Leucovorin and Fluorouracil With or Without Oxaliplatin as First-Line Treatment in Advanced Colorectal Cancer
- Study type
- Clinical trial
- Study name
- de Gramont 2000
- Phase
- Phase 3
- Design
- Randomised phase 3 trial (LV5FU2 plus oxaliplatin versus LV5FU2 alone)
- Sample size
- 420 patients
- Source
- JCO · 2000
In plain words
In this study, patients with advanced bowel (colorectal) cancer who had not yet been treated received either standard chemotherapy (leucovorin and fluorouracil) or the same treatment plus oxaliplatin. Adding oxaliplatin kept the disease under control for longer and made tumours shrink in more patients. On the other hand, side effects such as a drop in white blood cells, diarrhoea and tingling or numbness from nerve damage were more common, but patients' quality of life did not get worse.
Key results
Treatment arms and regimens
Leucovorin (LV) 200 mg/m²/day as a 2-hour infusion, followed by fluorouracil (5FU) 400 mg/m²/day bolus and 600 mg/m²/day as a 22-hour infusion, for 2 consecutive days every 2 weeks, with oxaliplatin 85 mg/m² as a 2-hour infusion on day 1.
Leucovorin 200 mg/m²/day as a 2-hour infusion, followed by fluorouracil 400 mg/m²/day bolus and 600 mg/m²/day as a 22-hour infusion, for 2 consecutive days every 2 weeks.
Source of the regimen details: Abstract of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Previously untreated patients with advanced colorectal cancer and measurable disease.
Endpoints
Primary endpoint: progression-free survival. Secondary endpoints listed in the abstract included response rate, overall survival, toxicity, quality of life and survival without progression or deterioration of global health status.
Safety and side effects
In the oxaliplatin plus LV5FU2 group versus the control group: grade 3/4 neutropenia in 41.7% versus 5.3%, grade 3/4 diarrhoea in 11.9% versus 5.3%, and grade 3 neurosensory toxicity in 18.2% versus 0% of patients. These toxicities did not lead to a deterioration in quality of life.
Clinical significance and place in guidelines
Based on the abstract, adding oxaliplatin to LV5FU2 as first-line treatment of advanced colorectal cancer improved progression-free survival and response rate, although the improvement in overall survival was not significant. The combination had acceptable tolerability and preserved quality of life. Its current status in treatment guidelines should be checked in up-to-date sources.
Limitations
The improvement in overall survival was not statistically significant. Grade 3/4 toxicities (neutropenia, diarrhoea) and grade 3 neurosensory toxicity were considerably more frequent in the oxaliplatin group.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.