Difference between revisions of "Colon cancer - null regimens"

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. While not clinically relevant, these references provide further insight into the historical development of the treatment landscape. See the [[Colon cancer|main colon cancer page]] for current regimens.
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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the [[Colon cancer|main colon cancer page]] for regimens that include active anticancer treatment.
  
 
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=Adjuvant therapy, stage II=
 
=Adjuvant therapy, stage II=
 
==Observation==
 
==Observation==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
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<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen===
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
Line 20: Line 21:
 
|1984-1987
 
|1984-1987
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|5-FU & Levamisole
+
|[[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://link.springer.com/article/10.1007%2Fs00384-008-0543-8 Laffer et al. 2008 (SAKK 40/87)]
+
|[https://doi.org/10.1007/s00384-008-0543-8 Laffer et al. 2008 (SAKK 40/87)]
 
|1987-1993
 
|1987-1993
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|1. Portal venous 5-FU & Mitomycin<br> 2. 5-FU & Mitomycin
+
|1. Portal venous 5-FU & Mitomycin<br>2. [[#Fluorouracil_.26_Mitomycin_999|5-FU & Mitomycin]]
 +
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 +
|-
 +
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9807536/ Kemeny et al. 2022 (ECOG-ACRIN E1292)]
 +
|1993-2000
 +
| style="background-color:#1a9851" |Phase 3 (C)
 +
|[[#Fluorouracil_monotherapy_999|Peri-operative 5-FU]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
Line 35: Line 42:
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02214-5/fulltext Gray et al. 2000 (QUASAR)]
+
|[https://doi.org/10.1159/000084595 Hartung et al. 2005]
−
|1994-1997
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#FULV|FULV]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.karger.com/Article/Abstract/84595 Hartung et al. 2005]
 
 
|1997-2000
 
|1997-2000
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
Line 55: Line 56:
 
|}
 
|}
 
''No systemic treatment after surgery for stage II colon cancer.''
 
''No systemic treatment after surgery for stage II colon cancer.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
  
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
−
 
+
</div></div>
 
===References===
 
===References===
  
−
#'''INT-0035:''' Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA; North Central Cancer Treatment Group; [[Study_Groups#SWOG|SWOG]]; [[Study_Groups#ECOG|ECOG]]. Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. J Clin Oncol. 1995 Dec;13(12):2936-43. [https://doi.org/10.1200/jco.1995.13.12.2936 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8523058 PubMed]
+
#'''INT-0035:''' Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA; North Central Cancer Treatment Group; [[Study_Groups#SWOG|SWOG]]; [[Study_Groups#ECOG|ECOG]]. Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. J Clin Oncol. 1995 Dec;13(12):2936-43. [https://doi.org/10.1200/jco.1995.13.12.2936 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8523058/ PubMed]
−
#'''QUASAR:''' Gray RG, Kerr DJ, McConkey CC, Williams NS, Hills RK; QUASAR Collaborative Group. Comparison of fluorouracil with additional levamisole, higher-dose folinic acid, or both, as adjuvant chemotherapy for colorectal cancer: a randomised trial. Lancet. 2000 May 6;355(9215):1588-96. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(00)02214-5/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/10821362 PubMed] ISRCTN82375386
+
#Hartung G, Hofheinz RD, Dencausse Y, Sturm J, Kopp-Schneider A, Dietrich G, Fackler-Schwalbe I, Bornbusch D, Gonnermann M, Wojatschek C, Lindemann W, Eschenburg H, Jost K, Edler L, Hochhaus A, Queisser W. Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study. Onkologie. 2005 Jun;28(6-7):347-50. Epub 2005 Jun 2. [https://doi.org/10.1159/000084595 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15933423/ PubMed]
−
##'''Update:''' Gray R, Barnwell J, McConkey C, Hills RK, Williams NS, Kerr DJ; Quasar Collaborative Group. Adjuvant chemotherapy versus observation in patients with colorectal cancer: a randomised study. Lancet. 2007 Dec 15;370(9604):2020-9. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(07)61866-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/18083404 PubMed]
+
#Schippinger W, Samonigg H, Schaberl-Moser R, Greil R, Thödtmann R, Tschmelitsch J, Jagoditsch M, Steger GG, Jakesz R, Herbst F, Hofbauer F, Rabl H, Wohlmuth P, Gnant M, Thaler J; ABCSG. A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer. Br J Cancer. 2007 Oct 22;97(8):1021-7. Epub 2007 Sep 25. [https://doi.org/10.1038/sj.bjc.6604011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360441/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17895886/ PubMed]
−
#Hartung G, Hofheinz RD, Dencausse Y, Sturm J, Kopp-Schneider A, Dietrich G, Fackler-Schwalbe I, Bornbusch D, Gonnermann M, Wojatschek C, Lindemann W, Eschenburg H, Jost K, Edler L, Hochhaus A, Queisser W. Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study. Onkologie. 2005 Jun;28(6-7):347-50. Epub 2005 Jun 2. [https://www.karger.com/Article/Abstract/84595 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15933423 PubMed]
+
#'''SAKK 40/87:''' Laffer U, Metzger U, Aeberhard P, Lorenz M, Harder F, Maibach R, Zuber M, Herrmann R. Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial. Int J Colorectal Dis. 2008 Dec;23(12):1233-41. Epub 2008 Aug 8. [https://doi.org/10.1007/s00384-008-0543-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18688620/ PubMed]
−
#Schippinger W, Samonigg H, Schaberl-Moser R, Greil R, Thödtmann R, Tschmelitsch J, Jagoditsch M, Steger GG, Jakesz R, Herbst F, Hofbauer F, Rabl H, Wohlmuth P, Gnant M, Thaler J; ABCSG. A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer. Br J Cancer. 2007 Oct 22;97(8):1021-7. Epub 2007 Sep 25. [https://www.nature.com/articles/6604011 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360441/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/17895886 PubMed]
+
#'''CALGB 9581:''' Niedzwiecki D, Bertagnolli MM, Warren RS, Compton CC, Kemeny NE, Benson AB 3rd, Eckhardt SG, Alberts S, Porjosh GN, Kerr DJ, Fields A, Rougier P, Pipas JM, Schwartz JH, Atkins J, O'Rourke M, Perry MC, Goldberg RM, Mayer RJ, Colacchio TA. Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol. 2011 Aug 10;29(23):3146-52. Epub 2011 Jul 11. [https://doi.org/10.1200/JCO.2010.32.5357 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157980/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21747085/ PubMed] [https://clinicaltrials.gov/study/NCT00002968 NCT00002968]
−
#'''SAKK 40/87:''' Laffer U, Metzger U, Aeberhard P, Lorenz M, Harder F, Maibach R, Zuber M, Herrmann R. Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial. Int J Colorectal Dis. 2008 Dec;23(12):1233-41. Epub 2008 Aug 8. [https://link.springer.com/article/10.1007%2Fs00384-008-0543-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18688620 PubMed]
+
#'''ECOG-ACRIN E1292:''' Kemeny MM, Zhao F, Forastiere AA, Catalano P, Hamilton SR, Miedema BW, Dawson NA, Weiner LM, Smith BD, Mason BA, Graziano SL, Gilman PB, Venook AP, Pinto HA, Whitehead RP, O'Dwyer PJ, Benson AB. Phase III Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection for Colon Cancer: An Intergroup Trial of the ECOG-ACRIN Cancer Research Group (E1292). Ann Surg Oncol. 2023 Feb;30(2):1099-1109. Epub 2022 Oct 28. [https://doi.org/10.1245/s10434-022-12705-8 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9807536/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36305992/ PubMed] [https://clinicaltrials.gov/study/NCT00002525 NCT00002525]
−
#'''CALGB 9581:''' Niedzwiecki D, Bertagnolli MM, Warren RS, Compton CC, Kemeny NE, Benson AB 3rd, Eckhardt SG, Alberts S, Porjosh GN, Kerr DJ, Fields A, Rougier P, Pipas JM, Schwartz JH, Atkins J, O'Rourke M, Perry MC, Goldberg RM, Mayer RJ, Colacchio TA. Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol. 2011 Aug 10;29(23):3146-52. Epub 2011 Jul 11. [https://doi.org/10.1200/JCO.2010.32.5357 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3157980/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21747085 PubMed] NCT00002968
 
 
#'''PanDRa-BD:''' jRCTs031190186
 
#'''PanDRa-BD:''' jRCTs031190186
  
 
==Placebo==
 
==Placebo==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
 
===Regimen===
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
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|2002-2004
 
|2002-2004
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|Rofecoxib
+
|[[#Rofecoxib_monotherapy_999|Rofecoxib]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
 
''No active antineoplastic treatment.''
 
