COLORECTAL CANCER

Mismatch repair status in the prediction of benefit from adjuvant fluorouracil chemotherapy in colorectal cancer

R Jover¹, P Zapater², A Castells³, X Llor⁴, M Andreu⁵, J Cubiella⁶, V Piñol³, R M Xicola⁴, L Bujanda⁷, J M Reñé⁸, J Clofent⁹, X Bessa⁵, J D Morillas¹⁰, D Nicolás-Pérez¹¹, A Payá¹², C Alenda¹² for the Gastrointestinal Oncology Group of the Spanish Gastroenterological Association

¹ Department of Gastroenterology. Hospital General Universitario de Alicante, Alicante, Spain
² Department of Clinical Pharmacology, Hospital General Universitario de Alicante, Alicante, Spain
³ Department of Gastroenterology, Institut de Malaties Digestives, Hospital Clínic, IDIBAPS, University of Barcelona, Barcelona, Spain
⁴ Germans Trias i Pujol Hospital, Universitat Autonoma de Barcelona, Badalona, Spain
⁵ Department of Gastroenterology, Hospital del Mar, Barcelona, Spain
⁶ Department of Gastroenterology, Hospital Cristal Piñor, Orense, Spain
⁷ Department of Gastroenterology, Hospital Donostia, San Sebastian, Spain
⁸ Department of Gastroenterology, Hospital Arnau de Vilanova, Lleida, Spain
⁹ Department of Gastroenterology, Complejo Hospitalario Universitario de Vigo, Vigo, Spain
¹⁰ Department of Gastroenterology, Hospital 12 de Octubre, Madrid, Spain
¹¹ Department of Gastroenterology, Hospital Universitario de Canarias, Santa Cruz de Tenerife, Spain
¹² Department of Pathology, Hospital General Universitario de Alicante, Alicante, Spain

Correspondence to:
Dr R Jover
Gastroenterology Department, Hospital General Universitario de Alicante, C/ Pintor Baeza, sn 03010 Alicante, Spain; jover_rod{at}gva.es

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.

Abbreviations: MMR, mismatch repair; 5-FU, 5-fluorouracil; MSI, microsatellite instability; TNM, tumour, node, metastases

Keywords: colorectal cancer; mismatch repair system; prognosis; treatment; 5-fluorouracil

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Authors’ reply

J M Carethers
Gut 2006 55: 1819. [Extract] [Full Text] [PDF]

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