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Title of Journal: Med Oncol

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Abbravation: Medical Oncology

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Springer US

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DOI

10.1007/s40134-015-0106-z

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ISSN

1559-131X

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The effect of DNA mismatch repair MMR status on

Authors: Seung Tae Kim Jeeyun Lee Se Hoon Park Joon Oh Park Ho Yeong Lim Won Ki Kang Jin Yong Kim Young Ho Kim Dong Kyung Chang PoongLyul Rhee Dae Shick Kim Haeran Yun Yong Beom Cho Hee Cheol Kim Seong Hyeon Yun HoKyung Chun Woo Yong Lee Young Suk Park
Publish Date: 2009/12/01
Volume: 27, Issue: 4, Pages: 1277-1285
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Abstract

Colon cancer with DNA mismatch repair MMR defects reveals distinct clinical and pathologic features including a better prognosis but reduced response to 5fluorouracil 5FUbased chemotherapy A current standard treatment for recurrent or metastatic colon cancer uses capecitabine plus oxaliplatin CAPOX or continuousinfusion fluorouracil plus oxaliplatin FOLFOX This study investigated the effect of MMR status on the treatment outcomes for CAPOX and FOLFOX as firstline combination chemotherapy in recurrent or metastatic colon cancer We analyzed 171 patients who had been treated with CAPOX or FOLFOX as firstline 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 dyelabeled primers specific to microsatellite loci Tumors with MMR defect were defined as those demonstrating a loss of MMR protein expression MMRD and/or a microsatellite instabilityhigh MSIH genotype In all 75 patients 44 received FOLFOX and 96 patients 56 received CAPOX as firstline combination chemotherapy The incidence of colon cancer with MMR defect was 10/171 6 Colon cancers with MMR defect MSIH and/or MMRD are more commonly located in proximal to the splenic flexure p = 003 The MMR status did not significantly influence the overall response p = 095 to firstline 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 = 050 and OS p = 047 in patients with recurrent or metastatic colon cancer treated with firstline CAPOX or FOLFOX In colon cancers with MMR defect there was no significant difference for PFS p = 048 and OS p = 056 between CAPOX and FOLFOX as firstline combination chemotherapy However in MMR intact there was significant difference for OS between CAPOX and FOLFOX p = 004 OS was significantly better in patients treated with CAPOX when compared to patients with FOLFOX The MMR status does not predict the effect of oxaliplatinbased combination chemotherapy as 1st line in recurrent or metastatic colon cancers CAPOX in the firstline treatment of recurrent or metastatic colon cancer with MMR intacts showed a superior OS compared with FOLFOX unlike colon cancer with MMR defects

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