APPENDIX B.
Dosing by trial
| Reference | Regimen (mg/m2daily, frequency) |
|---|---|
| First-line treatment | |
| Lévi et al., 1994 7 (iocc trial) | 5-fu 600, fa 300, oxaliplatin 20, days 1–5, every 21 days (16-day intermission) via programmable pump
Arm A: flat infusion Arm B: cm infusion (5-fu/fa peak at 04:00 hours; oxaliplatin peak at 16:00 hours) |
| Lévi et al., 1997 8 (iocc trial) | 5-fu 600, fa 300, oxaliplatin 20, days 1–5, every 21 days (16-day intermission)
Arm A: flat infusion Arm B: cm infusion |
| Buechele et al., 2000, Germany 9 | Oxaliplatin 50, 2-hour infusion + fa 500, 2-hour infusion + 5-fu 2000, 24-hour infusion; days 1, 8, 15, and 22; every 36 days versus
Bolus 5-fu/fa (Mayo Clinic regimen) |
| de Gramont et al., 2000 10 | Oxaliplatin 85, 2-hour infusion, day 1 + 5-fu 400 bolus, then 600 continuous infusion, days 1 and 2 + fa 200, continuous infusion, days 1 and 2, every 2 weeks versus
5-fu 400 bolus, then 600 continuous infusion, days 1 and 2 + fa 200, continuous infusion, days 1 and 2, every 2 weeks (lv5fu2 regimen) |
| Giacchetti et al., 2000 11 | Oxaliplatin 125, 6-hour infusion, day 1 + 5-fu 700 + fa 300, cm infusion; days 1–5; every 3 weeks versus 5-fu 700 + fa 300, cm infusion, days 1–5, every 3 weeks |
| Giacchetti et al., 2002 12 (eortc trial) | Oxaliplatin 25, cm infusion (peak at 16:00), 5-fu 750, cm infusion (peak at 04:00), fa 300, cm infusion (peak at 04:00); all three drugs given daily for 4 days and repeated every 2 weeks versus
Oxaliplatin 100, 2-hour infusion, day 1; 5-fu 1500, 22-hour infusion, daily for 2 days; fa 600, 2-hour infusion daily for 2 days; repeat every 2 weeks (folfox2) |
| Grothey et al., 2002, Germany 13 | Oxaliplatin 50, 2-hour infusion + 5-fu 2000, 24-hour infusion + fa 500, 24-hour infusion; days 1, 8, 15, and 22; every 5 weeks (fufox) versus
5-fu 425 bolus + fa 20, days 1–5, every 29 days (Mayo) |
| Colucci et al., 2003 14 (goim trial) | Oxaliplatin 85, day 1; fa 100, 2-hour infusion, days 1 and 2; 5-fu 400 bolus, followed by 5-fu 600, 22-hour infusion, days 1 and 2; every 2 weeks versus
Irinotecan 180, day 1; fa 100, 2-hour infusion, days 1 and 2; 5-fu 400 bolus, followed by 5-fu 600, 22-hour infusion, days 1 and 2; every 2 weeks |
| Goldberg et al., 2004 15 (Intergroup N9741 trial) | Oxaliplatin 85, day 1, followed by 5 fu - 400 bolus + 600 22-hour infusion, days 1 and 2; fa 200, days 1 and 2; every 2 weeks (de Gramont folfox4) versus
Irinotecan 125 + 5-fu 500 + fa 20; days 1, 8, 15, and 22; every 6 weeks (Saltz ifl) versus Oxaliplatin 85, day 1 + irinotecan 200, day 1; every 3 weeks (Wasserman irox) |
| Tournigand et al., 200416 (gercor trial) | First-line folfiri: irinotecan 180 2-hour infusion, day 1; fa 200 2-hour infusion, day 1; 5-fu 400 bolus, day 1; followed by 5-fu 2400–3000 48-hour infusion, day 2; every 2 weeks until progression, then follow with second-line folfox6 (as below) versus
First-line folfox6: oxaliplatin 100 2-hour infusion, day 1; fa 200 2-hour infusion, day 1; 5-fu 400 bolus, day 1; followed by 5-fu 2400–3000 48-hour infusion, day 2; every 2 weeks until progression, then follow with second-line folfiri (as above) |
| Comella et al., 2005 31 (sicog) |
irifafu: irinotecan 200 intravenously, day 1; fa 250 intravenously, followed by 5-fu 850, day 2 versus High-dose oxafafu: oxaliplatin 100, day 1; followed by fa 250 and 5-fu 1050, day 2 versus
Low-dose oxafafu: oxaliplatin 85, day 1; fa 250 and 5-fu 850, day 1 |
| Colucci et al., 2005 32 (goim) |
folfiri: irinotecan 180, day 1; fa 100 2-hour infusion, 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2 versus
folfox4: oxaliplatin 85, day 1; irinotecan 180, day 1; fa 100 2-hour infusion, 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2 |
| Falcone et al., 2006 33 (gono) |