''No active antineoplastic treatment.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
  
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
−
 
+
</div></div>
 
===References===
 
===References===
  
−
#'''VICTOR:''' Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010 Oct 20;28(30):4575-80. Epub 2010 Sep 13. [https://doi.org/10.1200/JCO.2010.29.6244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20837956 PubMed] NCT00031863
+
#'''VICTOR:''' Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010 Oct 20;28(30):4575-80. Epub 2010 Sep 13. [https://doi.org/10.1200/JCO.2010.29.6244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20837956/ PubMed] [https://clinicaltrials.gov/study/NCT00031863 NCT00031863]
  
 
=Adjuvant therapy, stage III=
 
=Adjuvant therapy, stage III=
 
==Observation==
 
==Observation==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
 
===Regimen===
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
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|1975-1977
 
|1975-1977
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|1. 5-FU & Semustine<br> 2. 5-FU, Semustine, BCG
+
|1. [[#Fluorouracil_.26_Semustine_999|5-FU & Semustine]]<br>2. [[#Fluorouracil.2C_Semustine.2C_BCG_999|5-FU, Semustine, BCG]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint
 
| style="background-color:#ffffbf" |Did not meet primary endpoint
 
|-
 
|-
−
|[https://www.nejm.org/doi/full/10.1056/NEJM198403223101201 Lessner et al. 1984]
+
|[https://doi.org/10.1056/NEJM198403223101201 Lessner et al. 1984]
 
|1975-1979
 
|1975-1979
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|1. 5-FU & Semustine<br> 2. 5-FU, Semustine, BCG<br> 3. BCG
+
|1. [[#Fluorouracil_.26_Semustine_999|5-FU & Semustine]]<br>2. [[#Fluorouracil.2C_Semustine.2C_BCG_999|5-FU, Semustine, BCG]]<br> 3. [[#BCG_vaccine_monotherapy|BCG]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://academic.oup.com/jnci/article-abstract/80/1/30/886027 Wolmark et al. 1988 (NSABP C-01)]
+
|[https://doi.org/10.1093/jnci/80.1.30 Wolmark et al. 1988 (NSABP C-01)]
 
|1977-1983
 
|1977-1983
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|1. [[Colon_cancer_-_historical#MOF|MOF]]<br> 2. BCG
+
|1. [[Colon_cancer_-_historical#MOF|MOF]]<br>2. [[#BCG_vaccine_monotherapy|BCG]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<sup>1</sup>
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673695903402/fulltext Laffer et al. 1995 (SAKK 40/81)]
+
|[https://doi.org/10.1016/s0140-6736(95)90340-2 Laffer et al. 1995 (SAKK 40/81)]
 
|1981-1987
 
|1981-1987
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|Portal venous chemotherapy
 
|Portal venous chemotherapy
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|rowspan=2|[https://doi.org/10.1056/NEJM199002083220602 Moertel et al. 1990 (SWOG S8591)]
 +
|rowspan=2|1984-1987
 +
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
 +
| style="background-color:#d73027" |Inferior OS
 +
|-
 +
|2. [[#Levamisole_monotherapy|Levamisole]]
 +
| style="background-color:#d3d3d3" |Not reported
 
|-
 
|-
 
|[https://doi.org/10.1200/JCO.1990.8.9.1466 Wolmark et al. 1990 (NSABP C-02)]
 
|[https://doi.org/10.1200/JCO.1990.8.9.1466 Wolmark et al. 1990 (NSABP C-02)]
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| style="background-color:#fee08b" |Might have inferior OS
 
| style="background-color:#fee08b" |Might have inferior OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PII0140-6736(92)91708-G/fulltext Fielding et al. 1992 (AXIS-CRC)]
+
|rowspan=2|[https://doi.org/10.1200/jco.1989.7.10.1447 Laurie et al. 1989]
−
|NR
+
|rowspan=2|Not reported
 +
|rowspan=2 style="background-color:#1a9851"|Phase 3 (C)
 +
|1. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]]
 +
| style="background-color:#fc8d59" |Seems to have inferior OS
 +
|-
 +
|2. [[#Levamisole_monotherapy|Levamisole]]
 +
| style="background-color:#d3d3d3" |Not reported
 +
|-
 +
|[https://doi.org/10.1016/0140-6736(92)91708-G Fielding et al. 1992 (AXIS-CRC)]
 +
|Not reported
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|Portal venous chemotherapy
 
|Portal venous chemotherapy
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)92398-1/fulltext Riethmüller et al. 1994]
+
|[https://doi.org/10.1016/S0140-6736(94)92398-1 Riethmüller et al. 1994]
 
|1985-1990
 
|1985-1990
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
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| style="background-color:#fc8d59" |Seems to have inferior OS
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673695906967/fulltext Marsoni et al. 1995 (SITAC-01)]
+
|[https://doi.org/10.1016/s0140-6736(95)90696-7 Marsoni et al. 1995 (SITAC-01)]
−
|NR
+
|Not reported
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Colon_cancer#FULV|FULV]]
 
|[[Colon_cancer#FULV|FULV]]
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673695906967/fulltext Marsoni et al. 1995 (NCIC-CTG C-03)]
+
|[https://doi.org/10.1016/s0140-6736(95)90696-7 Marsoni et al. 1995 (NCIC-CTG C-03)]
−
|NR
+
|Not reported
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Colon_cancer#FULV|FULV]]
 
|[[Colon_cancer#FULV|FULV]]
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673695906967/fulltext Marsoni et al. 1995 (FFCD 8802)]
+
|[https://doi.org/10.1016/s0140-6736(95)90696-7 Marsoni et al. 1995 (FFCD 8802)]
−
|NR
+
|Not reported
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Colon_cancer#FULV|FULV]]
 
|[[Colon_cancer#FULV|FULV]]
Line 177: Line 190:
 
|1986-1991
 
|1986-1991
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|IP 5-FU
+
|[[Colon_cancer_-_historical#Fluorouracil_monotherapy|5-FU]]; IP
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of DFS60/OS60
+
| style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS60/OS60
 
|-
 
|-
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)08169-5/fulltext Rougier et al. 1998]
+
|[https://doi.org/10.1016/S0140-6736(97)08169-5 Rougier et al. 1998]
 
|1987-1993
 
|1987-1993
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
Line 186: Line 199:
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://link.springer.com/article/10.1007%2Fs00384-008-0543-8 Laffer et al. 2008 (SAKK 40/87)]
+
|[https://doi.org/10.1007/s00384-008-0543-8 Laffer et al. 2008 (SAKK 40/87)]
 
|1987-1993
 
|1987-1993
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|1. Portal venous 5-FU & Mitomycin<br> 2. 5-FU & Mitomycin
+
|1. Portal venous 5-FU & Mitomycin<br>2. [[#Fluorouracil_.26_Mitomycin_999|5-FU & Mitomycin]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
−
|[https://doi.org/10.1200/jco.1997.15.1.246 O'Connell et al. 1997]
+
|[https://doi.org/10.1200/jco.1997.15.1.246 O'Connell et al. 1997 (CALGB 8896)]
−
|1988-1989
+
|1988-02 to 1989-08
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
 
|[[Colon_cancer#FULV|FULV]]
 
|[[Colon_cancer#FULV|FULV]]
 
| style="background-color:#fc8d59" |Seems to have inferior OS
 
| style="background-color:#fc8d59" |Seems to have inferior OS
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010179/ Hasegawa et al. 2016]
 
−
|2004-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Leucovorin]]
 
−
| style="background-color:#d73027" |Inferior RFS
 
 
|-
 
|-
 
|}
 
|}
 
''<sup>1</sup>Reported efficacy for NSABP C-01 is based on the 2004 update.''<br>
 
''<sup>1</sup>Reported efficacy for NSABP C-01 is based on the 2004 update.''<br>
 
''No systemic treatment after surgery. The AXIS trial is named "AXIS-CRC" here so as not to confuse it with the AXIS trial in renal cell carcinoma. Note that Marsoni et al. 1995 (IMPACT) is a pooled report of three RCTs.''
 
''No systemic treatment after surgery. The AXIS trial is named "AXIS-CRC" here so as not to confuse it with the AXIS trial in renal cell carcinoma. Note that Marsoni et al. 1995 (IMPACT) is a pooled report of three RCTs.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
  
