Survival after adjuvant 5-FU treatment for stage III colon cancer in hereditary nonpolyposis colorectal cancer.

Abstract

In vitro studies suggest that a deficient mismatch repair (MMR) system reduces 5-Fluorouracil cytotoxicity. Colon cancer (CC) in hereditary nonpolyposis colorectal cancer (HNPCC) is due to a dysfunctioning MMR gene that leads to microsatellite instability (MSI). Clinical studies on the efficacy of 5-Fluorouracil (5-FU) in MSI high tumours are contradictory. In a retrospective study, we compared the survival of subjects with stage III CC from HNPCC families that were treated with and without adjuvant 5-FU. The Dutch HNPCC family registry was used. Information on adjuvant chemotherapy for stage III CC was obtained from subjects of families with a mutation and/or who fulfilled the AMS criteria or who were strongly suspicious for HNPCC. CC specific survival was calculated. Observation time was measured either until the date of death, date of a second primary CC or until the closing date of the study, i.e., June 1, 2001. Statistical analysis was done by Kaplan-Meier survival analysis. A total of 92 subjects with stage III CC were included. Twenty-eight of them (17 males) had adjuvant treatment with 5-FU. The median follow-up was 4 (range: 1-17) years; 8 subjects died of CC. The 5-year survival was 70% (95% Cl: 49-90). Sixty-four subjects (36 males) did not have adjuvant therapy. Their median follow-up was 6 (range: 0-23) years. Twenty of them died of CC. The 5-year survival in this group was also 70% (95% Cl: 59-83). To date, the selection of patients with CC for 5-FU treatment is based on the stage rather than the biology of the tumour. In our study, the 5-year survival of subjects treated with and without adjuvant 5-FU did not differ. Further studies are necessary to elucidate the role of MSI in 5-FU treatment of MSI-H tumours in HNPCC.

• Authors: Wouter H de Vos tot Nederveen Cappel, Hielke J Meulenbeld, Jan H Kleibeuker, Fokko M Nagengast, Fred H Menko, Gerrit Griffioen, Annemiek Cats, Hans Morreau, Hans Gelderblom, Hans F A Vasen
• Journal: International journal of cancer (Int J Cancer) Vol. 109 Issue 3 Pg. 468-71 (Apr 10 2004) ISSN: 0020-7136 [Print] United States
• PMID: 14961589 (Publication Type: Journal Article)
• Copyright: Copyright 2004 Wiley-Liss, Inc.

Chemical References

• Antineoplastic Agents
• Fluorouracil

Topics

• Adult
• Antineoplastic Agents (therapeutic use)
• Chemotherapy, Adjuvant
• Colonic Neoplasms (drug therapy, mortality, pathology)
• Colorectal Neoplasms, Hereditary Nonpolyposis (drug therapy, mortality, pathology)
• Female
• Fluorouracil (therapeutic use)
• Follow-Up Studies
• Genetic Predisposition to Disease
• Humans
• Male
• Microsatellite Repeats
• Middle Aged
• Neoplasm Staging
• Prognosis
• Retrospective Studies
• Survival Rate