Difference between revisions of "Colon cancer"

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|}
 
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===Regimen {{#subobject:ed4e3f|Variant=1}}===
 
===Regimen {{#subobject:ed4e3f|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://www.nejm.org/doi/full/10.1056/NEJMoa043116 Twelves et al. 2005]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
*[[Capecitabine (Xeloda)]] 1250 mg/m2 PO BID on days 1 to 14
 
*[[Capecitabine (Xeloda)]] 1250 mg/m2 PO BID on days 1 to 14
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|}
 
|}
 
CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin <br>
 
CapeOX: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin <br>
−
XELOX: '''<u>XEL</u>'''oda, '''<u>OX</u>'''aliplatin
+
XELOX: '''<u>XEL</u>'''oda (Capecitabine), '''<u>OX</u>'''aliplatin
  
−
===Regimen #1, Schmoll et al. 2007 {{#subobject:1ef938|Variant=1}}===
+
===Regimen #1 {{#subobject:1ef938|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/25/1/102.long Schmoll et al. 2007]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
''Note: This is the same trial as described by Haller et al. 2011, but the schedule for [[Capecitabine (Xeloda)]] is slightly different.''
 
''Note: This is the same trial as described by Haller et al. 2011, but the schedule for [[Capecitabine (Xeloda)]] is slightly different.''
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'''21-day cycles x 8 cycles'''
 
'''21-day cycles x 8 cycles'''
  
−
===Regimen #2, Haller et al. 2011 {{#subobject:205ad6|Variant=1}}===
+
===Regimen #2 {{#subobject:205ad6|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/29/11/1465.long Haller et al. 2011]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
''Note: This is the same trial as described by Schmoll et al. 2007, but the schedule for [[Capecitabine (Xeloda)]] is slightly different.''
 
''Note: This is the same trial as described by Schmoll et al. 2007, but the schedule for [[Capecitabine (Xeloda)]] is slightly different.''
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|}
 
|}
 
===Regimen #1, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), O'Connell et al. 1997 & Haller et al. 2005 (Intergroup 0089) {{#subobject:e24014|Variant=1}}===
 
===Regimen #1, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), O'Connell et al. 1997 & Haller et al. 2005 (Intergroup 0089) {{#subobject:e24014|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[xx]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[|]]
 +
|-
 +
|}
  
 
*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV push once per day on days 1 to 5, before 5-FU
 
*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV push once per day on days 1 to 5, before 5-FU
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===Regimen #2, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), Twelves et al. 2005 & Schmoll et al. 2007 {{#subobject:4bd336|Variant=1}}===
 
===Regimen #2, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), Twelves et al. 2005 & Schmoll et al. 2007 {{#subobject:4bd336|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[xx]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[|]]
 +
|-
 +
|}
  
 
*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV push once per day on days 1 to 5, given before before 5-FU
 
*[[Folinic acid (Leucovorin)]] 20 mg/m2 IV push once per day on days 1 to 5, given before before 5-FU
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===Regimen #3, 5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV); Haller et al. 2005 (Intergroup 0089); Lembersky et al. 2006; Schmoll et al. 2007; Kuebler et al. 2007 {{#subobject:489be0|Variant=1}}===
 
===Regimen #3, 5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV); Haller et al. 2005 (Intergroup 0089); Lembersky et al. 2006; Schmoll et al. 2007; Kuebler et al. 2007 {{#subobject:489be0|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[xx]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[|]]
 +
|-
 +
|}
  
 
*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first
 
*[[Folinic acid (Leucovorin)]] 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first
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|}
 
|}
  
−
===Regimen, Haller et al. 2005 (Intergroup 0089) {{#subobject:895ddd|Variant=1}}===
+
===Regimen {{#subobject:895ddd|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/23/34/8671.long Haller et al. 2005 (Intergroup 0089)]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|High-dose 5-FU & Leucovorin]]; [[Colon_cancer#Fluorouracil_.26_Folinic_acid|Low-dose 5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
''Not in routine use; used as a comparator arm and here for reference purposes only.''
 
''Not in routine use; used as a comparator arm and here for reference purposes only.''
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===Regimen {{#subobject:c80e20|Variant=1}}===
 
===Regimen {{#subobject:c80e20|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/25/16/2198.full Kuebler et al. 2007 (NSABP C-07)]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus on days 1, 8, 15, 22, 29, 36, to start 1 hour after start of leucovorin
 
*[[Fluorouracil (5-FU)]] 500 mg/m2 IV bolus on days 1, 8, 15, 22, 29, 36, to start 1 hour after start of leucovorin
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===Regimen {{#subobject:671bbe|Variant=1}}===
 
===Regimen {{#subobject:671bbe|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://www.nejm.org/doi/full/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Folinic acid]]
 +
|-
 +
|}
  
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours once per day on days 1 & 2 (both bolus and continuous infusion are given on days 1 & 2)
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours once per day on days 1 & 2 (both bolus and continuous infusion are given on days 1 & 2)
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===Regimen {{#subobject:30b6e7|Variant=1}}===
 
===Regimen {{#subobject:30b6e7|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/27/20/3385.long Allegra et al. 2009 (NSABP C-08)]
 +
|<span
 +
style="background:#00CD00;
 +
padding:3px 6px 3px 6px;
 +
border-color:black;
 +
border-width:2px;
 +
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#mFOLFOX_6_.26_Bevacizumab|mFOLFOX 6 & Bevacizumab]]
 +
|-
 +
!colspan="4" align="center"|
 +
|-
 +
|[http://jama.jamanetwork.com/article.aspx?articleid=1148329 Alberts et al. 2012]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#mFOLFOX_6_.26_Cetuximab|mFOLFOX 6 & Cetuximab]]
 +
|-
 +
|}
  
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 46 to 48 hours on days 1 to 2
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 46 to 48 hours on days 1 to 2
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===Regimen {{#subobject:52276|Variant=1}}===
 
===Regimen {{#subobject:52276|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/27/20/3385.long Allegra et al. 2009 (NSABP C-08)]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#mFOLFOX_6|mFOLFOX 6]]
 +
|-
 +
|}
  
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 46 to 48 hours on days 1 to 2
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 46 to 48 hours on days 1 to 2
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===Regimen {{#subobject:7abe3e|Variant=1}}===
 
===Regimen {{#subobject:7abe3e|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jama.jamanetwork.com/article.aspx?articleid=1148329 Alberts et al. 2012]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#mFOLFOX_6|mFOLFOX 6]]
 +
|-
 +
|}
  
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 46 to 48 hours on days 1 to 2
 
*[[Fluorouracil (5-FU)]] 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 46 to 48 hours on days 1 to 2
Line 309: Line 416:
  
 
===Regimen {{#subobject:9e42fb|Variant=1}}===
 
===Regimen {{#subobject:9e42fb|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/15/1/246.long O'Connell et al. 1997]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
''No treatment; used as a comparator arm and here for reference purposes only.''
 
