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Journal of Clinical Oncology, Vol 23, No 3 (January 20), 2005: pp. 653-654 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.190
Re: Pooled Analysis of Fluorouracil-Based Adjuvant Therapy of Stage II and III Colon Cancer: Who Benefits and by How Much?Department of Radiation Oncology and Experimental Biology, David Geffen School of Medicine at University of California Los Angeles, Los Angeles, CA
School of Surgery and Pathology, University of Western Australia, Nedlands, Australia To the Editor: Contrary to the conclusions of Gill et al,1 we believe that the findings from their pooled analysis of benefit of fluorouracil-based adjuvant therapy for stage II and III colon cancer patients support our earlier observations.2 Our population-based study also found benefit from adjuvant chemotherapy in stage III right-sided colon cancers (proximal to splenic flexure) for both men and women. However, we also reported that patients with left-sided colon (distal to splenic flexure) and rectal cancer gained substantially less benefit, if any, from adjuvant chemotherapy. While the differential survival benefits for site subgroups and sex subgroups correlated with the presence of microsatellite instability (MSI-H or MSI positive), we also noted a survival benefit from adjuvant chemotherapy in the MSI-negative, or microsatellite-stable, patient group. We therefore hypothesized that a more common phenotype that was nevertheless closely related to the MSI-positive phenotype may be responsible for survival benefit achieved with fluorouracil-based chemotherapy in population-based colorectal cancer trials. At the time, we speculated that this might be the cytosine-phosphate-guanine island methylator phenotype because of known sex and site differences in its frequency; we recently published direct evidence in support of this hypothesis.3 We urge workers in this field to give careful consideration to the site of tumor origin when comparing their results with our earlier observations. It is also important to bear in mind that results obtained with the highly selected and generally younger patients who enter clinical trials may be different than those seen in population-based studies. This is an essential consideration if age-, sex- and tumor-site-related phenomena such as aberrant folate metabolism and DNA methylation are involved in the response to fluorouracil-based therapies. Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES
1. Gill S, Loprinzi CL, Sargent DJ, et al: Pooled analysis of fluorouracil-based adjuvant therapy for stage II and III colon cancer: Who benefits and by how much? J Clin Oncol 22:1797-1806, 2004 2. Elsaleh H, Joseph D, Grieu F, et al: Association of tumour site and sex with survival benefit from adjuvant chemotherapy in colorectal cancer. Lancet 355:1745-1750, 2000[CrossRef][Medline]
3. Van Rijnsoever M, Elsaleh H, Joseph D, et al: CpG island methylator phenotype is an independent predictor of survival benefit from 5-fluorouracil in stage III colorectal cancer. Clin Cancer Res 9:2898-2903, 2003
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Copyright © 2005 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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