FOLFOXIRI chemotherapy, the Kras gene were sequenced in the observation group and the observation group received targeted therapy, which accorded to Kras gene test results on the basis of conventional FOLFOXIRI chemotherapy. The effects of chemotherapy in the two groups were compared, the occurrence of side effects during chemotherapy were recorded. The 3 years of survival after chemotherapy of two groups were recorded by followed up. Results There were 17 cases of Kras mutation occurred in the observation group, the incidence was 42. 50%, the control rate of tumor disease in the observation group after chemotherapy was significantly higher than that in the control group( P < 0. 05). There were no significant difference in digestive tract reaction,neutropenia, rash, anemia, thrombocytopenia and severity of nervous system symptoms between the two groups during chemotherapy( P> 0. 05). There was no significant difference in the overall survival rate between the two groups after 3 years of chemotherapy( Log rank x~2= 0. 679,P = 0. 410). The progression free survival rate of the observation group was significantly higher than that of the control group in 3 years after chemotherapy,the difference was statistically significant( Log rank x~2= 5. 267,P = 0. 022). Conclusion The FOLFOXIRI chemotherapy combined with Kras gene targeting therapy for advanced CRC patients can significantly improve the treatment effect, prolong progression-free survival, and it has high safety.
Objective To study effect of FOLFOXIRI combined with Kras gene targeting therapy on prognosis of advanced colorectal cancer( CRC). Methods 80 patients with advanced CRC in our hospital from April 2013 to April 2015 were as the research objects and were divided into two groups by random number table method, 40 cases in each group. The control group received conventional FOLFOXIRI chemotherapy, the Kras gene were sequenced in the observation group and the observation group received targeted therapy, which accorded to Kras gene test results on the basis of conventional FOLFOXIRI chemotherapy. The effects of chemotherapy in the two groups were compared, the occurrence of side effects during chemotherapy were recorded. The 3 years of survival after chemotherapy of two groups were recorded by followed up. Results There were 17 cases of Kras mutation occurred in the observation group, the incidence was 42. 50%, the control rate of tumor disease in the observation group after chemotherapy was significantly higher than that in the control group( P < 0. 05). There were no significant difference in digestive tract reaction,neutropenia, rash, anemia, thrombocytopenia and severity of nervous system symptoms between the two groups during chemotherapy( P> 0. 05). There was no significant difference in the overall survival rate between the two groups after 3 years of chemotherapy( Log rank x~2= 0. 679,P = 0. 410). The progression free survival rate of the observation group was significantly higher than that of the control group in 3 years after chemotherapy,the difference was statistically significant( Log rank x~2= 5. 267,P = 0. 022). Conclusion The FOLFOXIRI chemotherapy combined with Kras gene targeting therapy for advanced CRC patients can significantly improve the treatment effect, prolong progression-free survival, and it has high safety.
引文
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[12]刘启志,高显华,傅传刚,等. K-ras基因在结直肠癌中的表达及与病理的关系[J].结直肠肛门外科,2012,18(4):222-224.
[13]Therkildsen C,Bergmann TK,Henrichsenschnack T,et al. The predictive value of KRAS,NRAS,BRAF,PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer:A systematic review and meta-analysis[J]. Acta Oncologica,2014,53(7):852-864.
[14]Laiyemo AO,Brawley O,Irabor D,et al. Towards colorectal cancer control in Africa[J]. International Journal of Cancer,2016,138(4):1033.
[15]Engstrom PF,Arnoletti JP,Benson AB,et al. NCCN clinical practice guideline in oncology:colon cancer[J]. J Natl Comprcane Netw,2009,7(8):778-831.
[16]谢玲,陈劼,孙怡,等.中国结直肠癌、肺癌和胃癌患者KRAS基因突变情况分析[J].临床与实验病理学杂志,2016,32(2):210-213.
[17]张秦,朱有才,鲍晋,等.贝伐珠单抗联合FOLFOX4化疗方案治疗晚期转移性结直肠癌的临床研究[J].中国临床药理学杂志,2015,31(5):345-347.
