Difference between revisions of "Colon cancer"
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− | ''' | + | <span id="BackToTop"></span> |
− | + | <div class="noprint" style="background-color:LightGray; position:fixed; bottom:2%; right:0.25%; padding-left:5px; padding-right:5px; margin: 15px; opacity:0.8; border-style: solid; border-color:DarkGray; border-width: 1px"> | |
− | + | [[#top|Back to Top]] | |
− | + | </div> | |
+ | {{#lst:Editorial board transclusions|gi}} | ||
+ | ''Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the [[Colon_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Colon cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | ||
+ | <br>'''Note: This page has recently been reorganized, with regimens intended more generically for colorectal cancer being moved to a [[Colorectal_cancer|dedicated page]]. Now, this page has adjuvant regimens specific to colon cancer. Please see the [[Rectal_cancer|'''rectal cancer page''']] for (neo-)adjuvant regimens specific to rectal cancer. | ||
+ | *See the [[Colon_cancer,_RAS_wild-type|'''RAS wild-type page''']] for biomarker-specific adjuvant regimens. | ||
{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
|- | |- | ||
− | |<div style="background-color: # | + | |<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div> |
− | <div style="background-color: # | + | <div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div> |
|} | |} | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
− | |||
=Guidelines= | =Guidelines= | ||
− | ==ESMO== | + | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' |
− | *[ | + | ==[https://www.asco.org/ ASCO]== |
− | *[ | + | *'''2022:''' Baxter et al. [https://doi.org/10.1200/jco.21.02538 Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update] [https://pubmed.ncbi.nlm.nih.gov/34936379/ PubMed] |
− | *[ | + | *'''2019:''' Lieu et al. [https://doi.org/10.1200/JCO.19.00281 Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline] [https://pubmed.ncbi.nlm.nih.gov/30986117/ PubMed] |
+ | ==[https://www.esmo.org/ ESMO]== | ||
+ | *'''2021:''' Yoshino et al. [https://doi.org/10.1016/j.annonc.2021.08.1752 Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer] [https://pubmed.ncbi.nlm.nih.gov/34411693 PubMed] | ||
+ | *'''2020:''' Argilés et al. [https://doi.org/10.1016/j.annonc.2020.06.022 Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/32702383 PubMed] | ||
+ | **'''2013:''' Labianca et al. [https://doi.org/10.1093/annonc/mdt354 Early Colon Cancer: ESMO Clinical Practice Guidelines] [https://pubmed.ncbi.nlm.nih.gov/24078664 PubMed] | ||
+ | **'''2009:''' van Cutsem & Oliveira. [https://doi.org/10.1093/annonc/mdp126 Primary colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454461/ PubMed] | ||
+ | **'''2008:''' van Cutsem & Oliveira. [https://doi.org/10.1093/annonc/mdn077 Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456758/ PubMed] | ||
+ | **'''2007:''' van Cutsem. [https://doi.org/10.1093/annonc/mdm021 Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491030/ PubMed] | ||
+ | **'''2005:''' van Cutsem & Kataja. [https://doi.org/10.1093/annonc/mdi808 ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer] [https://pubmed.ncbi.nlm.nih.gov/15888737/ PubMed] | ||
+ | **'''2001:''' [https://doi.org/10.1023/a:1017492920758 ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer] [https://pubmed.ncbi.nlm.nih.gov/11583182/ PubMed] | ||
+ | *'''2019:''' Stjepanovic et al. [https://doi.org/10.1093/annonc/mdz233 Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/31378807 PubMed] | ||
==NCCN== | ==NCCN== | ||
− | *[https://www.nccn.org/ | + | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1428 NCCN Guidelines - Colon Cancer] |
+ | *'''2021:''' Benson et al. [https://doi.org/10.6004/Jnccn.2021.0012 Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology.] [https://pubmed.ncbi.nlm.nih.gov/33724754/ PubMed] | ||
+ | *'''2017:''' Benson et al. [https://doi.org/10.6004/jnccn.2017.0036 Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology] [https://pubmed.ncbi.nlm.nih.gov/28275037/ PubMed] | ||
+ | *'''2014:''' Benson et al. [https://doi.org/10.6004/jnccn.2014.0099 Colon Cancer, Version 3.2014] [https://pubmed.ncbi.nlm.nih.gov/24994923/ PubMed] | ||
+ | *'''2013:''' Benson et al. [https://doi.org/10.6004/Jnccn.2013.0069 Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines.] [https://pubmed.ncbi.nlm.nih.gov/23667203/ PubMed] | ||
+ | *'''2011:''' Benson et al. [https://doi.org/10.6004/Jnccn.2011.0104 Colon cancer.] [https://pubmed.ncbi.nlm.nih.gov/22056656/ PubMed] | ||
+ | *'''2009:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2009.0056 NCCN Clinical Practice Guidelines in Oncology: colon cancer.] [https://pubmed.ncbi.nlm.nih.gov/19755046/ PubMed] | ||
+ | *'''2007:''' Engstrom et al. Colon cancer. [https://pubmed.ncbi.nlm.nih.gov/17977501/ PubMed] | ||
+ | *'''2005:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2005.0024 Colon cancer clinical practice guidelines in oncology.] [https://pubmed.ncbi.nlm.nih.gov/16038639/ PubMed] | ||
+ | *'''2003:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2003.0006 Colon cancer. Clinical practice guidelines in oncology.] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8613831/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19764149/ PubMed] | ||
− | = | + | =Perioperative therapy= |
− | == | + | ==mFOLFOX6 (L-Leucovorin) {{#subobject:8uy6d7|Regimen=1}}== |
− | {| class="wikitable" style=" | + | mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin |
+ | <div class="toccolours" style="background-color:#c8a2c8"> | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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.ncbi.nlm.nih.gov/pmc/articles/PMC10022855/ Morton et al. 2023 (FOxTROT)] | ||
+ | |2008-05-15 to 2016-12-23 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
+ | |[[#mFOLFOX6_.28L-Leucovorin.29_2|mFOLFOX6]]; adjuvant | ||
+ | | style="background-color:#91cf60" |Seems to have superior rate of residual or recurrent disease within 2 years (primary endpoint)<br>Rate: 16.9% vs 21.5%<br>(RR 0.72, 95% CI 0.54-0.98) | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''Note: FOxTROT was a 2 x 2 factorial trial, with a sub-randomization to panitumumab, or not, for patients with KRASwt tumors. See paper for details.'' | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Neoadjuvant {{#subobject:30juz2|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>) | ||
+ | *[[Levoleucovorin (Fusilev)]] 175 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin''' | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid''' | ||
+ | '''14-day cycle for 3 cycles, followed by:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Local therapy==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Adjuvant=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>) | ||
+ | *[[Levoleucovorin (Fusilev)]] 175 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin''' | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid''' | ||
+ | '''14-day cycle for 9 cycles''' | ||
+ | </div></div></div> | ||
+ | ===References=== | ||
+ | #'''FOxTROT:''' Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552. Epub 2023 Jan 19. [https://doi.org/10.1200/JCO.22.00046 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10022855/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/36657089/ PubMed] [https://clinicaltrials.gov/study/NCT00647530 NCT00647530] | ||
+ | |||
+ | =Adjuvant therapy= | ||
+ | ==Capecitabine monotherapy {{#subobject:7b50df|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:ed4e3f|Variant=1}}=== | ===Regimen {{#subobject:ed4e3f|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJMoa043116 Twelves et al. 2005 (X-ACT)] |
− | |style="background-color:# | + | |1998-2001 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) |
− | |style="background-color:# | + | |[[#FULV|FULV]] |
+ | | style="background-color:#d9ef8b" |Might have superior OS<sup>1</sup> (secondary endpoint)<br>Median OS: NYR vs NYR<br>(HR 0.86, 95% CI 0.74-1.01)<br><br>Equivalent DFS (primary endpoint)<br>(HR 0.87, 95% CI 0.75-1.00) | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6461756/ Tomita et al. 2019 (JFMC37-0801)] |
− | |style="background-color:# | + | |2008-09 to 2009-12 |
− | |Capecitabine | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Capecitabine_monotherapy|Capecitabine]] x 12 mo |
+ | | style="background-color:#fee08b" |Might have inferior DFS | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO | + | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
− | |||
'''21-day cycle for 8 cycles''' | '''21-day cycle for 8 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Twelves C, Wong A, Nowacki MP, Abt M, Burris | + | #'''X-ACT:''' Twelves C, Wong A, Nowacki MP, Abt M, Burris HA 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. [https://doi.org/10.1056/NEJMoa043116 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15987918/ PubMed] [https://clinicaltrials.gov/study/NCT00009737 NCT00009737] |
− | # | + | ##'''Update:''' Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, Díaz-Rubio E, Gilberg F, Cassidy J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012 May;23(5):1190-7. Epub 2011 Sep 6. [https://doi.org/10.1093/annonc/mdr366 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21896539/ PubMed] |
+ | #'''JFMC37-0801:''' Tomita N, Kunieda K, Maeda A, Hamada C, Yamanaka T, Sato T, Yoshida K, Boku N, Nezu R, Yamaguchi S, Mishima H, Sadahiro S, Muro K, Ishiguro M, Sakamoto J, Saji S, Maehara Y. Phase III randomised trial comparing 6 vs 12-month of capecitabine as adjuvant chemotherapy for patients with stage III colon cancer: final results of the JFMC37-0801 study. Br J Cancer. 2019 Apr;120(7):689-696. Epub 2019 Mar 5. [https://doi.org/10.1038/s41416-019-0410-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6461756/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30833647/ PubMed] | ||
− | ==CapeOx | + | ==CapeOx {{#subobject:cf9acc|Regimen=1}}== |
− | + | CapeOx: '''<u>Cape</u>'''citabine & '''<u>Ox</u>'''aliplatin | |
− | + | <br>CAPOX: '''<u>CAP</u>'''ecitabine & '''<u>OX</u>'''aliplatin | |
− | + | <br>XELOX: '''<u>XEL</u>'''oda (Capecitabine) & '''<u>OX</u>'''aliplatin | |
− | |||
− | |||
− | XELOX: '''<u>XEL</u>'''oda (Capecitabine) | ||
===Example orders=== | ===Example orders=== | ||
*[[Example orders for CapeOx (XELOX) in colon cancer]] | *[[Example orders for CapeOx (XELOX) in colon cancer]] | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen #1 {{#subobject: | + | ===Regimen variant #1, 3 months {{#subobject:jgui19a|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)] |
− | |style="background-color:# | + | |2012-08-01 to 2014-06-30 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-de-esc) |
− | |style="background-color:# | + | |1a. [[#CapeOx|CapeOx]] x 6 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 6 mo |
+ | | style="background-color:#eeee01" |Seems to have non-inferior DFS<sup>1</sup> (primary endpoint)<br>DFS60: 75.2% vs 74.2%<br>(HR 0.95, 95% CI 0.77-1.18) | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO | + | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
+ | **Some references specify from the evening of day 1 to the morning of day 15 (28 doses per cycle) | ||
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1 | *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1 | ||
− | + | '''21-day cycle for 4 cycles''' | |
− | '''21-day cycle for | + | </div></div><br> |
− | ===Regimen #2, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| | + | ===Regimen variant #2, 6 months {{#subobject:1ef938|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Efficacy| | + | !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.2006.08.1075 Schmoll et al. 2007 (XELOXA)] | ||
+ | |2003-04 to 2004-10 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) | ||
+ | |[[#FULV|FULV]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>OS84: 73% vs 67%<br>(HR 0.83, 95% CI 0.70-0.99)<br><br>Superior DFS<sup>1</sup> (primary endpoint)<br>DFS84: 63% vs 56%<br>(HR 0.80, 95% CI 0.69-0.93) | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)] |
− | |style="background-color:# | + | |2012-08-01 to 2014-06-30 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#CapeOx|CapeOx]] x 3 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo |
+ | | style="background-color:#eeee01" |Seems to have non-inferior DFS | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''<sup>1</sup>Reported efficacy for XELOXA is based on the 2015 update.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO | + | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
+ | **Some references specify from the evening of day 1 to the morning of day 15 (28 doses per cycle) | ||
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1 | *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1 | ||
− | |||
'''21-day cycle for 8 cycles''' | '''21-day cycle for 8 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # 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. [ | + | #'''XELOXA:''' 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. [https://doi.org/10.1200/jco.2006.08.1075 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17194911/ PubMed] [https://clinicaltrials.gov/study/NCT00069121 NCT00069121] |
− | ## '''Update:''' 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. [ | + | ##'''Update:''' 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. [https://doi.org/10.1200/jco.2010.33.6297 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21383294/ PubMed] |
− | ## '''Update:''' Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine | + | ##'''Update:''' Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015 Nov 10;33(32):3733-40. Epub 2015 Aug 31. [https://doi.org/10.1200/jco.2015.60.9107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26324362/ PubMed] |
− | + | #'''IDEA:''' Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. [https://doi.org/10.1056/NEJMoa1713709 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29590544/ PubMed] [https://clinicaltrials.gov/study/NCT01308086 NCT01308086] | |
− | + | ##'''Subgroup analysis:''' Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203/ PubMed] | |
− | + | ##'''Update:''' André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7786835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33271092/ PubMed] | |
− | + | #'''ACHIEVE:''' Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Takeuchi S, Bando H, Taniguchi H, Gamoh M, Shiozawa M, Mizushima T, Saji S, Maehara Y, Ohtsu A, Mori M. Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1574-1581. Erratum in: JAMA Oncol. 2019 Nov 1;5(11):1643. Epub 2019 Sep 12. Erratum in: JAMA Oncol. 2019 Dec 19. [https://doi.org/10.1001/jamaoncol.2019.2572 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31513248/ PubMed] UMIN000008543 | |
− | + | ##'''Update:''' Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. Epub 2022 May 5. [https://doi.org/10.1200/jco.21.02628 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35512259/ PubMed] | |
