Difference between revisions of "Rectal 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? For placebo or observational studies in this condition, please visit [[Rectal cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | |
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− | ''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Rectal cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!'' | ||
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{| class="wikitable" style="float:right; margin-right: 5px;" | {| class="wikitable" style="float:right; margin-right: 5px;" | ||
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<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> | <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> | ||
|} | |} | ||
+ | Note: the page has (neo-)adjuvant regimens specific to rectal cancer. Please see the [[Colon_cancer|'''colon cancer page''']] for adjuvant regimens specific to colon cancer (e.g., adjuvant [[Colon_cancer#CapeOx|CapeOx]]) and the [[Colorectal_cancer|'''colorectal cancer page''']] for regimens intended more generically for colorectal cancer. | ||
{{TOC limit|limit=3}} | {{TOC limit|limit=3}} | ||
− | |||
=Guidelines= | =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.''' |
− | *'''2017:''' Glynne-Jones et al. [https:// | + | ==[https://www.esmo.org/ ESMO]== |
− | **'''[https:// | + | *'''2018:''' Glynne-Jones et al. [https://doi.org/10.1093/annonc/mdy161 Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/29741565/ PubMed] |
− | == | + | **'''2017:''' Glynne-Jones et al. [https://doi.org/10.1093/annonc/mdx224 Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/28881920/ PubMed] |
− | *''' | + | **'''2013:''' Glimelius et al. [https://doi.org/10.1093/annonc/mdt240 Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/24078665/ PubMed] |
+ | **'''2010:''' Glimelius et al. [https://doi.org/10.1093/annonc/mdq170 Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/20555109/ PubMed] | ||
+ | **'''2009:''' Glimelius & Oliveira. [https://doi.org/10.1093/annonc/mdp128 Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/19454463/ PubMed] | ||
+ | **'''2008:''' Glimelius & Oliveira. [https://doi.org/10.1093/annonc/mdn078 Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/18456759/ PubMed] | ||
+ | **'''2007:''' Glimelius. [https://doi.org/10.1093/annonc/mdm022 Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/17491031/ PubMed] | ||
+ | **'''2005:''' Tveit & Kataja. [https://doi.org/10.1093/annonc/mdi827 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer] [https://pubmed.ncbi.nlm.nih.gov/15888739/ PubMed] | ||
+ | **'''2003:''' Tveit. [https://doi.org/10.1093/annonc/mdg297 ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer] [https://pubmed.ncbi.nlm.nih.gov/12853337/ PubMed] | ||
+ | ==French Intergroup== | ||
+ | *'''2017:''' Gérard et al. [https://doi.org/10.1016/j.dld.2017.01.152 Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO)] [https://pubmed.ncbi.nlm.nih.gov/28179091/ PubMed] | ||
+ | ==NCCN== | ||
+ | *[https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1461 NCCN Guidelines - Rectal Cancer] | ||
+ | **'''2015:''' Benson et al. [https://doi.org/10.6004/jnccn.2015.0087 Rectal Cancer, Version 2.2015] [https://pubmed.ncbi.nlm.nih.gov/26085388/ PubMed] | ||
+ | **'''2009:''' Engstrom et al. [https://doi.org/10.6004/Jnccn.2009.0057 NCCN Clinical Practice Guidelines in Oncology: rectal cancer.] [https://pubmed.ncbi.nlm.nih.gov/19755047/ PubMed] | ||
− | ==[https:// | + | ==SIOG== |
− | + | *'''2018''': Montroni et al. [https://doi.org/10.1016/j.ejso.2018.08.003 Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer] [https://pubmed.ncbi.nlm.nih.gov/30150158/ PubMed] | |
− | |||
− | |||
=Neoadjuvant therapy= | =Neoadjuvant therapy= | ||
− | |||
==Capecitabine & RT {{#subobject:1887b9|Regimen=1}}== | ==Capecitabine & RT {{#subobject:1887b9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Capecitabine & RT: Capecitabine & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Capecitabine & RT: Capecitabine & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | ===Regimen variant #1, interrupted capecitabine, 1600 mg/m<sup>2</sup>/day, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, interrupted capecitabine, 1600 mg/m<sup>2</sup>/day, 4500 cGy {{#subobject:19cc2a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 49: | Line 49: | ||
