Annals of Oncology 9:535-541, 1998
© 1998 European Society for Medical Oncology
research-article |
The impact of adding low-dose leucovorin to monthly 5-fluorouracil in advanced colorectal carcinoma: Results of a phase III trial
Bern Switzerland
Correspondence to: M. M. Borner, MD Institute of Medical Oncology, Inselspital 3010 Bern Switzerland
PURPOSE: A wide variety of fiuorouracil (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 fiuorouracil 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 biomo-dulating 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.
colorectal cancer, fiuorouracil, low-dose leucovorin, phase III trial, survival benefit
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