− | + | #'''TOSCA:''' Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. [https://doi.org/10.1016/j.annonc.2020.10.477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33098997/ PubMed] [https://clinicaltrials.gov/study/NCT00646607 NCT00646607] | |
− | + | #'''KCSG CO09-07:''' Kim ST, Kim SY, Lee J, Yun SH, Kim HC, Lee WY, Kim TW, Hong YS, Lim SB, Baek JY, Oh JH, Ahn JB, Shin SJ, Han SW, Kim SG, Kang SY, Sym SJ, Zang DY, Kim YH, Choi IS, Kang JH, Kim MJ, Park YS. Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07. J Clin Oncol. 2022 Nov 20;40(33):3868-3877. Epub 2022 Jun 30. [https://doi.org/10.1200/jco.21.02962 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9671755/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35772045/ PubMed] [https://clinicaltrials.gov/study/NCT01092481 NCT01092481] | |
− | + | #'''CIRCULATE-IDEA:''' [https://clinicaltrials.gov/study/NCT05174169 NCT05174169] | |
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==FLOX {{#subobject:617cc1|Regimen=1}}== | ==FLOX {{#subobject:617cc1|Regimen=1}}== | ||
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FLOX: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>OX</u>'''aliplatin | FLOX: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>OX</u>'''aliplatin | ||
− | |||
===Example orders=== | ===Example orders=== | ||
*[[Example orders for FLOX in colon cancer]] | *[[Example orders for FLOX in colon cancer]] | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen {{#subobject:c80e20|Variant=1}}=== | ===Regimen {{#subobject:c80e20|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2006.08.2974 Kuebler et al. 2007 (NSABP C-07)] |
− | |style="background-color:# | + | |2000-2002 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[#FULV|FULV]] |
+ | | style="background-color:#1a9850" |Superior DFS (primary endpoint)<br>DFS48: 73.2% vs 67%<br>(HR 0.80, 95% CI 0.69-0.93) | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus on days 1, 8, 15, 22, 29, 36, ''' | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given third, 1 hour after start of leucovorin''' |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given second''' |
− | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, '''given | + | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, '''given first''' |
− | |||
'''8-week cycle for 3 cycles''' | '''8-week cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # 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. [ | + | #'''NSABP C-07:''' 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. [https://doi.org/10.1200/jco.2006.08.2974 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17470851/ PubMed] [https://clinicaltrials.gov/study/NCT00004931 NCT00004931] |
− | + | ##'''Update:''' Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2011.36.4539 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188282/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21859995/ PubMed] | |
− | == | + | ==FOLFOX4 {{#subobject:f61339|Regimen=1}}== |
− | + | FOLFOX4: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
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===Regimen {{#subobject:671bbe|Variant=1}}=== | ===Regimen {{#subobject:671bbe|Variant=1}}=== | ||
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)] |
− | |style="background-color:# | + | |1998-2001 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-RT-esc) |
− | |style="background-color:# | + | |[[#FULV|FULV]] |
+ | | style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup> (secondary endpoint)<br>OS120: 71.7% vs 67.1%<br>(HR 0.85, 95% CI 0.73-0.99)<br><br>Superior DFS (primary endpoint)<br>DFS36: 78.2% vs 72.9% | ||
|- | |- | ||
− | | | + | | rowspan="2" |[https://doi.org/10.1016/S1470-2045(12)70509-0 de Gramont et al. 2012 (AVANT)] |
− | = | + | |rowspan=2|2004-2007 |
− | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |1. [[#FOLFOX4_.26_Bevacizumab_999|FOLFOX4 & Bevacizumab]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | |
− | |||
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− | == | ||
− | # | ||
− | # | ||
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|- | |- | ||
− | |[[# | + | |2. [[#CapeOx_.26_Bevacizumab_999|XELOX & Bevacizumab]] |
− | | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS |
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|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/S1470-2045(14)70227-X Taieb et al. 2014 (PETACC-8)] |
− | |style="background-color:# | + | |2005-2009 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#FOLFOX4_.26_Cetuximab_999|FOLFOX4 & Cetuximab]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ Grothey et al. 2018 (IDEA)] |
− | |style="background-color:# | + | |2007-2015 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1a. [[#FOLFOX4|FOLFOX4]] x 6<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo<br>1c. [[#CapeOx|CapeOx]] x 3 mo |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36 | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2015 update.''<br> | ||
+ | ''IDEA is a pooled analysis of six phase 3 RCTs.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>) |
− | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first, with oxaliplatin on day 1''' | |
− | *[[ | + | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with leucovorin''' |
− | + | '''14-day cycle for 12 cycles''' | |
− | + | </div></div> | |
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− | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1 | ||
− | |||
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− | '''14-day cycle for 12 cycles | ||
===References=== | ===References=== | ||
− | + | #'''MOSAIC:''' 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. [https://doi.org/10.1056/NEJMoa032709 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15175436/ PubMed] [https://clinicaltrials.gov/study/NCT00275210 NCT00275210] | |
− | + | ##'''Update:''' André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. Epub 2009 May 18. [https://doi.org/10.1200/JCO.2008.20.6771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19451431/ PubMed] | |
− | ## '''Update:''' | + | ##'''Update:''' André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015 Dec 10;33(35):4176-87. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.63.4238 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527776/ PubMed] |
− | ## '''Update:''' | + | #'''AVANT:''' de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, Cunningham D, Cartwright TH, Hecht JR, Rivera F, Im SA, Bodoky G, Salazar R, Maindrault-Goebel F, Shacham-Shmueli E, Bajetta E, Makrutzki M, Shang A, André T, Hoff PM. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012 Dec;13(12):1225-33. Epub 2012 Nov 16. [https://doi.org/10.1016/S1470-2045(12)70509-0 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23168362/ PubMed] [https://clinicaltrials.gov/study/NCT00112918 NCT00112918] |
− | + | ##'''Update:''' André T, Vernerey D, Im SA, Bodoky G, Buzzoni R, Reingold S, Rivera F, McKendrick J, Scheithauer W, Ravit G, Fountzilas G, Yong WP, Isaacs R, Österlund P, Liang JT, Creemers GJ, Rakez M, Van Cutsem E, Cunningham D, Tabernero J, de Gramont A. Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group. Ann Oncol. 2020 Feb;31(2):246-256. Epub 2019 Dec 18. [https://doi.org/10.1016/j.annonc.2019.12.006 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31959341/ PubMed] | |
− | + | #'''PETACC-8:''' Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Petersen LN, Blons H, Collette L, Van Cutsem E, Rougier P, Salazar R, Bedenne L, Emile JF, Laurent-Puig P, Lepage C; PETACC-8 Study Investigators. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Jul;15(8):862-73. Epub 2014 Jun 11. [https://doi.org/10.1016/S1470-2045(14)70227-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/24928083/ PubMed] [https://clinicaltrials.gov/study/NCT00265811 NCT00265811] | |
− | + | #'''IDEA:''' Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. [https://doi.org/10.1056/NEJMoa1713709 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29590544/ PubMed] [https://clinicaltrials.gov/study/NCT01308086 NCT01308086] | |
− | + | ##'''Subgroup analysis:''' Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203/ PubMed] | |
− | + | ##'''Update:''' André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7786835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33271092/ PubMed] | |
− | + | #'''TOSCA:''' Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. [https://doi.org/10.1016/j.annonc.2020.10.477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33098997/ PubMed] [https://clinicaltrials.gov/study/NCT00646607 NCT00646607] | |
− | + | ==mFOLFOX6 {{#subobject:32d6c5|Regimen=1}}== | |
− | + | mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | |
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===Example orders=== | ===Example orders=== | ||
− | *[[Example orders for | + | *[[Example orders for mFOLFOX 6 in colon cancer]] |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen | + | ===Regimen {{#subobject:30juz2|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ Allegra et al. 2009 (NSABP C-08)] | |
− | | | + | |2004-2006 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[Colon_cancer_-_historical#mFOLFOX6-B|mFOLFOX6-B]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
− | |[[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ Grothey et al. 2018 (IDEA)] |
− | |style="background-color:# | + | |2007-2015 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#FOLFOX4|FOLFOX4]] x 6<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo<br>1c. [[#CapeOx|CapeOx]] x 3 mo | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior DFS36 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2017.76.0355 André et al. 2018 (IDEA France)] |
− | |style="background-color:# | + | |2009-2014 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#mFOLFOX6_2|mFOLFOX6]] x 3 mo |
+ | | style="background-color:#91cf60" |Seems to have superior DFS | ||
|- | |- | ||
− | | | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8025124/ Meyerhardt et al. 2021 (CALGB 80702)] |
− | + | |2010-2015 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#mFOLFOX6_.26_Celecoxib_999|mFOLFOX6 & Celecoxib]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | |
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− | |style="background-color:# | ||
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− | |[[# | ||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: CALGB 80702 was a 2 x 2 factorial trial, with the other comparison being 3 vs 6 months of mFOLFOX6. This comparison was made as part of the IDEA collaborative and is reported separately.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]], within 10 weeks | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>) |
− | + | *[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin''' | |
− | *[[Oxaliplatin (Eloxatin)]] | + | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid''' |
− | + | '''14-day cycle for 12 cycles''' | |
− | ''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | <!-- Presented in part at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL. --> | |
− | + | #'''NSABP C-08:''' 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. [https://doi.org/10.1200/jco.2009.21.9220 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2717026/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/19414665/ PubMed] [https://clinicaltrials.gov/study/NCT00096278 NCT00096278] | |
− | + | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, O'Reilly S, Chu L, Azar CA, Lopa S, Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011 Jan 1;29(1):11-6. Epub 2010 Oct 12. [https://doi.org/10.1200/JCO.2010.30.0855 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3055856/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20940184/ PubMed] | |
− | + | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Lopa SH, Wolmark N. Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial. J Clin Oncol. 2013 Jan 20;31(3):359-64. Epub 2012 Dec 10. [https://doi.org/10.1200/JCO.2012.44.4711 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3732014/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23233715/ PubMed] | |
− | # | + | #'''IDEA:''' Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. [https://doi.org/10.1056/NEJMoa1713709 link to original article] '''does not contain dosing details''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6426127/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29590544/ PubMed] [https://clinicaltrials.gov/study/NCT01308086 NCT01308086] |
− | + | ##'''Subgroup analysis:''' Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. [https://doi.org/10.1093/annonc/mdz193 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31228203/ PubMed] | |
− | # | + | ##'''Update:''' André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. [https://doi.org/10.1016/S1470-2045(20)30527-1 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7786835/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33271092/ PubMed] |
− | + | #'''IDEA France:''' André T, Vernerey D, Mineur L, Bennouna J, Desrame J, Faroux R, Fratte S, Hug de Larauze M, Paget-Bailly S, Chibaudel B, Bez J, Dauba J, Louvet C, Lepere C, Dupuis O, Becouarn Y, Mabro M, Egreteau J, Bouche O, Deplanque G, Ychou M, Galais MP, Ghiringhelli F, Dourthe LM, Bachet JB, Khalil A, Bonnetain F, de Gramont A, Taieb J; PRODIGE investigators, GERCOR, Fédération Française de Cancérologie Digestive, UNICANCER. Three versus 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer: disease-free survival results from a randomized, open-label, International Duration Evaluation of Adjuvant (IDEA) France, phase III trial. J Clin Oncol. 2018 May 20;36(15):1469-1477. Epub 2018 Apr 5. [https://doi.org/10.1200/JCO.2017.76.0355 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29620995/ PubMed] [https://clinicaltrials.gov/study/NCT00958737 NCT00958737] | |
− | + | #'''TOSCA:''' Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. [https://doi.org/10.1016/j.annonc.2020.10.477 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33098997/ PubMed] [https://clinicaltrials.gov/study/NCT00646607 NCT00646607] | |
− | + | #'''ACHIEVE-2:''' Yamazaki K, Yamanaka T, Shiozawa M, Manaka D, Kotaka M, Gamoh M, Shiomi A, Makiyama A, Munemoto Y, Rikiyama T, Fukunaga M, Ueki T, Shitara K, Shinkai H, Tanida N, Oki E, Sunami E, Ohtsu A, Maehara Y, Yoshino T. Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial. Ann Oncol. 2021 Jan;32(1):77-84. Epub 2020 Oct 26. [https://doi.org/10.1016/j.annonc.2020.10.480 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33121997/ PubMed] UMIN000013036 | |
− | + | #'''CALGB 80702:''' Meyerhardt JA, Shi Q, Fuchs CS, Meyer J, Niedzwiecki D, Zemla T, Kumthekar P, Guthrie KA, Couture F, Kuebler P, Bendell JC, Kumar P, Lewis D, Tan B, Bertagnolli M, Grothey A, Hochster HS, Goldberg RM, Venook A, Blanke C, O'Reilly EM, Shields AF. Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial. JAMA. 2021 Apr 6;325(13):1277-1286. [https://doi.org/10.1001/jama.2021.2454 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8025124/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33821899/ PubMed] [https://clinicaltrials.gov/study/NCT01150045 NCT01150045] | |
