Department of Internal Medicine, Knappschaftskrankenhaus, Ruhr-University Bochum, Bochum, Germany.
BMC Cancer. 2012 Aug 9;12:349. doi: 10.1186/1471-2407-12-349.
To evaluate the value of KRAS codon 13 mutations in patients with advanced colorectal cancer (advanced CRC) treated with oxaliplatin and fluoropyrimidines.
Tumor specimens from 201 patients with advanced CRC from a randomized, phase III trial comparing oxaliplatin/5-FU vs. oxaliplatin/capecitabine were retrospectively analyzed for KRAS mutations. Mutation data were correlated to response data (Overall response rate, ORR), progression-free survival (PFS) and overall survival (OS).
201 patients were analysed for KRAS mutation (61.2% males; mean age 64.2 ± 8.6 years). KRAS mutations were identified in 36.3% of tumors (28.8% in codon 12, 7.4% in codon 13). The ORR in codon 13 patients compared to codon 12 and wild type patients was significantly lower (p = 0.008). There was a tendency for a better overall survival in KRAS wild type patients compared to mutants (p = 0.085). PFS in all patients was not different in the three KRAS genetic groups (p = 0.72). However, we found a marked difference in PFS between patients with codon 12 and 13 mutant tumors treated with infusional 5-FU versus capecitabine based regimens.
Our data suggest that the type of KRAS mutation may be of clinical relevance under oxaliplatin combination chemotherapies without the addition of monoclonal antibodies in particular when overall response rates are important.
2002-04-017.
评估 KRAS 密码子 13 突变在接受奥沙利铂和氟嘧啶治疗的晚期结直肠癌（晚期 CRC）患者中的价值。
回顾性分析 201 例来自一项比较奥沙利铂/5-FU 与奥沙利铂/卡培他滨的随机、III 期试验的晚期 CRC 患者的肿瘤标本中的 KRAS 突变。将突变数据与反应数据（总缓解率，ORR）、无进展生存期（PFS）和总生存期（OS）相关联。
对 201 例患者进行了 KRAS 突变分析（61.2%为男性；平均年龄 64.2±8.6 岁）。肿瘤中发现 KRAS 突变 36.3%（密码子 12 为 28.8%，密码子 13 为 7.4%）。与密码子 12 和野生型患者相比，密码子 13 患者的 ORR 显著降低（p=0.008）。KRAS 野生型患者的总生存时间明显优于突变型患者（p=0.085）。在三个 KRAS 遗传组中，所有患者的 PFS 无差异（p=0.72）。然而，我们发现密码子 12 和 13 突变型肿瘤患者在接受输注 5-FU 与卡培他滨方案治疗时，PFS 存在显著差异。
我们的数据表明，在不添加单克隆抗体的情况下，KRAS 突变类型可能在奥沙利铂联合化疗中具有临床相关性，尤其是在总反应率很重要的情况下。
2002-04-017。