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
 +
</div></div>
  
 
===References===
 
===References===
  
−
#Lessner HE, Mayer RJ, Ellenberg SS, Holyoke ED; Gastrointestinal Tumor Study Group. Adjuvant therapy of colon cancer--results of a prospectively randomized trial. N Engl J Med. 1984 Mar 22;310(12):737-43. [https://www.nejm.org/doi/full/10.1056/NEJM198403223101201 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6366550 PubMed]
+
#Lessner HE, Mayer RJ, Ellenberg SS, Holyoke ED; Gastrointestinal Tumor Study Group. Adjuvant therapy of colon cancer--results of a prospectively randomized trial. N Engl J Med. 1984 Mar 22;310(12):737-43. [https://doi.org/10.1056/NEJM198403223101201 link to original article] [https://pubmed.ncbi.nlm.nih.gov/6366550/ PubMed]
−
#'''NSABP C-01:''' Wolmark N, Fisher B, Rockette H, Redmond C, Wickerham DL, Fisher ER, Jones J, Glass A, Lerner H, Lawrence W, Prager D, Wexler M, Evans J, Cruz A, Dimitrov N, Jochimsen P; NSABP. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst. 1988 Mar 2;80(1):30-6. [https://academic.oup.com/jnci/article-abstract/80/1/30/886027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3276901 PubMed]
+
#'''NSABP C-01:''' Wolmark N, Fisher B, Rockette H, Redmond C, Wickerham DL, Fisher ER, Jones J, Glass A, Lerner H, Lawrence W, Prager D, Wexler M, Evans J, Cruz A, Dimitrov N, Jochimsen P; NSABP. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst. 1988 Mar 2;80(1):30-6. [https://doi.org/10.1093/jnci/80.1.30 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3276901/ PubMed]
−
##'''Update:''' Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst. 2004 Aug 4;96(15):1128-32. [https://academic.oup.com/jnci/article/96/15/1128/2520926 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15292384 PubMed]
+
##'''Update:''' Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst. 2004 Aug 4;96(15):1128-32. [https://doi.org/10.1093/jnci/djh220 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15292384/ PubMed]
−
##'''Pooled update:''' Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. [https://link.springer.com/article/10.1245%2Fs10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144 PubMed]
+
##'''Pooled update:''' Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. [https://doi.org/10.1245/s10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144/ PubMed]
−
#'''SWOG S7510:''' Panettiere FJ, Goodman PJ, Costanzi JJ, Cruz AB Jr, Vaitkevicius VK, McCracken JD, Brownlee RW, Laufman L, Stephens RL, Bonnet J, Bottomley R, Rivkin S, Fletcher W, Oishi N, Chen TT. Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study. J Clin Oncol. 1988 Jun;6(6):947-54. [https://doi.org/10.1200/JCO.1988.6.6.947 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3286830 PubMed]
+
#'''SWOG S7510:''' Panettiere FJ, Goodman PJ, Costanzi JJ, Cruz AB Jr, Vaitkevicius VK, McCracken JD, Brownlee RW, Laufman L, Stephens RL, Bonnet J, Bottomley R, Rivkin S, Fletcher W, Oishi N, Chen TT. Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study. J Clin Oncol. 1988 Jun;6(6):947-54. [https://doi.org/10.1200/JCO.1988.6.6.947 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3286830/ PubMed]
−
#Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352-8. [https://www.nejm.org/doi/full/10.1056/NEJM199002083220602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2300087 PubMed]
+
# Laurie JA, Moertel CG, Fleming TR, Wieand HS, Leigh JE, Rubin J, McCormack GW, Gerstner JB, Krook JE, Malliard J, Twito DI, Morton RF, Tschetter LK, Barlow JF; The North Central Cancer Treatment Group and the Mayo Clinic. Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. J Clin Oncol. 1989 Oct;7(10):1447-56. [https://doi.org/10.1200/jco.1989.7.10.1447 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2778478/ PubMed]
−
##'''Update:''' Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321-6. [http://annals.org/aim/article-abstract/708455/fluorouracil-plus-levamisole-effective-adjuvant-therapy-after-resection-stage-iii link to original article] [https://pubmed.ncbi.nlm.nih.gov/7847642 PubMed]
+
#Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352-8. [https://doi.org/10.1056/NEJM199002083220602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2300087/ PubMed]
−
#'''NSABP C-02:''' Wolmark N, Rockette H, Wickerham DL, Fisher B, Redmond C, Fisher ER, Potvin M, Davies RJ, Jones J, Robidoux A, Wexler M, Gordon P, Cruz AB, Horsley S, Nims TA, Thirlwell M, Phillips WA, Prager D, Stern HS, Lerner HJ, Frazier TG. Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project protocol C-02. J Clin Oncol. 1990 Sep;8(9):1466-75. [https://doi.org/10.1200/JCO.1990.8.9.1466 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2202789 PubMed]
+
##'''Update:''' Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321-6. [https://doi.org/10.7326/0003-4819-122-5-199503010-00001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7847642/ PubMed]
−
##'''Pooled update:''' Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. [https://link.springer.com/article/10.1245%2Fs10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144 PubMed]
+
# '''SWOG S8591:''' Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352-8. [https://doi.org/10.1056/NEJM199002083220602 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2300087/ PubMed]
−
#'''AXIS:''' Fielding LP, Hittinger R, Grace RH, Fry JS. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Lancet. 1992 Aug 29;340(8818):502-6. [https://www.thelancet.com/journals/lancet/article/PII0140-6736(92)91708-G/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/1354275 PubMed]
+
## '''Update:''' Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321-6. [https://doi.org/10.7326/0003-4819-122-5-199503010-00001 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7847642/ PubMed]
−
#Riethmüller G, Schneider-Gädicke E, Schlimok G, Schmiegel W, Raab R, Höffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J; German Cancer Aid 17-1A Study Group. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. Lancet. 1994 May 14;343(8907):1177-83. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(94)92398-1/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/7909866 PubMed]
+
#'''NSABP C-02:''' Wolmark N, Rockette H, Wickerham DL, Fisher B, Redmond C, Fisher ER, Potvin M, Davies RJ, Jones J, Robidoux A, Wexler M, Gordon P, Cruz AB, Horsley S, Nims TA, Thirlwell M, Phillips WA, Prager D, Stern HS, Lerner HJ, Frazier TG. Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project protocol C-02. J Clin Oncol. 1990 Sep;8(9):1466-75. [https://doi.org/10.1200/JCO.1990.8.9.1466 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2202789/ PubMed]
−
#'''SAKK 40/81:''' Laffer U, Metzger U, Aeberhard P, Maibach R, Castiglione M, Goldhirsch A; Swiss Group for Clinical Cancer Research. Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer. Lancet. 1995 Feb 11;345(8946):349-53. [https://www.thelancet.com/journals/lancet/article/PIIS0140673695903402/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/7845115 PubMed]
+
##'''Pooled update:''' Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. [https://doi.org/10.1245/s10434-009-0881-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2935319/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20082144/ PubMed]
−
#'''IMPACT:''' Marsoni S, Labianca R, Pancera G, Torri V, Zaniboni A, Erlichman C, Pater J, Shepherd L, Zee B, Seitz JF, Milan C, Pignon JP; International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet. 1995 Apr 15;345(8955):939-44. [https://www.thelancet.com/journals/lancet/article/PIIS0140673695906967/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/7715291 PubMed]
+
#'''AXIS:''' Fielding LP, Hittinger R, Grace RH, Fry JS. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Lancet. 1992 Aug 29;340(8818):502-6. [https://doi.org/10.1016/0140-6736(92)91708-G link to original article] [https://pubmed.ncbi.nlm.nih.gov/1354275/ PubMed]
−
#O'Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, Wieand HS. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997 Jan;15(1):246-50. [https://doi.org/10.1200/jco.1997.15.1.246 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/8996149 PubMed]
+
#Riethmüller G, Schneider-Gädicke E, Schlimok G, Schmiegel W, Raab R, Höffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J; German Cancer Aid 17-1A Study Group. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. Lancet. 1994 May 14;343(8907):1177-83. [https://doi.org/10.1016/S0140-6736(94)92398-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7909866/ PubMed]
−
##'''Pooled update:''' Erlichman C, O'Connell M, Kahn M, Marsoni S, Torri V, Tardio B, Zaniboni A, Pancera G, Martignoni G, Labianca R, Barni A, Seitz JF, Milan C, Bedenne L, Giovannini M, Letreut YP, Skillings J, Shepard L, Zee B, Petrioli R, Francini G; International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol. 1999 May;17(5):1356-63. [https://doi.org/10.1200/JCO.1999.17.5.1356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334519 PubMed]
+
#'''SAKK 40/81:''' Laffer U, Metzger U, Aeberhard P, Maibach R, Castiglione M, Goldhirsch A; Swiss Group for Clinical Cancer Research. Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer. Lancet. 1995 Feb 11;345(8946):349-53. [https://doi.org/10.1016/s0140-6736(95)90340-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7845115/ PubMed]
−
#Rougier P, Sahmoud T, Nitti D, Curran D, Doci R, De Waele B, Nakajima T, Rauschecker H, Labianca R, Pector JC, Marsoni S, Apolone G, Lasser P, Couvreur ML, Wils J; [[Study_Groups#EORTC|EORTC]] Gastrointestinal Tract Cancer Cooperative Group; Gruppo Interdisciplinare Valutazione Interventi in Oncologia; Japanese Foundation for Cancer Research. Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. Lancet. 1998 Jun 6;351(9117):1677-81. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(97)08169-5/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/9734883 PubMed]
+
#'''IMPACT:''' Marsoni S, Labianca R, Pancera G, Torri V, Zaniboni A, Erlichman C, Pater J, Shepherd L, Zee B, Seitz JF, Milan C, Pignon JP; International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet. 1995 Apr 15;345(8955):939-44. [https://doi.org/10.1016/s0140-6736(95)90696-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7715291/ PubMed]
−
#Vaillant JC, Nordlinger B, Deuffic S, Arnaud JP, Pelissier E, Favre JP, Jaeck D, Fourtanier G, Grandjean JP, Marre P, Letoublon C. Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: a multicenter phase III trial. Ann Surg. 2000 Apr;231(4):449-56. [https://insights.ovid.com/pubmed?pmid=10749603 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421018/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/10749603 PubMed]
+
##'''Update:''' Zaniboni A, Labianca R, Marsoni S, Torri V, Mosconi P, Grilli R, Apolone G, Cifani S, Tinazzi A; Gruppo Italiano Valutazione Interventi in Oncologia. GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Cancer. 1998 Jun 1;82(11):2135-44. [https://doi.org/10.1002/(sici)1097-0142(19980601)82:11%3C2135::aid-cncr7%3E3.0.co;2-u link to original article] [https://pubmed.ncbi.nlm.nih.gov/9610692/ PubMed]
−
#'''SAKK 40/87:''' Laffer U, Metzger U, Aeberhard P, Lorenz M, Harder F, Maibach R, Zuber M, Herrmann R. Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial. Int J Colorectal Dis. 2008 Dec;23(12):1233-41. Epub 2008 Aug 8. [https://link.springer.com/article/10.1007%2Fs00384-008-0543-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18688620 PubMed]
+
#'''CALGB 8896:''' O'Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, Wieand HS. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997 Jan;15(1):246-50. [https://doi.org/10.1200/jco.1997.15.1.246 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8996149/ PubMed]
−
#Hasegawa K, Saiura A, Takayama T, Miyagawa S, Yamamoto J, Ijichi M, Teruya M, Yoshimi F, Kawasaki S, Koyama H, Oba M, Takahashi M, Mizunuma N, Matsuyama Y, Watanabe T, Makuuchi M, Kokudo N. Adjuvant oral uracil-tegafur with leucovorin for colorectal cancer liver metastases: A randomized controlled trial. PLoS One. 2016 Sep 2;11(9):e0162400. eCollection 2016. [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0162400 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5010179/ link to PMC article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/27588959 PubMed] UMIN C000000013
+
##'''Pooled update:''' Erlichman C, O'Connell M, Kahn M, Marsoni S, Torri V, Tardio B, Zaniboni A, Pancera G, Martignoni G, Labianca R, Barni A, Seitz JF, Milan C, Bedenne L, Giovannini M, Letreut YP, Skillings J, Shepard L, Zee B, Petrioli R, Francini G; International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol. 1999 May;17(5):1356-63. [https://doi.org/10.1200/JCO.1999.17.5.1356 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10334519/ PubMed]
−
#'''POLEM:''' NCT03827044
+
#Rougier P, Sahmoud T, Nitti D, Curran D, Doci R, De Waele B, Nakajima T, Rauschecker H, Labianca R, Pector JC, Marsoni S, Apolone G, Lasser P, Couvreur ML, Wils J; [[Study_Groups#EORTC|EORTC]] Gastrointestinal Tract Cancer Cooperative Group; Gruppo Interdisciplinare Valutazione Interventi in Oncologia; Japanese Foundation for Cancer Research. Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. Lancet. 1998 Jun 6;351(9117):1677-81. [https://doi.org/10.1016/S0140-6736(97)08169-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9734883/ PubMed]
 +
#Vaillant JC, Nordlinger B, Deuffic S, Arnaud JP, Pelissier E, Favre JP, Jaeck D, Fourtanier G, Grandjean JP, Marre P, Letoublon C. Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: a multicenter phase III trial. Ann Surg. 2000 Apr;231(4):449-56. [https://doi.org/10.1097/00000658-200004000-00001 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1421018/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/10749603/ PubMed]
 +
#'''SAKK 40/87:''' Laffer U, Metzger U, Aeberhard P, Lorenz M, Harder F, Maibach R, Zuber M, Herrmann R. Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial. Int J Colorectal Dis. 2008 Dec;23(12):1233-41. Epub 2008 Aug 8. [https://doi.org/10.1007/s00384-008-0543-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18688620/ PubMed]
 +
#'''ADAGE:''' [https://clinicaltrials.gov/study/NCT02355379 NCT02355379]
 +
#'''POLEM:''' [https://clinicaltrials.gov/study/NCT03827044 NCT03827044]
  