''No treatment; used as a comparator arm and here for reference purposes only.''
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|}
 
|}
 
===Regimen {{#subobject:643dbb|Variant=1}}===
 
===Regimen {{#subobject:643dbb|Variant=1}}===
−
Level of Evidence:
+
{| border="1" style="text-align:center;" !align="left"
−
<span  
+
|'''Study'''
 +
|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 +
|'''Comparator'''
 +
|-
 +
|[http://jco.ascopubs.org/content/24/13/2059.long Lembersky et al. 2006 (NSABP C-06)]
 +
|<span  
 
style="background:#00CD00;
 
style="background:#00CD00;
 
padding:3px 6px 3px 6px;
 
padding:3px 6px 3px 6px;
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border-width:2px;
 
border-width:2px;
 
border-style:solid;">Phase III</span>
 
border-style:solid;">Phase III</span>
 +
|[[Colon_cancer#Fluorouracil_.26_Folinic_acid|5-FU & Leucovorin]]
 +
|-
 +
|}
  
 
*[[Uracil-tegafur (UFT)]] 100 mg/m2 PO Q8H (total dose of 300 mg/m2/day) on days 1 to 28
 
*[[Uracil-tegafur (UFT)]] 100 mg/m2 PO Q8H (total dose of 300 mg/m2/day) on days 1 to 28

Revision as of 01:06, 29 March 2015

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Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are invited to contribute to the site.

10 regimens on this page
20 variants on this page


Adjuvant therapy

Capecitabine (Xeloda)

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Regimen

Study Evidence Comparator
Twelves et al. 2005 Phase III 5-FU & Leucovorin

21-day cycles x 8 cycles

References

  1. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. link to original article contains verified protocol PubMed

CapeOx, XELOX

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CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda (Capecitabine), OXaliplatin

Regimen #1

Study Evidence Comparator
Schmoll et al. 2007 Phase III 5-FU & Leucovorin

Note: This is the same trial as described by Haller et al. 2011, but the schedule for Capecitabine (Xeloda) is slightly different.

21-day cycles x 8 cycles

Regimen #2

Study Evidence Comparator
Haller et al. 2011 Phase III 5-FU & Leucovorin

Note: This is the same trial as described by Schmoll et al. 2007, but the schedule for Capecitabine (Xeloda) is slightly different.

21-day cycles x 8 cycles

References

  1. Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. link to original article contains verified protocol PubMed
  2. Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011 Apr 10;29(11):1465-71. Epub 2011 Mar 7. link to original article contains verified protocol PubMed

Fluorouracil & Folinic acid

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Regimen #1, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), O'Connell et al. 1997 & Haller et al. 2005 (Intergroup 0089)

Study Evidence Comparator
[xx] Phase III [[|]]

28-day cycles x 3 cycles, then 35-day cycles x 3 cycles

Regimen #2, 5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV), Twelves et al. 2005 & Schmoll et al. 2007

Study Evidence Comparator
[xx] Phase III [[|]]

28-day cycles x 6 cycles

Regimen #3, 5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV); Haller et al. 2005 (Intergroup 0089); Lembersky et al. 2006; Schmoll et al. 2007; Kuebler et al. 2007

Study Evidence Comparator
[xx] Phase III [[|]]

8-week cycles x 3-4 cycles

References

  1. 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 contains verified protocol PubMed
  2. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. link to original article contains verified protocol PubMed
  3. Twelves C, Wong A, Nowacki MP, Abt M, Burris H 3rd, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kröning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schüller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W. Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005 Jun 30;352(26):2696-704. link to original article contains verified protocol PubMed
  4. Haller DG, Catalano PJ, Macdonald JS, O'Rourke MA, Frontiera MS, Jackson DV, Mayer RJ. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol. 2005 Dec 1;23(34):8671-8. link to original article contains verified protocol PubMed
  5. Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006 May 1;24(13):2059-64. link to original article contains verified protocol PubMed
  6. Schmoll HJ, Cartwright T, Tabernero J, Nowacki MP, Figer A, Maroun J, Price T, Lim R, Van Cutsem E, Park YS, McKendrick J, Topham C, Soler-Gonzalez G, de Braud F, Hill M, Sirzén F, Haller DG. Phase III trial of capecitabine plus oxaliplatin as adjuvant therapy for stage III colon cancer: a planned safety analysis in 1,864 patients. J Clin Oncol. 2007 Jan 1;25(1):102-9. link to original article contains verified protocol PubMed
  7. Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. Epub 2007 Apr 30. link to original article contains protocol PubMed
  8. Haller DG, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Gilberg F, Rittweger K, Schmoll HJ. Capecitabine plus oxaliplatin compared with fluorouracil and folinic acid as adjuvant therapy for stage III colon cancer. J Clin Oncol. 2011 Apr 10;29(11):1465-71. Epub 2011 Mar 7. link to original article contains verified protocol PubMed

Fluorouracil, Folinic acid, Levamisole

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Regimen

Study Evidence Comparator
Haller et al. 2005 (Intergroup 0089) Phase III High-dose 5-FU & Leucovorin; Low-dose 5-FU & Leucovorin

Not in routine use; used as a comparator arm and here for reference purposes only.

28-day cycles x 3 cycles, then 35-day cycles x 3 cycles

References

  1. Haller DG, Catalano PJ, Macdonald JS, O'Rourke MA, Frontiera MS, Jackson DV, Mayer RJ. Phase III study of fluorouracil, leucovorin, and levamisole in high-risk stage II and III colon cancer: final report of Intergroup 0089. J Clin Oncol. 2005 Dec 1;23(34):8671-8. link to original article contains verified protocol PubMed

FLOX

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FLOX: Fluorouracil, Leucovorin, OXaliplatin

Regimen

Study Evidence Comparator
Kuebler et al. 2007 (NSABP C-07) Phase III 5-FU & Leucovorin
  • Fluorouracil (5-FU) 500 mg/m2 IV bolus on days 1, 8, 15, 22, 29, 36, to start 1 hour after start of leucovorin
  • Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given before Fluorouracil (5-FU)
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once per day on days 1, 15, 29, given prior to 5-FU and leucovorin

8-week cycles x 3 cycles

References

  1. Kuebler JP, Wieand HS, O'Connell MJ, Smith RE, Colangelo LH, Yothers G, Petrelli NJ, Findlay MP, Seay TE, Atkins JN, Zapas JL, Goodwin JW, Fehrenbacher L, Ramanathan RK, Conley BA, Flynn PJ, Soori G, Colman LK, Levine EA, Lanier KS, Wolmark N. Oxaliplatin combined with weekly bolus fluorouracil and leucovorin as surgical adjuvant chemotherapy for stage II and III colon cancer: results from NSABP C-07. J Clin Oncol. 2007 Jun 1;25(16):2198-204. Epub 2007 Apr 30. link to original article contains verified protocol PubMed

FOLFOX 4

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin
Also known as FOLFOX4.