[18]蔡月,胡华斌,王文静,等.改良FOLFOXIRI方案在晚期结直肠癌患者一线治疗中的安全性和疗效分析[J].中华胃肠外科杂志,2014,17(11):1081-1086.
[19]刘捷,林榕波,范南峰,等.改良FOLFOXIRI方案一线治疗晚期结直肠癌的疗效及生存预后分析[J].现代肿瘤医学,2017,25(7):1083-1088.
[2]Loupakis F,Cremolini C,Salvatore L,et al. FOLFOXIRI plus bevacizumab as first-line treatment in BRAF, mutant metastatic colorectal cancer[J]. European Journal of Cancer,2014,50(1):57-63.
[3]林泽鑫. VEGF靶向治疗及其生物标志物在晚期结直肠癌中的研究进展[J].中国普通外科杂志,2015,24(4):575-580.
[4]彭健,陈颖,董先龙,等. KRAS基因突变与结直肠癌患者临床病理特征及预后的关系[J].中华消化外科杂志,2018,17(2):143-147.
[5]Edge SB,Byrd DR,Compton CC,et al. AJCC cancer staging manual.7th ed. New York Springer,2010.
[6]卫生部病理质控与评价中心.结直肠癌KRAS基因突变检测专家共识[J].中华病理学杂志,2012,41(9):635-636.
[7]Lencioni R. New data supporting modified RECIST(mRECIST)for hepatocellular carcinoma.[J]. Clinical Cancer Research An Official Journal of the American Association for Cancer Research,2013,19(6):1312-1314.
[8]TROTTO,ANDY,COLEVAS,et al. CTCAE v3. 0:development of a comprehensive grading system for the adverse effects of cancer treatment[C]. Seminars in Radiation Onchology,2003:176-181.
[9]薛艺珂.低强度FOLFOXIRI四联化疗方案治疗耐药转移性结直肠癌的试验研究[J].中国普外基础与临床杂志,2015,22(4):390.
[10]邵棋,茅国新,潘小明,等. FOLFOX和FOLFOXIRI方案在Ⅲ期结肠癌辅助化疗中的疗效[J].现代肿瘤医学,2015,23(15):2163-2166.
[11]房静远,陈慧敏,于亚男.肠道菌群与膳食纤维:影响结直肠肿瘤发生的环境因素[J].中华消化杂志,2013,33(3):145-147.
[12]刘启志,高显华,傅传刚,等. K-ras基因在结直肠癌中的表达及与病理的关系[J].结直肠肛门外科,2012,18(4):222-224.
[13]Therkildsen C,Bergmann TK,Henrichsenschnack T,et al. The predictive value of KRAS,NRAS,BRAF,PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer:A systematic review and meta-analysis[J]. Acta Oncologica,2014,53(7):852-864.
[14]Laiyemo AO,Brawley O,Irabor D,et al. Towards colorectal cancer control in Africa[J]. International Journal of Cancer,2016,138(4):1033.
[15]Engstrom PF,Arnoletti JP,Benson AB,et al. NCCN clinical practice guideline in oncology:colon cancer[J]. J Natl Comprcane Netw,2009,7(8):778-831.
[16]谢玲,陈劼,孙怡,等.中国结直肠癌、肺癌和胃癌患者KRAS基因突变情况分析[J].临床与实验病理学杂志,2016,32(2):210-213.
[17]张秦,朱有才,鲍晋,等.贝伐珠单抗联合FOLFOX4化疗方案治疗晚期转移性结直肠癌的临床研究[J].中国临床药理学杂志,2015,31(5):345-347.
[18]蔡月,胡华斌,王文静,等.改良FOLFOXIRI方案在晚期结直肠癌患者一线治疗中的安全性和疗效分析[J].中华胃肠外科杂志,2014,17(11):1081-1086.
[19]刘捷,林榕波,范南峰,等.改良FOLFOXIRI方案一线治疗晚期结直肠癌的疗效及生存预后分析[J].现代肿瘤医学,2017,25(7):1083-1088.