− | + | ##'''Dataset:''' [https://data.projectdatasphere.org/projectdatasphere/html/content/489 Project Data Sphere] | |
− | + | #'''KCSG CO09-07:''' Kim ST, Kim SY, Lee J, Yun SH, Kim HC, Lee WY, Kim TW, Hong YS, Lim SB, Baek JY, Oh JH, Ahn JB, Shin SJ, Han SW, Kim SG, Kang SY, Sym SJ, Zang DY, Kim YH, Choi IS, Kang JH, Kim MJ, Park YS. Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07. J Clin Oncol. 2022 Nov 20;40(33):3868-3877. Epub 2022 Jun 30. [https://doi.org/10.1200/jco.21.02962 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9671755/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35772045/ PubMed] [https://clinicaltrials.gov/study/NCT01092481 NCT01092481] | |
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+ | ==mFOLFOX6 (L-Leucovorin) {{#subobject:32d6d7|Regimen=1}}== | ||
+ | mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | ||
===Example orders=== | ===Example orders=== | ||
− | *[[Example orders for | + | *[[Example orders for mFOLFOX 6 in colon cancer]] |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen #1 {{#subobject: | + | ===Regimen variant #1, 3 months, 200 mg/m<sup>2</sup> L-LCV {{#subobject:38ig9a|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)] |
− | | | + | |2012-08-01 to 2014-06-30 |
− | + | | style="background-color:#1a9851" |Phase 3 (E-de-esc) | |
− | + | |1a. [[#CapeOx|CapeOx]] x 6 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 6 mo | |
− | + | | style="background-color:#eeee01" |Seems to have non-inferior DFS<sup>1</sup> (primary endpoint)<br>DFS60: 75.2% vs 74.2%<br>(HR 0.95, 95% CI 0.77-1.18) | |
− | |||
− | |style="background-color:# | ||
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− | |[ | ||
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− | |[[ | ||
− | |style="background-color:# | ||
− | |||
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|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy is based on the 2022 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>) |
− | + | *[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin''' | |
− | + | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid''' | |
− | *[[ | + | '''14-day cycle for 6 cycles''' |
− | + | </div></div><br> | |
− | ''' | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen variant #2, 6 months, 200 mg/m<sup>2</sup> L-LCV {{#subobject:38guh7|Variant=1}}=== | |
− | ===Regimen #2 {{#subobject: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | {| | + | !style="width: 20%"|Study |
− | | | + | !style="width: 20%"|Dates of enrollment |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ Yoshino et al. 2019 (ACHIEVE)] |
− | |style="background-color:# | + | |2012-08-01 to 2014-06-30 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#CapeOx|CapeOx]] x 3 mo<br>1b. [[#mFOLFOX6|mFOLFOX6]] x 3 mo | ||
+ | | style="background-color:#eeee01" |Seems to have non-inferior DFS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given second''' (total dose per cycle: 2800 mg/m<sup>2</sup>) |
− | + | *[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with oxaliplatin''' | |
− | + | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first, with folinic acid''' | |
− | + | '''14-day cycle for 12 cycles''' | |
− | *[[ | + | </div></div> |
− | |||
− | '''14-day cycles''' | ||
− | |||
===References=== | ===References=== | ||
− | # | + | #'''ACHIEVE:''' Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Takeuchi S, Bando H, Taniguchi H, Gamoh M, Shiozawa M, Mizushima T, Saji S, Maehara Y, Ohtsu A, Mori M. Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1574-1581. Erratum in: JAMA Oncol. 2019 Nov 1;5(11):1643. Epub 2019 Sep 12. Erratum in: JAMA Oncol. 2019 Dec 19. [https://doi.org/10.1001/jamaoncol.2019.2572 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6743062/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31513248/ PubMed] UMIN000008543 |
− | + | ##'''Update:''' Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. Epub 2022 May 5. [https://doi.org/10.1200/jco.21.02628 link to original article] [https://pubmed.ncbi.nlm.nih.gov/35512259/ PubMed] | |
− | + | ==FULV {{#subobject:a93a|Regimen=1}}== | |
− | + | FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin | |
− | ## ''' | + | <br>LV5FU2: '''<u>L</u>'''euco'''<u>V</u>'''orin & '''<u>5-FU</u>''' for '''<u>2</u>''' days |
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===Example orders=== | ===Example orders=== | ||
− | *[[Example orders for 5-FU & low-dose Leucovorin (Mayo Clinic regimen | + | *[[Example orders for 5-FU & low-dose Leucovorin (Mayo Clinic regimen - LDLV) in colon cancer]] |
− | *[[Example orders for 5-FU & high-dose Leucovorin (Roswell Park regimen | + | *[[Example orders for 5-FU & high-dose Leucovorin (Roswell Park regimen - HDLV) in colon cancer]] |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, 500/200, 6 out of 8 weeks {{#subobject:2c3f1b|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ===Regimen #1 {{#subobject: | + | !style="width: 20%"|Study |
− | {| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Comparator |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038965/ Papadimitriou et al. 2011] |
− | |style="background-color:# | + | |1999-2004 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#IFL_999|IFL]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36 |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36 |
− | + | '''8-week cycle for 4 cycles''' | |
− | ''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ===Regimen #2 | + | ===Regimen variant #2, 500/500, 6 out of 8 weeks {{#subobject:489be0|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates 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.1993.11.10.1879 Wolmark et al. 1993 (NSABP C-03)] |
− | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-258-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | |
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|- | |- | ||
− | | | + | |} --> |
− | |style="background-color:# | + | |1987-1989 |
− | | | + | | style="background-color:#1a9851" |Phase 3 (E-de-esc) |
− | |style="background-color:# | + | |[[Colon_cancer_-_historical#MOF|MOF]] |
+ | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
− | | | + | | rowspan="2" |[https://doi.org/10.1200/JCO.1999.17.11.3553 Wolmark et al. 1999 (NSABP C-04)] |
− | = | + | |rowspan=2|1989-07 to 1990-12 |
− | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | |
− | + | |1. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]] | |
− | + | | style="background-color:#d9ef8b" |Might have superior OS (co-primary endpoint) | |
− | |||
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− | |[[ | ||
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|- | |- | ||
− | | | + | |2. [[Colon_cancer_-_historical#FULV_.26_Levamisole|FULV & Levamisole]] |
− | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS | |
− | |||
− | |style="background-color:# | ||
|- | |- | ||
− | | | + | | rowspan="3" |[https://doi.org/10.1200/jco.2004.00.5686 Haller et al. 2005 (Intergroup 0089)] |
− | = | + | |rowspan=3|1988-1992 |
− | + | | rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc) | |
− | + | |1. [[#FULV|FULV]]; low-dose | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | |
− | |||
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− | # | ||
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− | # | ||
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|- | |- | ||
− | |[[# | + | |2. [[Colon_cancer_-_historical#FULV_.26_Levamisole|FULV & Levamisole]]; LDLV |
− | | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
− | |||
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|- | |- | ||
− | |[ | + | |3. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]] |
− | | | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
− | |||
− | |style="background-color:# | ||
|- | |- | ||
− | + | |[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)] | |
− | | | + | |1997-1999 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Folinic acid]] |
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS | ||
|- | |- | ||
− | | | + | |[https://doi.org/10.1200/JCO.2007.11.2144 Saltz et al. 2007 (CALGB 89803)] |
− | |style="background-color:# | + | |1999-2001 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#IFL_999|IFL]] | ||
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2006.08.2974 Kuebler et al. 2007 (NSABP C-07)] |
− | |style="background-color:# | + | |2000-2002 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#FLOX|FLOX]] |
+ | | style="background-color:#d73027" |Inferior DFS | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)] |
− | |style="background-color:# | + | |2003-04 to 2004-10 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#CapeOx|CapeOx]] |
+ | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''<sup>1</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br> |
+ | ''Note: this is often called the "Roswell Park regimen" but the original regimen described by Petrelli et al. 1987 & 1989 used a 5-FU dose of 600 mg/m<sup>2</sup>.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 hour after start of leucovorin''' |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first''' |
− | + | '''8-week cycle for varying durations: 3 cycles (NSABP C-07); 3 to 6 cycles''' | |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | + | ===Regimen variant #3, 600/500, 6 out of 8 weeks ("Roswell Park regimen") {{#subobject:50ybe0|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | === | + | !style="width: 20%"|Study |
− | # | + | !style="width: 20%"|Dates of enrollment |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
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− | # | ||
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|- | |- | ||
− | |[ | + | |[https://doi.org/10.1159/000012105 Fountzilas et al. 2000] |
− | + | |1989-1997 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#FULV_.26_Interferon_alfa-2a_999|FULV & IFN alfa-2a]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
− | |[[# | ||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 1 hour after start of leucovorin''' | |
− | *[[Fluorouracil (5-FU)]] | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first''' |
− | *[[ | + | '''8-week cycle for 4 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | ''' | + | ===Regimen variant #4, 1850/100 ("Mayo Clinic regimen") {{#subobject:4bnc36|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | ===Regimen # | + | !style="width: 20%"|Study |
− | {| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Comparator |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ejca.2008.07.002 Popov et al. 2008 (PETACC-1)] |
− | |style="background-color:# | + | |Not reported-1999 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Raltitrexed_monotherapy_999|Raltitrexed]] |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS/OS | ||
|- | |- | ||
|} | |} | ||
− | + | ''Note: This was the lower bound of 5-FU dosing in PETACC-1.'' | |
− | ''Note: | + | <div class="toccolours" style="background-color:#cbd5e8"> |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second''' | |
− | *[[Fluorouracil (5-FU)]] | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first''' |
− | *[[ | + | '''28-day cycle for 6 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #5, 1850/2500 ("NCI schedule") {{#subobject:7cc2b9|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | < | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen {{#subobject: | ||
− | {| | ||
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/jnci/90.23.1810 Wolmark et al. 1998 (NSABP C-05)] |
− | |style="background-color:# | + | |1991-1994 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#FULV_.26_Interferon_alfa_999|FULV & Interferon alfa]] |
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fluorouracil (5-FU)]] 370 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 5, '''given second''' | |
− | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5, '''given first''' | |
− | *[[Fluorouracil (5-FU)]] | + | '''28-day cycle for 6 cycles''' |
− | *[[ | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #6, 2000/400 ("de Gramont regimen"/LV5FU2) {{#subobject:685f89|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | ''' | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | == | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | |||
− | |||
− | # | ||
− | |||
− | |||
− | |||
− | |||
− | {| class="wikitable" style=" | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2003.10.065 André et al. 2003 (GERCOR C96.1)] |
− | + | |1996-1999 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#FULV|FULV]]; monthly | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
− | |[[ | ||
− | |style="background-color:# | ||
|- | |- | ||
− | | | + | |[https://doi.org/10.1056/NEJMoa032709 André et al. 2004 (MOSAIC)] |
− | + | |1998-2001 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#FOLFOX4|FOLFOX4]] | |
− | + | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | = | ||
− | # | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1093/annonc/mdn680 Ychou et al. 2009 (FFCD 9802)] |
− | + | |1998-2002 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#IFL_999|IFL]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | |
− | |||
− | | | ||
− | |[[ | ||
− | | | ||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2008.21.6663 Van Cutsem et al. 2009 (PETACC-3)] |
− | |style="background-color:# | + | |2000-2002 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#IFL_999|IFL]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy for MOSAIC is based on the 2015 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus, '''given second''' (total dose per cycle: 2000 mg/m<sup>2</sup>) | |
− | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2, '''given first''' |
− | *[[ | + | '''14-day cycle for 12 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | '''14-day cycles | + | ===Regimen variant #7, 2000/1000 {{#subobject:6igjc9|Variant=1}}=== |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | === | + | !style="width: 20%"|Study |
− | # | + | !style="width: 20%"|Dates of enrollment |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | + | !style="width: 20%"|Comparator | |
− | {| class="wikitable" style=" | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/0016-5085(94)90748-x Francini et al. 1994] |
− | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-259-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | |
− | |||
− | {| | ||
− | |''' | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | | | + | |} --> |
− | |style="background-color:# | + | |1985-1990 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[Colon_cancer_-_null_regimens#Observation_2|Observation]] |
+ | | style="background-color:#1a9850" |Superior OS (secondary endpoint)<br>OS60: 79% vs 65% | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]], within 3 weeks | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once per day on days 1 to 5 |
− | + | '''28-day cycle for 12 cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #8, 2125/100 ("Mayo Clinic regimen") {{#subobject:4bd336|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | === | + | !style="width: 20%"|Comparator |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | # | ||
