Affiliation of authors: Department of Hematology/Oncology, University of Arkansas Medical Sciences, Little Rock
Correspondence to: Mir Asif Alikhan, MD, Department of Hematology/Oncology, University of Arkansas Medical Sciences, Little Rock, AR 72205 (e-mail: alikhanmira{at}uams.edu)
We read with great interest the first report on long-term (10-year) outcomes of adjuvant chemotherapy in colon cancer in the Journal (1). The fluorouracil-based regimens in this report demonstrate the benefit of adjuvant chemotherapy for both disease-free and overall survival at 8 years, at which point survival benefits are lost. Tumor resistance, dormancy, and recurrence after extended periods of time have been observed in other tumor types. Administering a limited period of chemotherapy after primary therapy is the current paradigm for treating almost all cancers but, as exemplified by this article, does not appear to have a permanent, sustained, and beneficial effect on the chronic nature of this disease process.
In this regard, prolongation of survival observed in breast cancer patients receiving adjuvant treatments with a combination of short-term adjuvant chemotherapy and prolonged hormonal-based interventions, such as treatment with tamoxifen for 5 years followed by treatment with letrozole (2), may serve as a model for enhancing long-term adjuvant therapy benefits in other tumor types including colon cancer. Although the underlying biologic mechanisms responsible for prolonging survival benefits in breast cancer are likely to be different from other tumor types and are not clearly elucidated, prolonged targeting of estrogen pathways after cytotoxic chemotherapy has clearly been successful.
Colon cancer patients, who appear to lose all survival benefits of fluorouracil-based adjuvant treatments 8 years after primary therapy, may similarly sustain prolonged therapeutic benefits if treated with a well tolerated, easily administered, and cost-effective regimen targeting a component of a critical pathway, such as the epidermal growth factor receptor (3). Expression analysis of targets in the resected primary tumor could serve to guide interventions to prevent the observed loss of long-term survival benefits with adjuvant chemotherapy in colon cancer survivors. Prevention of late relapses is also gaining relevance because of the increasing cancer survivor population in the United States (4).
We commend the authors for bringing to light an issue that directly affects the health of colon cancer survivors and urge that future investigations focus on the role of easily administered, target-based maintenance treatments in patients responding to adjuvant chemotherapy.
REFERENCES
1 Smith RE, Colangelo L, Wieand HS, Begovic M,Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst 2004;96:112832.
2 Goss PE, Ingle JN, Martino S, Robert NJ, Muss HB, Piccart MJ, et al .A randomized trial of letrozole in postmenopausal women after five years of tamoxifen therapy for early-stage breast cancer. N Engl J Med 2003;349:1793802.
3 Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, et al. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med 2004;351:33745.
4 Hewitt M, Breen N, Devesa S. Cancer prevalence and survivorship issues: analyses of the 1992 National Health Interview Survey. J Natl Cancer Inst 1999;91:14806.
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