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Copyright ©The Author(s) 2016.
World J Gastroenterol. Jan 14, 2016; 22(2): 519-533
Published online Jan 14, 2016. doi: 10.3748/wjg.v22.i2.519
Table 2 Systemic adjuvant chemotherapy studies after metastasectomy
Ref.No. of patientsSettingRandomized studyRegimes of chemotherapyOutcomes
DFSPFSOS
Controlled studies
Langer et al[90], 2002arm2 = 55 vs arm1 = 52Phase IIIYES5-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], 2006171 (86 vs 85)Phase IIIYES5-FU/LV vs surgery alone5-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], 2008278 (138 vs 140)Pooled analysis of two phase III studiesYES5-FU/LV vs surgery aloneMedian 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], 2009300Phase II/IIIYESFOLFOX6 vs surgery aloneIn progress (results not yet available)
Ychou et al[99], 2009306 (153 vs 153)Phase IIIYESFOLFIRI vs 5-FU/LV2-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], 2009156 [58 + 48 + 50]RetrospectiveNOOxaliplatin 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], 201050 [31 (17 + 14) vs 19]RetrospectiveNOFOLFOX/FOLFIRI vs 5-FU/LV3-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], 2010CAPOX + Bevacizumab vs CAPOX aloneIn progress (results not yet available)
Kemeny et al[104], 201173 (35 vs 38)Phase IIYESHAI/systemic therapy + BEVA vs HAI/systemic therapy alone4-yr DFS: 71% vs 83% (P = 0.4)-4-yr OS: 81% vs 85% (P = 0.5)
Brandi et al[101], 2013151 (78 vs 73)Cohort studyNOOxaliplatinregimes or Irinotecan regimes vs surgery aloneMedian 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], 2013204 (87 vs 117)Cohort studyNOIrinotecan regimes or oxaliplatin regimes + bevacizumab vs chemotherapy aloneMedian DFS: 14 vs 18 mo (P = 0.37)-Median OS: 43 vs 54 mo (P = 0.25)
Nordlinger et al[93], 20131364 (171 vs 152)Phase III studyYESPeri-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], 20141236 (119 vs 117)Phase IIIYESFOLFOX/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], 2014177 (88 vs 89)Phase IIIYESUFT/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], 201160Single armedNOFOLFOX6Median 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], 201560Single armedNOS-11-yr DFS: 68.30%3-yr DFS: 47.40%-1-yr OS: 96.70%3-yr OS: 80%
Nakayama et al[95], 201588Single armedNOOxaliplatin regimes3-yr DFS: 54%--
Katayose et al[96], 201549Phase II single armedNOmFOLFOX62-yr DFS: 59.20%--
1The 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.