 
==Placebo==
 
==Placebo==
−
{| class="wikitable" style="float:right; margin-left: 5px;"
+
<div class="toccolours" style="background-color:#eeeeee">
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
 
===Regimen===
 
===Regimen===
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
{| class="wikitable sortable" style="width: 100%; text-align:center;"  
 
!style="width: 20%"|Study
 
!style="width: 20%"|Study
−
!style="width: 20%"|Years of enrollment
+
!style="width: 20%"|Dates of enrollment
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
!style="width: 20%"|Comparator
 
!style="width: 20%"|Comparator
Line 251: Line 260:
 
|2002-2004
 
|2002-2004
 
| style="background-color:#1a9851" |Phase 3 (C)
 
| style="background-color:#1a9851" |Phase 3 (C)
−
|Rofecoxib
+
|[[#Rofecoxib_monotherapy_999|Rofecoxib]]
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
|-
 
|-
 
|}
 
|}
 
''No active antineoplastic treatment.''
 
''No active antineoplastic treatment.''
 +
<div class="toccolours" style="background-color:#cbd5e8">
 
====Preceding treatment====
 
====Preceding treatment====
  
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
 
*[[Surgery#Colorectal_cancer_surgery|Surgery]]
−
 
+
</div></div>
−
===References===
 
−
 
 
−
#'''VICTOR:''' Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010 Oct 20;28(30):4575-80. Epub 2010 Sep 13. [https://doi.org/10.1200/JCO.2010.29.6244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20837956 PubMed] NCT00031863
 
−
 
 
−
=Therapy for oligometastatic disease, including perioperative therapy and hyperthermic intra-peritoneal chemotherapy=
 
−
==Observation==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140673694907501/fulltext Allen-Mersh et al. 1994]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Hepatic_arterial_chemotherapy|Hepatic arterial chemotherapy]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJM199912303412702 Kemeny et al. 1999]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Hepatic_arterial_chemotherapy|Hepatic arterial chemotherapy]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2006.06.8353 Portier et al. 2006 (FFCD 9002)]
 
−
|1991-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#FULV_2|FULV]]
 
−
| style="background-color:#fee08b" |Might have inferior PFS<sup>1</sup>
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277487/ Nordlinger et al. 2008 (EORTC 40983)]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#FOLFOX4_2|FOLFOX4]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for FFCD 9002 is based on the 2008 pooled update.''<br>
 
−
''No treatment other than surgical resection of oligometastatic disease.''
 
−
===References===
 
−
#Allen-Mersh TG, Earlam S, Fordy C, Abrams K, Houghton J. Quality of life and survival with continuous hepatic-artery floxuridine infusion for colorectal liver metastases. Lancet. 1994 Nov 5;344(8932):1255-60. [https://www.thelancet.com/journals/lancet/article/PIIS0140673694907501/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/7526096 PubMed]
 
−
#Kemeny N, Huang Y, Cohen AM, Shi W, Conti JA, Brennan MF, Bertino JR, Turnbull AD, Sullivan D, Stockman J, Blumgart LH, Fong Y. Hepatic arterial infusion of chemotherapy after resection of hepatic metastases from colorectal cancer. N Engl J Med. 1999 Dec 30;341(27):2039-48. [https://www.nejm.org/doi/full/10.1056/NEJM199912303412702 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10615075 PubMed]
 
−
#'''FFCD 9002:''' Portier G, Elias D, Bouche O, Rougier P, Bosset JF, Saric J, Belghiti J, Piedbois P, Guimbaud R, Nordlinger B, Bugat R, Lazorthes F, Bedenne L. Multicenter randomized trial of adjuvant fluorouracil and folinic acid compared with surgery alone after resection of colorectal liver metastases: FFCD ACHBTH AURC 9002 trial. J Clin Oncol. 2006 Nov 1;24(31):4976-82. [https://doi.org/10.1200/JCO.2006.06.8353 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17075115 PubMed]
 
−
##'''Pooled update:''' Mitry E, Fields AL, Bleiberg H, Labianca R, Portier G, Tu D, Nitti D, Torri V, Elias D, O'Callaghan C, Langer B, Martignoni G, Bouché O, Lazorthes F, Van Cutsem E, Bedenne L, Moore MJ, Rougier P. Adjuvant chemotherapy after potentially curative resection of metastases from colorectal cancer: a pooled analysis of two randomized trials. J Clin Oncol. 2008 Oct 20;26(30):4906-11. Epub 2008 Sep 15. [https://doi.org/10.1200/JCO.2008.17.3781 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18794541 PubMed]
 
−
#'''EORTC 40983:''' Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Collette L, Praet M, Bethe U, Van Cutsem E, Scheithauer W, Gruenberger T; [[Study_Groups#EORTC|EORTC]] Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und-tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie; Australasian Gastro-Intestinal Trials Group; Fédération Francophone de Cancérologie Digestive. Perioperative chemotherapy with FOLFOX4 and surgery versus surgery alone for resectable liver metastases from colorectal cancer (EORTC Intergroup trial 40983): a randomised controlled trial. Lancet. 2008 Mar 22;371(9617):1007-16. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(08)60455-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2277487/ link to PMC article] '''does not contain protocol''' [https://pubmed.ncbi.nlm.nih.gov/18358928 PubMed] NCT00006479
 
−
##'''Update:''' Nordlinger B, Sorbye H, Glimelius B, Poston GJ, Schlag PM, Rougier P, Bechstein WO, Primrose JN, Walpole ET, Finch-Jones M, Jaeck D, Mirza D, Parks RW, Mauer M, Tanis E, Van Cutsem E, Scheithauer W, Gruenberger T; [[Study_Groups#EORTC|EORTC]] Gastro-Intestinal Tract Cancer Group; Cancer Research UK; Arbeitsgruppe Lebermetastasen und–tumoren in der Chirurgischen Arbeitsgemeinschaft Onkologie; Australasian Gastro-Intestinal Trials Group; Fédération Francophone de Cancérologie Digestive. Perioperative FOLFOX4 chemotherapy and surgery versus surgery alone for resectable liver metastases from colorectalcancer (EORTC 40983): long-term results of a randomised, controlled, phase 3 trial. Lancet Oncol. 2013 Nov;14(12):1208-15. Epub 2013 Oct 11. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70447-9/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/24120480 PubMed]
 
−
#'''ECOG E1292:''' NCT00002525
 
−
 
 
−
=Metastatic disease, first-line=
 
−
==Best supportive care==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19950915)76:6%3C961::AID-CNCR2820760608%3E3.0.CO;2-A Goldberg et al. 1995]
 
−
|1988-1992
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|Octreotide
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoints of PFS/OS
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a059365 Smyth et al. 1995 (N-trial)]
 
−
|1989-1992
 
−
|style="background-color:#1a9851"|Phase III (C)
 
−
|TCNU
 
−
| style="background-color:#ffffbf" |Did not meet endpoint of OS50%
 
−
|-
 
−
|}
 
−
''No active treatment.''
 