Regimen

Study Evidence Comparator
André et al. 2004 (MOSAIC) Phase III 5-FU & Folinic acid
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours once per day on days 1 & 2 (both bolus and continuous infusion are given on days 1 & 2)
  • Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, before 5-FU
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, concurrent with leucovorin

14-day cycles x 12 cycles

References

  1. André T, Boni C, Mounedji-Boudiaf L, Navarro M, Tabernero J, Hickish T, Topham C, Zaninelli M, Clingan P, Bridgewater J, Tabah-Fisch I, de Gramont A; Multicenter International Study of Oxaliplatin/5-Fluorouracil/Leucovorin in the Adjuvant Treatment of Colon Cancer (MOSAIC) Investigators. Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer. N Engl J Med. 2004 Jun 3;350(23):2343-51. link to original article contains verified protocol PubMed
  2. Retrospective: Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. link to original article PubMed

mFOLFOX 6

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mFOLFOX: modified FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Study Evidence Comparator
Allegra et al. 2009 (NSABP C-08) Phase III mFOLFOX 6 & Bevacizumab
Alberts et al. 2012 Phase III mFOLFOX 6 & Cetuximab

14-day cycles x 12 cycles, to start within 10 weeks of surgery

References

  1. Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Colangelo LH, Lopa SH, Petrelli NJ, Goldberg RM, Atkins JN, Seay TE, Fehrenbacher L, O'Reilly S, Chu L, Azar CA, Wolmark N. Initial safety report of NSABP C-08: A randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer. J Clin Oncol. 2009 Jul 10;27(20):3385-90. Epub 2009 May 4. link to original article contains verified protocol PubMed
  2. Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012 Apr 4;307(13):1383-93. link to original article contains verified protocol PubMed

mFOLFOX 6 & Bevacizumab

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

The NCCN, Colon Cancer version 1.2015, does not recommend using bevacizumab as adjuvant therapy outside of a clinical trial.

Regimen

Study Evidence Comparator
Allegra et al. 2009 (NSABP C-08) Phase III mFOLFOX 6

14-day cycles x 12 cycles, to start within 10 weeks of surgery

References

  1. Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Colangelo LH, Lopa SH, Petrelli NJ, Goldberg RM, Atkins JN, Seay TE, Fehrenbacher L, O'Reilly S, Chu L, Azar CA, Wolmark N. Initial safety report of NSABP C-08: A randomized phase III study of modified FOLFOX6 with or without bevacizumab for the adjuvant treatment of patients with stage II or III colon cancer. J Clin Oncol. 2009 Jul 10;27(20):3385-90. Epub 2009 May 4. link to original article contains verified protocol PubMed

mFOLFOX 6 & Cetuximab

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

The NCCN, Colon Cancer version 1.2015, does not recommend using cetuximab as adjuvant therapy outside of a clinical trial.

Regimen

Study Evidence Comparator
Alberts et al. 2012 Phase III mFOLFOX 6

14-day cycles x 12 cycles, to start within 10 weeks of surgery

References

  1. Alberts SR, Sargent DJ, Nair S, Mahoney MR, Mooney M, Thibodeau SN, Smyrk TC, Sinicrope FA, Chan E, Gill S, Kahlenberg MS, Shields AF, Quesenberry JT, Webb TA, Farr GH Jr, Pockaj BA, Grothey A, Goldberg RM. Effect of oxaliplatin, fluorouracil, and leucovorin with or without cetuximab on survival among patients with resected stage III colon cancer: a randomized trial. JAMA. 2012 Apr 4;307(13):1383-93. link to original article contains verified protocol PubMed

Observation

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Regimen

Study Evidence Comparator
O'Connell et al. 1997 Phase III 5-FU & Leucovorin

No treatment; used as a comparator arm and here for reference purposes only.

References

  1. 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 contains verified protocol PubMed

Uracil-tegafur & Folinic acid

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Regimen

Study Evidence Comparator
Lembersky et al. 2006 (NSABP C-06) Phase III 5-FU & Leucovorin
  • Uracil-tegafur (UFT) 100 mg/m2 PO Q8H (total dose of 300 mg/m2/day) on days 1 to 28
  • Folinic acid (Leucovorin) 30 mg PO Q8H (total dose of 90 mg/day) on days 1 to 28
  • No food for 1 hour before and after each dose of medication.

35-day cycles x 5 cycles

References

  1. Lembersky BC, Wieand HS, Petrelli NJ, O'Connell MJ, Colangelo LH, Smith RE, Seay TE, Giguere JK, Marshall ME, Jacobs AD, Colman LK, Soran A, Yothers G, Wolmark N. Oral uracil and tegafur plus leucovorin compared with intravenous fluorouracil and leucovorin in stage II and III carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project Protocol C-06. J Clin Oncol. 2006 May 1;24(13):2059-64. link to original article contains verified protocol PubMed

Advanced or metastatic disease

Capecitabine (Xeloda)

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Regimen

Level of Evidence: Phase III

Note: The NCCN, Colon Cancer version 1.2015, lists Capecitabine (Xeloda) 850 to 1250 mg/m2 as the dosage range. No primary reference for the lower monotherapy dosages could be found.

21-day cycles

References

  1. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. link to original article contains verified protocol PubMed
  2. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. link to original article contains verified protocol PubMed

Capecitabine & Bevacizumab

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Regimen

Level of Evidence: Phase III

Note: The NCCN, Colon Cancer version 1.2015, lists Capecitabine (Xeloda) 850 to 1250 mg/m2 as the dosage range.

21-day cycles

References

  1. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. link to original article contains verified protocol--this regimen did not include bevacizumab PubMed
  2. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. link to original article contains verified protocol--this regimen did not include bevacizumab PubMed
  3. Moehler M, Sprinzl MF, Abdelfattah M, Schimanski CC, Adami B, Godderz W, Majer K, Flieger D, Teufel A, Siebler J, Hoehler T, Galle PR, Kanzler S. Capecitabine and irinotecan with and without bevacizumab for advanced colorectal cancer patients. World J Gastroenterol. 2009 Jan 28;15(4):449-56. link to original article contains verified protocol--this regimen also included treatment with irinotecan PubMed
  4. Pietrantonio F, Biondani P, Pellegrinelli A, Marchianò A, Dotti KF, Buzzoni R, Bartolomeo MD. Hepatic colorectal cancer metastases showing a distinctive pattern of pathological response after metronomic capecitabine and bevacizumab. Med Oncol. 2012 Jan 21. [Epub ahead of print] link to original article contains verified protocol PubMed
  5. David Cunningham, Istvan Lang, Vito Lorusso, Janja Ocvirk, Dongbok Shin, Derek J. Jonker, Stuart Osborne, Niko Alexander Andre, Daniel Waterkamp, Mark P. Saunders. Bevacizumab (bev) in combination with capecitabine (cape) for the first-line treatment of elderly patients with metastatic colorectal cancer (mCRC): Results of a randomized international phase III trial (AVEX). 2013 ASCO Gastrointestinal Cancers Symposium abstract 337. link to abstract

CapeOx (XELOX)

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CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin

Regimen #1, Cassidy et al. 2008; Saltz et al. 2008; Hochster et al. 2008 (TREE-1)

Level of Evidence: Phase III

  • Capecitabine (Xeloda) 1000 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
    • Note: In Saltz et al. 2008--the same study as Cassidy et al. 2008--capecitabine was described as being given 1000 mg/m2 PO BID on days 1 to 14
  • Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1

21-day cycles, given until progression of disease, or unacceptable toxicity; Cassidy et al. 2008 & Saltz et al. 2008 said that initial treatment could be given up to 16 cycles, but then could continue beyond that for patients who did not have progression of disease

Regimen #2, Hochster et al. 2008 (TREE-2)

