PURPOSE: A wide variety of fluorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical use for the treatment of advanced colorectal cancer. Only the monthly low-dose LV-plus-FU regimen, as used by the North Central Cancer Treatment Group, has demonstrated a lasting survival benefit as opposed to FU alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this regimen for a confirmatory phase III trial but used the same dose-intensity of fluorouracil in both treatment arms. PATIENTS AND METHODS: Patients with inoperable or metastatic colorectal cancer were randomized to receive monthly FU 400 mg/m2/day plus LV 20 mg/m2/day as intravenous push daily for five days, or FU alone. RESULTS:Three hundred nine of the 310 patients randomized were eligible and included in the analysis. The objective response rate for patients with measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors for survival were performance status, weight loss, and disease symptoms. WHO > 2 toxicity, consisting of stomatitis (P = 0.001), diarrhea (P = 0.001), and nausea (P = 0.001), was more pronounced for FU-plus-LV, without fatal events. CONCLUSIONS: This is the largest published randomized trial to compare FU-plus-LV to FU alone in advanced colorectal cancer. It confirms the survival benefit obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU-plus-LV were acceptable to most patients, and they responded well to FU dose reductions. In the absence of an ideal dose-intense FU monotherapy regimen, monthly FU with low-dose LV provides a simple and economical means by which to achieve adequate FU efficacy in the treatment of advanced colorectal cancer.
RCT Entities:
PURPOSE: A wide variety of fluorouracil (FU)-plus-leucovorin (LV) dose schedules are in clinical use for the treatment of advanced colorectal cancer. Only the monthly low-dose LV-plus-FU regimen, as used by the North Central Cancer Treatment Group, has demonstrated a lasting survival benefit as opposed to FU alone (J Clin Oncol 1989; 7: 1407-1417). The Swiss Cancer Group adopted this regimen for a confirmatory phase III trial but used the same dose-intensity of fluorouracil in both treatment arms. PATIENTS AND METHODS: Patients with inoperable or metastatic colorectal cancer were randomized to receive monthly FU 400 mg/m2/day plus LV 20 mg/m2/day as intravenous push daily for five days, or FU alone. RESULTS: Three hundred nine of the 310 patients randomized were eligible and included in the analysis. The objective response rate for patients with measurable disease was 9% with FU alone and 22% with FU-plus-LV (P = 0.0001). The median progression-free survival was 3.9 versus 6.2 months (P = 0.003) and the overall survival 10 versus 12.4 months (P = 0.02). The major prognostic factors for survival were performance status, weight loss, and disease symptoms. WHO > 2 toxicity, consisting of stomatitis (P = 0.001), diarrhea (P = 0.001), and nausea (P = 0.001), was more pronounced for FU-plus-LV, without fatal events. CONCLUSIONS: This is the largest published randomized trial to compare FU-plus-LV to FU alone in advanced colorectal cancer. It confirms the survival benefit obtained from biomodulating monthly FU with low-dose LV. The toxic effects of FU-plus-LV were acceptable to most patients, and they responded well to FU dose reductions. In the absence of an ideal dose-intense FU monotherapy regimen, monthly FU with low-dose LV provides a simple and economical means by which to achieve adequate FU efficacy in the treatment of advanced colorectal cancer.
Authors: Janja Ocvirk; Thomas Brodowicz; Fritz Wrba; Tudor E Ciuleanu; Galina Kurteva; Semir Beslija; Ivan Koza; Zsuzsanna Pápai; Diethelm Messinger; Ugur Yilmaz; Zsolt Faluhelyi; Suayib Yalcin; Demetris Papamichael; Miklós Wenczl; Zrinka Mrsic-Krmpotic; Einat Shacham-Shmueli; Damir Vrbanec; Regina Esser; Werner Scheithauer; Christoph C Zielinski Journal: World J Gastroenterol Date: 2010-07-07 Impact factor: 5.742
Authors: Shuai Wang; Chun Hui Yin; Xin Yan Zhang; Zhi Mei Shang; Li Min Huang; Nan Luo; An Quan Wang; Ling Ling Dong; Hong Xing Liu; Jing Yan Zhu Journal: J Res Med Sci Date: 2019-10-25 Impact factor: 1.852
Authors: J-P Delord; J Bennouna; P Artru; H Perrier; F Husseini; F Desseigne; E François; R Faroux; D Smith; P Piedbois; H Naman; J Y Douillard; R Bugat Journal: Br J Cancer Date: 2007-07-17 Impact factor: 7.640