Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, 50 Irwon-dong, Gangnam-gu, Seoul, 135-710, South Korea.
Med Oncol. 2010 Dec;27(4):1277-85. doi: 10.1007/s12032-009-9374-x. Epub 2009 Dec 1.
Colon cancer with DNA mismatch repair (MMR) defects reveals distinct clinical and pathologic features, including a better prognosis but reduced response to 5-fluorouracil (5-FU)-based chemotherapy. A current standard treatment for recurrent or metastatic colon cancer uses capecitabine plus oxaliplatin (CAPOX), or continuous-infusion fluorouracil plus oxaliplatin (FOLFOX). This study investigated the effect of MMR status on the treatment outcomes for CAPOX and FOLFOX as first-line combination chemotherapy in recurrent or metastatic colon cancer. We analyzed 171 patients who had been treated with CAPOX or FOLFOX as first-line combination chemotherapy in recurrent or metastatic colon adenocarcinoma between February 2004 and July 2008. Tumor expression of the MMR proteins, MLH1 and MSH2, was detected by immunohistochemistry (IHC) in surgically resected tumor specimens. The microsatellite instability (MSI) was analyzed by polymerase chain reaction (PCR) amplification, using fluorescent dye-labeled primers specific to microsatellite loci. Tumors with MMR defect were defined as those demonstrating a loss of MMR protein expression (MMR-D) and/or a microsatellite instability-high (MSI-H) genotype. In all, 75 patients (44%) received FOLFOX, and 96 patients (56%) received CAPOX as first-line combination chemotherapy. The incidence of colon cancer with MMR defect was 10/171 (6%). Colon cancers with MMR defect (MSI-H and/or MMR-D) are more commonly located in proximal to the splenic flexure (p=0.03). The MMR status did not significantly influence the overall response (p=0.95) to first-line CAPOX or FOLFOX treatment in patients with recurrent or metastatic colon cancer. According to the MMR status, there was no significant difference for PFS (p=0.50) and OS (p=0.47) in patients with recurrent or metastatic colon cancer treated with first-line CAPOX or FOLFOX. In colon cancers with MMR defect, there was no significant difference for PFS (p=0.48) and OS (p=0.56) between CAPOX and FOLFOX as first-line combination chemotherapy. However, in MMR intact, there was significant difference for OS between CAPOX and FOLFOX (p=0.04). OS was significantly better in patients treated with CAPOX when compared to patients with FOLFOX. The MMR status does not predict the effect of oxaliplatin-based combination chemotherapy as 1st line in recurrent or metastatic colon cancers. CAPOX in the first-line treatment of recurrent or metastatic colon cancer with MMR intacts showed a superior OS compared with FOLFOX unlike colon cancer with MMR defects.
结直肠癌伴有 DNA 错配修复 (MMR) 缺陷表现出明显的临床和病理特征，包括更好的预后，但对基于 5-氟尿嘧啶 (5-FU) 的化疗反应降低。目前，复发性或转移性结直肠癌的标准治疗方法是使用卡培他滨加奥沙利铂 (CAPOX) 或持续输注氟尿嘧啶加奥沙利铂 (FOLFOX)。本研究旨在探讨 MMR 状态对 CAPOX 和 FOLFOX 作为复发性或转移性结直肠腺癌一线联合化疗的治疗结果的影响。我们分析了 2004 年 2 月至 2008 年 7 月期间接受 CAPOX 或 FOLFOX 作为复发性或转移性结直肠腺癌一线联合化疗的 171 例患者。通过免疫组织化学 (IHC) 检测手术切除的肿瘤标本中 MMR 蛋白 MLH1 和 MSH2 的表达。通过聚合酶链反应 (PCR) 扩增，使用针对微卫星位点的荧光染料标记引物分析微卫星不稳定性 (MSI)。将显示 MMR 蛋白表达缺失 (MMR-D) 和/或微卫星不稳定高 (MSI-H) 基因型的肿瘤定义为 MMR 缺陷肿瘤。共有 75 例患者 (44%)接受 FOLFOX 治疗，96 例患者 (56%)接受 CAPOX 作为一线联合化疗。结直肠癌 MMR 缺陷的发生率为 10/171 (6%)。MMR 缺陷的结直肠癌 (MSI-H 和/或 MMR-D) 更常见于脾曲近端 (p=0.03)。MMR 状态对复发性或转移性结直肠癌患者一线 CAPOX 或 FOLFOX 治疗的总体反应无显著影响 (p=0.95)。根据 MMR 状态，复发性或转移性结直肠癌患者接受一线 CAPOX 或 FOLFOX 治疗后，PFS (p=0.50)和 OS (p=0.47)无显著差异。在 MMR 缺陷的结直肠癌中，CAPOX 和 FOLFOX 作为一线联合化疗的 PFS (p=0.48)和 OS (p=0.56)无显著差异。然而，在 MMR 完整的情况下，CAPOX 和 FOLFOX 之间的 OS 有显著差异 (p=0.04)。与接受 FOLFOX 治疗的患者相比，接受 CAPOX 治疗的患者的 OS 显著更好。在复发性或转移性结直肠癌中，MMR 状态不能预测奥沙利铂为基础的联合化疗的效果。在 MMR 完整的复发性或转移性结直肠癌中，与 FOLFOX 相比，CAPOX 一线治疗的 OS 明显优于 FOLFOX。而在 MMR 缺陷的结直肠癌中，CAPOX 和 FOLFOX 的 OS 无显著差异。