Level of Evidence: Phase III

  • Capecitabine (Xeloda) 850 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
    • In Hochster et al. 2008 (TREE-2), based on safety data from TREE-1, the initial capecitabine dose was decreased to 850 mg/m2 PO BID. Patients with a creatinine clearance of 30 to 50 mL/min received Capecitabine (Xeloda) 650 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
  • Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. link to original article contains verified protocol PubMed
  2. Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. link to original article contains verified protocol PubMed
  3. Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523-9. link to original article contains verified protocol PubMed

CapeOx (XELOX) & Bevacizumab

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CapeOX: Capecitabine, OXaliplatin
XELOX: XELoda, OXaliplatin

Regimen

Level of Evidence: Phase III

Regimen #1, Cassidy et al. 2008 & Saltz et al. 2008

Level of Evidence: Phase III

  • Capecitabine (Xeloda) 1000 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
    • Note: In Saltz et al. 2008--the same study as Cassidy et al. 2008--capecitabine was described as being given 1000 mg/m2 PO BID on days 1 to 14
  • Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
  • Bevacizumab (Avastin) 7.5 mg/kg IV over 30 to 90 minutes once on day 1, given before oxaliplatin

21-day cycles, given until progression of disease, or unacceptable toxicity; Cassidy et al. 2008 & Saltz et al. 2008 said that initial treatment could be given up to 16 cycles, but then could continue beyond that for patients who did not have progression of disease

Regimen #2, Hochster et al. 2008 (TREE-2)

Level of Evidence: Phase III

  • Capecitabine (Xeloda) 850 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
    • In Hochster et al. 2008 (TREE-2), patients with a creatinine clearance of 30 to 50 mL/min received Capecitabine (Xeloda) 650 mg/m2 PO BID, starting the evening of day 1, to continue through the morning of day 15 (28 total doses)
  • Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
  • Bevacizumab (Avastin) 7.5 mg/kg IV once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. link to original article contains verified protocol PubMed
  2. Saltz LB, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Cassidy J. Bevacizumab in combination with oxaliplatin-based chemotherapy as first-line therapy in metastatic colorectal cancer: a randomized phase III study. J Clin Oncol. 2008 Apr 20;26(12):2013-9. link to original article contains verified protocol PubMed
  3. Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523-9. link to original article contains verified protocol PubMed

Cetuximab (Erbitux)

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Regimen #1, Cunningham et al. 2004; Lenz et al. 2006; Jonker et al. 2007; Asmis et al. 2011

Level of Evidence: Phase III

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once on day 1 of cycle 1, then 250 mg/m2 IV over 1 hour once on day 8 (cycle 1); for cycles 2 to 12: Cetuximab (Erbitux) 250 mg/m2 IV over 2 hours once per day on days 1 & 8

14-day cycles, given until progression of disease or unacceptable toxicity

Supportive medications (varies depending on reference):

  • Antihistamine (such as Diphenhydramine (Benadryl) 50 mg IV) prior to at least the first infusion cetuximab

Regimen #2, Martín-Martorell et al. 2008

Level of Evidence: Phase II

Note: The NCCN, Colon Cancer version 1.2015, lists this dosage and schedule as an option, although no primary reference could be found for this exact regimen. The regimen described by Martín-Martorell et al. 2008 they cited used cetuximab together with irinotecan.

  • Cetuximab (Erbitux) 500 mg/m2 IV over 2 hours once on day 1
    • If tolerated, subsequent doses of cetuximab can be given over 1 hour

14-day cycles

Supportive medications:

  • Antihistamine prior to cetuximab

References

  1. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. link to original article contains verified protocol PubMed
  2. Lenz HJ, Van Cutsem E, Khambata-Ford S, Mayer RJ, Gold P, Stella P, Mirtsching B, Cohn AL, Pippas AW, Azarnia N, Tsuchihashi Z, Mauro DJ, Rowinsky EK. Multicenter phase II and translational study of cetuximab in metastatic colorectal carcinoma refractory to irinotecan, oxaliplatin, and fluoropyrimidines. J Clin Oncol. 2006 Oct 20;24(30):4914-21. link to original article contains verified protocol PubMed
  3. 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. link to original report contains verified protocol
  4. 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. link to original article contains verified protocol PubMed
  5. Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008 Aug 5;99(3):455-8. link to original article contains verified protocol--see note above PubMed
  6. 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. link to original article contains verified protocol PubMed

Cetuximab & Irinotecan

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Regimen #1, Cunningham et al. 2004 & Sobrero et al. 2008

Level of Evidence: Phase III

21-day cycles

Supportive medications:

  • Antihistamine prior to at least the first infusion of cetuximab

Regimen #2, Cunningham et al. 2004

Level of Evidence: Phase III

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8, 15, 22, 29, 36 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
  • Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22

42-day cycles

Supportive medications:

  • Antihistamine prior to at least the first infusion cetuximab

Regimen #3

Note: In contrast to Cunningham et al. 2004, the NCCN, Colon Cancer version 1.2015, lists Irinotecan (Camptosar) as being given on days 1 & 8 of a 21-day cycle. No primary reference could be found for this.

  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8 & 15 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) 250 mg/m2 IV over 60 minutes once per day on days 1, 8, 15
  • Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1 & 8

21-day cycles

Supportive medications:

  • Antihistamine prior to at least the first infusion cetuximab

Regimen #4, Martín-Martorell et al. 2008

Level of Evidence: Phase II

14-day cycles

Supportive medications:

  • Antihistamine prior to cetuximab
  • Dexamethasone & ondansetron prior to irinotecan

References

  1. Cunningham D, Humblet Y, Siena S, Khayat D, Bleiberg H, Santoro A, Bets D, Mueser M, Harstrick A, Verslype C, Chau I, Van Cutsem E. Cetuximab monotherapy and cetuximab plus irinotecan in irinotecan-refractory metastatic colorectal cancer. N Engl J Med. 2004 Jul 22;351(4):337-45. link to original article contains verified protocol PubMed
  2. Sobrero AF, Maurel J, Fehrenbacher L, Scheithauer W, Abubakr YA, Lutz MP, Vega-Villegas ME, Eng C, Steinhauer EU, Prausova J, Lenz HJ, Borg C, Middleton G, Kröning H, Luppi G, Kisker O, Zubel A, Langer C, Kopit J, Burris HA 3rd. EPIC: phase III trial of cetuximab plus irinotecan after fluoropyrimidine and oxaliplatin failure in patients with metastatic colorectal cancer. J Clin Oncol. 2008 May 10;26(14):2311-9. Epub 2008 Apr 7. link to original article contains verified protocol PubMed
  3. Martín-Martorell P, Roselló S, Rodríguez-Braun E, Chirivella I, Bosch A, Cervantes A. Biweekly cetuximab and irinotecan in advanced colorectal cancer patients progressing after at least one previous line of chemotherapy: results of a phase II single institution trial. Br J Cancer. 2008 Aug 5;99(3):455-8. link to original article contains verified protocol PubMed

Fluorouracil & Folinic acid

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Regimen #1, de Gramont et al. 2000

Level of Evidence: Phase III

  • Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given first before 5-FU
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours once per day on days 1 & 2 (both bolus and continuous infusion are given on days 1 & 2)

14-day cycles

Regimen #2, Cheeseman et al. 2002 (modified de Gramont)

Level of Evidence: Non-randomized

14-day cycles

Supportive medications:

  • No routine prophylactic antiemetics and antidiarrheal medications were used, but patients could use metoclopramide (Reglan) prn nausea and loperamide (Imodium) prn diarrhea.

