World Journal of Surgery

, Volume 37, Issue 10, pp 2497–2503

Oncologic Outcomes after Adjuvant Chemotherapy Using FOLFOX in MSI-H Sporadic Stage III Colon Cancer

  • Seung Yeop Oh
  • Do Yoon Kim
  • Young Bae Kim
  • Kwang Wook Suh
Article

Abstract

Background

Little is known of the oncological outcomes after adjuvant FOLFOX chemotherapy in patients with stage III colon cancer showing microsatellite instability high (MSI-H). In the present study we investigated the prognostic impact of MSI-H in patients with stage III colon cancer receiving FOLFOX chemotherapy.

Methods

We analyzed the MSI status in 127 patients with stage III colon cancer who underwent curative surgical resection followed by FOLFOX chemotherapy between January 2003 and December 2010. We assessed disease-free and overall survival (OS) in patients with MSI-H colon cancer compared with those showing microsatellite instability low or microsatellite stable (MSI-L/MSS) disease.

Results

Sixteen of the patients (12.6 %) were MSI-H, and 111 patients (87.4 %) were MSI-L/MSS. There was no significant difference between patients showing MSI-H and MSI-L/MSS except for age (P = 0.030), tumor location (P < 0.001), and differentiation (P = 0.031). Compared with MSI-L/MSS colon cancer, patients with MSI-H colon cancer had no significant difference in 5-year disease-free and OS (72.2 vs 68.5 %, P = 0.874; 68.1 vs 71.1 %, P = 0.437).

Conclusions

Our study indicates that FOLFOX chemotherapy can be considered to treat stage III colon cancer patients with MSI-H after surgery, although the study was not randomized and included only a limited number of patients.