− | |||
− | |||
− | |||
− | {| class="wikitable" style=" | ||
|- | |- | ||
− | | | + | ||[https://doi.org/10.1056/NEJMoa043116 Twelves et al. 2005 (X-ACT)] |
− | + | |1998-2001 | |
− | + | | style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |[[#Capecitabine_monotherapy|Capecitabine]] | |
− | + | | style="background-color:#fee08b" |Might have inferior OS<sup>1</sup> | |
− | |||
− | |||
− | |||
− | |[ | ||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
− | |[[ | ||
− | |style="background-color:# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ejca.2008.07.002 Popov et al. 2008 (PETACC-1)] |
− | |style="background-color:# | + | |Not reported-1999 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Raltitrexed_monotherapy_999|Raltitrexed]] |
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS/OS | ||
|- | |- | ||
− | + | |[https://doi.org/10.1016/j.ejca.2013.01.030 Köhne et al. 2013 (PETACC-2)] | |
− | | | + | |1999-2004 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |1. [[#FULV|FULV]]; LV5FU2<br>2. [[#FULV|FULV]]; AIO regimen<br> 3. [[#FULV|FULV]]; TTD regimen |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS60 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2006.08.1075 Schmoll et al. 2007 (XELOXA)] |
− | |style="background-color:# | + | |2003-04 to 2004-10 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#CapeOx|XELOX]] | ||
+ | | style="background-color:#fc8d59" |Seems to have inferior OS<sup>2</sup> | ||
|- | |- | ||
|} | |} | ||
+ | ''<sup>1</sup>X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.''<br> | ||
+ | ''<sup>2</sup>Reported efficacy for XELOXA is based on the 2015 update.''<br> | ||
+ | ''Note: This was the upper bound of 5-FU dosing in PETACC-1.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] | + | *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second''' |
− | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first''' | |
− | + | '''28-day cycle for 6 cycles''' | |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
− | |||
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− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | *[[ | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen # | + | ===Regimen variant #9, 2125/100, with cycle elongation ("Mayo Clinic regimen") {{#subobject:e24014|Variant=1}}=== |
− | {| | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | | | + | !style="width: 20%"|Study |
− | |[[Levels_of_Evidence#Evidence| | + | !style="width: 20%"|Dates of enrollment |
− | | | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Comparator |
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | + | |[https://doi.org/10.1200/jco.1997.15.1.246 O'Connell et al. 1997 (CALGB 8896)] | |
− | | | + | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" |
− | + | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-260-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | |
− | |style=" | ||
|- | |- | ||
− | |[[# | + | |} --> |
− | |style="background-color:# | + | |1988-02 to 1989-08 |
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Colon_cancer_-_null_regimens#Observation|Observation]] | ||
+ | | style="background-color:#91cf60" |Seems to have superior OS | ||
|- | |- | ||
− | |[ | + | | rowspan="3" |[https://doi.org/10.1200/jco.2004.00.5686 Haller et al. 2005 (Intergroup 0089)] |
− | |style="background-color:# | + | |rowspan=3|1988-1992 |
− | | | + | | rowspan="3" style="background-color:#1a9851" |Phase 3 (E-de-esc) |
− | |style="background-color:# | + | |1. [[#FULV|FULV]]; high-dose |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |[ | + | |2. [[Colon_cancer_-_historical#FULV_.26_Levamisole|FULV & Levamisole]]; LDLV |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | |
− | | | ||
− | |style="background-color:# | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |3. [[Colon_cancer_-_historical#Fluorouracil_.26_Levamisole|5-FU & Levamisole]] |
− | |style="background-color:# | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS |
|- | |- | ||
− | | | + | | rowspan="2" |[https://doi.org/10.1016/s0140-6736(02)09836-7 Punt et al. 2002 (Study 157-002)] |
− | = | + | |rowspan=2|1995-1999 |
− | + | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | |
− | + | |1. [[#FULV_.26_Edrecolomab_999|FULV & Edrecolomab]] | |
− | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | # | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[[# | + | |2. [[Colon_cancer_-_historical#Edrecolomab_monotherapy|Edrecolomab]] |
− | | | + | | style="background-color:#91cf60" |Seems to have superior OS |
− | |||
− | |||
− | |||
− | | | ||
− | |||
− | |||
− | |||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/JCO.2008.18.5710 Fields et al. 2009 (Study 157-001)] |
− | |style="background-color:# | + | |1995-1999 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | | | + | |[[#FULV_.26_Edrecolomab_999|FULV & Edrecolomab]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] | + | *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second''' |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first''' |
− | + | '''28-day cycle for 3 cycles, then 35-day cycle for 3 cycles''' | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | ' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | #'''NSABP C-03:''' Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, Jones J, Mamounas EP, Ore L, Petrelli NJ, Spurr CL, Dimitrov N, Romond EH, Sutherland CM, Kardinal CG, DeFusco PA, Jochimsen P. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol. 1993 Oct;11(10):1879-87. [https://doi.org/10.1200/JCO.1993.11.10.1879 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8410113/ 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] |
+ | #Francini G, Petrioli R, Lorenzini L, Mancini S, Armenio S, Tanzini G, Marsili S, Aquino A, Marzocca G, Civitelli S, Mariani L, De Sando D, Bovenga S, Lorenzi M. Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology. 1994 Apr;106(4):899-906. [https://doi.org/10.1016/0016-5085(94)90748-x link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8143995/ 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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8996149/ 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] | ||
+ | #'''NSABP C-05:''' Wolmark N, Bryant J, Smith R, Grem J, Allegra C, Hyams D, Atkins J, Dimitrov N, Oishi R, Prager D, Fehrenbacher L, Romond E, Colangelo L, Fisher B. Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J Natl Cancer Inst. 1998 Dec 2;90(23):1810-6. [https://doi.org/10.1093/jnci/90.23.1810 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9839521/ 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] | ||
+ | #'''NSABP C-04:''' Wolmark N, Rockette H, Mamounas E, Jones J, Wieand S, Wickerham DL, Bear HD, Atkins JN, Dimitrov NV, Glass AG, Fisher ER, Fisher B. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999 Nov;17(11):3553-9. [https://doi.org/10.1200/JCO.1999.17.11.3553 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10550154/ PubMed] [https://clinicaltrials.gov/study/NCT00425152 NCT00425152] | ||
+ | ##'''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] | ||
+ | #Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Papavramidis S, Bousoulegas A, Basdanis G, Giannoulis E, Dokmetzioglou J, Katsohis C, Nenopoulou E, Karvounis N, Briassoulis E, Aravantinos G, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Oncology. 2000 Apr;58(3):227-36. [https://doi.org/10.1159/000012105 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10765125/ PubMed] | ||
+ | #'''Study 157-002:''' Punt CJ, Nagy A, Douillard JY, Figer A, Skovsgaard T, Monson J, Barone C, Fountzilas G, Riess H, Moylan E, Jones D, Dethling J, Colman J, Coward L, MacGregor S. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002 Aug 31;360(9334):671-7. [https://doi.org/10.1016/s0140-6736(02)09836-7 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/12241873/ PubMed] | ||
+ | #'''GERCOR C96.1:''' Andre T, Colin P, Louvet C, Gamelin E, Bouche O, Achille E, Colbert N, Boaziz C, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Buyse M, de Gramont A. Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol. 2003 Aug 1;21(15):2896-903. [https://doi.org/10.1200/JCO.2003.10.065 link to original article] [https://pubmed.ncbi.nlm.nih.gov/12885807/ PubMed] | ||
+ | ##'''Update:''' André T, Quinaux E, Louvet C, Colin P, Gamelin E, Bouche O, Achille E, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Lledo G, Raoul Y, Debrix I, Buyse M, de Gramont A. Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol. 2007 Aug 20;25(24):3732-8. [https://doi.org/10.1200/JCO.2007.12.2234 link to original article] [https://pubmed.ncbi.nlm.nih.gov/17704423/ PubMed] | ||
+ | #'''MOSAIC:''' 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. [https://doi.org/10.1056/NEJMoa032709 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15175436/ PubMed] [https://clinicaltrials.gov/study/NCT00275210 NCT00275210] | ||
+ | ##'''Update:''' André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. Epub 2009 May 18. [https://doi.org/10.1200/JCO.2008.20.6771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19451431/ PubMed] | ||
+ | ##'''Update:''' André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015 Dec 10;33(35):4176-87. Epub 2015 Nov 2. [https://doi.org/10.1200/JCO.2015.63.4238 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26527776/ PubMed] | ||
+ | #'''X-ACT:''' Twelves C, Wong A, Nowacki MP, Abt M, Burris HA 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. [https://doi.org/10.1056/NEJMoa043116 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15987918/ PubMed] [https://clinicaltrials.gov/study/NCT00009737 NCT00009737] | ||
+ | ##'''Update:''' Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, Díaz-Rubio E, Gilberg F, Cassidy J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012 May;23(5):1190-7. Epub 2011 Sep 6. [https://doi.org/10.1093/annonc/mdr366 link to original article] [https://pubmed.ncbi.nlm.nih.gov/21896539/ PubMed] | ||
+ | <!-- Presented in part at the 33rd Annual Meeting of the American Society of Clinical Oncology, Denver, CO, May 20, 1997. --> | ||
+ | #'''Intergroup 0089:''' 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. [https://doi.org/10.1200/jco.2004.00.5686 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16314627/ PubMed] | ||
+ | <!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 13-17, 2004. --> | ||
+ | #'''NSABP C-06:''' 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. [https://doi.org/10.1200/jco.2005.04.7498 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16648506/ PubMed] [https://clinicaltrials.gov/study/NCT00378716 NCT00378716] | ||
+ | #'''XELOXA:''' 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. [https://doi.org/10.1200/jco.2006.08.1075 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17194911/ PubMed] [https://clinicaltrials.gov/study/NCT00069121 NCT00069121] | ||
+ | ##'''Update:''' 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. [https://doi.org/10.1200/jco.2010.33.6297 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21383294/ PubMed] | ||
+ | ##'''Update:''' Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015 Nov 10;33(32):3733-40. Epub 2015 Aug 31. [https://doi.org/10.1200/jco.2015.60.9107 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26324362/ PubMed] | ||
+ | #'''NSABP C-07:''' 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. [https://doi.org/10.1200/jco.2006.08.2974 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17470851/ PubMed] [https://clinicaltrials.gov/study/NCT00004931 NCT00004931] | ||
+ | ##'''Update:''' Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. Epub 2011 Aug 22. [https://doi.org/10.1200/JCO.2011.36.4539 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3188282/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21859995/ PubMed] | ||
+ | #'''CALGB 89803:''' Saltz LB, Niedzwiecki D, Hollis D, Goldberg RM, Hantel A, Thomas JP, Fields AL, Mayer RJ. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007 Aug 10;25(23):3456-61. [https://doi.org/10.1200/JCO.2007.11.2144 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17687149/ PubMed] [https://clinicaltrials.gov/study/NCT00003835 NCT00003835] | ||
+ | #'''PETACC-1:''' Popov I, Carrato A, Sobrero A, Vincent M, Kerr D, Labianca R, Raffaele Bianco A, El-Serafi M, Bedenne L, Paillot B, Mini E, Sanches E, Welch J, Collette L, Praet M, Wils J. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1). Eur J Cancer. 2008 Oct;44(15):2204-11. Epub 2008 Aug 15. [https://doi.org/10.1016/j.ejca.2008.07.002 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18707870/ PubMed] | ||
+ | #'''FFCD 9802:''' Ychou M, Raoul JL, Douillard JY, Gourgou-Bourgade S, Bugat R, Mineur L, Viret F, Becouarn Y, Bouché O, Gamelin E, Ducreux M, Conroy T, Seitz JF, Bedenne L, Kramar A. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802). Ann Oncol. 2009 Apr;20(4):674-80. Epub 2009 Jan 29. [https://doi.org/10.1093/annonc/mdn680 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19179549/ PubMed] [https://clinicaltrials.gov/study/NCT00005979 NCT00005979] | ||
+ | #'''Study 157-001:''' Fields AL, Keller A, Schwartzberg L, Bernard S, Kardinal C, Cohen A, Schulz J, Eisenberg P, Forster J, Wissel P. Adjuvant therapy with the monoclonal antibody edrecolomab plus fluorouracil-based therapy does not improve overall survival of patients with stage III colon cancer. J Clin Oncol. 2009 Apr 20;27(12):1941-7. Epub 2009 Mar 9. [https://doi.org/10.1200/JCO.2008.18.5710 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19273708/ PubMed] | ||
+ | #'''PETACC-3:''' Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, André T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009 Jul 1;27(19):3117-25. Epub 2009 May 18. [https://doi.org/10.1200/JCO.2008.21.6663 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19451425/ PubMed] [https://clinicaltrials.gov/study/NCT00026273 NCT00026273] | ||
+ | #Papadimitriou CA, Papakostas P, Karina M, Malettou L, Dimopoulos MA, Pentheroudakis G, Samantas E, Bamias A, Miliaras D, Basdanis G, Xiros N, Klouvas G, Bafaloukos D, Kafiri G, Papaspirou I, Pectasides D, Karanikiotis C, Economopoulos T, Efstratiou I, Korantzis I, Pisanidis N, Makatsoris T, Matsiakou F, Aravantinos G, Kalofonos HP, Fountzilas G; Hellenic Cooperative Oncology Group. A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study. BMC Med. 2011 Jan 31;9:10. [https://doi.org/10.1186/1741-7015-9-10 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038965/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21281463/ PubMed] ACTRN12610000148077 | ||
+ | #'''PETACC-2:''' Köhne CH, Bedenne L, Carrato A, Bouché O, Popov I, Gaspà L, Valladares M, Rougier P, Gog C, Reichardt P, Wils J, Pignatti F, Biertz F; EORTC; FFCD; GETTD. A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: the Pan-European Trial in Adjuvant Colon Cancer 2 study. Eur J Cancer. 2013 May;49(8):1868-75. Epub 2013 Apr 6. [https://doi.org/10.1016/j.ejca.2013.01.030 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23571150/ PubMed] [https://clinicaltrials.gov/study/NCT00004150 NCT00004150] | ||
− | == | + | ==S-1 monotherapy {{#subobject:5gh25a|Regimen=1}}== |