Regimen #3, Saltz et al. 2000; Hoff et al. 2001; Van Cutsem et al. 2001 (5-FU & low-dose Leucovorin (Mayo Clinic regimen/LDLV))

Level of Evidence: Phase III

28-day cycles

Regimen #4, Kabbinavar et al. 2003 (5-FU & high-dose Leucovorin (Roswell Park regimen/HDLV))

Level of Evidence: Randomized Phase II, >20 per arm

8-week cycles

Regimen #5, Jäger et al. 1996

Level of Evidence: Phase III

7-day cycles

Regimen #6, André et al. 1999 (simplified biweekly (sLV5FU2))

  • Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given first
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1 after leucovorin, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46 to 48 hours on days 1 to 2

14-day cycles

Regimen #7, Douillard et al. 2000

Level of Evidence: Phase III

7-day cycles

References

  1. Jäger E, Heike M, Bernhard H, Klein O, Bernhard G, Lautz D, Michaelis J, Meyer zum Büschenfelde KH, Knuth A. Weekly high-dose leucovorin versus low-dose leucovorin combined with fluorouracil in advanced colorectal cancer: results of a randomized multicenter trial. Study Group for Palliative Treatment of Metastatic Colorectal Cancer Study Protocol 1. J Clin Oncol. 1996 Aug;14(8):2274-9. link to original article contains verified protocol PubMed
  2. André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999 Sep;35(9):1343-7. link to original article contains verified protocol PubMed
  3. Douillard JY, Cunningham D, Roth AD, Navarro M, James RD, Karasek P, Jandik P, Iveson T, Carmichael J, Alakl M, Gruia G, Awad L, Rougier P. Irinotecan combined with fluorouracil compared with fluorouracil alone as first-line treatment for metastatic colorectal cancer: a multicentre randomised trial. Lancet. 2000 Mar 25;355(9209):1041-7. link to original article contains verified protocol PubMed
  4. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. link to original article contains verified protocol PubMed
  5. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000 Sep 28;343(13):905-14. link to original article contains verified protocol PubMed
  6. Hoff PM, Ansari R, Batist G, Cox J, Kocha W, Kuperminc M, Maroun J, Walde D, Weaver C, Harrison E, Burger HU, Osterwalder B, Wong AO, Wong R. Comparison of oral capecitabine versus intravenous fluorouracil plus leucovorin as first-line treatment in 605 patients with metastatic colorectal cancer: results of a randomized phase III study. J Clin Oncol. 2001 Apr 15;19(8):2282-92. link to original article contains verified protocol PubMed
  7. Van Cutsem E, Twelves C, Cassidy J, Allman D, Bajetta E, Boyer M, Bugat R, Findlay M, Frings S, Jahn M, McKendrick J, Osterwalder B, Perez-Manga G, Rosso R, Rougier P, Schmiegel WH, Seitz JF, Thompson P, Vieitez JM, Weitzel C, Harper P; Xeloda Colorectal Cancer Study Group. Oral capecitabine compared with intravenous fluorouracil plus leucovorin in patients with metastatic colorectal cancer: results of a large phase III study. J Clin Oncol. 2001 Nov 1;19(21):4097-106. link to original article contains verified protocol PubMed
  8. Cheeseman SL, Joel SP, Chester JD, Wilson G, Dent JT, Richards FJ, Seymour MT. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002 Aug 12;87(4):393-9. link to original article contains verified protocol PubMed
  9. Kabbinavar F, Hurwitz HI, Fehrenbacher L, Meropol NJ, Novotny WF, Lieberman G, Griffing S, Bergsland E. Phase II, randomized trial comparing bevacizumab plus fluorouracil (FU)/leucovorin (LV) with FU/LV alone in patients with metastatic colorectal cancer. J Clin Oncol. 2003 Jan 1;21(1):60-5. link to original article contains verified protocol PubMed

FOLFIRI

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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Regimen #1, André et al. 1999 (GERCOR); Fuchs et al. 2007 (BICC-C); Peeters et al. 2010

Level of Evidence: Phase III

  • Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, given during irinotecan infusion
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46 to 48 hours on days 1 to 2, given last
    • In André et al. 1999, the continuous infusion dose of Fluorouracil (5-FU) could be increased from 1200 mg/m2/day to 1500 mg/m2/day if there were no toxicities higher than grade 1
  • Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given first together with leucovorin

14-day cycles

Regimen #2, Saltz et al. 2000 & Hurwitz et al. 2004 (weekly dosing)

Level of Evidence: Phase III

6-week cycles

References

  1. André T, Louvet C, Maindrault-Goebel F, Couteau C, Mabro M, Lotz JP, Gilles-Amar V, Krulik M, Carola E, Izrael V, de Gramont A. CPT-11 (irinotecan) addition to bimonthly, high-dose leucovorin and bolus and continuous-infusion 5-fluorouracil (FOLFIRI) for pretreated metastatic colorectal cancer. GERCOR. Eur J Cancer. 1999 Sep;35(9):1343-7. link to original article contains verified protocol PubMed
  2. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000 Sep 28;343(13):905-14. link to original article contains verified protocol PubMed
  3. Hurwitz H, Fehrenbacher L, Novotny W, Cartwright T, Hainsworth J, Heim W, Berlin J, Baron A, Griffing S, Holmgren E, Ferrara N, Fyfe G, Rogers B, Ross R, Kabbinavar F. Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med. 2004 Jun 3;350(23):2335-42. link to original article contains verified protocol PubMed
  4. Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007 Oct 20;25(30):4779-86. link to original article contains verified protocol PubMed
  5. Update: Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol. 2008 Feb 1;26(4):689-90. link to original article PubMed
  6. Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. link to original article contains verified protocol PubMed

FOLFIRI & Bevacizumab

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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Regimen #1, Fuchs et al. 2007 (BICC-C) & Bendell et al. 2012 (ARIES)

Level of Evidence: Phase III

14-day cycles

Regimen #2, Loupakis et al. 2014 (TRIBE)

Level of Evidence: Phase III

Note: Loupakis et al. 2014 listed Folinic acid (Leucovorin) 200 mg/m2 in the body of the paper, whereas the protocol in the supplementary material stated that Levoleucovorin (Fusilev) 200 mg/m2 was used. We have contacted NEJM regarding this suspected error.

14-day cycles x up to 12 cycles, then followed by maintenance fluorouracil, leucovorin, and bevacizumab given until progression of disease or unacceptable adverse event. Loupakis et al. 2014 (TRIBE) did not provide specific details about the maintenance therapy.

