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Journal of Clinical Oncology, Vol 23, No 3 (January 20), 2005: pp. 654-655 © 2005 American Society of Clinical Oncology. DOI: 10.1200/JCO.2005.05.260
In ReplyMayo Clinic Cancer Center, Rochester, MN Dr Elsaleh and Dr Iacopetta raise several interesting points in their letter. We do feel that our results show several important distinctions from their earlier work.1 First, in our pooled analysis of 3,302 patients from randomized trials, we found no differential benefit of adjuvant fluorouracil (FU) -based therapy, founded on either tumor location or sex.2 Data on microsatellite instability (MSI) status were not available for patients in our study, as routine assessment of MSI had not been a standard part of clinical testing when patients were enrolled in the studies used in our analysis. Reports have been inconsistent regarding a differential benefit of FU-based chemotherapy based on MSI status, with reports suggesting that patients with high-level MSI (MSI-H) tumors receive both a greater and a lesser benefit from adjuvant chemotherapy.1,3,4 Future revisions to our analysis may need to take into account the influence of MSI-H on adjuvant therapy when prospective data become available. It is also important to note that the apparent influence of MSI status on adjuvant therapy pertains specifically to FU. As adjuvant therapy evolves to include drugs such as oxaliplatin, we will need to reassess the level of benefit achieved relative to prognostic and predictive factors. We fully agree that further research to define predictive factors for chemotherapy efficacy is vital. Second, the question is raised regarding the generalizability of results obtained from a clinical trial to the general patient population. It is well recognized that clinical trials have traditionally involved less than 5% of patients with cancer.5 Efforts are ongoing to increase accrual to clinical trials and to insure that a representative sample of the population is included. The results presented in our analysis are derived from patients participating in clinical trials conducted through cooperative groups that have relied, in large part, on the participation of community oncologists. While it is possible that this mechanism leads to participation of younger patients with fewer associated health problems, there is no alternative method of assessing the benefits of therapy that approaches the rigors of a randomized clinical trial. Results derived from single-institution experience, or population-based registries, typically rely on a sampling of the population derived primarily from tumor registries. Clinical data from such registries, particularly pertaining to therapy, are limited and are often incomplete. More importantly, treatment allocation is not randomized, subjecting any conclusions regarding the benefit of treatment to possible bias. Of note, the results from the same data set used for our analysis (an individual-patient pooled analysis of multicenter randomized clinical trials), when exploring the benefits of FU-based treatment in the elderly,6 were recently verified in a population-based cohort.7 Authors’ Disclosures of Potential Conflicts of Interest The authors indicated no potential conflicts of interest. REFERENCES 1. 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]
2. 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
3. Lara PU Jr, Higdon R, Lim N, et al: Prospective evaluation of cancer clinical trial accrual patterns: Identifying potential barriers to involvement. J Clin Oncol 19:1728-1733, 2001
4. Ribic CM, Sargent DJ, Moore MJ, et al: Tumor microsatellite-instability status as a predictor of benefit from fluorouracil-based adjuvant chemotherapy for colon cancer. N Engl J Med 349:247-257, 2003
5. Cohen GI: Clinical research by community oncologists. CA Cancer J Clin 53:73-81, 2003
6. Sargent DJ, Goldberg RM, Jacobson SD, et al: A pooled analysis of adjuvant chemotherapy for resected colon cancer in elderly patients. N Engl J Med 345:1091-1097, 2001
7. Sundararajan V, Mitra N, Jacobson JS, et al: Survival associated with 5-fluorouracil-based adjuvant chemotherapy among elderly patients with node-positive colon cancer. Ann Intern Med 136:349-357, 2002 Related Correspondence
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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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