Clinical identification of colorectal cancer patients benefiting from adjuvant uracil–tegafur (UFT): a randomized controlled trial
Tóm tắt
A randomized controlled trial was conducted to determine whether pathologic necrosis in response to preoperative treatment with uracil–tegafur(UFT) could be used to identify patients with colorectal cancer most likely to benefit from postoperative adjuvant therapy with the drug. The 152 patients with colorectal cancer who received preoperative UFT at a dose of 600 mg/day for at least 10 days were classified into two groups according to the pathologic necrosis in resected tumor specimens: 90% or more necrosis (sensitive) versus less than 90% necrosis (insensitive). After excluding 13 ineligible patients, the remaining 139 were then randomly assigned to receive postoperative adjuvant UFT (400 mg/day) for 12 months or no treatment. Preoperative and postoperative UFT produced no serious toxicity in any of the patients. Among the 22 patients with sensitive tumors, overall survival was significantly better in the UFT group (n = 12) than in the control (n = 10) (100 vs. 70.0%; P = 0.023). Among the 117 patients with insensitive tumors, there was no significant difference between the two groups (n = 60, 68.1% vs. n = 57, 76.6%; P = 0.373). Our method involving neoadjuvant UFT can identify patients most likely to benefit from postoperative UFT, as well as those unlikely to benefit from such treatment.
Tài liệu tham khảo
Bleiberg H (1998) Oxaliplatin (L-OHP): a new reality in colorectal cancer. Br J Cancer 77(Suppl 4):1–3
Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P et al (2000) Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet 355:1041–1047. doi:10.1016/S0140-6736(00)02034-1
Eilber FC, Rosen G, Eckaradt J, Forscher C, Nelson SD, Selch M et al (2001) Treatment-induced pathologic necrosis: a predictor of local recurrence and survival in patients receiving neoadjuvant therapy for high-grade extremity soft tissue sarcomas. J Clin Oncol 19:3203–3209
Fujii M, Kochi M, Kasakura Y (2000) Randomized trial of adjuvant chemotherapy by the results of histopathologic evaluation of patients with operable colorectal cancer following preoperative chemotherapy using UFT. J Clin Oncol 19:abstract 257a
Fujii S, Kitano S, Ikenaka K, Shirasaka T (1979) Effect of coadministration of uracil or cytosine on the anti-tumor activity of clinical doses of 1-(2-tetrahydrofulyl)-5-fluorouracil and level of 5-fluorouracil in rodents. Gann 70:209–214
Goldberg RM, Sargent DJ, Morton RF, Fuchs CS, Ramanathan RK, Williamson SK et al (2004) A randomized controlled trial of fluorouracil plus leucovorin, irinotecan and oxaliplatin combination in patients with previously untreated metastatic colorectal cancer. J Clin Oncol 22:23–30. doi:10.1200/JCO.2004.09.046
Hamaguchi T (2007) Adjuvant chemotherapy with uracil–tegafur (UFT) for stage III colorectal cancer: final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC) ASCO 2007, abstract #4049
Ikenaka K, Shirasaka T, Kitano S, Fujii S (1979) Effect of uracil on metabolism of 5-fluorouracil in vitro. Gann 70:353–359
Lembersky BC, Wieand HS, Petrelli NJ, O’Connell MJ, Colangelo LH, Smith RE et al (2006) Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol 24:2059–2064. doi:10.1200/JCO.2005.04.7498
Ota K, Taguchi T, Kimura K (1988) Report on nationwide pooled data and cohort investigation in UFT phase II study. Cancer Chemother Pharmacol 22:333–338. doi:10.1007/BF00254241
Pazdur R (1997) Phase II study of UFT plus leucovorin in colorectal cancer. Oncology 54(Suppl 1):19–23
Picci P, Bohling T, Bacci G, Ferrari S, Sangiorgi L, Mercuri M et al (1997) Chemotherapy-induced tumor necrosis as a prognostic factor in localized Ewing’s sarcoma of extremities. J Clin Oncol 15:1553–1559
Punt CJ (1998) New drugs in the treatment of colorectal carcinoma. Cancer 83:679–689. doi:10.1002/(SICI)1097-0142(19980815)83:4<679::AID-CNCR8>3.0.CO;2-F
Thirion P, Michiels S, Pignon JP, Buyse M, Braud AC, Carlson RW et al (2004) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: an updated meta-analysis. J Clin Oncol 22:3766–3775. doi:10.1200/JCO.2004.03.104
Tournigand C, Andre T, Achille E, Liedo G, Flesh M, Mery-Mignard D et al (2004) FOLFIRI followed by FOLFOX6 or the reverse sequence in advanced colorectal cancer: a randomized GEOCOR study. J Clin Oncol 22:229–237. doi:10.1200/JCO.2004.05.113