References

  1. Fuchs CS, Marshall J, Mitchell E, Wierzbicki R, Ganju V, Jeffery M, Schulz J, Richards D, Soufi-Mahjoubi R, Wang B, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: results from the BICC-C Study. J Clin Oncol. 2007 Oct 20;25(30):4779-86. link to original article contains verified protocol PubMed
  2. Fuchs CS, Marshall J, Barrueco J. Randomized, controlled trial of irinotecan plus infusional, bolus, or oral fluoropyrimidines in first-line treatment of metastatic colorectal cancer: updated results from the BICC-C study. J Clin Oncol. 2008 Feb 1;26(4):689-90. link to original article PubMed
  3. Bendell JC, Bekaii-Saab TS, Cohn AL, Hurwitz HI, Kozloff M, Tezcan H, Roach N, Mun Y, Fish S, Flick ED, Dalal D, Grothey A. Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist. 2012;17(12):1486-95. link to original article PubMed
  4. Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, Cortesi E, Tomasello G, Ronzoni M, Spadi R, Zaniboni A, Tonini G, Buonadonna A, Amoroso D, Chiara S, Carlomagno C, Boni C, Allegrini G, Boni L, Falcone A. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014 Oct 23;371(17):1609-18. link to original article link to protocol in supplementary material contains verified protocol PubMed

FOLFIRI & Cetuximab

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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Regimen

Level of Evidence: Phase III

  • Folinic acid (Leucovorin) 400 mg/m2 IV over 2 hours once on day 1, started during irinotecan infusion on day 1
  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day (total dose of 2400 mg/m2) IV continuous infusion over 46 hours on days 1 to 2, given last
  • Irinotecan (Camptosar) 180 mg/m2 IV over 30 to 90 minutes once on day 1, given 1 hour after completion of cetuximab
  • Cetuximab (Erbitux) 400 mg/m2 IV over 2 hours once on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on day 8 of cycle 1; then on subsequent cycles, Cetuximab (Erbitux) is 250 mg/m2 IV over 60 minutes once per day on days 1 & 8; cetuximab is given first and infusion is to finish 1 hour before FOLFIRI begins

14-day cycles, given until progression of disease or unacceptable toxicity

References

  1. Van Cutsem E, Köhne CH, Hitre E, Zaluski J, Chang Chien CR, Makhson A, D'Haens G, Pintér T, Lim R, Bodoky G, Roh JK, Folprecht G, Ruff P, Stroh C, Tejpar S, Schlichting M, Nippgen J, Rougier P. Cetuximab and chemotherapy as initial treatment for metastatic colorectal cancer. N Engl J Med. 2009 Apr 2;360(14):1408-17. link to original article contains verified protocol PubMed
  2. E. Van Cutsem, I. Lang, G. Folprecht, M. Nowacki, C. Barone, I. Shchepotin, J. Maurel, D. Cunningham, I. Celik, C. Kohne. Cetuximab plus FOLFIRI: Final data from the CRYSTAL study on the association of KRAS and BRAF biomarker status with treatment outcome. 2010 ASCO Annual Meeting abstract 3570. link to abstract
  3. Van Cutsem E, Köhne CH, Láng I, Folprecht G, Nowacki MP, Cascinu S, Shchepotin I, Maurel J, Cunningham D, Tejpar S, Schlichting M, Zubel A, Celik I, Rougier P, Ciardiello F. Cetuximab plus irinotecan, fluorouracil, and leucovorin as first-line treatment for metastatic colorectal cancer: updated analysis of overall survival according to tumor KRAS and BRAF mutation status. J Clin Oncol. 2011 May 20;29(15):2011-9. Epub 2011 Apr 18. link to original article contains verified protocol PubMed
  4. Bokemeyer C, Cutsem EV, Rougier P, Ciardiello F, Heeger S, Schlichting M, Celik I, Köhne CH. Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: Pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur J Cancer. 2012 Jul;48(10):1466-75. Epub 2012 Mar 23. link to original article PubMed

FOLFIRI & Panitumumab

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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Regimen

Level of Evidence: Phase III

14-day cycles

References

  1. Peeters M, Price TJ, Cervantes A, Sobrero AF, Ducreux M, Hotko Y, André T, Chan E, Lordick F, Punt CJ, Strickland AH, Wilson G, Ciuleanu TE, Roman L, Van Cutsem E, Tzekova V, Collins S, Oliner KS, Rong A, Gansert J. Randomized phase III study of panitumumab with fluorouracil, leucovorin, and irinotecan (FOLFIRI) compared with FOLFIRI alone as second-line treatment in patients with metastatic colorectal cancer. J Clin Oncol. 2010 Nov 1;28(31):4706-13. Epub 2010 Oct 4. link to original article contains verified protocol PubMed

FOLFIRI & Ziv-aflibercept

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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan

Regimen, Tabernero et al. 2014 (VELOUR)

Level of Evidence: Phase III

Supportive medications:

  • "Premedication with atropine and anti-emetics was permitted. Granulocyte-colony stimulating factor (G-CSF) was used according to the American Society of Clinical Oncology guidelines."

14-day cycles, given until progression of disease or unacceptable toxicity

References

  1. J. Tabernero, E. Van Cutsem, R. Lakomy, J. Prausova, P. Ruff, G. Van Hazel, V. Moiseyenko, D. Ferry, J. McKendrick, K. Soussan-Lazard, E. Boelle, C. Allegra. VELOUR, a Phase 3 Study of Aflibercept (A) Versus Placebo (pbo) in Combination with FOLFIRI for the Treatment of Patients (pt) with Previously Treated Metastatic Colorectal Cancer (MCRC). 2011 European Multidisciplinary Congress. Abstract 6LBA. Presented September 25, 2011. link to abstract
  2. Tabernero J, Van Cutsem E, Lakomý R, Prausová J, Ruff P, van Hazel GA, Moiseyenko VM, Ferry DR, McKendrick JJ, Soussan-Lazard K, Chevalier S, Allegra CJ. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: prespecified subgroup analyses from the VELOUR trial. Eur J Cancer. 2014 Jan;50(2):320-31. link to original article contains verified protocol PubMed

FOLFOX 4

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin
Also known as FOLFOX4.

Regimen #1, de Gramont et al. 2000 & Tournigand et al. 2006 (OPTIMOX1)

Level of Evidence: Phase III

  • Fluorouracil (5-FU) 400 mg/m2 IV bolus, then 600 mg/m2/day IV continuous infusion over 22 hours once per day on days 1 & 2 (both bolus and continuous infusion are given on days 1 & 2)
  • Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, before 5-FU
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, concurrent with leucovorin