− | {| class="wikitable" style=" | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:8cug1c|Variant=1}}=== | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates 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.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ Yoshida et al. 2014 (ACTS-CC)] |
− | + | |2008-04 to 2009-06 | |
− | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | |
− | + | |[[#Tegafur.2C_Uracil.2C_Folinic_acid|UFT + LV]] | |
− | + | | style="background-color:#eeee01" |Non-inferior DFS36 (primary endpoint)<br>DFS36: 75.5% vs 72.5%<br>(HR 0.85, 95% CI 0.70-1.03) | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |style="background-color:# | ||
− | |[[ | ||
− | |style="background-color:# | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria: |
− | * | + | **Less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28 |
− | + | **BSA between 1.25 m<sup>2</sup> and 1.50 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28 | |
− | * | + | **BSA greater than 1.50 m<sup>2</sup>: 60 mg PO twice per day on days 1 to 28 |
− | + | '''42-day cycle for 4 cycles''' | |
− | ''' | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #'''ACTS-CC:''' Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-9. Epub 2014 Jun 18. [https://doi.org/10.1093/annonc/mdu232 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24942277/ PubMed] [https://clinicaltrials.gov/study/NCT00660894 NCT00660894] | |
− | + | ==SOX {{#subobject:617cc1|Regimen=1}}== | |
− | + | SOX: '''<u>S</u>'''-1, '''<u>OX</u>'''aliplatin | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | + | ===Regimen {{#subobject:c80e20|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | + | !style="width: 20%"|Study | |
− | + | !style="width: 20%"|Dates of enrollment | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | |
− | ===Regimen {{#subobject: | + | !style="width: 20%"|Comparator |
− | {| | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] |
− | | | ||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.clcc.2019.10.002 Sunami et al. 2019 (ACTS-CC 02)] |
− | |style="background-color:# | + | |2010-2014 |
− | |[[Colon_cancer# | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |style="background-color:# | + | |[[Colon_cancer#Tegafur.2C_Uracil.2C_Folinic_acid|Tegafur, Uracil, Folinic Acid]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | + | ====Preceding treatment==== | |
+ | *[[Surgery#Colorectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14 |
− | + | *[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1 | |
− | *[[Oxaliplatin (Eloxatin)]] | + | '''21-day cycle for 8 cycles''' |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | + | #'''ACTS-CC 02:''' Sunami E, Kusumoto T, Ota M, SakamotoY, Yoshida K, Tomita N, Maeda A, Teshima J, Okabe M, Tanaka C, Yamauchi J, Itabashi M, Kotake K, Takahashi K, Baba H, Boku N, Aiba K, Ishiguro M, Morita S, Takenaka N, Okude R, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as postoperative adjuvant chemotherapy in patients with high-risk stage III colon cancer (ACTS-CC 02): a randomized, open-label, multicenter, phase 3, superiority trial. Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. Epub 2019 Oct 18. [https://doi.org/10.1016/j.clcc.2019.10.002 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073 | |
− | + | ##'''Update:''' Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. [https://doi.org/10.1016/j.esmoop.2021.100077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7966838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33714860/ PubMed] | |
− | ## '''Update:''' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | ===Regimen {{#subobject: | + | ==Tegafur, Uracil, Folinic acid {{#subobject:5ed2aa|Regimen=1}}== |
− | {| | + | UFT + LV: '''<u>UFT</u>''' (Tegafur and uracil) & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid) |
− | | | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |[[Levels_of_Evidence#Evidence| | + | ===Regimen variant #1, 300/75 {{#subobject:8cc7d8|Variant=1}}=== |
− | | | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | |[[Levels_of_Evidence# | + | !style="width: 20%"|Study |
+ | !style="width: 20%"|Dates 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.ncbi.nlm.nih.gov/pmc/articles/PMC4621030/ Sadahiro et al. 2015 (JFMC33-0502)] | |
− | | | + | |2005-2007 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#Tegafur.2C_Uracil.2C_Folinic_acid|UFT + LV]]; weekly x 18 mo |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
− | |[[ | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ Yoshida et al. 2014 (ACTS-CC)] |
− | |style="background-color:# | + | |2008-04 to 2009-06 |
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#S-1_monotherapy|S-1]] | ||
+ | | style="background-color:#eeee01" |Non-inferior DFS36 | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.clcc.2019.10.002 Sunami et al. 2019 (ACTS-CC 02)] |
− | |style="background-color:# | + | |2010-2014 |
− | |[[ | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |style="background-color:# | + | |[[#SOX|SOX]] |
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: In ACTS-CC, this dosing was used for patients with BSA less than 1.17 m<sup>2</sup>.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> PO every 8 hours on days 1 to 28 |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] 25 mg PO every 8 hours on days 1 to 28 |
− | + | '''35-day cycle for 5 cycles''' | |
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | + | ===Regimen variant #2, 300/90 {{#subobject:643dbb|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" | |
− | === | + | !style="width: 20%"|Study |
− | + | !style="width: 20%"|Dates of enrollment | |
− | # | + | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | + | !style="width: 20%"|Comparator | |
− | + | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | |
− | |||
− | |||
− | |||
− | {| class="wikitable" style=" | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | = | ||
− | |||
− | |||
− | |[[Levels_of_Evidence#Evidence| | ||
− | | | ||
− | |[[Levels_of_Evidence# | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1200/jco.2005.04.7498 Lembersky et al. 2006 (NSABP C-06)] |
− | |style="background-color:# | + | |1997-1999 |
− | |[[# | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
− | |style="background-color:# | + | |[[#FULV|FULV]] |
+ | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *A potentially curative [[Surgery#Colorectal_cancer_surgery|resection]] of stage II or stage III colon cancer | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Tegafur and uracil (UFT)]] 100 mg/m<sup>2</sup> PO every 8 hours on days 1 to 28 |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] 30 mg PO every 8 hours on days 1 to 28 |
− | + | *No food for 1 hour before and after each dose of medication. | |
− | * | + | '''35-day cycle for 5 cycles''' |
− | + | </div></div> | |
− | ''' | ||
− | |||
===References=== | ===References=== | ||
− | # | + | <!-- Presented at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 13-17, 2004. --> |
− | + | #'''NSABP C-06:''' 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. [https://doi.org/10.1200/jco.2005.04.7498 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16648506/ PubMed] [https://clinicaltrials.gov/study/NCT00378716 NCT00378716] | |
− | # | + | #'''ACTS-CC:''' Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-9. Epub 2014 Jun 18. [https://doi.org/10.1093/annonc/mdu232 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4143094/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24942277/ PubMed] [https://clinicaltrials.gov/study/NCT00660894 NCT00660894] |
− | ## '''Update:''' | + | #'''JFMC33-0502:''' Sadahiro S, Tsuchiya T, Sasaki K, Kondo K, Katsumata K, Nishimura G, Kakeji Y, Baba H, Sato S, Koda K, Yamaguchi Y, Morita T, Matsuoka J, Usuki H, Hamada C, Kodaira S. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502. Ann Oncol. 2015 Nov;26(11):2274-80. Epub 2015 Sep 7. [https://doi.org/10.1093/annonc/mdv358 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4621030/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26347106/ PubMed] UMIN C000000245 |
+ | #'''ACTS-CC 02:''' Sunami E, Kusumoto T, Ota M, SakamotoY, Yoshida K, Tomita N, Maeda A, Teshima J, Okabe M, Tanaka C, Yamauchi J, Itabashi M, Kotake K, Takahashi K, Baba H, Boku N, Aiba K, Ishiguro M, Morita S, Takenaka N, Okude R, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as postoperative adjuvant chemotherapy in patients with high-risk stage III colon cancer (ACTS-CC 02): a randomized, open-label, multicenter, phase 3, superiority trial. Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. Epub 2019 Oct 18. [https://doi.org/10.1016/j.clcc.2019.10.002 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31917122/ PubMed] JapicCTI-101073 | ||
+ | ##'''Update:''' Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. [https://doi.org/10.1016/j.esmoop.2021.100077 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7966838/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33714860/ PubMed] | ||
− | = | + | =Advanced or metastatic disease= |
− | + | ''See the [[Colorectal cancer|colorectal cancer page]] for colorectal cancer regimens.'' | |
− | + | [[Category:Colon cancer regimens]] | |
− | + | [[Category:Disease-specific pages]] | |
− | + | [[Category:Colorectal cancers]] | |
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Latest revision as of 18:17, 21 July 2024
Section editor | |
---|---|
Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA |
Are you looking for a regimen, but can't find it here? It is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!
Note: This page has recently been reorganized, with regimens intended more generically for colorectal cancer being moved to a dedicated page. Now, this page has adjuvant regimens specific to colon cancer. Please see the rectal cancer page for (neo-)adjuvant regimens specific to rectal cancer.
- See the RAS wild-type page for biomarker-specific adjuvant regimens.
10 regimens on this page
20 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
ASCO
- 2022: Baxter et al. Adjuvant Therapy for Stage II Colon Cancer: ASCO Guideline Update PubMed
- 2019: Lieu et al. Duration of oxaliplatin-containing adjuvant therapy for stage III colon cancer: ASCO Clinical Practice Guideline PubMed
ESMO
- 2021: Yoshino et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the diagnosis treatment and follow-up of patients with localised colon cancer PubMed
- 2020: Argilés et al. Localised colon cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2013: Labianca et al. Early Colon Cancer: ESMO Clinical Practice Guidelines PubMed
- 2009: van Cutsem & Oliveira. Primary colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up PubMed
- 2008: van Cutsem & Oliveira. Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up PubMed
- 2007: van Cutsem. Colon cancer: ESMO clinical recommendations for diagnosis, adjuvant treatment and follow-up PubMed
- 2005: van Cutsem & Kataja. ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer PubMed
- 2001: ESMO Minimum Clinical Recommendations for diagnosis, adjuvant treatment and follow-up of colon cancer PubMed
- 2019: Stjepanovic et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
NCCN
- NCCN Guidelines - Colon Cancer
- 2021: Benson et al. Colon Cancer, Version 2.2021, NCCN Clinical Practice Guidelines in Oncology. PubMed
- 2017: Benson et al. Colon Cancer, Version 1.2017, NCCN Clinical Practice Guidelines in Oncology PubMed
- 2014: Benson et al. Colon Cancer, Version 3.2014 PubMed
- 2013: Benson et al. Localized colon cancer, version 3.2013: featured updates to the NCCN Guidelines. PubMed
- 2011: Benson et al. Colon cancer. PubMed
- 2009: Engstrom et al. NCCN Clinical Practice Guidelines in Oncology: colon cancer. PubMed
- 2007: Engstrom et al. Colon cancer. PubMed
- 2005: Engstrom et al. Colon cancer clinical practice guidelines in oncology. PubMed
- 2003: Engstrom et al. Colon cancer. Clinical practice guidelines in oncology. link to PMC article PubMed
Perioperative therapy
mFOLFOX6 (L-Leucovorin)
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Morton et al. 2023 (FOxTROT) | 2008-05-15 to 2016-12-23 | Phase 3 (E-switch-ic) | mFOLFOX6; adjuvant | Seems to have superior rate of residual or recurrent disease within 2 years (primary endpoint) Rate: 16.9% vs 21.5% (RR 0.72, 95% CI 0.54-0.98) |
Note: FOxTROT was a 2 x 2 factorial trial, with a sub-randomization to panitumumab, or not, for patients with KRASwt tumors. See paper for details.
Neoadjuvant
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given second (total dose per cycle: 2800 mg/m2)
- Levoleucovorin (Fusilev) 175 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 3 cycles, followed by:
Definitive
Local therapy
Adjuvant
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours, given second (total dose per cycle: 2800 mg/m2)
- Levoleucovorin (Fusilev) 175 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 9 cycles
References
- FOxTROT: Morton D, Seymour M, Magill L, Handley K, Glasbey J, Glimelius B, Palmer A, Seligmann J, Laurberg S, Murakami K, West N, Quirke P, Gray R. Preoperative Chemotherapy for Operable Colon Cancer: Mature Results of an International Randomized Controlled Trial. J Clin Oncol. 2023 Mar 10;41(8):1541-1552. Epub 2023 Jan 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00647530
Adjuvant therapy
Capecitabine monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Twelves et al. 2005 (X-ACT) | 1998-2001 | Phase 3 (E-RT-switch-ic) | FULV | Might have superior OS1 (secondary endpoint) Median OS: NYR vs NYR (HR 0.86, 95% CI 0.74-1.01) Equivalent DFS (primary endpoint) (HR 0.87, 95% CI 0.75-1.00) |
Tomita et al. 2019 (JFMC37-0801) | 2008-09 to 2009-12 | Phase 3 (C) | Capecitabine x 12 mo | Might have inferior DFS |
1X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 8 cycles
References
- X-ACT: Twelves C, Wong A, Nowacki MP, Abt M, Burris HA 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00009737
- Update: Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, Díaz-Rubio E, Gilberg F, Cassidy J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012 May;23(5):1190-7. Epub 2011 Sep 6. link to original article PubMed
- JFMC37-0801: Tomita N, Kunieda K, Maeda A, Hamada C, Yamanaka T, Sato T, Yoshida K, Boku N, Nezu R, Yamaguchi S, Mishima H, Sadahiro S, Muro K, Ishiguro M, Sakamoto J, Saji S, Maehara Y. Phase III randomised trial comparing 6 vs 12-month of capecitabine as adjuvant chemotherapy for patients with stage III colon cancer: final results of the JFMC37-0801 study. Br J Cancer. 2019 Apr;120(7):689-696. Epub 2019 Mar 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
CapeOx
CapeOx: Capecitabine & Oxaliplatin
CAPOX: CAPecitabine & OXaliplatin
XELOX: XELoda (Capecitabine) & OXaliplatin
Example orders
Regimen variant #1, 3 months
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yoshino et al. 2019 (ACHIEVE) | 2012-08-01 to 2014-06-30 | Phase 3 (E-de-esc) | 1a. CapeOx x 6 mo 1b. mFOLFOX6 x 6 mo |
Seems to have non-inferior DFS1 (primary endpoint) DFS60: 75.2% vs 74.2% (HR 0.95, 95% CI 0.77-1.18) |
1Reported efficacy is based on the 2022 update.