−
===References===
 
−
# Goldberg RM, Moertel CG, Wieand HS, Krook JE, Schutt AJ, Veeder MH, Mailliard JA, Dalton RJ; North Central Cancer Treatment Group. A phase III evaluation of a somatostatin analogue (octreotide) in the treatment of patients with asymptomatic advanced colon carcinoma. Cancer. 1995 Sep 15;76(6):961-6. [https://onlinelibrary.wiley.com/doi/abs/10.1002/1097-0142(19950915)76:6%3C961::AID-CNCR2820760608%3E3.0.CO;2-A link to original article] [https://pubmed.ncbi.nlm.nih.gov/8625221 PubMed]
 
−
# '''N-trial:''' Smyth JF, Hardcastle JD, Denton G, Alderson D, Grace RH, Mansi JL, Yosef HM, Nordle O, Lauri H, Wählby S. Two phase III trials of tauromustine (TCNU) in advanced colorectal cancer. Ann Oncol. 1995 Nov;6(9):948-9. [https://doi.org/10.1093/oxfordjournals.annonc.a059365 link to original article] [https://pubmed.ncbi.nlm.nih.gov/8624301 PubMed]
 
−
 
 
−
=Maintenance after first-line therapy=
 
−
==Observation==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdv011 Koeberle et al. 2015 (SAKK 41/06)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Bevacizumab_monotherapy|Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior TTP
 
−
|-
 
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62004-3/fulltext Simkens et al. 2015 (CAIRO3)]
 
−
|2007-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Capecitabine_.26_Bevacizumab_2|CAP-B]]
 
−
| style="background-color:#d73027" |Inferior PFS2
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdw101 Luo et al. 2016]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Capecitabine_monotherapy|Capecitabine]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.75.2931 Aparicio et al. 2018 (PRODIGE 9)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Bevacizumab_monotherapy|Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of TCD
 
−
|-
 
−
|}
 
−
''No further treatment after first-line induction.''
 
−
====Preceding treatment====
 
−
 
 
−
*CAIRO3: [[Colon_cancer#CapeOx_.26_Bevacizumab|CAPOX-B]] x 6
 
−
*Luo et al. 2016: [[Colon_cancer#mFOLFOX6_3|FOLFOX]] or [[Colon_cancer#CapeOx_2|XELOX]]
 
−
 
 
−
===References===
 
−
#'''SAKK 41/06:''' Koeberle D, Betticher DC, von Moos R, Dietrich D, Brauchli P, Baertschi D, Matter K, Winterhalder R, Borner M, Anchisi S, Moosmann P, Kollar A, Saletti P, Roth A, Frueh M, Kueng M, Popescu RA, Schacher S, Hess V, Herrmann R. Bevacizumab continuation versus no continuation after first-line chemotherapy plus bevacizumab in patients with metastatic colorectal cancer: a randomized phase III non-inferiority trial (SAKK 41/06). Ann Oncol. 2015 Apr;26(4):709-14. Epub 2015 Jan 20. [https://doi.org/10.1093/annonc/mdv011 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25605741 PubMed] NCT00544700
 
−
#'''CAIRO3:''' Simkens LH, van Tinteren H, May A, ten Tije AJ, Creemers GJ, Loosveld OJ, de Jongh FE, Erdkamp FL, Erjavec Z, van der Torren AM, Tol J, Braun HJ, Nieboer P, van der Hoeven JJ, Haasjes JG, Jansen RL, Wals J, Cats A, Derleyn VA, Honkoop AH, Mol L, Punt CJ, Koopman M; Dutch Colorectal Cancer Group. Maintenance treatment with capecitabine and bevacizumab in metastatic colorectal cancer (CAIRO3): a phase 3 randomised controlled trial of the Dutch Colorectal Cancer Group. Lancet. 2015 May 9;385(9980):1843-52. Epub 2015 Apr 7. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(14)62004-3/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25862517 PubMed] NCT00442637
 
−
##'''Update:''' Goey KKH, Elias SG, van Tinteren H, Laclé MM, Willems SM, Offerhaus GJA, de Leng WWJ, Strengman E, Ten Tije AJ, Creemers GM, van der Velden A, de Jongh FE, Erdkamp FLG, Tanis BC, Punt CJA, Koopman M. Maintenance treatment with capecitabine and bevacizumab versus observation in metastatic colorectal cancer: updated results and molecular subgroup analyses of the phase 3 CAIRO3 study. Ann Oncol. 2017 Sep 1;28(9):2128-2134. [https://doi.org/10.1093/annonc/mdx322 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28911067 PubMed]
 
−
#Luo HY, Li YH, Wang W, Wang ZQ, Yuan X, Ma D, Wang FH, Zhang DS, Lin DR, Lin YC, Jia J, Hu XH, Peng JW, Xu RH. Single-agent capecitabine as maintenance therapy after induction of XELOX (or FOLFOX) in first-line treatment of metastatic colorectal cancer: randomized clinical trial of efficacy and safety. Ann Oncol. 2016 Jun;27(6):1074-81. Epub 2016 Mar 2. [https://doi.org/10.1093/annonc/mdw101 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/26940686 PubMed] NCT02027363
 
−
#'''PRODIGE 9:''' Aparicio T, Ghiringhelli F, Boige V, Le Malicot K, Taieb J, Bouché O, Phelip JM, François E, Borel C, Faroux R, Dahan L, Jacquot S, Genet D, Khemissa F, Suc E, Desseigne F, Texereau P, Lepage C, Bennouna J; PRODIGE 9 Investigators. Bevacizumab maintenance versus no maintenance during chemotherapy-free intervals in metastatic colorectal cancer: a randomized phase III trial (PRODIGE 9). J Clin Oncol. 2018 Mar 1;36(7):674-681. Epub 2018 Jan 18. [https://doi.org/10.1200/JCO.2017.75.2931 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29346040 PubMed] NCT00952029
 
−
 
 
−
=Advanced or metastatic disease, subsequent lines of therapy=
 
−
==Best supportive care==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2898%2902309-5/fulltext Cunningham et al. 1998 (V301)]
 
−
|1995-NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Irinotecan_monotherapy_3|Irinotecan]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJMoa071834 Jonker et al. 2007 (NCIC-CTG CO.17)]
 
−
|2003-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer,_RAS_wild-type#Cetuximab_monotherapy_2|Cetuximab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.1620 Van Cutsem et al. 2007 (20020408)]
 
−
|2004-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer,_RAS_wild-type#Panitumumab_monotherapy|Panitumumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104888/ Kim et al. 2016 (20100007)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer,_RAS_wild-type#Panitumumab_monotherapy|Panitumumab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|}
 
−
 
 
−
''No treatment except for supportive care.''
 
−
 
 
−
===References===
 
−
 
 
−
#'''V301:''' Cunningham D, Pyrhönen S, James RD, Punt CJ, Hickish TF, Heikkila R, Johannesen TB, Starkhammar H, Topham CA, Awad L, Jacques C, Herait P. Randomised trial of irinotecan plus supportive care versus supportive care alone after fluorouracil failure for patients with metastatic colorectal cancer. Lancet. 1998 Oct 31;352(9138):1413-8. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2898%2902309-5/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/9807987 PubMed]
 
−
<!-- Presented at the 97th Annual Meeting of the American Association for Cancer Research, April 1-5, 2006, Washington, DC; 2nd Annual Conference of the Hematology/Oncology Pharmacy Association, June 15-18, 2006, Orlando, FL; 8th Annual Conference of the World Congress on Gastrointestinal Cancer, June 28-July 1, 2006, Barcelona, Spain; and at the 31st European Society of Medical Oncology Congress, September 29-October 3, 2006, Istanbul, Turkey. -->
 
−
#'''20020408:''' Van Cutsem E, Peeters M, Siena S, Humblet Y, Hendlisz A, Neyns B, Canon JL, Van Laethem JL, Maurel J, Richardson G, Wolf M, Amado RG. Open-label phase III trial of panitumumab plus best supportive care compared with best supportive care alone in patients with chemotherapy-refractory metastatic colorectal cancer. J Clin Oncol. 2007 May 1;25(13):1658-64. [https://doi.org/10.1200/jco.2006.08.1620 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/17470858 PubMed] NCT00113763
 
−
<!-- # Bristol-Myers Squibb and ImClone. A Phase III Randomized Study of Cetuximab (Erbitux, C225) and Best Supportive Care Versus Best Supportive Care in Patients with Pretreated Metastatic Epidermal Growth Factor Receptor (EGFR)-Positive Colorectal Carcinoma. Final Clinical Study Report for CA225025. 2007 Mar 5. [http://ctr.bms.com/pdf//CA225025.pdf link to original report] '''contains verified protocol''' -->
 
−
#'''NCIC-CTG CO.17:''' Jonker DJ, O'Callaghan CJ, Karapetis CS, Zalcberg JR, Tu D, Au HJ, Berry SR, Krahn M, Price T, Simes RJ, Tebbutt NC, van Hazel G, Wierzbicki R, Langer C, Moore MJ. Cetuximab for the treatment of colorectal cancer. N Engl J Med. 2007 Nov 15;357(20):2040-8. [https://www.nejm.org/doi/full/10.1056/NEJMoa071834 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/18003960 PubMed] NCT00079066
 
−
##'''Subgroup analysis:''' Karapetis CS, Khambata-Ford S, Jonker DJ, O'Callaghan CJ, Tu D, Tebbutt NC, Simes RJ, Chalchal H, Shapiro JD, Robitaille S, Price TJ, Shepherd L, Au HJ, Langer C, Moore MJ, Zalcberg JR. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N Engl J Med. 2008 Oct 23;359(17):1757-65. [https://www.nejm.org/doi/10.1056/NEJMoa0804385 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18946061 PubMed]
 
−
##'''Subgroup analysis:''' Asmis TR, Powell E, Karapetis CS, Jonker DJ, Tu D, Jeffery M, Pavlakis N, Gibbs P, Zhu L, Dueck DA, Whittom R, Langer C, O'Callaghan CJ. Comorbidity, age and overall survival in cetuximab-treated patients with advanced colorectal cancer (ACRC)--results from NCIC-CTG CO.17: a phase III trial of cetuximab versus best supportive care. Ann Oncol. 2011 Jan;22(1):118-26. Epub 2010 Jul 5. [https://doi.org/10.1093/annonc/mdq309 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/20603436 PubMed]
 
