Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan.
Impact of second-line and later cetuximab-containing therapy and KRAS genotypes in patients with metastatic colorectal cancer: a multicenter study in Japan.
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二线及后续含西妥昔单抗治疗和 KRAS 基因型对转移性结直肠癌患者的影响：日本的一项多中心研究。
DOI：
10.1007/s00595-013-0716-0
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发表时间：
2014
期刊：
影响因子：
--
通讯作者：
Maehara Y
中科院分区：
文献类型：
--
作者：
Saeki H;Emi Y;Kumashiro R;Otsu H;Kawano H;Ando K;Ida S;Kimura Y;Tokunaga E;Oki E;Morita M;Shimokawa M;Maehara Y
PurposesThis回顾性研究评估的治疗结果和临床相关性的KRAS突变状态在日本转移性结直肠癌患者治疗与二线和以后的西妥昔单抗含therapeutic.MethodsThe科目包括65例转移性结直肠癌患者接受西妥昔单抗含治疗。在含西妥昔单抗治疗开始时，12例患者的KRAS突变状态已被证实为野生型。采用直接测序法对肿瘤进行回顾性KRAS突变筛查，结果详细分析显示存在24例野生型（57.1%）和18例突变型肿瘤（42.9%）。分别在21例（32.3%）和9例（13.8%）患者中观察到3-4级中性粒细胞减少和贫血。在50例患者（76.9%）中观察到痤疮样皮疹，其中3例患者（4.6%）发生3级皮疹。AKRAS突变与对含西妥昔单抗治疗的耐药性相关（18例突变型和36例野生型患者中分别有11.1%和41.7%的应答者;P= 0.03）。AKRAS突变也与较差的生存期（MST：6.9与14.1个月，18突变型和36野生型患者，分别为;P= 0.018）。结论目前的结果表明，临床相关性ofKRAS突变在预测西妥昔单抗治疗转移性结直肠癌患者在日本人口的疗效。
PurposesThis retrospective study evaluated the treatment outcomes and clinical relevance of theKRASmutation status in Japanese metastatic colorectal cancer patients treated with second-line and later cetuximab-containing therapy.MethodsThe subjects comprised 65 patients with metastatic colorectal cancer who received cetuximab-containing therapy. At the start of cetuximab-containing therapy, theKRASmutation status had been proven to be wild type in 12 patients. Tumors were retrospectively screened forKRASmutations using direct sequencing.ResultsA detailed analysis revealed the presence of 24 wild-type (57.1 %) and 18 mutant tumors (42.9 %). Grade 3–4 neutropenia and anemia were observed in 21 (32.3 %) and nine (13.8 %) patients, respectively. An acne-like rash was observed in 50 patients (76.9 %), and among them three patients (4.6 %) experienced a Grade 3 rash. AKRASmutation was associated with resistance to cetuximab-containing treatment (11.1 vs. 41.7 % responders among 18 mutant and 36 wild-type patients, respectively;P= 0.03). AKRASmutation was also associated with poorer survival (MST: 6.9 vs. 14.1 months in 18 mutant and 36 wild-type patients, respectively;P= 0.018).ConclusionsThe present results indicated the clinical relevance ofKRASmutations in predicting the efficacy of cetuximab-containing therapy for metastatic colorectal patients in the Japanese population.