|2005-2008 | |2005-2008 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CapeOx & RT | + | |[[#CapeOx_.26_RT_333|CapeOx & RT]] |
| style="background-color:#fee08b" |Might have inferior pCR rate | | style="background-color:#fee08b" |Might have inferior pCR rate | ||
|- | |- | ||
|} | |} | ||
''Note: adjuvant therapy was not specified. Treatment is assumed to start on a Monday.'' | ''Note: adjuvant therapy was not specified. Treatment is assumed to start on a Monday.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | + | </div></div><br> | |
− | ===Regimen variant #2, interrupted capecitabine, 1600 mg/m<sup>2</sup>/day, | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable sortable" style="width: | + | ===Regimen variant #2, interrupted capecitabine, 1600 mg/m<sup>2</sup>/day, 5000 cGy {{#subobject:19ff2a|Variant=1}}=== |
− | !style="width: | + | {| class="wikitable sortable" style="width: 100%; text-align:center;" |
− | !style="width: | + | !style="width: 20%"|Study |
− | !style="width: | + | !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/10.1016/s1470-2045(21)00079-6 Conroy et al. 2021 (UNICANCER-PRODIGE 23)] | |[https://doi.org/10.1016/s1470-2045(21)00079-6 Conroy et al. 2021 (UNICANCER-PRODIGE 23)] | ||
|2012-2017 | |2012-2017 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
+ | | style="background-color:#d3d3d3" | | ||
+ | | style="background-color:#d3d3d3" | | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.ejca.2022.11.020 François et al. 2022] | ||
+ | |2016-2019 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#Radiation_therapy|RT]]; 5 x 5 | ||
+ | | style="background-color:#ffffbf" |Inconclusive whether non-inferior R0 resection rate | ||
|- | |- | ||
|} | |} | ||
''Note: Treatment is assumed to start on a Monday.'' | ''Note: Treatment is assumed to start on a Monday.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#FOLFIRINOX|FOLFIRINOX]] versus no neoadjuvant chemotherapy | + | *UNICANCER-PRODIGE 23: Neoadjuvant [[#FOLFIRINOX|FOLFIRINOX]] versus [[Rectal_cancer_-_null_regimens#No_neoadjuvant_therapy|no neoadjuvant chemotherapy]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery#Total_mesorectal_excision|TME]], then mFOLFOX6 | + | *UNICANCER-PRODIGE 23: [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[#mFOLFOX6_2|mFOLFOX6]] |
+ | *François et al. 2022: [[Surgery#Rectal_cancer_surgery|Surgery]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | ===Regimen variant #3, interrupted capecitabine, 1650 mg/m<sup>2</sup>/day, | + | ===Regimen variant #3, interrupted capecitabine, 1650 mg/m<sup>2</sup>/day, 4500 cGy {{#subobject:19c7tg|Variant=1}}=== |
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 99: | Line 117: | ||
|2008-2011 | |2008-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CapeOx & RT | + | |[[#CapeOx_.26_RT_999|CapeOx & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#Capecitabine_monotherapy|capecitabine]] |
− | + | </div></div><br> | |
− | ===Regimen variant #4, continuous capecitabine, 1650 mg/m<sup>2</sup>/day, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #4, continuous capecitabine, 1650 mg/m<sup>2</sup>/day, 4500 cGy {{#subobject:a05392|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 123: | Line 142: | ||
!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | !style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2812%2970116-X Hofheinz et al. 2012 (Rektum-III)] |
|2002-2007 | |2002-2007 | ||
− | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) |
|[[#Fluorouracil_.26_RT|5-FU & RT]] | |[[#Fluorouracil_.26_RT|5-FU & RT]] | ||
− | | style="background-color:#eeee01" |Non-inferior OS | + | | style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>OS60: 76% vs 67% |
| | | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1002/cncr.25943 Park et al. 2011 (AMC Rectal Pre Vs Post 2004)] |