−
#'''20100007:''' Kim TW, Elme A, Kusic Z, Park JO, Udrea AA, Kim SY, Ahn JB, Valencia RV, Krishnan S, Bilic A, Manojlovic N, Dong J, Guan X, Lofton-Day C, Jung AS, Vrdoljak E. A phase 3 trial evaluating panitumumab plus best supportive care vs best supportive care in chemorefractory wild-type KRAS or RAS metastatic colorectal cancer. Br J Cancer. 2016 Nov 8;115(10):1206-1214. Epub 2016 Oct 13. [https://doi.org/10.1038/bjc.2016.309 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5104888/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27736842 PubMed] NCT01412957
 
−
 
 
−
==Placebo==
 
−
{| class="wikitable" style="float:right; margin-left: 5px;"
 
−
|-
 
−
|[[#top|back to top]]
 
−
|}
 
−
 
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2004.10.037 Rao et al. 2004]
 
−
|2000-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Tipifarnib
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70345-5/fulltext Yoshino et al. 2012]
 
−
|2009-2010
 
−
| style="background-color:#1a9851" |Randomized Phase II (C)
 
−
|[[Colon_cancer#Trifluridine_and_tipiracil_monotherapy|Trifluridine and tipiracil]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961900-X/fulltext Grothey et al. 2012 (CORRECT)]
 
−
|2010-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Regorafenib_monotherapy_2|Regorafenib]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70156-7/fulltext Li et al. 2015 (CONCUR)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Regorafenib_monotherapy_2|Regorafenib]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.nejm.org/doi/full/10.1056/NEJMoa1414325 Mayer et al. 2015 (RECOURSE)]
 
−
|2012-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Trifluridine_and_tipiracil_monotherapy|Trifluridine and tipiracil]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.thelancet.com/journals/langas/article/PIIS2468-1253(18)30009-8/fulltext Jonker et al. 2018 (NCIC-CTG CO.23)]
 
−
|2013-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Napabucasin
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2017.74.3245 Xu et al. 2017 (TERRA)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Colon_cancer#Trifluridine_and_tipiracil_monotherapy|Trifluridine and tipiracil]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30006-2/fulltext Hickish et al. 2017 (2014-PT026)]
 
−
|2014-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|MABp1
 
−
| style="background-color:#d73027" |Inferior primary endpoint
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/fullarticle/2685988 Li et al. 2018 (FRESCO)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Fruquintinib
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158765/ Van Cutsem et al. 2018 (LUME-Colon 1)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Nintedanib
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488800/ Chi et al. 2021 (ALTER0703)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|Anlotinib
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''No active antineoplastic treatment.''
 
 
===References===
 
===References===
  
−
#Rao S, Cunningham D, de Gramont A, Scheithauer W, Smakal M, Humblet Y, Kourteva G, Iveson T, Andre T, Dostalova J, Illes A, Belly R, Perez-Ruixo JJ, Park YC, Palmer PA. Phase III double-blind placebo-controlled study of farnesyl transferase inhibitor R115777 in patients with refractory advanced colorectal cancer. J Clin Oncol. 2004 Oct 1;22(19):3950-7. [https://doi.org/10.1200/JCO.2004.10.037 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15459217 PubMed]
+
#'''VICTOR:''' Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010 Oct 20;28(30):4575-80. Epub 2010 Sep 13. [https://doi.org/10.1200/JCO.2010.29.6244 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20837956/ PubMed] [https://clinicaltrials.gov/study/NCT00031863 NCT00031863]
−
#Yoshino T, Mizunuma N, Yamazaki K, Nishina T, Komatsu Y, Baba H, Tsuji A, Yamaguchi K, Muro K, Sugimoto N, Tsuji Y, Moriwaki T, Esaki T, Hamada C, Tanase T, Ohtsu A. TAS-102 monotherapy for pretreated metastatic colorectal cancer: a double-blind, randomised, placebo-controlled phase 2 trial. Lancet Oncol. 2012 Oct;13(10):993-1001. Epub 2012 Aug 28. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(12)70345-5/fulltext link to original article] '''contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/22951287 PubMed] JapicCTI-090880
 
−
<!-- # '''Abstract:''' Axel Grothey, Alberto F. Sobrero, Salvatore Siena, Alfredo Falcone, Marc Ychou, Heinz-Josef Lenz, Takayuki Yoshino, Frank Cihon, Andrea Wagner, Eric Van Cutsem, on behalf of the CORRECT Study Team. Results of a phase III randomized, double-blind, placebo-controlled, multicenter trial (CORRECT) of regorafenib plus best supportive care (BSC) versus placebo plus BSC in patients (pts) with metastatic colorectal cancer (mCRC) who have progressed after standard therapies. 2012 ASCO Gastrointestinal Cancers Symposium abstract LBA385 [http://www.asco.org/ASCOv2/Meetings/Abstracts?&vmview=abst_detail_view&confID=115&abstractID=87795 link to abstract] '''contains verified protocol''' -->
 
−
#'''CORRECT:''' Grothey A, Van Cutsem E, Sobrero A, Siena S, Falcone A, Ychou M, Humblet Y, Bouché O, Mineur L, Barone C, Adenis A, Tabernero J, Yoshino T, Lenz HJ, Goldberg RM, Sargent DJ, Cihon F, Cupit L, Wagner A, Laurent D; CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet. 2013 Jan 26;381(9863):303-12. Epub 2012 Nov 22. [https://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2812%2961900-X/fulltext link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/23177514 PubMed] NCT01103323
 
−
##'''Dataset:''' [https://www.projectdatasphere.org/projectdatasphere/html/content/273 Project Data Sphere]
 
−
#'''CONCUR:''' Li J, Qin S, Xu R, Yau TC, Ma B, Pan H, Xu J, Bai Y, Chi Y, Wang L, Yeh KH, Bi F, Cheng Y, Le AT, Lin JK, Liu T, Ma D, Kappeler C, Kalmus J, Kim TW; CONCUR Investigators. Regorafenib plus best supportive care versus placebo plus best supportive care in Asian patients with previously treated metastatic colorectal cancer (CONCUR): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2015 Jun;16(6):619-29. Epub 2015 May 13. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(15)70156-7/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/25981818 PubMed] NCT01584830
 
−
#'''RECOURSE:''' Mayer RJ, Van Cutsem E, Falcone A, Yoshino T, Garcia-Carbonero R, Mizunuma N, Yamazaki K, Shimada Y, Tabernero J, Komatsu Y, Sobrero A, Boucher E, Peeters M, Tran B, Lenz HJ, Zaniboni A, Hochster H, Cleary JM, Prenen H, Benedetti F, Mizuguchi H, Makris L, Ito M, Ohtsu A; RECOURSE Study Group. Randomized trial of TAS-102 for refractory metastatic colorectal cancer. N Engl J Med. 2015 May 14;372(20):1909-19. [https://www.nejm.org/doi/full/10.1056/NEJMoa1414325 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/25970050 PubMed] NCT01607957
 
−
##'''Subgroup analysis:''' Van Cutsem E, Mayer RJ, Laurent S, Winkler R, Grávalos C, Benavides M, Longo-Munoz F, Portales F, Ciardiello F, Siena S, Yamaguchi K, Muro K, Denda T, Tsuji Y, Makris L, Loehrer P, Lenz HJ, Ohtsu A; RECOURSE Study Group. The subgroups of the phase III RECOURSE trial of trifluridine/tipiracil (TAS-102) versus placebo with best supportive care in patients with metastatic colorectal cancer. Eur J Cancer. 2018 Feb;90:63-72. Epub 2017 Dec 21. [https://doi.org/10.1016/j.ejca.2017.10.009 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29274618 PubMed]
 
−
#'''2014-PT026:''' Hickish T, Andre T, Wyrwicz L, Saunders M, Sarosiek T, Kocsis J, Nemecek R, Rogowski W, Lesniewski-Kmak K, Petruzelka L, Apte RN, Mohanty P, Stecher M, Simard J, de Gramont A. MABp1 as a novel antibody treatment for advanced colorectal cancer: a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2017 Feb;18(2):192-201. Epub 2017 Jan 14. [https://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30006-2/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/28094194 PubMed] NCT02138422
 
−
#'''TERRA:''' Xu J, Kim TW, Shen L, Sriuranpong V, Pan H, Xu R, Guo W, Han SW, Liu T, Park YS, Shi C, Bai Y, Bi F, Ahn JB, Qin S, Li Q, Wu C, Ma D, Lin D, Li J. Results of a randomized, double-blind, placebo-controlled, phase III trial of trifluridine/tipiracil (TAS-102) monotherapy in Asian patients with previously treated metastatic colorectal cancer: The TERRA study. J Clin Oncol. 2018 Feb 1;36(4):350-358. Epub 2017 Dec 7. [https://doi.org/10.1200/JCO.2017.74.3245 link to original article] '''contains verified protocol''' [https://pubmed.ncbi.nlm.nih.gov/29215955 PubMed] NCT01955837
 
−
#'''NCIC-CTG CO.23:''' Jonker DJ, Nott L, Yoshino T, Gill S, Shapiro J, Ohtsu A, Zalcberg J, Vickers MM, Wei AC, Gao Y, Tebbutt NC, Markman B, Price T, Esaki T, Koski S, Hitron M, Li W, Li Y, Magoski NM, Li CJ, Simes J, Tu D, O'Callaghan CJ. Napabucasin versus placebo in refractory advanced colorectal cancer: a randomised phase 3 trial. Lancet Gastroenterol Hepatol. 2018 Apr;3(4):263-270. Epub 2018 Feb 1. [https://www.thelancet.com/journals/langas/article/PIIS2468-1253(18)30009-8/fulltext link to original article] [https://pubmed.ncbi.nlm.nih.gov/29397354 PubMed] NCT01830621
 
