Table 2.
Systemic adjuvant chemotherapy studies after metastasectomy
| Ref. | No. of patients | Setting | Randomized study | Regimes of chemotherapy |
Outcomes |
||
| DFS | PFS | OS | |||||
| Controlled studies | |||||||
| Langer et al[90], 2002 | arm2 = 55 vs arm1 = 52 | Phase III | YES | 5-FU/LV vs surgery + 5-FU/LV (arm2 vs arm1) | 4-yr DFS:35% vs 45%(P = 0.35) HR = 1.28 (95%CI: 0.76-2.14) | - | 4-yr OS:47% vs 57% (P = 0.39)HR = 1.30 (95%CI: 0.71-2.36) |
| Portier et al[91], 2006 | 171 (86 vs 85) | Phase III | YES | 5-FU/LV vs surgery alone | 5-yr DFS: 33.5% vs 26.7% (P = 0.028) HR = 0.66 (95%CI: 0.46-0.96) | - | 5-yr OS:51.1% vs 41.9% (P = 0.13) HR = 0.73 (95%CI: 0.48-1.10) |
| Mitry et al[92], 2008 | 278 (138 vs 140) | Pooled analysis of two phase III studies | YES | 5-FU/LV vs surgery alone | Median DFS: 27.9 mo vs 18.8 mo (P = 0.058) 5-yr DFS: 36.7% vs 27.7% HR = 0.76 (95%CI: 0.57-1.01) | - | Median OS: 62.2 vs 47.3 mo (P = 0.095) 5-yr OS: 52.8% 39.6%HR = 0.76 (95%CI: 0.55-1.05) |
| Kanemitsu et al[94], 2009 | 300 | Phase II/III | YES | FOLFOX6 vs surgery alone | In progress (results not yet available) | ||
| Ychou et al[99], 2009 | 306 (153 vs 153) | Phase III | YES | FOLFIRI vs 5-FU/LV | 2-yr DFS: 50.7% vs 46.2% (P = 0.44) HR = 0.89 (95%CI: 0.66-1.19) | - | 3-yr OS: 72.7% vs 71.6% (P = 0.69) HR = 1.09 (95%CI: 0.72-1.64) |
| Kim et al[98], 2009 | 156 [58 + 48 + 50] | Retrospective | NO | Oxaliplatin regimes (group I); Irinotecanregimes (group II) orFluoropyrimidine alone(group III) | Median DFS:23.4, 14.1 and 16.3 mo(respectively, P = 0.088)HR group1 vs 3: 0.63 (95%CI: 0.39-1.03) HR group2 vs 3: 0.98 (95%CI: 0.61-1.56) | - | Median OS:51.2, 47.9 and 60 mo(respectively, P = 0.219) |
| Liu et al[100], 2010 | 50 [31 (17 + 14) vs 19] | Retrospective | NO | FOLFOX/FOLFIRI vs 5-FU/LV | 3-yr DFS: 50.8% vs 21.1% (P = 0.022) HR = 0.37 (95%CI: 0.15-0.94) | - | 3-yr OS: 85.7% vs 51.8% (P = 0.027)5-yr OS: 54.0% vs 34.6% (P = 0.027) HR = 0.27 (95%CI: 0.083-0.86) |
| Snoeren et al[106], 2010 | CAPOX + Bevacizumab vs CAPOX alone | In progress (results not yet available) | |||||
| Kemeny et al[104], 2011 | 73 (35 vs 38) | Phase II | YES | HAI/systemic therapy + BEVA vs HAI/systemic therapy alone | 4-yr DFS: 71% vs 83% (P = 0.4) | - | 4-yr OS: 81% vs 85% (P = 0.5) |
| Brandi et al[101], 2013 | 151 (78 vs 73) | Cohort study | NO | Oxaliplatinregimes or Irinotecan regimes vs surgery alone | Median DFS: 16 vs 9.7 mo(P = 0.014) 5-yr DFS: 17.4% vs 10.5% (P = 0.82) HR = 0.64 (95%CI: 0.46-0.90) | - | Median OS: 42 vs 39 mo (P = 0.8) |
| Turan et al[105], 2013 | 204 (87 vs 117) | Cohort study | NO | Irinotecan regimes or oxaliplatin regimes + bevacizumab vs chemotherapy alone | Median DFS: 14 vs 18 mo (P = 0.37) | - | Median OS: 43 vs 54 mo (P = 0.25) |
| Nordlinger et al[93], 20131 | 364 (171 vs 152) | Phase III study | YES | Peri-operative FOLFOX4 vs surgery alone | - | 3-yr PFS: 38.2% vs 30.3% (P = 0.0068) HR = 0.81 (95%CI: 0.64-1.02) | 5-yr OS:51.2% vs 47.8% (P = 0.3) HR = 0.88 (95%CI: 0.68-1.14) |
| Primrose et al[107], 20141 | 236 (119 vs 117) | Phase III | YES | FOLFOX/CAPOX + cetuximab vs FOLFOX/CAPOX alone | - | Median PFS: 14.1 vs 20.5 mo(P = 0.03) HR = 1.48 (95%CI: 1.04-2.12) | Median OS: 39.1 vs 32 mo (P = 0.16) HR = 1.49 (95%CI: 0.86-2.60) |
| Kobayashi et al[102], 2014 | 177 (88 vs 89) | Phase III | YES | UFT/LV vs surgery alone | - | 3-yr PFS: 38.6% vs 32.3% (P = 0.003) HR = 0.56 (95%CI: 0.38-0.83) | 3-yr OS: 82.8% vs 81.6% (P = 0.41) HR = 0.80 (95%CI: 0.48-1.35) |
| Non controlled studies | |||||||
| Kim et al[97], 2011 | 60 | Single armed | NO | FOLFOX6 | Median DFS: 32.8 mo (95%CI: 5.8-59.6)5-yr DFS: 39.20% | - | Median OS: 62.8 mo (95%CI: 44.1-81.3)5-yr OS: 55.5% |
| Kato et al[103], 2015 | 60 | Single armed | NO | S-1 | 1-yr DFS: 68.30%3-yr DFS: 47.40% | - | 1-yr OS: 96.70%3-yr OS: 80% |
| Nakayama et al[95], 2015 | 88 | Single armed | NO | Oxaliplatin regimes | 3-yr DFS: 54% | - | - |
| Katayose et al[96], 2015 | 49 | Phase II single armed | NO | mFOLFOX6 | 2-yr DFS: 59.20% | - | - |
1
The primary end-point was PFS because these studies evaluated the role of peri-operative chemotherapy, but some patients became ineligible for surgical treatment during the study. 5-FU/LV: 5-fluorouracil/leucovorin; FOLFOX: 5-FU/LV plus oxaliplatin; DFS: Disease-free survival; PFS: Progression-free survival; OS: Overall survival; UFT: Tegafur-uracil.