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Some references specify from the evening of day 1 to the morning of day 15 (28 doses per cycle)
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
21-day cycle for 4 cycles
Regimen variant #2, 6 months
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmoll et al. 2007 (XELOXA) | 2003-04 to 2004-10 | Phase 3 (E-RT-switch-ic) | FULV | Seems to have superior OS1 (secondary endpoint) OS84: 73% vs 67% (HR 0.83, 95% CI 0.70-0.99) Superior DFS1 (primary endpoint) DFS84: 63% vs 56% (HR 0.80, 95% CI 0.69-0.93) |
Yoshino et al. 2019 (ACHIEVE) | 2012-08-01 to 2014-06-30 | Phase 3 (C) | 1a. CapeOx x 3 mo 1b. mFOLFOX6 x 3 mo |
Seems to have non-inferior DFS |
1Reported efficacy for XELOXA is based on the 2015 update.
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Some references specify from the evening of day 1 to the morning of day 15 (28 doses per cycle)
- Oxaliplatin (Eloxatin) 130 mg/m2 IV over 2 hours once on day 1
21-day cycle for 8 cycles
References
- XELOXA: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00069121
- Update: 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 PubMed
- Update: Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015 Nov 10;33(32):3733-40. Epub 2015 Aug 31. link to original article PubMed
- IDEA: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. link to original article does not contain dosing details link to PMC article PubMed NCT01308086
- Subgroup analysis: Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. link to original article PubMed
- Update: André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. link to original article link to PMC article PubMed
- ACHIEVE: Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Takeuchi S, Bando H, Taniguchi H, Gamoh M, Shiozawa M, Mizushima T, Saji S, Maehara Y, Ohtsu A, Mori M. Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1574-1581. Erratum in: JAMA Oncol. 2019 Nov 1;5(11):1643. Epub 2019 Sep 12. Erratum in: JAMA Oncol. 2019 Dec 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed UMIN000008543
- Update: Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. Epub 2022 May 5. link to original article PubMed
- TOSCA: Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. link to original article PubMed NCT00646607
- KCSG CO09-07: Kim ST, Kim SY, Lee J, Yun SH, Kim HC, Lee WY, Kim TW, Hong YS, Lim SB, Baek JY, Oh JH, Ahn JB, Shin SJ, Han SW, Kim SG, Kang SY, Sym SJ, Zang DY, Kim YH, Choi IS, Kang JH, Kim MJ, Park YS. Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07. J Clin Oncol. 2022 Nov 20;40(33):3868-3877. Epub 2022 Jun 30. link to original article link to PMC article PubMed NCT01092481
- CIRCULATE-IDEA: NCT05174169
FLOX
FLOX: Fluorouracil, Leucovorin, OXaliplatin
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Kuebler et al. 2007 (NSABP C-07) | 2000-2002 | Phase 3 (E-esc) | FULV | Superior DFS (primary endpoint) DFS48: 73.2% vs 67% (HR 0.80, 95% CI 0.69-0.93) |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36, given third, 1 hour after start of leucovorin
- Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given second
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once per day on days 1, 15, 29, given first
8-week cycle for 3 cycles
References
- NSABP C-07: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00004931
- Update: Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. Epub 2011 Aug 22. link to original article link to PMC article PubMed
FOLFOX4
FOLFOX4: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
André et al. 2004 (MOSAIC) | 1998-2001 | Phase 3 (E-RT-esc) | FULV | Seems to have superior OS1 (secondary endpoint) OS120: 71.7% vs 67.1% (HR 0.85, 95% CI 0.73-0.99) Superior DFS (primary endpoint) DFS36: 78.2% vs 72.9% |
de Gramont et al. 2012 (AVANT) | 2004-2007 | Phase 3 (C) | 1. FOLFOX4 & Bevacizumab | Did not meet primary endpoint of DFS |
2. XELOX & Bevacizumab | Did not meet primary endpoint of DFS | |||
Taieb et al. 2014 (PETACC-8) | 2005-2009 | Phase 3 (C) | FOLFOX4 & Cetuximab | Did not meet primary endpoint of DFS |
Grothey et al. 2018 (IDEA) | 2007-2015 | Phase 3 (C) | 1a. FOLFOX4 x 6 1b. mFOLFOX6 x 3 mo 1c. CapeOx x 3 mo |
Inconclusive whether non-inferior DFS36 |
1Reported efficacy for MOSAIC is based on the 2015 update.
IDEA is a pooled analysis of six phase 3 RCTs.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus, given second (total dose per cycle: 2000 mg/m2)
- Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given first, with oxaliplatin on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with leucovorin
14-day cycle for 12 cycles
References
- MOSAIC: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00275210
- Update: André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. Epub 2009 May 18. link to original article PubMed
- Update: André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015 Dec 10;33(35):4176-87. Epub 2015 Nov 2. link to original article PubMed
- AVANT: de Gramont A, Van Cutsem E, Schmoll HJ, Tabernero J, Clarke S, Moore MJ, Cunningham D, Cartwright TH, Hecht JR, Rivera F, Im SA, Bodoky G, Salazar R, Maindrault-Goebel F, Shacham-Shmueli E, Bajetta E, Makrutzki M, Shang A, André T, Hoff PM. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol. 2012 Dec;13(12):1225-33. Epub 2012 Nov 16. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00112918
- Update: André T, Vernerey D, Im SA, Bodoky G, Buzzoni R, Reingold S, Rivera F, McKendrick J, Scheithauer W, Ravit G, Fountzilas G, Yong WP, Isaacs R, Österlund P, Liang JT, Creemers GJ, Rakez M, Van Cutsem E, Cunningham D, Tabernero J, de Gramont A. Bevacizumab as adjuvant treatment of colon cancer: updated results from the S-AVANT phase III study by the GERCOR Group. Ann Oncol. 2020 Feb;31(2):246-256. Epub 2019 Dec 18. link to original article PubMed
- PETACC-8: Taieb J, Tabernero J, Mini E, Subtil F, Folprecht G, Van Laethem JL, Thaler J, Bridgewater J, Petersen LN, Blons H, Collette L, Van Cutsem E, Rougier P, Salazar R, Bedenne L, Emile JF, Laurent-Puig P, Lepage C; PETACC-8 Study Investigators. Oxaliplatin, fluorouracil, and leucovorin with or without cetuximab in patients with resected stage III colon cancer (PETACC-8): an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Jul;15(8):862-73. Epub 2014 Jun 11. link to original article PubMed NCT00265811
- IDEA: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. link to original article does not contain dosing details link to PMC article PubMed NCT01308086
- Subgroup analysis: Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. link to original article PubMed
- Update: André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. link to original article link to PMC article PubMed
- TOSCA: Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. link to original article PubMed NCT00646607
mFOLFOX6
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Example orders
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Allegra et al. 2009 (NSABP C-08) | 2004-2006 | Phase 3 (C) | mFOLFOX6-B | Did not meet primary endpoint of DFS |
Grothey et al. 2018 (IDEA) | 2007-2015 | Phase 3 (C) | 1a. FOLFOX4 x 6 1b. mFOLFOX6 x 3 mo 1c. CapeOx x 3 mo |
Inconclusive whether non-inferior DFS36 |
André et al. 2018 (IDEA France) | 2009-2014 | Phase 3 (C) | mFOLFOX6 x 3 mo | Seems to have superior DFS |
Meyerhardt et al. 2021 (CALGB 80702) | 2010-2015 | Phase 3 (C) | mFOLFOX6 & Celecoxib | Did not meet primary endpoint of DFS |
Note: CALGB 80702 was a 2 x 2 factorial trial, with the other comparison being 3 vs 6 months of mFOLFOX6. This comparison was made as part of the IDEA collaborative and is reported separately.
Preceding treatment
- Surgery, within 10 weeks
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 12 cycles
References
- NSABP C-08: 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 dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00096278
- Update: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Colangelo LH, Atkins JN, Seay TE, Fehrenbacher L, Goldberg RM, O'Reilly S, Chu L, Azar CA, Lopa S, Wolmark N. Phase III trial assessing bevacizumab in stages II and III carcinoma of the colon: results of NSABP protocol C-08. J Clin Oncol. 2011 Jan 1;29(1):11-6. Epub 2010 Oct 12. link to original article link to PMC article PubMed
- Update: Allegra CJ, Yothers G, O'Connell MJ, Sharif S, Petrelli NJ, Lopa SH, Wolmark N. Bevacizumab in stage II-III colon cancer: 5-year update of the National Surgical Adjuvant Breast and Bowel Project C-08 trial. J Clin Oncol. 2013 Jan 20;31(3):359-64. Epub 2012 Dec 10. link to original article link to PMC article PubMed
- IDEA: Grothey A, Sobrero AF, Shields AF, Yoshino T, Paul J, Taieb J, Souglakos J, Shi Q, Kerr R, Labianca R, Meyerhardt JA, Vernerey D, Yamanaka T, Boukovinas I, Meyers JP, Renfro LA, Niedzwiecki D, Watanabe T, Torri V, Saunders M, Sargent DJ, Andre T, Iveson T. Duration of adjuvant chemotherapy for stage III colon cancer. N Engl J Med. 2018 Mar 29;378(13):1177-1188. link to original article does not contain dosing details link to PMC article PubMed NCT01308086
- Subgroup analysis: Souglakos J, Boukovinas I, Kakolyris S, Xynogalos S, Ziras N, Athanasiadis A, Androulakis N, Christopoulou A, Vaslamatzis M, Ardavanis A, Emmanouilides C, Bompolaki I, Kourousis C, Makrantonakis P, Christofyllakis C, Athanasiadis E, Kentepozidis N, Karampeazis A, Katopodi U, Anagnosopoulos A, Papadopoulos G, Prinarakis E, Kalisperi A, Mavroudis D, Georgoulias V; Hellenic Oncology Research Group. Three versus six months adjuvant FOLFOX or CAPOX for high risk stage II and stage III colon cancer patients: the efficacy results of Hellenic Oncology Research Group (HORG) participation to the International Duration Evaluation of Adjuvant chemotherapy (IDEA) project. Ann Oncol. 2019 Aug 1;30(8):1304-1310. Epub 2019 Jun 22. link to original article PubMed
- Update: André T, Meyerhardt J, Iveson T, Sobrero A, Yoshino T, Souglakos I, Grothey A, Niedzwiecki D, Saunders M, Labianca R, Yamanaka T, Boukovinas I, Vernerey D, Meyers J, Harkin A, Torri V, Oki E, Georgoulias V, Taieb J, Shields A, Shi Q. Effect of duration of adjuvant chemotherapy for patients with stage III colon cancer (IDEA collaboration): final results from a prospective, pooled analysis of six randomised, phase 3 trials. Lancet Oncol. 2020 Dec;21(12):1620-1629. link to original article link to PMC article PubMed
- IDEA France: André T, Vernerey D, Mineur L, Bennouna J, Desrame J, Faroux R, Fratte S, Hug de Larauze M, Paget-Bailly S, Chibaudel B, Bez J, Dauba J, Louvet C, Lepere C, Dupuis O, Becouarn Y, Mabro M, Egreteau J, Bouche O, Deplanque G, Ychou M, Galais MP, Ghiringhelli F, Dourthe LM, Bachet JB, Khalil A, Bonnetain F, de Gramont A, Taieb J; PRODIGE investigators, GERCOR, Fédération Française de Cancérologie Digestive, UNICANCER. Three versus 6 months of oxaliplatin-based adjuvant chemotherapy for patients with stage III colon cancer: disease-free survival results from a randomized, open-label, International Duration Evaluation of Adjuvant (IDEA) France, phase III trial. J Clin Oncol. 2018 May 20;36(15):1469-1477. Epub 2018 Apr 5. link to original article PubMed NCT00958737
- TOSCA: Petrelli F, Rulli E, Labianca R, Lonardi S, Rosati G, Dotti K, Ronzoni M, Pella N, Pusceddu V, Banzi M, Zampino MG, Yasmina M, Marchetti P, Cantore M, Zaniboni A, Rimassa L, Ciuffreda L, Ferrari D, Zagonel V, Maiello E, Sobrero A; TOSCA Investigators. Overall survival with 3 or 6 months of adjuvant chemotherapy in Italian TOSCA phase 3 randomised trial. Ann Oncol. 2021 Jan;32(1):66-76. Epub 2020 Oct 21. link to original article PubMed NCT00646607
- ACHIEVE-2: Yamazaki K, Yamanaka T, Shiozawa M, Manaka D, Kotaka M, Gamoh M, Shiomi A, Makiyama A, Munemoto Y, Rikiyama T, Fukunaga M, Ueki T, Shitara K, Shinkai H, Tanida N, Oki E, Sunami E, Ohtsu A, Maehara Y, Yoshino T. Oxaliplatin-based adjuvant chemotherapy duration (3 versus 6 months) for high-risk stage II colon cancer: the randomized phase III ACHIEVE-2 trial. Ann Oncol. 2021 Jan;32(1):77-84. Epub 2020 Oct 26. link to original article PubMed UMIN000013036
- CALGB 80702: Meyerhardt JA, Shi Q, Fuchs CS, Meyer J, Niedzwiecki D, Zemla T, Kumthekar P, Guthrie KA, Couture F, Kuebler P, Bendell JC, Kumar P, Lewis D, Tan B, Bertagnolli M, Grothey A, Hochster HS, Goldberg RM, Venook A, Blanke C, O'Reilly EM, Shields AF. Effect of Celecoxib vs Placebo Added to Standard Adjuvant Therapy on Disease-Free Survival Among Patients With Stage III Colon Cancer: The CALGB/SWOG 80702 (Alliance) Randomized Clinical Trial. JAMA. 2021 Apr 6;325(13):1277-1286. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT01150045
