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结直肠癌患者接受辅助 FOLFOX 治疗时 K-ras 突变的临床影响。

Clinical impact of K-ras mutation in colorectal cancer patients treated with adjuvant FOLFOX.

机构信息

Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea, School of Medicine, Seoul, Korea.

出版信息

Cancer Chemother Pharmacol. 2011 Aug;68(2):317-23. doi: 10.1007/s00280-010-1496-5. Epub 2010 Oct 24.

DOI:10.1007/s00280-010-1496-5
PMID:20972872
Abstract

BACKGROUND

K-ras proto-oncogene is commonly mutated in colorectal cancer (CRC) and has been associated with predictive markers for anti-EGFR (epidermal growth factor receptor) therapy. However, the prognostic role of K-ras status is still unclear. The aim of this study was to evaluate the association between k-ras status and addition of oxaliplatin to fluorouracil plus leucovorin (FOLFOX) chemotherapy in CRC patients with curative surgical resection.

METHODS

Sixty-six patients with stage II or III CRC were treated with FOLFOX or fluorouracil plus leucovorin (FL) followed by curative surgery between January 2004 and October 2007. K-ras status was assessed by direct sequencing.

RESULTS

Fifteen patients (22.7%) had K-ras mutations of codon 12 (11/15) or codon 13 (4/15). There were no significant differences in clinicopathological parameters, such as age, sex, stage, or adjuvant regimen between the wild-type K-ras and mutant K-ras. With a median follow-up of 41.6 months (range 25.1-72.3 months), median disease-free survival (DFS) and overall survival (OS) were not reached. With regard to K-ras status, DFS and OS were not statistically different (P = 0.269 and P = 0.917, respectively). Even in the group treated with FOLFOX only, neither DFS (P = 0.651) nor OS (P = 0.265) was significantly different according to K-ras status. With the exception of tumor location in DFS and OS, no differences in other variables were observed. Proximal colon cancer patients had a longer DFS than distal CRC patients (P = 0.079); this trend was maintained only in the wild-type K-ras group (P = 0.051).

CONCLUSIONS

These results showed that K-ras status was not associated with clinical outcome in patients treated with adjuvant FOLFOX.

摘要

背景

K-ras 原癌基因在结直肠癌(CRC)中经常发生突变,并且与抗表皮生长因子受体(EGFR)治疗的预测标志物相关。然而,K-ras 状态的预后作用仍不清楚。本研究旨在评估 K-ras 状态与奥沙利铂联合氟尿嘧啶加亚叶酸(FOLFOX)化疗在接受根治性手术切除的 CRC 患者中的关系。

方法

2004 年 1 月至 2007 年 10 月期间,66 例 II 期或 III 期 CRC 患者接受 FOLFOX 或氟尿嘧啶加亚叶酸(FL)治疗,然后进行根治性手术。通过直接测序评估 K-ras 状态。

结果

15 例患者(22.7%)存在密码子 12(11/15)或密码子 13(4/15)的 K-ras 突变。野生型 K-ras 和突变型 K-ras 之间的临床病理参数(如年龄、性别、分期或辅助治疗方案)无显著差异。中位随访 41.6 个月(范围 25.1-72.3 个月),无疾病进展生存(DFS)和总生存(OS)未达到。关于 K-ras 状态,DFS 和 OS 无统计学差异(P = 0.269 和 P = 0.917)。即使在仅接受 FOLFOX 治疗的组中,根据 K-ras 状态,DFS(P = 0.651)和 OS(P = 0.265)也无显著差异。除了 DFS 和 OS 中的肿瘤位置外,其他变量没有差异。在 DFS 和 OS 中,近端结肠癌患者的生存时间长于远端 CRC 患者(P = 0.079);这种趋势仅在野生型 K-ras 组中维持(P = 0.051)。

结论

这些结果表明,在接受辅助 FOLFOX 治疗的患者中,K-ras 状态与临床结局无关。

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