Asai Hiroaki, Shinozaki Eiji, Nozaki Akira, Watanabe Toshiyasu, Suenaga Mitsukuni, Matuzaka Satoshi, Chin Keisho, Mizunuma Nobuyuki, Yasukawa Masaki, Hatake Kiyohiko
The Cancer Institute Hospital of the Japanese Foundation For Cancer Research.
Gan To Kagaku Ryoho. 2011 Aug;38(8):1285-91.
Mutation of the KRAS gene in patients with metastatic colorectal cancer(mCRC)has been established as a predictive marker of poor response to anti-EGFR cetuximab. The Japanese Society of Medical Oncology recommends that the KRAS mutation status at codon 12 and codon 13 should be genotyped by direct-sequencing or allele-specific PCR. In this study, we tested the point mutation of codon 12 and 13 in the KRAS gene by Luminex(xMAP)flow cytometry with sequence-specific oligonucleotide probes for 39 out of 64 unresectable mCRC patients enrolled from Sep 2008 to Oct 2009, who were administered cetuximab in combination with irinotecan(CPT-11)as third-line therapy. We retrospectively analyzed the relationship between KRAS mutation status and responses to combination therapy. Mutations in the KRAS gene were detected in 38. 5% of cases(codon12: 73%, codon 13: 27%), and the median follow-up time was 8. 2 months(range, 1. 4-15. 2 months). The response rates for patients with KRAS wild-type and patients with KRAS mutations were 33. 3%(95%CI 14. 5-52. 2%)and 0%(p=0. 015); the disease control rates were 75%(95%CI 57. 7-92. 3%)and 40%(95%CI, 15. 2-64. 8%; p=0. 044); the median TTF was 7 months(95%CI 4. 6-9. 3)and 2. 3 months(95%CI 1. 3-3. 2; p=0. 0007), and the median OS was 12. 9 months(95%CI 6. 7-19. 1)and 10. 8 months(95%CI 5. 0-16. 7; p=0. 15), respectively. Therefore, we concluded that the KRAS mutation in mCRC is a predictive factor for the lack of response to combination therapy with cetuximab plus CPT- 11, as reported in previous clinical studies.
转移性结直肠癌（mCRC）患者的KRAS基因突变已被确认为抗表皮生长因子受体（EGFR）西妥昔单抗疗效不佳的预测指标。日本临床肿瘤学会建议，应通过直接测序或等位基因特异性聚合酶链反应（PCR）对KRAS基因第12和13密码子的突变状态进行基因分型。在本研究中，我们采用Luminex（xMAP）流式细胞术，使用序列特异性寡核苷酸探针，检测了2008年9月至2009年10月入组的64例不可切除mCRC患者中39例患者KRAS基因第12和13密码子的点突变情况，这些患者接受西妥昔单抗联合伊立替康（CPT-11）作为三线治疗。我们回顾性分析了KRAS突变状态与联合治疗反应之间的关系。KRAS基因突变在38.5%的病例中被检测到（第12密码子：73%，第13密码子：27%），中位随访时间为8.2个月（范围1.4 - 15.2个月）。KRAS野生型患者和KRAS突变患者的缓解率分别为33.3%（95%可信区间14.5 - 52.2%）和0%（p = 0.015）；疾病控制率分别为75%（95%可信区间57.7 - 92.3%）和40%（95%可信区间15.2 - 64.8%；p = 0.044）；中位至疾病进展时间（TTF）分别为7个月（95%可信区间4.6 - 9.3）和2.3个月（95%可信区间1.3 - 3.2；p = 0.0007），中位总生存期（OS）分别为12.9个月（95%可信区间6.7 - 19.1）和10.8个月（95%可信区间5.0 - 16.7；p =