|2004-2006 | |2004-2006 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
Line 144: | Line 163: | ||
| style="background-color:#eeee01" |Similar toxicity | | style="background-color:#eeee01" |Similar toxicity | ||
|- | |- | ||
− | |2. CapeOx & RT<br> 3. [[#FUOX_.26_RT|FUOX & RT]] | + | |2. [[#CapeOx_.26_RT_999|CapeOx & RT]]<br> 3. [[#FUOX_.26_RT|FUOX & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | | style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | ||
+ | | style="background-color:#1a9850" |Superior toxicity | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/j.radonc.2018.11.023 Valentini et al. 2016 (INTERACT)] | ||
+ | |2005-2013 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#CapeOx_.26_RT_999|CapeOx & RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet efficacy endpoints | ||
| style="background-color:#1a9850" |Superior toxicity | | style="background-color:#1a9850" |Superior toxicity | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 38 | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 38 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions/4500 cGy), with boost depending on stage |
− | + | '''5.5-week course''' | |
− | '''5-week course''' | + | </div> |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#Capecitabine_monotherapy|capecitabine]] |
− | + | </div></div><br> | |
− | ===Regimen variant #5, interrupted capecitabine, 1650 mg/m<sup>2</sup>/day, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #5, interrupted capecitabine, 1650 mg/m<sup>2</sup>/day, 5000 cGy {{#subobject:19ihaa|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 174: | Line 203: | ||
|} | |} | ||
''Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.'' | ''Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#CapeOx|CapeOx]] x 1, then [[Surgery# | + | *Neoadjuvant [[#CapeOx|CapeOx]] x 1, then [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[#CapeOx|CapeOx]] x 5 |
− | + | </div></div><br> | |
− | ===Regimen variant #6, interrupted capecitabine, 1650 mg/m<sup>2</sup>/day, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #6, interrupted capecitabine, 1650 mg/m<sup>2</sup>/day, 5040 cGy {{#subobject:17tatg|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 195: | Line 226: | ||
|2008-2011 | |2008-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CapeOx & RT | + | |[[#CapeOx_.26_RT_888|CapeOx & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
|} | |} | ||
''Note: Treatment starts on a Monday.'' | ''Note: Treatment starts on a Monday.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (5040 cGy total in 28 fractions) |
− | |||
'''5.5-week course''' | '''5.5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#Capecitabine_monotherapy|capecitabine]] |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''ACCORD 12:''' Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-PRODIGE 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. Epub 2010 Mar 1. [https://doi.org/10.1200/JCO.2009.25.8376 link to original article] ''' | + | # '''ACCORD 12:''' Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-PRODIGE 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. Epub 2010 Mar 1. [https://doi.org/10.1200/JCO.2009.25.8376 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20194850/ PubMed] [https://clinicaltrials.gov/study/NCT00227747 NCT00227747] |
− | ## '''Update:''' Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Seitz JF, Bedenne L, Juzyna B, Conroy T. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012 Dec 20;30(36):4558-65. Epub 2012 Oct 29. [https://doi.org/10.1200/JCO.2012.42.8771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23109696 PubMed] | + | ## '''Update:''' Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Seitz JF, Bedenne L, Juzyna B, Conroy T. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012 Dec 20;30(36):4558-65. Epub 2012 Oct 29. [https://doi.org/10.1200/JCO.2012.42.8771 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23109696/ PubMed] |
