Medical Oncology

, Volume 27, Issue 4, pp 1277–1285

The effect of DNA mismatch repair (MMR) status on oxaliplatin-based first-line chemotherapy as in recurrent or metastatic colon cancer

Authors

  • Seung Tae Kim
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Jeeyun Lee
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Se Hoon Park
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Joon Oh Park
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Ho Yeong Lim
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Won Ki Kang
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Jin Yong Kim
    • Divisions of Gastroenterology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Young Ho Kim
    • Divisions of Gastroenterology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Dong Kyung Chang
    • Divisions of Gastroenterology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Poong-Lyul Rhee
    • Divisions of Gastroenterology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Dae Shick Kim
    • Department of Pathology, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Haeran Yun
    • Department of Surgery, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Yong Beom Cho
    • Department of Surgery, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Hee Cheol Kim
    • Department of Surgery, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Seong Hyeon Yun
    • Department of Surgery, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Ho-Kyung Chun
    • Department of Surgery, Samsung Medical CenterSungkyunkwan University School of Medicine
  • Woo Yong Lee
    • Department of Surgery, Samsung Medical CenterSungkyunkwan University School of Medicine
    • Division of Hematology-Oncology, Department of Medicine, Samsung Medical CenterSungkyunkwan University School of Medicine
Original Paper

DOI: 10.1007/s12032-009-9374-x

Cite this article as:
Kim, S.T., Lee, J., Park, S.H. et al. Med Oncol (2010) 27: 1277. doi:10.1007/s12032-009-9374-x

Abstract

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.

Keywords

MMRMSICAPOXFOLFOX

Copyright information

© Springer Science+Business Media, LLC 2009