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Colorectal cancer
Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer
  1. R Jover1,
  2. P Zapater2,
  3. A Castells3,
  4. X Llor4,
  5. M Andreu5,
  6. J Cubiella6,
  7. V Piñol3,
  8. R M Xicola4,
  9. L Bujanda7,
  10. J M Reñé8,
  11. J Clofent9,
  12. X Bessa5,
  13. J D Morillas10,
  14. D Nicolás-Pérez11,
  15. A Payá12,
  16. C Alenda12,
  17. for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association
  1. 1Department of Gastroenterology. Hospital General Universitario de Alicante, Alicante, Spain
  2. 2Department of Clinical Pharmacology, Hospital General Universitario de Alicante, Alicante, Spain
  3. 3Department of Gastroenterology, Institut de Malaties Digestives, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
  4. 4Germans Trias i Pujol Hospital, Universitat Autonoma de Barcelona, Badalona, Spain
  5. 5Department of Gastroenterology, Hospital del Mar, Barcelona, Spain
  6. 6Department of Gastroenterology, Hospital Cristal Piñor, Orense, Spain
  7. 7Department of Gastroenterology, Hospital Donostia, San Sebastian, Spain
  8. 8Department of Gastroenterology, Hospital Arnau de Vilanova, Lleida, Spain
  9. 9Department of Gastroenterology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
  10. 10Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
  11. 11Department of Gastroenterology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
  12. 12Department of Pathology, Hospital General Universitario de Alicante, Alicante, Spain
  1. Correspondence to:
    Dr R Jover
    Gastroenterology Department, Hospital General Universitario de Alicante, C/ Pintor Baeza, sn 03010 Alicante, Spain; jover_rod{at}gva.es

Abstract

Aim: Some retrospective studies have shown a lack of benefit of 5-fluorouracil (5-FU) adjuvant chemotherapy in patients with mismatch repair (MMR) deficient colorectal cancer. Our aim was to assess if this molecular marker can predict benefit from 5-FU adjuvant chemotherapy. A second objective was to determine if MMR status influences short term survival.

Methods: We included 754 patients with a median follow up of 728.5 days (range 1–1097). A total of 260 patients with stage II or III tumours received 5-FU adjuvant chemotherapy, according to standard clinical criteria and irrespective of their MMR status. A tumour was considered MMR deficient when either BAT-26 showed instability or there was loss of MLH1 or MSH2 protein expression.

Results: At the end of the follow up period, 206 patients died and 120 presented with tumour recurrence. Sixty six (8.8%) patients had MMR deficient tumours. There were no significant differences in overall survival (MMR competent 72.1%; MMR deficient 78.8%; p = 0.3) or disease free survival (MMR competent 61.3%; MMR deficient 72.3%; p = 0.08). In patients with stage II and III tumours, benefit from 5-FU adjuvant chemotherapy was restricted to patients with MMR competent tumours (overall survival: chemotherapy 87.1%; non-chemotherapy 73.5%; log rank, p = 0.00001). Patients with MMR deficient tumours did not benefit from adjuvant chemotherapy (overall survival: chemotherapy 89.5%; non-chemotherapy 82.4%; log rank, p = 0.4).

Conclusions: Benefit from 5-FU adjuvant chemotherapy depends on the MMR status of tumours in patients with colorectal cancer. 5-FU adjuvant chemotherapy improves survival in patients with MMR competent tumours but this benefit from chemotherapy cannot be extended to patients with MMR deficient tumours.

  • MMR, mismatch repair
  • 5-FU, 5-fluorouracil
  • MSI, microsatellite instability
  • TNM, tumour, node, metastases
  • colorectal cancer
  • mismatch repair system
  • prognosis
  • treatment
  • 5-fluorouracil

https://doi.org/10.1136/gut.2005.073015

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    Footnotes

    • Published online first 18 November 2005

    • This work was supported by grants from the Fondo de Investigación Sanitaria (FIS 01/0104) and from the Instituto de Salud Carlos III (RC03/02 and RC03/10). Xavier Llor is a recipient of a Ramon y Cajal grant from Ministerio de Ciencia y Tecnología of the Spanish government. Virgínia Piñol received a research grant from the Institut d’Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS).

    • Conflict of interest: None declared.

    • All authors for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association are listed in the appendix.

    • This work was presented in part as a poster at the 2004 Digestive Diseases Week meeting, New Orleans, LA, USA.

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