14-day cycles

References

  1. de Gramont A, Figer A, Seymour M, Homerin M, Hmissi A, Cassidy J, Boni C, Cortes-Funes H, Cervantes A, Freyer G, Papamichael D, Le Bail N, Louvet C, Hendler D, de Braud F, Wilson C, Morvan F, Bonetti A. Leucovorin and fluorouracil with or without oxaliplatin as first-line treatment in advanced colorectal cancer. J Clin Oncol. 2000 Aug;18(16):2938-47. link to original article contains verified protocol PubMed
  2. Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, Mineur L, Carola E, Etienne PL, Rivera F, Chirivella I, Perez-Staub N, Louvet C, André T, Tabah-Fisch I, de Gramont A. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study. J Clin Oncol. 2006 Jan 20;24(3):394-400. link to original article contains verified protocol PubMed
  3. Goldberg RM, Tabah-Fisch I, Bleiberg H, de Gramont A, Tournigand C, Andre T, Rothenberg ML, Green E, Sargent DJ. Pooled analysis of safety and efficacy of oxaliplatin plus fluorouracil/leucovorin administered bimonthly in elderly patients with colorectal cancer. J Clin Oncol. 2006 Sep 1;24(25):4085-91. link to original article PubMed content property of HemOnc.org
  4. Cassidy J, Clarke S, Díaz-Rubio E, Scheithauer W, Figer A, Wong R, Koski S, Lichinitser M, Yang TS, Rivera F, Couture F, Sirzén F, Saltz L. Randomized phase III study of capecitabine plus oxaliplatin compared with fluorouracil/folinic acid plus oxaliplatin as first-line therapy for metastatic colorectal cancer. J Clin Oncol. 2008 Apr 20;26(12):2006-12. link to original article PubMed

mFOLFOX 6

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen #1, Cheeseman et al. 2002 & Hochster et al. 2008 (TREE)

Level of Evidence: Phase III

14-day cycles

Regimen #2, Boccia et al. 2010 & Saltz et al. 2011

Level of Evidence: Phase III

Note: Neither of the references cited by the NCCN, Colon Cancer version 1.2015, contained this 400 mg/m2 dosage of leucovorin. The two references listed here contain the 400 mg/m2 dosage, but mFOLFOX 6 is in combination with cetuximab and/or bevacizumab. No primary reference for this dosage of mFOLFOX 6 by itself could be found.

14-day cycles

References

  1. Cheeseman SL, Joel SP, Chester JD, Wilson G, Dent JT, Richards FJ, Seymour MT. A 'modified de Gramont' regimen of fluorouracil, alone and with oxaliplatin, for advanced colorectal cancer. Br J Cancer. 2002 Aug 12;87(4):393-9. link to original article contains verified protocol PubMed
  2. Hochster HS, Hart LL, Ramanathan RK, Childs BH, Hainsworth JD, Cohn AL, Wong L, Fehrenbacher L, Abubakr Y, Saif MW, Schwartzberg L, Hedrick E. Safety and efficacy of oxaliplatin and fluoropyrimidine regimens with or without bevacizumab as first-line treatment of metastatic colorectal cancer: results of the TREE Study. J Clin Oncol. 2008 Jul 20;26(21):3523-9. link to original article contains verified protocol PubMed
  3. Boccia RV, Cosgriff TM, Headley DL, Badarinath S, Dakhil SR. A phase II trial of FOLFOX6 and cetuximab in the first-line treatment of patients with metastatic colorectal cancer. Clin Colorectal Cancer. 2010 Apr;9(2):102-7. link to original article contains protocol PubMed
  4. Saltz L, Badarinath S, Dakhil S, Bienvenu B, Harker WG, Birchfield G, Tokaz LK, Barrera D, Conkling PR, O'Rourke MA, Richards DA, Reidy D, Solit D, Vakiani E, Capanu M, Scales A, Zhan F, Boehm KA, Asmar L, Cohn A. Phase III Trial of Cetuximab, Bevacizumab, and 5-Fluorouracil/Leucovorin vs. FOLFOX-Bevacizumab in Colorectal Cancer. Clin Colorectal Cancer. 2011 Nov 4. [Epub ahead of print] link to original article contains protocol PubMed

FOLFOX 7 & sLV5FU2

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin
sLV5FU2: simplified LeucoVorin, 5-FU, 2-weekly (every 2 weeks)

Regimen, Tournigand et al. 2006 (OPTIMOX1)

Level of Evidence: Phase III

FOLFOX 7

14-day cycles x 6 cycles, until progression of disease or unacceptable toxicity, then proceed to sLV5FU2

Simplified LV5FU2 (sLV5FU2)

14-day cycles x 12 cycles, until progression of disease or unacceptable toxicity, then resume FOLFOX 7 for 6 additional cycles as described above

References

  1. Tournigand C, Cervantes A, Figer A, Lledo G, Flesch M, Buyse M, Mineur L, Carola E, Etienne PL, Rivera F, Chirivella I, Perez-Staub N, Louvet C, André T, Tabah-Fisch I, de Gramont A. OPTIMOX1: a randomized study of FOLFOX4 or FOLFOX7 with oxaliplatin in a stop-and-Go fashion in advanced colorectal cancer--a GERCOR study. J Clin Oncol. 2006 Jan 20;24(3):394-400. link to original article contains verified protocol PubMed

FOLFOX & Bevacizumab

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen #1, Saltz et al. 2011 (mFOLFOX 6 & Bevacizumab)

Level of Evidence: Phase III

14-day cycles

Regimen #2, Emmanouilides et al. 2007 (FOLFOX 4 & Bevacizumab)

Level of Evidence: Phase II

  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 600 mg/m2/day IV continuous infusion over 22 hours; both bolus and continuous infusion given on days 1 & 2
  • Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once per day on days 1 & 2
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
  • Bevacizumab (Avastin) 5 mg/kg IV once on day 1, given first
    • Infusion times for bevacizumab are 2 hours for cycle 1, 1 hour for cycle 2, then 30 minutes for cycles 3 and later

14-day cycles

References

  1. Emmanouilides C, Sfakiotaki G, Androulakis N, Kalbakis K, Christophylakis C, Kalykaki A, Vamvakas L, Kotsakis A, Agelaki S, Diamandidou E, Touroutoglou N, Chatzidakis A, Georgoulias V, Mavroudis D, Souglakos J. Front-line bevacizumab in combination with oxaliplatin, leucovorin and 5-fluorouracil (FOLFOX) in patients with metastatic colorectal cancer: a multicenter phase II study. BMC Cancer. 2007 May 30;7:91. link to original article PubMed
  2. Saltz L, Badarinath S, Dakhil S, Bienvenu B, Harker WG, Birchfield G, Tokaz LK, Barrera D, Conkling PR, O'Rourke MA, Richards DA, Reidy D, Solit D, Vakiani E, Capanu M, Scales A, Zhan F, Boehm KA, Asmar L, Cohn A. Phase III Trial of Cetuximab, Bevacizumab, and 5-Fluorouracil/Leucovorin vs. FOLFOX-Bevacizumab in Colorectal Cancer. Clin Colorectal Cancer. 2011 Nov 4. [Epub ahead of print] link to original article contains protocol PubMed
  3. Bendell JC, Bekaii-Saab TS, Cohn AL, Hurwitz HI, Kozloff M, Tezcan H, Roach N, Mun Y, Fish S, Flick ED, Dalal D, Grothey A. Treatment patterns and clinical outcomes in patients with metastatic colorectal cancer initially treated with FOLFOX-bevacizumab or FOLFIRI-bevacizumab: results from ARIES, a bevacizumab observational cohort study. Oncologist. 2012;17(12):1486-95. doi: 10.1634/theoncologist.2012-0190. Epub 2012 Sep 26. link to original article PubMed

FOLFOX & Panitumumab

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen #1, Douillard et al. 2010 (FOLFOX 4 & Panitumumab)

Level of Evidence: Phase III

  • Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 600 mg/m2/day IV continuous infusion over 22 hours; both bolus and continuous infusion given on days 1 & 2
  • Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours once per day on days 1 & 2
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
  • Panitumumab (Vectibix) 6 mg/kg IV once on day 1, given first
    • Infusion times for panitumumab are 1 hour for cycle 1, then if tolerated, 30 minutes for cycle 2 and later

Regimen #2, mFOLFOX 6 & Panitumumab

Note: The two references cited by the NCCN, Colon Cancer version 1.2015, contained different regimens. No primary reference for this regimen could be found.

