Oxaliplatin in Colon Cancer
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《新英格兰医药杂志》
To the Editor: André et al. (June 3 issue)1 report that adding oxaliplatin to a regimen of fluorouracil plus leucovorin (FL) improves the adjuvant treatment of colon cancer. With regard to patients with stage II disease, previous studies have indicated that obstruction of the colon by tumor, the total number of lymph nodes examined, carcinoembryonic antigen levels, perforation, and the tumor grade can identify patients at high risk for recurrence.2,3 If one considers Figure 3 of the article by André et al., patients with these risk factors seemed to receive little benefit. It is not clear from this study how we can change our clinical practice with regard to patients with stage II colon cancer. In addition, it is not clear why promising molecular markers, including microsatellite instability, allelic loss of chromosome 18q, and tumor expression of thymidylate synthase, were not included in this study.
Mario Mandalà, M.D.
Treviglio Hospital
24047 Treviglio, Italy
mariomandala@tin.it
Gianluigi Ferretti, M.D.
Istituto Regina Elena
00144 Rome, Italy
Sandro Barni, M.D.
Treviglio Hospital
24047 Treviglio, Italy
References
André T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343-2351.
Wolmark N, Fisher B, Wieand HS, et al. The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer: results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg 1984;199:375-382.
Steinberg SM, Barkin JS, Kaplan RS, Stablein DM. Prognostic indicators of colon tumors: the Gastrointestinal Tumor Study Group experience. Cancer 1986;57:1866-1870.
The authors reply: Recently reported studies have shown that patients with stage II colon cancer can benefit from adjuvant FL.1,2 We compared FL with oxaliplatin plus FL in patients with stage II or III disease. Like most trials in this setting, ours was not powered to show a statistically significant improvement in stage II colon cancer.3 We analyzed data from patients with stage II disease who had at least one adverse prognostic factor (stage T4, obstruction, perforation, a poorly differentiated tumor, venous invasion, <10 lymph nodes analyzed).4 In this subpopulation, a 28 percent decrease in the risk of relapse was observed for patients receiving oxaliplatin plus FL (hazard ratio, 0.72 [95 percent confidence interval, 0.48 to 1.08]; three-year rate of disease-free survival; 84.9 percent vs. 79.8 percent), with limited toxicity — findings that are in line with the results in patients with stage III disease (a 24 percent decrease in the risk of relapse). No study of molecular markers was performed, since no samples were collected prospectively. When chemotherapy is recommended for a patient with stage II disease on the basis of individual risk assessment,5 physicians must be aware of the extra benefit from the addition of oxaliplatin to FL.
Aimery de Gramont, M.D.
H?pital Saint Antoine
75012 Paris, France
aimery.de-gramont@sat.ap-hop-paris.fr
Thierry André, M.D.
H?pital Tenon
75970 Paris, France
Tamas Hickish, M.D.
Dorset Cancer Center
Bournemouth BH15 2JB, United Kingdom
References
Gray RG, Barnwell J, Hills R, et al. QUASAR: a randomized study of adjuvant chemotherapy (CT) vs observation including 3238 colorectal cancer patients. J Clin Oncol 2004;22:245s-245s. abstract.
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 2004;22:1797-1806.
Buyse M, Piedbois P. Should Dukes' B patients receive adjuvant therapy? A statistical perspective. Semin Oncol 2001;28:Suppl 1:20-24.
Hickish T, Boni C, Navarro M, et al. FOLFOX4 as adjuvant treatment for stage II colon cancer (CC): subpopulation data from the MOSAIC trial. J Clin Oncol 2004;22:274s-274s. abstract.
Benson AB III, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004;22:3408-3419.
Mario Mandalà, M.D.
Treviglio Hospital
24047 Treviglio, Italy
mariomandala@tin.it
Gianluigi Ferretti, M.D.
Istituto Regina Elena
00144 Rome, Italy
Sandro Barni, M.D.
Treviglio Hospital
24047 Treviglio, Italy
References
André T, Boni C, Mounedji-Boudiaf L, et al. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med 2004;350:2343-2351.
Wolmark N, Fisher B, Wieand HS, et al. The prognostic significance of preoperative carcinoembryonic antigen levels in colorectal cancer: results from NSABP (National Surgical Adjuvant Breast and Bowel Project) clinical trials. Ann Surg 1984;199:375-382.
Steinberg SM, Barkin JS, Kaplan RS, Stablein DM. Prognostic indicators of colon tumors: the Gastrointestinal Tumor Study Group experience. Cancer 1986;57:1866-1870.
The authors reply: Recently reported studies have shown that patients with stage II colon cancer can benefit from adjuvant FL.1,2 We compared FL with oxaliplatin plus FL in patients with stage II or III disease. Like most trials in this setting, ours was not powered to show a statistically significant improvement in stage II colon cancer.3 We analyzed data from patients with stage II disease who had at least one adverse prognostic factor (stage T4, obstruction, perforation, a poorly differentiated tumor, venous invasion, <10 lymph nodes analyzed).4 In this subpopulation, a 28 percent decrease in the risk of relapse was observed for patients receiving oxaliplatin plus FL (hazard ratio, 0.72 [95 percent confidence interval, 0.48 to 1.08]; three-year rate of disease-free survival; 84.9 percent vs. 79.8 percent), with limited toxicity — findings that are in line with the results in patients with stage III disease (a 24 percent decrease in the risk of relapse). No study of molecular markers was performed, since no samples were collected prospectively. When chemotherapy is recommended for a patient with stage II disease on the basis of individual risk assessment,5 physicians must be aware of the extra benefit from the addition of oxaliplatin to FL.
Aimery de Gramont, M.D.
H?pital Saint Antoine
75012 Paris, France
aimery.de-gramont@sat.ap-hop-paris.fr
Thierry André, M.D.
H?pital Tenon
75970 Paris, France
Tamas Hickish, M.D.
Dorset Cancer Center
Bournemouth BH15 2JB, United Kingdom
References
Gray RG, Barnwell J, Hills R, et al. QUASAR: a randomized study of adjuvant chemotherapy (CT) vs observation including 3238 colorectal cancer patients. J Clin Oncol 2004;22:245s-245s. abstract.
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 2004;22:1797-1806.
Buyse M, Piedbois P. Should Dukes' B patients receive adjuvant therapy? A statistical perspective. Semin Oncol 2001;28:Suppl 1:20-24.
Hickish T, Boni C, Navarro M, et al. FOLFOX4 as adjuvant treatment for stage II colon cancer (CC): subpopulation data from the MOSAIC trial. J Clin Oncol 2004;22:274s-274s. abstract.
Benson AB III, Schrag D, Somerfield MR, et al. American Society of Clinical Oncology recommendations on adjuvant chemotherapy for stage II colon cancer. J Clin Oncol 2004;22:3408-3419.