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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 1 Adjuvant systemic chemotherapy after primary resectable colorectal cancer
TrialsNo. of patientsSchedulesDFSP valueOSP value
Oxaliplatin-based regimes
X-ACT1987CAPECITABINE (1004)64.2%0.1281.3%0.07
(Twelves et al[32], 2005)5FU/LV (983)60.6%77.6%
NSABP C-0724075FU/LV (1207)67.0%0.0034--
(Kuebler et al[30], 2007)FLOX (1200)73.2%
MOSAIC22465FU/LV (1123)67.4%0.00368.7%0.46
(André et al[29], 2009)FOLFOX4 (1123)73.3%78.5%
XELOXA1886XELOX (944)70.9%0.04577.6%0.15
(Haller et al[31], 2011)5FU/LV (942)66.5%74.2%
Irinotecan-based regimes
CALGB-898031264Irinotecan + 5FU/LV (635)59.0%0.8564.0%0.74
(Saltz et al[35], 2007)5FU/LV (629)61.0%67.0%
PETACC-32982Irinotecan + 5FU/LV (1485)56.7%0.10673.6%0.094
(Van Cutsem et al[36], 2009)5FU/LV (1497)54.3%71.3%
Bevacizumab + chemotherapy
NSABP C-082710FOLFOX6 + Bevacizumab (1354)77.4%0.15--
(Allegra et al[37], 2011)FOLFOX6 (1356)75.5%
AVANT2867FOLFOX4 + Bevacizumab (960)73.0%0.0781.0%0.02
(de Gramont et al[38], 2012)FOLFOX4 (955)76.0%85.0%
XELOX + Bevacizumab (952)75.0%0.4482.0%0.21
Cetuximab + chemotherapy
NCCTG NO1472686FOLFOX6 + Cetuximab (1349)71.5%0.0872.5%0.03
(Alberts et al[41], 2012)FOLFOX6 (1337)74.6%86.2%
PETACC-8337FOLFOX4 + Cetuximab (169)60.450.6046.0%0.064
(Taieb et al[42], 2012)FOLFOX4 (168)60.7%36.0%
Oral flupropyrimidine in monotherapy
JCOG0205110925-FU/LV (550)74.3%0.0236--
(Shimada et al[33], 2014)UFT/LV (551)73.6%
ACT-CC11518S-1 (758)75.5%< 0.01--
(Yoshida et al[34], 2014)UFT/LV (760)72.5%
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%--
Table 3 Hepatic arterial infusion plus systemic chemotherapy in the adjuvant setting
Ref.Numbers of patientsSettingRandomized studyRegimes of therapyOutcomes
DFSPFSOS/DSS
Controlled studies
Ota et al[115], 199984 (37 vs 47)Cohort studyNOHAI/5-FU vs control group5-yr DFS: 72.6% vs 29.8% (P = 0.0005)-5-yr OS:61.4% vs 28% (P = 0.0069)
Kemeny et al[112], 2005156 (74 vs 82)Phase IIIYESHAI/FUDR plus systemic 5-FU ± LV vs systemic 5-FU ± LV alone-Median PFS: 31.3 vs 17.2 mo (P = 0.02)Median OS:68.4 vs 58.8 mo (P = 0.10)
House et al[113], 2011250 (125 vs 125)Cohort studyNOHAI/FUDR plus systemic chemotherapy (5FU/LV + irinotecan or oxaliplatin) vs systemic chemotherapy alone5-yr DFS: 48% vs 25% (P < 0.01)HR = 0.71 (95%CI: 0.48-0.96)-5-yr DSS:75% vs 55% (P < 0.01) HR = 0.39 (95%CI: 0.23-0.68)
Goéré et al[116], 201398 (44 vs 54)Cohort studyNOHAI/oxaliplatin plus systemic 5-FU/LV vs systemic irinotecan regimes or oxaliplatin regimes alone3-yr DFS: 33% vs 5%(P < 0.0001) HR = 0.37 (95%CI: 0.23-0.60)-3-yr OS:75% vs 62% (P = 0.17) 5-yr OS:54% vs 52% (P = 0.34)
Non controlled studies
Alberts et al[114], 201055Phase II single armedNOHAI/FUDR plus systemic capecitabine + oxaliplatin2-yr DFS:59.7% Median DFS: 32.7 mo-2-yr OS:89.10%