Skip to main content
Log in

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

  • Published:
World Journal of Surgery Aims and scope Submit manuscript

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1

Similar content being viewed by others

References

  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 15:246–250

    PubMed  Google Scholar 

  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 350:2343–2351

    Article  PubMed  Google Scholar 

  3. Popat S, Hubner R, Houlston RS (2005) Systematic review of microsatellite instability and colorectal cancer prognosis. J Clin Oncol 23:609–618

    Article  PubMed  CAS  Google Scholar 

  4. Carethers JM, Chauhan DP, Fink D et al (1999) Mismatch repair proficiency and in vitro response to 5-fluorouracil. Gastroenterology 117:123–131

    Article  PubMed  CAS  Google Scholar 

  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 61:5193–5201

    PubMed  CAS  Google Scholar 

  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 25:767–772

    Article  PubMed  CAS  Google Scholar 

  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 119:921–928

    Article  PubMed  CAS  Google Scholar 

  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 355:1745–1750

    Article  PubMed  CAS  Google Scholar 

  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 349:247–257

    Article  PubMed  CAS  Google Scholar 

  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 28:3219–3226

    Article  PubMed  CAS  Google Scholar 

  11. Carethers JM, Smith EJ, Behling CA et al (2004) Use of 5-fluorouracil and survival in patients with microsatellite-unstable colorectal cancer. Gastroenterology 126:394–401

    Article  PubMed  CAS  Google Scholar 

  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 15:699–731

    Article  PubMed  Google Scholar 

  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 17:416–424

    Article  PubMed  Google Scholar 

  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 79:903–908

    Article  PubMed  CAS  Google Scholar 

  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 99:1867–1873

    Article  PubMed  CAS  Google Scholar 

  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 45:1890–1896

    Article  PubMed  CAS  Google Scholar 

  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 24:2359–2367

    Article  PubMed  CAS  Google Scholar 

  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 1:104–109

    Article  PubMed  CAS  Google Scholar 

  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 101:519–525

    Article  PubMed  CAS  Google Scholar 

  20. Meyers M, Wagner MW, Mazurek A et al (2005) DNA mismatch repair-dependent response to fluoropyrimidine-generated damage. J Biol Chem 280:5516–5526

    Article  PubMed  CAS  Google Scholar 

  21. Fink D, Nebel S, Aebi S et al (1996) The role of DNA mismatch repair in platinum drug resistance. Cancer Res 56:4881–4886

    PubMed  CAS  Google Scholar 

  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 58:3579–3585

    PubMed  CAS  Google Scholar 

  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 26:5919–5926

    Article  PubMed  CAS  Google Scholar 

  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 26:111–121

    Article  PubMed  CAS  Google Scholar 

  25. Martin LP, Hamilton TC, Schilder RJ (2008) Platinum resistance: the role of DNA repair pathways. Clin Cancer Res 14:1291–1295

    Article  PubMed  CAS  Google Scholar 

  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 66:659–667

    Article  PubMed  CAS  Google Scholar 

  27. Sinicrope FA, Sargent DJ (2009) Clinical implications of microsatellite instability in sporadic colon cancers. Curr Opin Oncol 21:369–373

    Article  PubMed  CAS  Google Scholar 

  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 21:772–780

    Article  PubMed  CAS  Google Scholar 

  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 17:7470–7478

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kwang Wook Suh.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Oh, S.Y., Kim, D.Y., Kim, Y.B. et al. Oncologic Outcomes after Adjuvant Chemotherapy Using FOLFOX in MSI-H Sporadic Stage III Colon Cancer. World J Surg 37, 2497–2503 (2013). https://doi.org/10.1007/s00268-013-2120-8

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00268-013-2120-8

Keywords

Navigation