The evidence for using this regimen comes from a randomised 2 x 2 factorial designed trial of monthly fluorouracil plus leucovorin (mFU/LV) versus a bi-monthly fluorouracil plus leucovorin (LV5FU2) also known as the De Gramont regimen for 24 or 36 weeks.r
Between July 1996 and November 1999, a total of 905 patients were enrolled and randomised to receive either:
- Leucovorin 200 mg/m2 (IV infusion) plus 5-FU 400 mg/m2 (IV bolus) followed by 5-FU 600 mg/m2 (continuous infusion) for 22 hours for 2 consecutive days every 14 days or
- Leucovorin 200 mg/m2 (IV infusion) plus 5-FU 400 mg/m2 (IV bolus) for 5 consecutive days every 28 days
In each arm the patients were then assigned to receive either 24- or 36 weeks of treatment.
The end points of the study were to compare the therapeutic ratio, efficacy, and toxicity of both regimens.
The modified De Gramont regimen is a simplified version of the standard regimen which avoids day 3 administration of 5FU/LV bolus. It has been shown to be a less costly option with equivalent efficacy and toxicity as the standard regimen.rr
A lower dose of folinic acid has also been used in this protocol as there is no evidence to suggest any differences in efficacy resulting from alterations in folinic acid dosing. Read more about folinic acid dosing.
After a median follow-up of 6 years, there was no statistically significant difference between mFU/LV and LV5FU2 in terms of DFS (150 v 148 events; HR: 1.01; 95% CI, 0.806 to 1.269; p=0.94) and overall survival (OS; 104 v 103 events; HR, 1.02; 95% CI, 0.77 to 1.34; p=0.91). No statistical difference was observed between 24 or 36 weeks of chemotherapy.r
Overall survival according to treatmentr
© Journal of Clinical Oncology 2007
The most commonly observed grade 3 to 4 toxicities were neutropenia, diarrhoea and mucositis. Toxicities were significantly lower in the LVFU2 group (all toxicities, p<0.001).
Maximum grade 3/4 toxicities per patientr
© Journal of Clinical Oncology 2003