References

  1. 1.
    O’Connell MJ, Mailliard JA, Kahn MJ et al (1997) Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol 15:246–250PubMedGoogle Scholar
  2. 2.
    André T, Boni C, Mounedji-Boudiaf L et al (2004) Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 350:2343–2351PubMedCrossRefGoogle Scholar
  3. 3.
    Popat S, Hubner R, Houlston RS (2005) Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 23:609–618PubMedCrossRefGoogle Scholar
  4. 4.
    Carethers JM, Chauhan DP, Fink D et al (1999) Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 117:123–131PubMedCrossRefGoogle Scholar
  5. 5.
    Meyers M, Wagner MW, Hwang HS et al (2001) Role of the hMLH1 DNA mismatch repair protein in fluoropyrimidine-mediated cell death and cell cycle responses. Cancer Res 61:5193–5201PubMedGoogle Scholar
  6. 6.
    Kim GP, Colangelo LH, Wieand HS et al (2007) Prognostic and predictive roles of high-degree microsatellite instability in colon cancer: a National Cancer Institute-National Surgical Adjuvant Breast and Bowel Project Collaborative Study. J Clin Oncol 25:767–772PubMedCrossRefGoogle Scholar
  7. 7.
    Hemminki A, Mecklin JP, Järvinen H et al (2000) Microsatellite instability is a favorable prognostic indicator in patients with colorectal cancer receiving chemotherapy. Gastroenterology 119:921–928PubMedCrossRefGoogle Scholar
  8. 8.
    Elsaleh H, Joseph D, Grieu F et al (2000) Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355:1745–1750PubMedCrossRefGoogle Scholar
  9. 9.
    Ribic CM, Sargent DJ, Moore MJ et al (2003) Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247–257PubMedCrossRefGoogle Scholar
  10. 10.
    Sargent DJ, Marsoni S, Monges G et al (2010) Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer. J Clin Oncol 28:3219–3226PubMedCrossRefGoogle Scholar
  11. 11.
    Carethers JM, Smith EJ, Behling CA et al (2004) Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 126:394–401PubMedCrossRefGoogle Scholar
  12. 12.
    Deschoolmeester V, Baay M, Specenier P et al (2010) A review of the most promising biomarkers in colorectal cancer: one step closer to targeted therapy. Oncologist 15:699–731PubMedCrossRefGoogle Scholar
  13. 13.
    Nash GM, Gimbel M, Cohen AM et al (2010) KRAS mutation and microsatellite instability: two genetic markers of early tumor development that influence the prognosis of colorectal cancer. Ann Surg Oncol 17:416–424PubMedCrossRefGoogle Scholar
  14. 14.
    Jernvall P, Mäkinen MJ, Karttunen TJ et al (1999) Loss of heterozygosity at 18q21 is indicative of recurrence and therefore poor prognosis in a subset of colorectal cancers. Br J Cancer 79:903–908PubMedCrossRefGoogle Scholar
  15. 15.
    Michel S, Benner A, Tariverdian M et al (2008) High density of FOXP3-positive T cells infiltrating colorectal cancers with microsatellite instability. Br J Cancer 99:1867–1873PubMedCrossRefGoogle Scholar
  16. 16.
    Des Guetz G, Schischmanoff O, Nicolas P et al (2009) Does microsatellite instability predict the efficacy of adjuvant chemotherapy in colorectal cancer? A systematic review with meta-analysis. Eur J Cancer 45:1890–1896PubMedCrossRefGoogle Scholar
  17. 17.
    Lanza G, Gafà R, Santini A et al (2006) Immunohistochemical test for MLH1 and MSH2 expression predicts clinical outcome in stage II and III colorectal cancer patients. J Clin Oncol 24:2359–2367PubMedCrossRefGoogle Scholar
  18. 18.
    Elsaleh H, Iacopetta B (2001) Microsatellite instability is a predictive marker for survival benefit from adjuvant chemotherapy in a population-based series of stage III colorectal carcinoma. Clin Colorectal Cancer 1:104–109PubMedCrossRefGoogle Scholar
  19. 19.
    Liang JT, Huang KC, Lai HS et al (2002) High-frequency microsatellite instability predicts better chemosensitivity to high-dose 5-fluorouracil plus leucovorin chemotherapy for stage IV sporadic colorectal cancer after palliative bowel resection. Int J Cancer 101:519–525PubMedCrossRefGoogle Scholar
  20. 20.
    Meyers M, Wagner MW, Mazurek A et al (2005) DNA mismatch repair-dependent response to fluoropyrimidine-generated damage. J Biol Chem 280:5516–5526PubMedCrossRefGoogle Scholar
  21. 21.
    Fink D, Nebel S, Aebi S et al (1996) The role of DNA mismatch repair in platinum drug resistance. Cancer Res 56:4881–4886PubMedGoogle Scholar
  22. 22.
    Vaisman A, Varchenko M, Umar A et al (1998) The role of hMLH1, hMSH3, and hMSH6 defects in cisplatin and oxaliplatin resistance: correlation with replicative bypass of platinum-DNA adducts. Cancer Res 58:3579–3585PubMedGoogle Scholar
  23. 23.
    Miquel C, Jacob S, Grandjouan S et al (2007) Frequent alteration of DNA damage signalling and repair pathways in human colorectal cancers with microsatellite instability. Oncogene 26:5919–5926PubMedCrossRefGoogle Scholar
  24. 24.
    Loire E, Praz F, Higuet D et al (2009) Hypermutability of genes in Homo sapiens due to the hosting of long mono-SSR. Mol Biol Evol 26:111–121PubMedCrossRefGoogle Scholar
  25. 25.
    Martin LP, Hamilton TC, Schilder RJ (2008) Platinum resistance: the role of DNA repair pathways. Clin Cancer Res 14:1291–1295PubMedCrossRefGoogle Scholar
  26. 26.
    Kim ST, Lee J, Park SH et al (2010) Clinical impact of microsatellite instability in colon cancer following adjuvant FOLFOX therapy. Cancer Chemother Pharmacol 66:659–667PubMedCrossRefGoogle Scholar
  27. 27.
    Sinicrope FA, Sargent DJ (2009) Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol 21:369–373PubMedCrossRefGoogle Scholar
  28. 28.
    Zaanan A, Cuilliere-Dartigues P, Guilloux A et al (2010) Impact of p53 expression and microsatellite instability on stage III colon cancer disease-free survival in patients treated by 5-fluorouracil and leucovorin with or without oxaliplatin. Ann Oncol 21:772–780PubMedCrossRefGoogle Scholar
  29. 29.
    Zaanan A, Fléjou JF, Emile JF et al (2011) Defective mismatch repair status as a prognostic biomarker of disease-free survival in stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy. Clin Cancer Res 17:7470–7478PubMedCrossRefGoogle Scholar

Copyright information

© Société Internationale de Chirurgie 2013

Authors and Affiliations

  • Seung Yeop Oh
    • 1
  • Do Yoon Kim
    • 1
  • Young Bae Kim
    • 2
  • Kwang Wook Suh
    • 1
  1. 1.Department of SurgeryAjou University School of MedicineSuwonKorea
  2. 2.Department of PathologyAjou University School of MedicineSuwonKorea

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