title: The effect of DNA mismatch repair (MMR) status on oxaliplatin-based first-line chemotherapy as in recurrent or metastatic colon cancer.
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.
authors: 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.
authors: Seung Tae
authors: ST
authors: Kim
authors: Jeeyun
authors: J
authors: Lee
authors: Se Hoon
authors: SH
authors: Park
authors: Joon Oh
authors: JO
authors: Park
authors: Ho Yeong
authors: HY
authors: Lim
authors: Won Ki
authors: WK
authors: Kang
authors: Jin Yong
authors: JY
authors: Kim
authors: Young Ho
authors: YH
authors: Kim
authors: Dong Kyung
authors: DK
authors: Chang
authors: Poong-Lyul
authors: PL
authors: Rhee
authors: Dae Shick
authors: DS
authors: Kim
authors: Haeran
authors: H
authors: Yun
authors: Yong Beom
authors: YB
authors: Cho
authors: Hee Cheol
authors: HC
authors: Kim
authors: Seong Hyeon
authors: SH
authors: Yun
authors: Ho-Kyung
authors: HK
authors: Chun
authors: Woo Yong
authors: WY
authors: Lee
authors: Young Suk
authors: YS
authors: Park
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D000069287:Capecitabine; D015179:Colorectal Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D053843:DNA Mismatch Repair / Q000187:drug effects*; D003841:Deoxycytidine / Q000008:administration & dosage / Q000031:analogs & derivatives; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage / Q000031:analogs & derivatives; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D007262:Infusions, Intravenous; D002955:Leucovorin / Q000008:administration & dosage; D008297:Male; D053842:Microsatellite Instability / Q000187:drug effects*; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds / Q000008:administration & dosage; D000077150:Oxaliplatin; D016133:Polymerase Chain Reaction; D011379:Prognosis; D015996:Survival Rate; D055815:Young Adult
chemical_list: D009944:Organoplatinum Compounds; D000077150:Oxaliplatin; D003841:Deoxycytidine; D000069287:Capecitabine; D002955:Leucovorin; D005472:Fluorouracil