Key Trials Supporting Infusional 5-FU Regimens in Colon Cancer Treatment
The most effective treatment regimens for colorectal cancer include infusional 5-FU combinations such as FOLFOX and FOLFIRI, which have demonstrated superior survival outcomes compared to older bolus regimens across multiple pivotal trials.
Key Trials of FOLFOX Regimen
| Trial Name | Year | Setting | Regimen | Comparator | Key Outcome | Reference |
|---|---|---|---|---|---|---|
| NSABP C-07 | 2007 | Adjuvant | FOLFOX | 5-FU/LV | Improved DFS | [1] |
| N9741 | 2004 | 1st line metastatic | FOLFOX4 | IFL (Irinotecan/5-FU/LV) | Improved OS (19.4 vs 14.6 months) | [2] |
| EFC4584 | 2004 | 2nd line metastatic | FOLFOX4 | 5-FU/LV | Improved response rate (9% vs 0%) | [2] |
| FOCUS | 2008 | 1st/2nd line | FOLFOX | Sequential therapy | Similar efficacy with combination | [1] |
| COIN | 2013 | 1st line metastatic | FOLFOX/CAPOX | FOLFOX/CAPOX + cetuximab | No OS benefit with cetuximab addition | [1] |
Key Trials of FOLFIRI Regimen
| Trial Name | Year | Setting | Regimen | Comparator | Key Outcome | Reference |
|---|---|---|---|---|---|---|
| GERCOR | 2004 | 1st line metastatic | FOLFIRI | FOLFOX | Similar efficacy, different toxicity profiles | [3] |
| TRIBE | 2015 | 1st line metastatic | FOLFIRI + bevacizumab | FOLFOXIRI + bevacizumab | Inferior to triplet therapy | [1] |
| VELOUR | 2012 | 2nd line | FOLFIRI + aflibercept | FOLFIRI + placebo | Improved OS with aflibercept | [1] |
| RAISE | 2015 | 2nd line | FOLFIRI + ramucirumab | FOLFIRI + placebo | Improved OS with ramucirumab | [1] |
Key Trials of FOLFOXIRI Regimen
| Trial Name | Year | Setting | Regimen | Comparator | Key Outcome | Reference |
|---|---|---|---|---|---|---|
| TRIBE | 2015 | 1st line metastatic | FOLFOXIRI + bevacizumab | FOLFIRI + bevacizumab | Improved PFS and response rate | [1] |
| TRIBE2 | 2020 | 1st/2nd line | FOLFOXIRI + bevacizumab | FOLFOX + bevacizumab | Improved PFS with triplet therapy | [1] |
| Falcone et al. | 2006 | 1st/2nd line | FOLFOXIRI | Sequential therapy | ORR 71-72%, median OS 26.5-28.4 months | [4] |
Key Trials of Sequencing Strategies
| Trial Name | Year | Setting | Regimen | Comparator | Key Outcome | Reference |
|---|---|---|---|---|---|---|
| CAIRO | 2009 | 1st/2nd line | Sequential therapy | Combination therapy | Similar efficacy | [1] |
| GERCOR | 2004 | 1st/2nd line | FOLFIRI→FOLFOX | FOLFOX→FOLFIRI | Similar OS (21 months) with either sequence | [3] |
| CALGB | 2019 | 1st line | FOLFOX or FOLFIRI + biologics | Various | Assessed MMR status impact on outcomes | [1] |
Key Trials in Elderly Patients
| Trial Name | Year | Setting | Regimen | Age Group | Key Outcome | Reference |
|---|---|---|---|---|---|---|
| AVEX | 2013 | 1st line | Capecitabine + bevacizumab | ≥70 years | Improved PFS vs capecitabine alone | [1] |
| FOCUS2 | 2010 | 1st line | Modified FOLFOX | Elderly/frail | Demonstrated feasibility in elderly | [1] |
Standard Dosing Regimens
| Regimen | Components | Schedule | Reference |
|---|---|---|---|
| FOLFOX | Oxaliplatin: 85 mg/m² IV day 1 Leucovorin: 400 mg/m² IV day 1 5-FU: 400 mg/m² IV bolus day 1, then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46-48h) continuous infusion |
Every 2 weeks | [1] |
| FOLFIRI | Irinotecan: 150-180 mg/m² IV over 30-90 min, day 1 Leucovorin: 400 mg/m² IV day 1 5-FU: 400 mg/m² IV bolus day 1, then 1200 mg/m²/day × 2 days (total 2400 mg/m² over 46-48h) continuous infusion |
Every 2 weeks | [1] |
| FOLFOXIRI | Irinotecan: 165 mg/m² IV day 1 Oxaliplatin: 85 mg/m² Leucovorin: 400 mg/m² IV day 1 5-FU: 3,200 mg/m² over 46-48h continuous infusion starting on day 1 |
Every 2 weeks | [1] |
These trials collectively established the superiority of infusional 5-FU regimens over older bolus regimens, with the FOLFOX and FOLFIRI combinations becoming standard of care in both adjuvant and metastatic settings based on improved efficacy and manageable toxicity profiles.