- Dataset: Project Data Sphere
- KCSG CO09-07: Kim ST, Kim SY, Lee J, Yun SH, Kim HC, Lee WY, Kim TW, Hong YS, Lim SB, Baek JY, Oh JH, Ahn JB, Shin SJ, Han SW, Kim SG, Kang SY, Sym SJ, Zang DY, Kim YH, Choi IS, Kang JH, Kim MJ, Park YS. Oxaliplatin (3 months v 6 months) With 6 Months of Fluoropyrimidine as Adjuvant Therapy in Patients With Stage II/III Colon Cancer: KCSG CO09-07. J Clin Oncol. 2022 Nov 20;40(33):3868-3877. Epub 2022 Jun 30. link to original article link to PMC article PubMed NCT01092481
mFOLFOX6 (L-Leucovorin)
mFOLFOX6: modified L-FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Example orders
Regimen variant #1, 3 months, 200 mg/m2 L-LCV
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yoshino et al. 2019 (ACHIEVE) | 2012-08-01 to 2014-06-30 | Phase 3 (E-de-esc) | 1a. CapeOx x 6 mo 1b. mFOLFOX6 x 6 mo |
Seems to have non-inferior DFS1 (primary endpoint) DFS60: 75.2% vs 74.2% (HR 0.95, 95% CI 0.77-1.18) |
1Reported efficacy is based on the 2022 update.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
- Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 6 cycles
Regimen variant #2, 6 months, 200 mg/m2 L-LCV
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yoshino et al. 2019 (ACHIEVE) | 2012-08-01 to 2014-06-30 | Phase 3 (C) | 1a. CapeOx x 3 mo 1b. mFOLFOX6 x 3 mo |
Seems to have non-inferior DFS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given second (total dose per cycle: 2800 mg/m2)
- Levoleucovorin (Fusilev) 200 mg/m2 IV over 2 hours once on day 1, given first, with oxaliplatin
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first, with folinic acid
14-day cycle for 12 cycles
References
- ACHIEVE: Yoshino T, Yamanaka T, Oki E, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Takeuchi S, Bando H, Taniguchi H, Gamoh M, Shiozawa M, Mizushima T, Saji S, Maehara Y, Ohtsu A, Mori M. Efficacy and Long-term Peripheral Sensory Neuropathy of 3 vs 6 Months of Oxaliplatin-Based Adjuvant Chemotherapy for Colon Cancer: The ACHIEVE Phase 3 Randomized Clinical Trial. JAMA Oncol. 2019 Nov 1;5(11):1574-1581. Erratum in: JAMA Oncol. 2019 Nov 1;5(11):1643. Epub 2019 Sep 12. Erratum in: JAMA Oncol. 2019 Dec 19. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed UMIN000008543
- Update: Yoshino T, Oki E, Misumi T, Kotaka M, Manaka D, Eto T, Hasegawa J, Takagane A, Nakamura M, Kato T, Munemoto Y, Nakamura F, Bando H, Taniguchi H, Sakamoto Y, Shiozawa M, Nishi M, Horiuchi T, Yamagishi H, Sakamoto J, Mizushima T, Ohtsu A, Mori M. Final Analysis of 3 Versus 6 Months of Adjuvant Oxaliplatin and Fluoropyrimidine-Based Therapy in Patients With Stage III Colon Cancer: The Randomized Phase III ACHIEVE Trial. J Clin Oncol. 2022 Oct 10;40(29):3419-3429. Epub 2022 May 5. link to original article PubMed
FULV
FULV: 5-FU & LeucoVorin
LV5FU2: LeucoVorin & 5-FU for 2 days
Example orders
- Example orders for 5-FU & low-dose Leucovorin (Mayo Clinic regimen - LDLV) in colon cancer
- Example orders for 5-FU & high-dose Leucovorin (Roswell Park regimen - HDLV) in colon cancer
Regimen variant #1, 500/200, 6 out of 8 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Papadimitriou et al. 2011 | 1999-2004 | Phase 3 (C) | IFL | Did not meet primary endpoint of DFS36 |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
- Leucovorin (Folinic acid) 200 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
8-week cycle for 4 cycles
Regimen variant #2, 500/500, 6 out of 8 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wolmark et al. 1993 (NSABP C-03) | 1987-1989 | Phase 3 (E-de-esc) | MOF | Superior OS |
Wolmark et al. 1999 (NSABP C-04) | 1989-07 to 1990-12 | Phase 3 (E-switch-ooc) | 1. 5-FU & Levamisole | Might have superior OS (co-primary endpoint) |
2. FULV & Levamisole | Did not meet co-primary endpoints of DFS/OS | |||
Haller et al. 2005 (Intergroup 0089) | 1988-1992 | Phase 3 (E-esc) | 1. FULV; low-dose | Did not meet primary endpoint of OS |
2. FULV & Levamisole; LDLV | Did not meet primary endpoint of OS | |||
3. 5-FU & Levamisole | Did not meet primary endpoint of OS | |||
Lembersky et al. 2006 (NSABP C-06) | 1997-1999 | Phase 3 (C) | Tegafur, Uracil, Folinic acid | Did not meet co-primary endpoints of DFS/OS |
Saltz et al. 2007 (CALGB 89803) | 1999-2001 | Phase 3 (C) | IFL | Did not meet co-primary endpoints of DFS/OS |
Kuebler et al. 2007 (NSABP C-07) | 2000-2002 | Phase 3 (C) | FLOX | Inferior DFS |
Schmoll et al. 2007 (XELOXA) | 2003-04 to 2004-10 | Phase 3 (C) | CapeOx | Seems to have inferior OS1 |
1Reported efficacy for XELOXA is based on the 2015 update.
Note: this is often called the "Roswell Park regimen" but the original regimen described by Petrelli et al. 1987 & 1989 used a 5-FU dose of 600 mg/m2.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36, given second, 1 hour after start of leucovorin
- Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first
8-week cycle for varying durations: 3 cycles (NSABP C-07); 3 to 6 cycles
Regimen variant #3, 600/500, 6 out of 8 weeks ("Roswell Park regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fountzilas et al. 2000 | 1989-1997 | Phase 3 (C) | FULV & IFN alfa-2a | Did not meet primary endpoint of OS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2 IV bolus once per day on days 1, 8, 15, 22, 29, 36, given second, 1 hour after start of leucovorin
- Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first
8-week cycle for 4 cycles
Regimen variant #4, 1850/100 ("Mayo Clinic regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Popov et al. 2008 (PETACC-1) | Not reported-1999 | Phase 3 (C) | Raltitrexed | Inconclusive whether non-inferior RFS/OS |
Note: This was the lower bound of 5-FU dosing in PETACC-1.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 370 mg/m2 IV bolus once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 6 cycles
Regimen variant #5, 1850/2500 ("NCI schedule")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wolmark et al. 1998 (NSABP C-05) | 1991-1994 | Phase 3 (C) | FULV & Interferon alfa | Did not meet co-primary endpoints of DFS/OS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 370 mg/m2 IV over 60 minutes once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) 500 mg/m2 IV over 30 minutes once per day on days 1 to 5, given first
28-day cycle for 6 cycles
Regimen variant #6, 2000/400 ("de Gramont regimen"/LV5FU2)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
André et al. 2003 (GERCOR C96.1) | 1996-1999 | Phase 3 (C) | FULV; monthly | Did not meet primary endpoint of DFS |
André et al. 2004 (MOSAIC) | 1998-2001 | Phase 3 (C) | FOLFOX4 | Seems to have inferior OS1 |
Ychou et al. 2009 (FFCD 9802) | 1998-2002 | Phase 3 (C) | IFL | Did not meet primary endpoint of DFS |
Van Cutsem et al. 2009 (PETACC-3) | 2000-2002 | Phase 3 (C) | IFL | Did not meet primary endpoint of DFS |
1Reported efficacy for MOSAIC is based on the 2015 update.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1 & 2, then 600 mg/m2 IV continuous infusion over 22 hours after each bolus, given second (total dose per cycle: 2000 mg/m2)
- Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1 & 2, given first
14-day cycle for 12 cycles
Regimen variant #7, 2000/1000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Francini et al. 1994 | 1985-1990 | Phase 3 (E-esc) | Observation | Superior OS (secondary endpoint) OS60: 79% vs 65% |
Preceding treatment
- Surgery, within 3 weeks
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV once per day on days 1 to 5
- Leucovorin (Folinic acid) 200 mg/m2 IV once per day on days 1 to 5
28-day cycle for 12 cycles
Regimen variant #8, 2125/100 ("Mayo Clinic regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Twelves et al. 2005 (X-ACT) | 1998-2001 | Phase 3 (C) | Capecitabine | Might have inferior OS1 |
Popov et al. 2008 (PETACC-1) | Not reported-1999 | Phase 3 (C) | Raltitrexed | Inconclusive whether non-inferior RFS/OS |
Köhne et al. 2013 (PETACC-2) | 1999-2004 | Phase 3 (C) | 1. FULV; LV5FU2 2. FULV; AIO regimen 3. FULV; TTD regimen |
Did not meet primary endpoint of OS60 |
Schmoll et al. 2007 (XELOXA) | 2003-04 to 2004-10 | Phase 3 (C) | XELOX | Seems to have inferior OS2 |
1X-ACT was a non-inferiority study. Reported efficacy is based on the 2011 update.
2Reported efficacy for XELOXA is based on the 2015 update.
Note: This was the upper bound of 5-FU dosing in PETACC-1.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 6 cycles
Regimen variant #9, 2125/100, with cycle elongation ("Mayo Clinic regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Connell et al. 1997 (CALGB 8896) | 1988-02 to 1989-08 | Phase 3 (E-esc) | Observation | Seems to have superior OS |
Haller et al. 2005 (Intergroup 0089) | 1988-1992 | Phase 3 (E-de-esc) | 1. FULV; high-dose | Did not meet primary endpoint of OS |
2. FULV & Levamisole; LDLV | Did not meet primary endpoint of OS | |||
3. 5-FU & Levamisole | Did not meet primary endpoint of OS | |||
Punt et al. 2002 (Study 157-002) | 1995-1999 | Phase 3 (C) | 1. FULV & Edrecolomab | Did not meet primary endpoint of OS |
2. Edrecolomab | Seems to have superior OS | |||
Fields et al. 2009 (Study 157-001) | 1995-1999 | Phase 3 (C) | FULV & Edrecolomab | Did not meet primary endpoint of OS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) 20 mg/m2 IV bolus once per day on days 1 to 5, given first
28-day cycle for 3 cycles, then 35-day cycle for 3 cycles
References
- NSABP C-03: Wolmark N, Rockette H, Fisher B, Wickerham DL, Redmond C, Fisher ER, Jones J, Mamounas EP, Ore L, Petrelli NJ, Spurr CL, Dimitrov N, Romond EH, Sutherland CM, Kardinal CG, DeFusco PA, Jochimsen P. The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol. 1993 Oct;11(10):1879-87. link to original article dosing details in manuscript have been reviewed by our editors 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. link to original article link to PMC article PubMed
- Francini G, Petrioli R, Lorenzini L, Mancini S, Armenio S, Tanzini G, Marsili S, Aquino A, Marzocca G, Civitelli S, Mariani L, De Sando D, Bovenga S, Lorenzi M. Folinic acid and 5-fluorouracil as adjuvant chemotherapy in colon cancer. Gastroenterology. 1994 Apr;106(4):899-906. link to original article dosing details in manuscript have been reviewed by our editors 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. link to original article dosing details in manuscript have been reviewed by our editors 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. link to original article PubMed
- NSABP C-05: Wolmark N, Bryant J, Smith R, Grem J, Allegra C, Hyams D, Atkins J, Dimitrov N, Oishi R, Prager D, Fehrenbacher L, Romond E, Colangelo L, Fisher B. Adjuvant 5-fluorouracil and leucovorin with or without interferon alfa-2a in colon carcinoma: National Surgical Adjuvant Breast and Bowel Project protocol C-05. J Natl Cancer Inst. 1998 Dec 2;90(23):1810-6. link to original article 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. link to original article link to PMC article PubMed
- NSABP C-04: Wolmark N, Rockette H, Mamounas E, Jones J, Wieand S, Wickerham DL, Bear HD, Atkins JN, Dimitrov NV, Glass AG, Fisher ER, Fisher B. Clinical trial to assess the relative efficacy of fluorouracil and leucovorin, fluorouracil and levamisole, and fluorouracil, leucovorin, and levamisole in patients with Dukes' B and C carcinoma of the colon: results from National Surgical Adjuvant Breast and Bowel Project C-04. J Clin Oncol. 1999 Nov;17(11):3553-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00425152
- 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
- Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Papavramidis S, Bousoulegas A, Basdanis G, Giannoulis E, Dokmetzioglou J, Katsohis C, Nenopoulou E, Karvounis N, Briassoulis E, Aravantinos G, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Fluorouracil and leucovorin with or without interferon alfa-2a as adjuvant treatment, in patients with high-risk colon cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Oncology. 2000 Apr;58(3):227-36. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Study 157-002: Punt CJ, Nagy A, Douillard JY, Figer A, Skovsgaard T, Monson J, Barone C, Fountzilas G, Riess H, Moylan E, Jones D, Dethling J, Colman J, Coward L, MacGregor S. Edrecolomab alone or in combination with fluorouracil and folinic acid in the adjuvant treatment of stage III colon cancer: a randomised study. Lancet. 2002 Aug 31;360(9334):671-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GERCOR C96.1: Andre T, Colin P, Louvet C, Gamelin E, Bouche O, Achille E, Colbert N, Boaziz C, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Buyse M, de Gramont A. Semimonthly versus monthly regimen of fluorouracil and leucovorin administered for 24 or 36 weeks as adjuvant therapy in stage II and III colon cancer: results of a randomized trial. J Clin Oncol. 2003 Aug 1;21(15):2896-903. link to original article PubMed
