A randomised comparison between six months of bolus fluorouracil (5-FU)/leucovorin (LV) and twelve weeks of protracted venous infusion (PVI) 5-FU as adjuvant treatment in colorectal cancer: An update with 5 years' follow-up.
Authors: Starling, N., Chau, I., Norman, A.R., Tait, D., Iveson, T., Hill, M., Hickish, T., Lofts, F., Jodrell, D. and Cunningham, D.
Journal: J Clin Oncol
Volume: 22
Issue: 14_suppl
Pages: 3523
eISSN: 1527-7755
Abstract:3523 Background: We performed a multicentre randomised trial to compare the efficacy and toxicity of 12 weeks of PVI 5-FU against the standard bolus monthly regimen of 5-FU/LV given for 6 months as adjuvant treatment in colorectal cancer. METHODS: Patients with curatively resected stage II and III colorectal cancer were randomly assigned to 5-FU/LV (5-FU 425mg/m(2) iv and LV 20mg/m(2) iv bolus days 1-5 every 28 days for 6 months) or to PVI 5-FU (300mg/m(2)/day for 12 weeks). RESULTS: Between 1993 and 2003, 801 eligible patients were randomised to 5-FU/LV (n=404) or PVI 5-FU (n=397). 59% of patients had stage III disease and 40% of patients had rectal cancer. With a median follow-up of 5.3 years, 231 relapses and 220 deaths have been observed. Five-year relapse free survival (RFS) was 66.7% (95% confidence interval [CI]: 61.6-71.3%) and 73.3% (95% CI: 68.4-77.6%) with bolus 5-FU/LV and PVI 5-FU respectively (Hazard ratio[HR]: 0.8; 95% CI: 0.62-1.04; p=0.10). Five-year overall survival (OS) was 71.5% (95% CI: 66.4-75.9%) and 75.7% (95% CI: 70.8-79.9%) with bolus 5-FU/LV and PVI 5-FU respectively (HR: 0.79; 95% CI: 0.61-1.03; p=0.083). For the rectal cancer patients (n=323), five-year RFS was 57.7% (95% CI: 48.4-65.9%) and 73.9% (95% CI: 65.3-80.6%) with bolus 5-FU/LV and PVI 5-FU respectively (p=0.035). Five-year OS was 65.3% (95% CI: 55.7-73.3%) and 78.7% (95% CI: 70.1-85.1%) with bolus 5-FU/LV and PVI 5-FU respectively (p=0.071). Significantly less diarrhoea, stomatitis, nausea & vomiting, alopecia, lethargy, neutropenia (all with p<0.0001) were seen with PVI 5-FU. CONCLUSIONS: PVI 5-FU was associated with a trend towards better relapse-free and overall survival compared to bolus 5-FU/LV, but with significantly less toxicity. Based on our results, the probability of twelve weeks of PVI 5-FU being inferior to 6 months of bolus 5-FU/LV is extremely low (p<0.005), and therefore shorter duration of adjuvant treatment should be further explored. No significant financial relationships to disclose.
Source: PubMed