14-day cycles

References

  1. Douillard JY, Siena S, Cassidy J, Tabernero J, Burkes R, Barugel M, Humblet Y, Bodoky G, Cunningham D, Jassem J, Rivera F, Kocákova I, Ruff P, B?asin'ska-Morawiec M, Šmakal M, Canon JL, Rother M, Oliner KS, Wolf M, Gansert J. Randomized, phase III trial of panitumumab with infusional fluorouracil, leucovorin, and oxaliplatin (FOLFOX4) versus FOLFOX4 alone as first-line treatment in patients with previously untreated metastatic colorectal cancer: the PRIME study. J Clin Oncol. 2010 Nov 1;28(31):4697-705. Epub 2010 Oct 4. link to original article PubMed

FOLFOXIRI

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FOLFOXIRI: FOLinic acid, Fluorouracil, OXaliplatin, IRInotecan

Regimen

Level of Evidence: Phase III

Note: In contrast to Falcone et al. 2007, the NCCN, Colon Cancer version 1.2015, listed the dose of Folinic acid (Leucovorin) as 400 mg/m2 IV on day 1. No primary reference could be found for this.

14-day cycles

References

  1. Falcone A, Ricci S, Brunetti I, Pfanner E, Allegrini G, Barbara C, Crinò L, Benedetti G, Evangelista W, Fanchini L, Cortesi E, Picone V, Vitello S, Chiara S, Granetto C, Porcile G, Fioretto L, Orlandini C, Andreuccetti M, Masi G; Gruppo Oncologico Nord Ovest. Phase III trial of infusional fluorouracil, leucovorin, oxaliplatin, and irinotecan (FOLFOXIRI) compared with infusional fluorouracil, leucovorin, and irinotecan (FOLFIRI) as first-line treatment for metastatic colorectal cancer: the Gruppo Oncologico Nord Ovest. J Clin Oncol. 2007 May 1;25(13):1670-6. link to original article contains verified protocol PubMed

FOLFOXIRI & Bevacizumab

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FOLFOXIRI: FOLinic acid, Fluorouracil, OXaliplatin, IRInotecan

Regimen, Loupakis et al. 2014 (TRIBE)

Level of Evidence: Phase III

Note: Loupakis et al. 2014 listed Folinic acid (Leucovorin) 200 mg/m2 in the body of the paper, whereas the protocol in the supplementary material stated that Levoleucovorin (Fusilev) 200 mg/m2 was used. We have contacted NEJM regarding this suspected error. The NCCN, Colon Cancer version 1.2015, listed either Folinic acid (Leucovorin) 400 mg/m2 IV once on day 1 or Levoleucovorin (Fusilev) 200 mg/m2 IV once on day 1 as options.

14-day cycles x up to 12 cycles, then followed by maintenance fluorouracil, leucovorin, and bevacizumab given until progression of disease or unacceptable adverse event. Loupakis et al. 2014 (TRIBE) did not provide specific details about the maintenance therapy.

References

  1. Loupakis F, Cremolini C, Masi G, Lonardi S, Zagonel V, Salvatore L, Cortesi E, Tomasello G, Ronzoni M, Spadi R, Zaniboni A, Tonini G, Buonadonna A, Amoroso D, Chiara S, Carlomagno C, Boni C, Allegrini G, Boni L, Falcone A. Initial therapy with FOLFOXIRI and bevacizumab for metastatic colorectal cancer. N Engl J Med. 2014 Oct 23;371(17):1609-18. link to original article link to protocol in supplementary material contains verified protocol PubMed

Irinotecan (Camptosar)

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Regimen #1, Cunningham et al. 1998 & Fuchs et al. 2003

Level of Evidence: Phase III

21-day cycles

Supportive medications (varied depending on reference):

  • "Standard regimens of antiemetics, atropine, and intensive loperamide," but no prophylactic atropine allowed on cycle 1 day 1

Regimen #2, Saltz et al. 2000 & Fuchs et al. 2003 (weekly irinotecan)

Level of Evidence: Phase III

Note: In contrast to Saltz et al. 2000 & Fuchs et al. 2003, the NCCN, Colon Cancer version 1.2015, listed Irinotecan (Camptosar) as being given on days 1 & 8 of a 21-day cycle. No primary reference could be found for this.

42-day cycles

References

  1. 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. link to original article contains verified protocol PubMed
  2. Saltz LB, Cox JV, Blanke C, Rosen LS, Fehrenbacher L, Moore MJ, Maroun JA, Ackland SP, Locker PK, Pirotta N, Elfring GL, Miller LL. Irinotecan plus fluorouracil and leucovorin for metastatic colorectal cancer. Irinotecan Study Group. N Engl J Med. 2000 Sep 28;343(13):905-14. link to original article contains verified protocol PubMed
  3. Fuchs CS, Moore MR, Harker G, Villa L, Rinaldi D, Hecht JR. Phase III comparison of two irinotecan dosing regimens in second-line therapy of metastatic colorectal cancer. J Clin Oncol. 2003 Mar 1;21(5):807-14. link to original article contains verified protocol PubMed
  4. Haller DG, Rothenberg ML, Wong AO, Koralewski PM, Miller WH Jr, Bodoky G, Habboubi N, Garay C, Olivatto LO. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol. 2008 Oct 1;26(28):4544-50. link to original article contains verified protocol PubMed

IROX

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IROX: IRinotecan, OXaliplatin

Regimen

Level of Evidence: Phase III

21-day cycles

References

  1. Haller DG, Rothenberg ML, Wong AO, Koralewski PM, Miller WH Jr, Bodoky G, Habboubi N, Garay C, Olivatto LO. Oxaliplatin plus irinotecan compared with irinotecan alone as second-line treatment after single-agent fluoropyrimidine therapy for metastatic colorectal carcinoma. J Clin Oncol. 2008 Oct 1;26(28):4544-50. link to original article contains verified protocol PubMed

Observation

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Regimen

Level of Evidence: Phase III

No treatment except for supportive care.

References

  1. 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. link to original article contains verified protocol PubMed
  2. 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. link to original article contains verified protocol PubMed

Panitumumab (Vectibix)

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Regimen

Level of Evidence: Phase III

14-day cycles, given until progression of disease or unacceptable toxicity

References

  1. 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. link to original article contains verified protocol PubMed

Panitumumab (Vectibix)

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Regimen

Level of Evidence: Phase III

14-day cycles, given until progression of disease or unacceptable toxicity

References

  1. 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. link to original article contains verified protocol PubMed

Regorafenib (Stivarga)

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Regimen, Grothey et al. 2013 (CORRECT)

Level of Evidence: Phase III

28-day cycles, given until progression of disease or unacceptable toxicity

References

  1. 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. link to original article contains verified protocol PubMed
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