- Update: André T, Quinaux E, Louvet C, Colin P, Gamelin E, Bouche O, Achille E, Piedbois P, Tubiana-Mathieu N, Boutan-Laroze A, Flesch M, Lledo G, Raoul Y, Debrix I, Buyse M, de Gramont A. Phase III study comparing a semimonthly with a monthly regimen of fluorouracil and leucovorin as adjuvant treatment for stage II and III colon cancer patients: final results of GERCOR C96.1. J Clin Oncol. 2007 Aug 20;25(24):3732-8. link to original article PubMed
- MOSAIC: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00275210
- Update: André T, Boni C, Navarro M, Tabernero J, Hickish T, Topham C, Bonetti A, Clingan P, Bridgewater J, Rivera F, de Gramont A. Improved overall survival with oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment in stage II or III colon cancer in the MOSAIC trial. J Clin Oncol. 2009 Jul 1;27(19):3109-16. Epub 2009 May 18. link to original article PubMed
- Update: André T, de Gramont A, Vernerey D, Chibaudel B, Bonnetain F, Tijeras-Raballand A, Scriva A, Hickish T, Tabernero J, Van Laethem JL, Banzi M, Maartense E, Shmueli E, Carlsson GU, Scheithauer W, Papamichael D, Möehler M, Landolfi S, Demetter P, Colote S, Tournigand C, Louvet C, Duval A, Fléjou JF, de Gramont A. Adjuvant fluorouracil, leucovorin, and oxaliplatin in stage II to III colon cancer: updated 10-year survival and outcomes according to BRAF mutation and mismatch repair status of the MOSAIC study. J Clin Oncol. 2015 Dec 10;33(35):4176-87. Epub 2015 Nov 2. link to original article PubMed
- X-ACT: Twelves C, Wong A, Nowacki MP, Abt M, Burris HA 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00009737
- Update: Twelves C, Scheithauer W, McKendrick J, Seitz JF, Van Hazel G, Wong A, Díaz-Rubio E, Gilberg F, Cassidy J. Capecitabine versus 5-fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: final results from the X-ACT trial with analysis by age and preliminary evidence of a pharmacodynamic marker of efficacy. Ann Oncol. 2012 May;23(5):1190-7. Epub 2011 Sep 6. link to original article PubMed
- Intergroup 0089: 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 dosing details in manuscript have been reviewed by our editors PubMed
- NSABP C-06: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00378716
- XELOXA: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00069121
- Update: 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 dosing details in manuscript have been reviewed by our editors PubMed
- Update: Schmoll HJ, Tabernero J, Maroun J, de Braud F, Price T, Van Cutsem E, Hill M, Hoersch S, Rittweger K, Haller DG. Capecitabine plus oxaliplatin compared with fluorouracil/folinic acid as adjuvant therapy for stage III colon cancer: Final results of the NO16968 randomized controlled phase III trial. J Clin Oncol. 2015 Nov 10;33(32):3733-40. Epub 2015 Aug 31. link to original article PubMed
- NSABP C-07: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00004931
- Update: Yothers G, O'Connell MJ, Allegra CJ, Kuebler JP, Colangelo LH, Petrelli NJ, Wolmark N. Oxaliplatin as adjuvant therapy for colon cancer: updated results of NSABP C-07 trial, including survival and subset analyses. J Clin Oncol. 2011 Oct 1;29(28):3768-74. Epub 2011 Aug 22. link to original article link to PMC article PubMed
- CALGB 89803: Saltz LB, Niedzwiecki D, Hollis D, Goldberg RM, Hantel A, Thomas JP, Fields AL, Mayer RJ. Irinotecan fluorouracil plus leucovorin is not superior to fluorouracil plus leucovorin alone as adjuvant treatment for stage III colon cancer: results of CALGB 89803. J Clin Oncol. 2007 Aug 10;25(23):3456-61. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00003835
- PETACC-1: Popov I, Carrato A, Sobrero A, Vincent M, Kerr D, Labianca R, Raffaele Bianco A, El-Serafi M, Bedenne L, Paillot B, Mini E, Sanches E, Welch J, Collette L, Praet M, Wils J. Raltitrexed (Tomudex) versus standard leucovorin-modulated bolus 5-fluorouracil: Results from the randomised phase III Pan-European Trial in Adjuvant Colon Cancer 01 (PETACC-1). Eur J Cancer. 2008 Oct;44(15):2204-11. Epub 2008 Aug 15. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- FFCD 9802: Ychou M, Raoul JL, Douillard JY, Gourgou-Bourgade S, Bugat R, Mineur L, Viret F, Becouarn Y, Bouché O, Gamelin E, Ducreux M, Conroy T, Seitz JF, Bedenne L, Kramar A. A phase III randomised trial of LV5FU2 + irinotecan versus LV5FU2 alone in adjuvant high-risk colon cancer (FNCLCC Accord02/FFCD9802). Ann Oncol. 2009 Apr;20(4):674-80. Epub 2009 Jan 29. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00005979
- Study 157-001: Fields AL, Keller A, Schwartzberg L, Bernard S, Kardinal C, Cohen A, Schulz J, Eisenberg P, Forster J, Wissel P. Adjuvant therapy with the monoclonal antibody edrecolomab plus fluorouracil-based therapy does not improve overall survival of patients with stage III colon cancer. J Clin Oncol. 2009 Apr 20;27(12):1941-7. Epub 2009 Mar 9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- PETACC-3: Van Cutsem E, Labianca R, Bodoky G, Barone C, Aranda E, Nordlinger B, Topham C, Tabernero J, André T, Sobrero AF, Mini E, Greil R, Di Costanzo F, Collette L, Cisar L, Zhang X, Khayat D, Bokemeyer C, Roth AD, Cunningham D. Randomized phase III trial comparing biweekly infusional fluorouracil/leucovorin alone or with irinotecan in the adjuvant treatment of stage III colon cancer: PETACC-3. J Clin Oncol. 2009 Jul 1;27(19):3117-25. Epub 2009 May 18. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00026273
- Papadimitriou CA, Papakostas P, Karina M, Malettou L, Dimopoulos MA, Pentheroudakis G, Samantas E, Bamias A, Miliaras D, Basdanis G, Xiros N, Klouvas G, Bafaloukos D, Kafiri G, Papaspirou I, Pectasides D, Karanikiotis C, Economopoulos T, Efstratiou I, Korantzis I, Pisanidis N, Makatsoris T, Matsiakou F, Aravantinos G, Kalofonos HP, Fountzilas G; Hellenic Cooperative Oncology Group. A randomized phase III trial of adjuvant chemotherapy with irinotecan, leucovorin and fluorouracil versus leucovorin and fluorouracil for stage II and III colon cancer: a Hellenic Cooperative Oncology Group study. BMC Med. 2011 Jan 31;9:10. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed ACTRN12610000148077
- PETACC-2: Köhne CH, Bedenne L, Carrato A, Bouché O, Popov I, Gaspà L, Valladares M, Rougier P, Gog C, Reichardt P, Wils J, Pignatti F, Biertz F; EORTC; FFCD; GETTD. A randomised phase III intergroup trial comparing high-dose infusional 5-fluorouracil with or without folinic acid with standard bolus 5-fluorouracil/folinic acid in the adjuvant treatment of stage III colon cancer: the Pan-European Trial in Adjuvant Colon Cancer 2 study. Eur J Cancer. 2013 May;49(8):1868-75. Epub 2013 Apr 6. link to original article PubMed NCT00004150
S-1 monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Yoshida et al. 2014 (ACTS-CC) | 2008-04 to 2009-06 | Phase 3 (E-switch-ic) | UFT + LV | Non-inferior DFS36 (primary endpoint) DFS36: 75.5% vs 72.5% (HR 0.85, 95% CI 0.70-1.03) |
Preceding treatment
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
- Less than 1.25 m2: 40 mg PO twice per day on days 1 to 28
- BSA between 1.25 m2 and 1.50 m2: 50 mg PO twice per day on days 1 to 28
- BSA greater than 1.50 m2: 60 mg PO twice per day on days 1 to 28
42-day cycle for 4 cycles
References
- ACTS-CC: Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-9. Epub 2014 Jun 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00660894
SOX
SOX: S-1, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sunami et al. 2019 (ACTS-CC 02) | 2010-2014 | Phase 3 (E-esc) | Tegafur, Uracil, Folinic Acid | Did not meet primary endpoint of DFS |
Preceding treatment
Chemotherapy
- Tegafur, gimeracil, oteracil (S-1) 40 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 100 mg/m2 IV once on day 1
21-day cycle for 8 cycles
References
- ACTS-CC 02: Sunami E, Kusumoto T, Ota M, SakamotoY, Yoshida K, Tomita N, Maeda A, Teshima J, Okabe M, Tanaka C, Yamauchi J, Itabashi M, Kotake K, Takahashi K, Baba H, Boku N, Aiba K, Ishiguro M, Morita S, Takenaka N, Okude R, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as postoperative adjuvant chemotherapy in patients with high-risk stage III colon cancer (ACTS-CC 02): a randomized, open-label, multicenter, phase 3, superiority trial. Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. Epub 2019 Oct 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed JapicCTI-101073
- Update: Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. link to original article link to PMC article PubMed
Tegafur, Uracil, Folinic acid
UFT + LV: UFT (Tegafur and uracil) & LeucoVorin (Folinic acid)
Regimen variant #1, 300/75
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sadahiro et al. 2015 (JFMC33-0502) | 2005-2007 | Phase 3 (C) | UFT + LV; weekly x 18 mo | Did not meet primary endpoint of DFS |
Yoshida et al. 2014 (ACTS-CC) | 2008-04 to 2009-06 | Phase 3 (C) | S-1 | Non-inferior DFS36 |
Sunami et al. 2019 (ACTS-CC 02) | 2010-2014 | Phase 3 (C) | SOX | Did not meet primary endpoint of DFS |
Note: In ACTS-CC, this dosing was used for patients with BSA less than 1.17 m2.
Chemotherapy
- Tegafur and uracil (UFT) 100 mg/m2 PO every 8 hours on days 1 to 28
- Leucovorin (Folinic acid) 25 mg PO every 8 hours on days 1 to 28
35-day cycle for 5 cycles
Regimen variant #2, 300/90
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lembersky et al. 2006 (NSABP C-06) | 1997-1999 | Phase 3 (E-switch-ic) | FULV | Did not meet co-primary endpoints of DFS/OS |
Preceding treatment
- A potentially curative resection of stage II or stage III colon cancer
Chemotherapy
- Tegafur and uracil (UFT) 100 mg/m2 PO every 8 hours on days 1 to 28
- Leucovorin (Folinic acid) 30 mg PO every 8 hours on days 1 to 28
- No food for 1 hour before and after each dose of medication.
35-day cycle for 5 cycles
References
- NSABP C-06: 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 dosing details in manuscript have been reviewed by our editors PubMed NCT00378716
- ACTS-CC: Yoshida M, Ishiguro M, Ikejiri K, Mochizuki I, Nakamoto Y, Kinugasa Y, Takagane A, Endo T, Shinozaki H, Takii Y, Mochizuki H, Kotake K, Kameoka S, Takahashi K, Watanabe T, Watanabe M, Boku N, Tomita N, Nakatani E, Sugihara K; ACTS-CC study group. S-1 as adjuvant chemotherapy for stage III colon cancer: a randomized phase III study (ACTS-CC trial). Ann Oncol. 2014 Sep;25(9):1743-9. Epub 2014 Jun 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00660894
- JFMC33-0502: Sadahiro S, Tsuchiya T, Sasaki K, Kondo K, Katsumata K, Nishimura G, Kakeji Y, Baba H, Sato S, Koda K, Yamaguchi Y, Morita T, Matsuoka J, Usuki H, Hamada C, Kodaira S. Randomized phase III trial of treatment duration for oral uracil and tegafur plus leucovorin as adjuvant chemotherapy for patients with stage IIB/III colon cancer: final results of JFMC33-0502. Ann Oncol. 2015 Nov;26(11):2274-80. Epub 2015 Sep 7. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed UMIN C000000245
- ACTS-CC 02: Sunami E, Kusumoto T, Ota M, SakamotoY, Yoshida K, Tomita N, Maeda A, Teshima J, Okabe M, Tanaka C, Yamauchi J, Itabashi M, Kotake K, Takahashi K, Baba H, Boku N, Aiba K, Ishiguro M, Morita S, Takenaka N, Okude R, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as postoperative adjuvant chemotherapy in patients with high-risk stage III colon cancer (ACTS-CC 02): a randomized, open-label, multicenter, phase 3, superiority trial. Clin Colorectal Cancer. 2020 Mar;19(1):22-31.e6. Epub 2019 Oct 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed JapicCTI-101073
- Update: Watanabe J, Sasaki S, Kusumoto T, Sakamoto Y, Yoshida K, Tomita N, Maeda A, Teshima J, Yokota M, Tanaka C, Yamauchi J, Uetake H, Itabashi M, Takahashi K, Baba H, Kotake K, Boku N, Aiba K, Morita S, Takenaka N, Sugihara K. S-1 and oxaliplatin versus tegafur-uracil and leucovorin as post-operative adjuvant chemotherapy in patients with high-risk stage III colon cancer: updated 5-year survival of the phase III ACTS-CC 02 trial. ESMO Open. 2021 Apr;6(2):100077. Epub 2021 Mar 11. link to original article link to PMC article PubMed
Advanced or metastatic disease
See the colorectal cancer page for colorectal cancer regimens.