−
#'''FRESCO:''' Li J, Qin S, Xu RH, Shen L, Xu J, Bai Y, Yang L, Deng Y, Chen ZD, Zhong H, Pan H, Guo W, Shu Y, Yuan Y, Zhou J, Xu N, Liu T, Ma D, Wu C, Cheng Y, Chen D, Li W, Sun S, Yu Z, Cao P, Chen H, Wang J, Wang S, Wang H, Fan S, Hua Y, Su W. Effect of fruquintinib vs placebo on overall survival in patients with previously treated metastatic colorectal cancer: the FRESCO randomized clinical trial. JAMA. 2018 Jun 26;319(24):2486-2496. [https://jamanetwork.com/journals/jama/fullarticle/2685988 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29946728 PubMed] NCT02314819
 
−
#'''LUME-Colon 1:''' Van Cutsem E, Yoshino T, Lenz HJ, Lonardi S, Falcone A, Limón ML, Saunders M, Sobrero A, Park YS, Ferreiro R, Hong YS, Tomasek J, Taniguchi H, Ciardiello F, Stoehr J, Oum'Hamed Z, Vlassak S, Studeny M, Argiles G. Nintedanib for the treatment of patients with refractory metastatic colorectal cancer (LUME-Colon 1): a phase III, international, randomized, placebo-controlled study. Ann Oncol. 2018 Sep 1;29(9):1955-1963. [https://doi.org/10.1093/annonc/mdy241 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6158765/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30010751 PubMed] NCT02149108
 
−
#'''ALTER0703:''' Chi Y, Shu Y, Ba Y, Bai Y, Qin B, Wang X, Xiong J, Xu N, Zhang H, Zhou J, Xu J, Cheng Y, Feng J, Hu C, Chen Y, Chen Z, Wang J, Dang C, Wang J, Wan Y, Tang Y, Wang D, Liu J, Wu M, Deng Y, Li X, Li Y, Dong J, Jiang D, Li G, Wu Q, Li J, Qi Y, Sun Y, Cai J. Anlotinib Monotherapy for Refractory Metastatic Colorectal Cancer: A Double-Blinded, Placebo-Controlled, Randomized Phase III Trial (ALTER0703). Oncologist. 2021 Oct;26(10):e1693-e1703. Epub 2021 Jun 25. [https://doi.org/10.1002/onco.13857 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8488800/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34105207 PubMed] NCT02332499
 
  
 
[[Category:Colon cancer regimens]]
 
[[Category:Colon cancer regimens]]

Latest revision as of 11:00, 6 July 2024

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The purpose of this page is to provide references to "null therapy" such as placebo and observation. These references provide further insight into the historical development of the treatment landscape. See the main colon cancer page for regimens that include active anticancer treatment.


Adjuvant therapy, stage II

Observation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Moertel et al. 1995 (INT-0035) 1984-1987 Phase 3 (C) 5-FU & Levamisole Did not meet primary endpoint of OS
Laffer et al. 2008 (SAKK 40/87) 1987-1993 Phase 3 (C) 1. Portal venous 5-FU & Mitomycin
2. 5-FU & Mitomycin 		Did not meet primary endpoint of OS
Kemeny et al. 2022 (ECOG-ACRIN E1292) 1993-2000 Phase 3 (C) Peri-operative 5-FU Did not meet primary endpoint of OS
Schippinger et al. 2007 1993-2003 Phase 3 (C) FULV Did not meet primary endpoint of OS
Hartung et al. 2005 1997-2000 Phase 3 (C) Edrecolomab Did not meet primary endpoint of OS
Niedzwiecki et al. 2011 (CALGB 9581) 1997-2002 Phase 3 (C) Edrecolomab Did not meet primary endpoint of OS

No systemic treatment after surgery for stage II colon cancer.

Preceding treatment

References

  1. INT-0035: Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA; North Central Cancer Treatment Group; SWOG; ECOG. Intergroup study of fluorouracil plus levamisole as adjuvant therapy for stage II/Dukes' B2 colon cancer. J Clin Oncol. 1995 Dec;13(12):2936-43. link to original article PubMed
  2. Hartung G, Hofheinz RD, Dencausse Y, Sturm J, Kopp-Schneider A, Dietrich G, Fackler-Schwalbe I, Bornbusch D, Gonnermann M, Wojatschek C, Lindemann W, Eschenburg H, Jost K, Edler L, Hochhaus A, Queisser W. Adjuvant therapy with edrecolomab versus observation in stage II colon cancer: a multicenter randomized phase III study. Onkologie. 2005 Jun;28(6-7):347-50. Epub 2005 Jun 2. link to original article PubMed
  3. Schippinger W, Samonigg H, Schaberl-Moser R, Greil R, Thödtmann R, Tschmelitsch J, Jagoditsch M, Steger GG, Jakesz R, Herbst F, Hofbauer F, Rabl H, Wohlmuth P, Gnant M, Thaler J; ABCSG. A prospective randomised phase III trial of adjuvant chemotherapy with 5-fluorouracil and leucovorin in patients with stage II colon cancer. Br J Cancer. 2007 Oct 22;97(8):1021-7. Epub 2007 Sep 25. link to original article link to PMC article PubMed
  4. SAKK 40/87: Laffer U, Metzger U, Aeberhard P, Lorenz M, Harder F, Maibach R, Zuber M, Herrmann R. Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial. Int J Colorectal Dis. 2008 Dec;23(12):1233-41. Epub 2008 Aug 8. link to original article PubMed
  5. CALGB 9581: Niedzwiecki D, Bertagnolli MM, Warren RS, Compton CC, Kemeny NE, Benson AB 3rd, Eckhardt SG, Alberts S, Porjosh GN, Kerr DJ, Fields A, Rougier P, Pipas JM, Schwartz JH, Atkins J, O'Rourke M, Perry MC, Goldberg RM, Mayer RJ, Colacchio TA. Documenting the natural history of patients with resected stage II adenocarcinoma of the colon after random assignment to adjuvant treatment with edrecolomab or observation: results from CALGB 9581. J Clin Oncol. 2011 Aug 10;29(23):3146-52. Epub 2011 Jul 11. link to original article link to PMC article PubMed NCT00002968
  6. ECOG-ACRIN E1292: Kemeny MM, Zhao F, Forastiere AA, Catalano P, Hamilton SR, Miedema BW, Dawson NA, Weiner LM, Smith BD, Mason BA, Graziano SL, Gilman PB, Venook AP, Pinto HA, Whitehead RP, O'Dwyer PJ, Benson AB. Phase III Prospectively Randomized Trial of Perioperative 5-FU After Curative Resection for Colon Cancer: An Intergroup Trial of the ECOG-ACRIN Cancer Research Group (E1292). Ann Surg Oncol. 2023 Feb;30(2):1099-1109. Epub 2022 Oct 28. link to original article link to PMC article PubMed NCT00002525
  7. PanDRa-BD: jRCTs031190186

Placebo

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Midgley et al. 2010 (VICTOR) 2002-2004 Phase 3 (C) Rofecoxib Did not meet primary endpoint of OS

No active antineoplastic treatment.

Preceding treatment

References

  1. VICTOR: Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010 Oct 20;28(30):4575-80. Epub 2010 Sep 13. link to original article PubMed NCT00031863

Adjuvant therapy, stage III

Observation

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Panettiere et al. 1988 (SWOG S7510) 1975-1977 Phase 3 (C) 1. 5-FU & Semustine
2. 5-FU, Semustine, BCG 		Did not meet primary endpoint
Lessner et al. 1984 1975-1979 Phase 3 (C) 1. 5-FU & Semustine
2. 5-FU, Semustine, BCG
3. BCG 		Did not meet primary endpoint of OS
Wolmark et al. 1988 (NSABP C-01) 1977-1983 Phase 3 (C) 1. MOF
2. BCG 		Did not meet primary endpoint of OS1
Laffer et al. 1995 (SAKK 40/81) 1981-1987 Phase 3 (C) Portal venous chemotherapy Seems to have inferior OS
Moertel et al. 1990 (SWOG S8591) 1984-1987 Phase 3 (C) 1. 5-FU & Levamisole Inferior OS
2. Levamisole Not reported
Wolmark et al. 1990 (NSABP C-02) 1984-1988 Phase 3 (C) Portal venous chemotherapy Might have inferior OS
Laurie et al. 1989 Not reported Phase 3 (C) 1. 5-FU & Levamisole Seems to have inferior OS
2. Levamisole Not reported
Fielding et al. 1992 (AXIS-CRC) Not reported Phase 3 (C) Portal venous chemotherapy Did not meet primary endpoint of OS
Riethmüller et al. 1994 1985-1990 Phase 3 (C) Edrecolomab Seems to have inferior OS
Marsoni et al. 1995 (SITAC-01) Not reported Phase 3 (C) FULV Seems to have inferior OS
Marsoni et al. 1995 (NCIC-CTG C-03) Not reported Phase 3 (C) FULV Seems to have inferior OS
Marsoni et al. 1995 (FFCD 8802) Not reported Phase 3 (C) FULV Seems to have inferior OS
Vaillant et al. 2000 1986-1991 Phase 3 (C) 5-FU; IP Did not meet co-primary endpoints of DFS60/OS60
Rougier et al. 1998 1987-1993 Phase 3 (C) Portal venous chemotherapy Did not meet primary endpoint of OS
Laffer et al. 2008 (SAKK 40/87) 1987-1993 Phase 3 (C) 1. Portal venous 5-FU & Mitomycin
2. 5-FU & Mitomycin 		Did not meet primary endpoint of OS
O'Connell et al. 1997 (CALGB 8896) 1988-02 to 1989-08 Phase 3 (C) FULV Seems to have inferior OS

1Reported efficacy for NSABP C-01 is based on the 2004 update.
No systemic treatment after surgery. The AXIS trial is named "AXIS-CRC" here so as not to confuse it with the AXIS trial in renal cell carcinoma. Note that Marsoni et al. 1995 (IMPACT) is a pooled report of three RCTs.

