Table 1.
Randomised studies comparing adjuvant systemic chemotherapy versus surgery alone after curative resection of colorectal cancer liver metastases
| Author (study) |
Arm | Chemo regimen | TOT | N | Country (N centres) |
ADJ begin from surgery | Follow -up | Statistical aim (randomisation ratio) |
Primary outcome (secondary outcome) |
Enrolment (phase) |
| Saiura et al16 | Surgery+UFT/LV Surgery alone |
((Tegafur 300 mg/m2/day+leucovorin 75 mg/m2/day) three times per day, D1–28, q5 wks) ×5 | 180 | 90 90 |
Japan (11) |
Within 8 wks | 6 years | 15% increase in 3-year RFS (from 30% to 45%) two-sided 95% CI, power 75%, 180 patients needed (1:1) |
3-year RFS (OS, RFS liver, RFS other organs, toxicity) |
Completed 01.2004–12.2010 (phase III) |
| Langer et al19
(ENG) |
Surgery + 5-FU/FA Surgery alone |
(L-leucovorin 100/m2, 5-FU 370/m2 bolus D1–5/q28) ×6 | 129 | 62 67 |
Canada and Europe (67) |
Within 8 wks | NA | 15% increase in 5-year survival (from 30% to 45%) two-sided 95% CI power 90%, 418 patients needed (1:1) | OS (DFS) |
Stopped: slow accrual 2.1994–1.1998 (phase III) |
| Portier et al21
(FFCD) |
Surgery + 5-FU/FA Surgery alone |
(DL-leucovorin 200/m2, 5-FU 400/m2 bolus D1–5/q28)×6 | 173 | 86 87 |
France, Belgium and Switzerland (47) |
2–5 wks | 87 months | 20% increase in 2-year DFS (from 20% to 40%) two-sided, 95% CI power 90%, 200 patients and 134 events needed (1:1) |
DFS at 2 years (OS, toxicity) |
Stopped: slow accrual 12.1991–12.2001 (phase III) |
| Lopez-Ladron et al13 | Surgery+CT Surgery alone |
Not reported | 38 | 28 10 |
Spain (3) |
NA | 15 months | NA, study underpowered (3:1) |
OS | Completed (phase II) |
| Kanemitsu et al14
(JCOG0603) |
Surgery+mFOLFOX Surgery alone |
(Oxaliplatin 85 mg/m2, + L-leucovorin 200/m2,+5-FU 400/m2 bolus,+5-FU 2400 mg/m2 CI over 48 hours) q14×12 |
Still recruiting | Japan (38) |
6–10 wks | NA | 12% increase in 5-year DFS (from 25% to 37%), one-sided, 95% CI power 80%, 300 patients, 150 per arm, and 233 events needed (1:1) |
DFS (OS, toxicity) |
Still recruiting -analyses planned in 2024 (phases II and III) |
|
ADJ, adjuvant; DFS, disease-free survival; RFS, relapse-free survival, DL, dextro-levogyre; ENG, European Organization for Research and Treatment of Cancer, National Cancer Institute of Canada, Gruppo Italiano di Valutazione Interventi in Oncologia; FFCD, Federation Francophone de Cancerologie Digestive; 5-FU, fluorouracil; JCOG, Japan Clinical Oncology Group; LV, leucovorin; OS, overall survival; TOT, total; UFT, uracil–tegafur