folfoxiri : oxaliplatin 85, day 1; irinotecan 165, day 1; 5-fu 3200 48-hour infusion starting on day 1; l-fa 200, day 1; every 2 weeks versus
folfiri: irinotecan 180, day 1; l-lv 100, days 1 and 2; 5-fu 400 bolus, days 1 and 2; followed by 5-fu 600 22-hour infusion, days 1 and 2; every 2 weeks At progression on folfiri, a folfox regimen was recommended |
| Hospers et al., 2006 34 | oxafafu: oxaliplatin 85 2-hour infusion, fa 200 1-hour infusion, 5-fu 2600 24-hour infusion, day 1, every 2 weeks versusfafu: 5-fu 425, days 1–5; fa 20, days 1–5; every 4 weeks |
| Souglakos et al., 2006 35 (horg) |
folfoxiri: oxaliplatin 65, day 2; irinotecan 150, day 1; fa 200, days 2 and 3; 5- fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 2 and 3 versus
folfiri: irinotecan 180, day 1; fa 200, days 2 and 3; 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 2 and 3 |
| Stanculeanu et al., 2006 36 |
folfox 4: oxaliplatin 85, day 1; fa 200, days 1 and 2; 5- fu 400 bolus, followed by 5- fu 600 22-hour infusion, days 1 and 2; every 15 days versus
folfiri: irinotecan 180, fa 400, 5-fu 400 bolus, followed by 5-fu 2400 46-hour infusion, every 15 days versus irox: irinotecan 300, day 1; oxaliplatin 85, day 2; every 3 weeks |
| Tournigand et al., 2006 37 (gercor) |
folfox 4: oxaliplatin 85 2-hour infusion, day 1; fa 2-hour infusion (either 100 l-lv or 200 dl-lv), 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2; every 2 weeks versus
folfox7 (6 cycles) → lv5fu2 (12 cycles) → folfox7 (6 cycles) folfox7: oxaliplatin 130 2-hour infusion, day 1; fa 2-hour infusion (either l-lv 200 or dl-lv 400), followed by 5-fu 2400 46-hour infusion; every 2 weeks lv5fu2: fa 2-hour infusion (either l-lv 200 or dl-lv 400), 5-fu 400 bolus, followed by 5-fu 3000 46-hour infusion, every 2 weeks |
| Second-line treatment | |
| Rothenberg et al., 2003 30 (EFC4584 trial) | Treatment given as second-line to ifl Oxaliplatin 85 2-hour infusion, day 1; 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2; every 2 weeks (folfox4) versus 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2; fa 200; every 2 weeks (lv5fu2) |
| Garay et al., 200317 (Sanofi/Memorial Sloan Kettering Cancer Centre crossover trial) | Treatment given as second-line to 5-fu + irinotecan ± fa Oxaliplatin 85 2-hour infusion, day 1; 5-fu 400 bolus; followed by 5-fu 600 22-hour infusion, days 1 and 2; every 2 weeks (folfox4) versus 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2; fa 200; every 2 weeks (lv5fu2) |
| Giantonio et al., 2005 38 (ecog) |
folfox 4 + bevacizumab: bevacizumab 10 mg/kg intravenously, biweekly; oxaliplatin 85, day 1; fa 200 2-hour infusion, 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2 versus
folfox4: oxaliplatin 85, day 1; fa 200 2-hour infusion, 5-fu 400 bolus, followed by 5-fu 600 22-hour infusion, days 1 and 2 versus Bevacizumab: bevacizumab 10 mg/kg intravenously, biweekly |
| Pitot et al., 2005 39 (N9841) | Irinotecan → folfox4 versus folfox4 → irinotecan
Irinotecan 350, day 1, every 3 weeks (reduced to 300 for ecog performance status 2, age ≥ 70, or prior pelvic radiation) folfox4: oxaliplatin 85, fa 200, 5-fu 400 bolus, followed by 600 22-hour infusion, days 1 and 2, every 2 weeks |
iocc = International Organization Against Cancer; 5-fu = 5-fluorouracil; fa = folinic acid; cm = chronomodulated; eortc = European Organization for Research and Treatment of Cancer; goim = Gruppo Oncologico Italia Meridionale; gercor = Groupe Coopérateur Multidisciplinaire en Oncologie; sicog = Southern Italy Cooperative Oncology Group; l-fa = levo-folinic acid; gono = Gruppo Oncologico Nord Ovest; l-lv = levo-leucovorin calcium; horg = Hellenic Oncology Research Group; dl-lv = racemic leucovorin calcium; ecog = Eastern Cooperative Oncology Group.