Preceding treatment

References

  1. Lessner HE, Mayer RJ, Ellenberg SS, Holyoke ED; Gastrointestinal Tumor Study Group. Adjuvant therapy of colon cancer--results of a prospectively randomized trial. N Engl J Med. 1984 Mar 22;310(12):737-43. link to original article PubMed
  2. NSABP C-01: Wolmark N, Fisher B, Rockette H, Redmond C, Wickerham DL, Fisher ER, Jones J, Glass A, Lerner H, Lawrence W, Prager D, Wexler M, Evans J, Cruz A, Dimitrov N, Jochimsen P; NSABP. Postoperative adjuvant chemotherapy or BCG for colon cancer: results from NSABP protocol C-01. J Natl Cancer Inst. 1988 Mar 2;80(1):30-6. link to original article PubMed
    1. Update: Smith RE, Colangelo L, Wieand HS, Begovic M, Wolmark N. Randomized trial of adjuvant therapy in colon carcinoma: 10-year results of NSABP protocol C-01. J Natl Cancer Inst. 2004 Aug 4;96(15):1128-32. link to original article PubMed
    2. Pooled update: Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. link to original article link to PMC article PubMed
  3. SWOG S7510: Panettiere FJ, Goodman PJ, Costanzi JJ, Cruz AB Jr, Vaitkevicius VK, McCracken JD, Brownlee RW, Laufman L, Stephens RL, Bonnet J, Bottomley R, Rivkin S, Fletcher W, Oishi N, Chen TT. Adjuvant therapy in large bowel adenocarcinoma: long-term results of a Southwest Oncology Group Study. J Clin Oncol. 1988 Jun;6(6):947-54. link to original article PubMed
  4. Laurie JA, Moertel CG, Fleming TR, Wieand HS, Leigh JE, Rubin J, McCormack GW, Gerstner JB, Krook JE, Malliard J, Twito DI, Morton RF, Tschetter LK, Barlow JF; The North Central Cancer Treatment Group and the Mayo Clinic. Surgical adjuvant therapy of large-bowel carcinoma: an evaluation of levamisole and the combination of levamisole and fluorouracil. J Clin Oncol. 1989 Oct;7(10):1447-56. link to original article PubMed
  5. Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352-8. link to original article PubMed
    1. Update: Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321-6. link to original article PubMed
  6. SWOG S8591: Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Goodman PJ, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Levamisole and fluorouracil for adjuvant therapy of resected colon carcinoma. N Engl J Med. 1990 Feb 8;322(6):352-8. link to original article PubMed
    1. Update: Moertel CG, Fleming TR, Macdonald JS, Haller DG, Laurie JA, Tangen CM, Ungerleider JS, Emerson WA, Tormey DC, Glick JH, Veeder MH, Mailliard JA. Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med. 1995 Mar 1;122(5):321-6. link to original article PubMed
  7. NSABP C-02: Wolmark N, Rockette H, Wickerham DL, Fisher B, Redmond C, Fisher ER, Potvin M, Davies RJ, Jones J, Robidoux A, Wexler M, Gordon P, Cruz AB, Horsley S, Nims TA, Thirlwell M, Phillips WA, Prager D, Stern HS, Lerner HJ, Frazier TG. Adjuvant therapy of Dukes' A, B, and C adenocarcinoma of the colon with portal-vein fluorouracil hepatic infusion: preliminary results of National Surgical Adjuvant Breast and Bowel Project protocol C-02. J Clin Oncol. 1990 Sep;8(9):1466-75. link to original article PubMed
    1. Pooled update: Wilkinson NW, Yothers G, Lopa S, Costantino JP, Petrelli NJ, Wolmark N. Long-term survival results of surgery alone versus surgery plus 5-fluorouracil and leucovorin for stage II and stage III colon cancer: pooled analysis of NSABP C-01 through C-05: a baseline from which to compare modern adjuvant trials. Ann Surg Oncol. 2010 Apr;17(4):959-66. link to original article link to PMC article PubMed
  8. AXIS: Fielding LP, Hittinger R, Grace RH, Fry JS. Randomised controlled trial of adjuvant chemotherapy by portal-vein perfusion after curative resection for colorectal adenocarcinoma. Lancet. 1992 Aug 29;340(8818):502-6. link to original article PubMed
  9. Riethmüller G, Schneider-Gädicke E, Schlimok G, Schmiegel W, Raab R, Höffken K, Gruber R, Pichlmaier H, Hirche H, Pichlmayr R, Buggisch P, Witte J; German Cancer Aid 17-1A Study Group. Randomised trial of monoclonal antibody for adjuvant therapy of resected Dukes' C colorectal carcinoma. Lancet. 1994 May 14;343(8907):1177-83. link to original article PubMed
  10. SAKK 40/81: Laffer U, Metzger U, Aeberhard P, Maibach R, Castiglione M, Goldhirsch A; Swiss Group for Clinical Cancer Research. Long-term results of single course of adjuvant intraportal chemotherapy for colorectal cancer. Lancet. 1995 Feb 11;345(8946):349-53. link to original article PubMed
  11. IMPACT: Marsoni S, Labianca R, Pancera G, Torri V, Zaniboni A, Erlichman C, Pater J, Shepherd L, Zee B, Seitz JF, Milan C, Pignon JP; International Multicentre Pooled Analysis of Colon Cancer Trials (IMPACT) investigators. Efficacy of adjuvant fluorouracil and folinic acid in colon cancer. Lancet. 1995 Apr 15;345(8955):939-44. link to original article PubMed
    1. Update: Zaniboni A, Labianca R, Marsoni S, Torri V, Mosconi P, Grilli R, Apolone G, Cifani S, Tinazzi A; Gruppo Italiano Valutazione Interventi in Oncologia. GIVIO-SITAC 01: A randomized trial of adjuvant 5-fluorouracil and folinic acid administered to patients with colon carcinoma--long term results and evaluation of the indicators of health-related quality of life. Cancer. 1998 Jun 1;82(11):2135-44. link to original article PubMed
  12. CALGB 8896: O'Connell MJ, Mailliard JA, Kahn MJ, Macdonald JS, Haller DG, Mayer RJ, Wieand HS. Controlled trial of fluorouracil and low-dose leucovorin given for 6 months as postoperative adjuvant therapy for colon cancer. J Clin Oncol. 1997 Jan;15(1):246-50. link to original article PubMed
    1. Pooled update: Erlichman C, O'Connell M, Kahn M, Marsoni S, Torri V, Tardio B, Zaniboni A, Pancera G, Martignoni G, Labianca R, Barni A, Seitz JF, Milan C, Bedenne L, Giovannini M, Letreut YP, Skillings J, Shepard L, Zee B, Petrioli R, Francini G; International Multicentre Pooled Analysis of B2 Colon Cancer Trials (IMPACT B2) Investigators. Efficacy of adjuvant fluorouracil and folinic acid in B2 colon cancer. J Clin Oncol. 1999 May;17(5):1356-63. link to original article PubMed
  13. Rougier P, Sahmoud T, Nitti D, Curran D, Doci R, De Waele B, Nakajima T, Rauschecker H, Labianca R, Pector JC, Marsoni S, Apolone G, Lasser P, Couvreur ML, Wils J; EORTC Gastrointestinal Tract Cancer Cooperative Group; Gruppo Interdisciplinare Valutazione Interventi in Oncologia; Japanese Foundation for Cancer Research. Adjuvant portal-vein infusion of fluorouracil and heparin in colorectal cancer: a randomised trial. Lancet. 1998 Jun 6;351(9117):1677-81. link to original article PubMed
  14. Vaillant JC, Nordlinger B, Deuffic S, Arnaud JP, Pelissier E, Favre JP, Jaeck D, Fourtanier G, Grandjean JP, Marre P, Letoublon C. Adjuvant intraperitoneal 5-fluorouracil in high-risk colon cancer: a multicenter phase III trial. Ann Surg. 2000 Apr;231(4):449-56. link to original article link to PMC article PubMed
  15. SAKK 40/87: Laffer U, Metzger U, Aeberhard P, Lorenz M, Harder F, Maibach R, Zuber M, Herrmann R. Adjuvant perioperative portal vein or peripheral intravenous chemotherapy for potentially curative colorectal cancer: long-term results of a randomized controlled trial. Int J Colorectal Dis. 2008 Dec;23(12):1233-41. Epub 2008 Aug 8. link to original article PubMed
  16. ADAGE: NCT02355379
  17. POLEM: NCT03827044

Placebo

Regimen

Study Dates of enrollment Evidence Comparator Comparative Efficacy
Midgley et al. 2010 (VICTOR) 2002-2004 Phase 3 (C) Rofecoxib Did not meet primary endpoint of OS

No active antineoplastic treatment.

Preceding treatment

References

  1. VICTOR: Midgley RS, McConkey CC, Johnstone EC, Dunn JA, Smith JL, Grumett SA, Julier P, Iveson C, Yanagisawa Y, Warren B, Langman MJ, Kerr DJ. Phase III randomized trial assessing rofecoxib in the adjuvant setting of colorectal cancer: final results of the VICTOR trial. J Clin Oncol. 2010 Oct 20;28(30):4575-80. Epub 2010 Sep 13. link to original article PubMed NCT00031863
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