− | # '''AMC Rectal Pre Vs Post 2004:''' Park JH, Yoon SM, Yu CS, Kim JH, Kim TW, Kim JC. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer. 2011 Aug 15;117(16):3703-12. Epub 2011 Feb 15. [https:// | + | # '''AMC Rectal Pre Vs Post 2004:''' Park JH, Yoon SM, Yu CS, Kim JH, Kim TW, Kim JC. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer. 2011 Aug 15;117(16):3703-12. Epub 2011 Feb 15. [https://doi.org/10.1002/cncr.25943 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21328328/ PubMed] [https://clinicaltrials.gov/study/NCT01186081 NCT01186081] |
− | + | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https://doi.org/10.1016/S1470-2045%2812%2970116-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22503032/ PubMed] [https://clinicaltrials.gov/study/NCT01500993 NCT01500993] | |
− | # '''NSABP R-04:''' O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. [https://doi.org/10.1200/JCO.2013.53.7753 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050205/ link to PMC article] ''' | + | # '''NSABP R-04:''' O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. [https://doi.org/10.1200/JCO.2013.53.7753 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050205/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24799484/ PubMed] [https://clinicaltrials.gov/study/NCT00058474 NCT00058474] |
− | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). [https:// | + | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). [https://doi.org/10.1093/jnci/djv248 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849360/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26374429/ PubMed] |
− | #''' | + | #'''INTERACT:''' Valentini V, Gambacorta MA, Cellini F, Aristei C, Coco C, Barbaro B, Alfieri S, D'Ugo D, Persiani R, Deodato F, Crucitti A, Lupattelli M, Mantello G, Navarria F, Belluco C, Buonadonna A, Boso C, Lonardi S, Caravatta L, Barba MC, Vecchio FM, Maranzano E, Genovesi D, Doglietto GB, Morganti AG, La Torre G, Pucciarelli S, De Paoli A. The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)-cT3 rectal cancer. Radiother Oncol. 2019 May;134:110-118. Epub 2019 Feb 7. [https://doi.org/10.1016/j.radonc.2018.11.023 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31005204/ PubMed] [https://clinicaltrials.gov/study/NCT01653301 NCT01653301] |
− | # ''' | + | #'''CinClare:''' Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. [https://doi.org/10.1200/jco.20.01932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33119477/ PubMed] [https://clinicaltrials.gov/study/NCT02605265 NCT02605265] |
− | + | # '''PETACC 6:''' Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. [https://doi.org/10.1200/jco.20.01740 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33001764/ PubMed] [https://clinicaltrials.gov/study/NCT00766155 NCT00766155] | |
+ | # '''UNICANCER-PRODIGE 23:''' Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. Epub 2021 Apr 13. [https://doi.org/10.1016/s1470-2045(21)00079-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33862000/ PubMed] [https://clinicaltrials.gov/study/NCT01804790 NCT01804790] | ||
+ | # '''STELLAR<sub>rectal</sub>:''' Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022 May 20;40(15):1681-1692. Epub 2022 Mar 9. [https://doi.org/10.1200/jco.21.01667 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9113208/ link to PMC article] [https://clinicaltrials.gov/study/NCT02533271 NCT02533271] [https://pubmed.ncbi.nlm.nih.gov/35263150/ PubMed] | ||
+ | #'''CONVERT<sub>rectal</sub>:''' Mei WJ, Wang XZ, Li YF, Sun YM, Yang CK, Lin JZ, Wu ZG, Zhang R, Wang W, Li Y, Zhuang YZ, Lei J, Wan XB, Ren YK, Cheng Y, Li WL, Wang ZQ, Xu DB, Mo XW, Ju HX, Ye SW, Zhao JL, Zhang H, Gao YH, Zeng ZF, Xiao WW, Zhang XP, Zhang X, Xie E, Feng YF, Tang JH, Wu XJ, Chen G, Li LR, Lu ZH, Wan DS, Bei JX, Pan ZZ, Ding PR. Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial. Ann Surg. 2023 Apr 1;277(4):557-564. Epub 2022 Dec 20. [https://doi.org/10.1097/SLA.0000000000005780 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9994847/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/36538627/ PubMed] [https://clinicaltrials.gov/study/NCT02288195 NCT02288195] | ||
+ | # François E, De Bari B, Ronchin P, Nouhaud E, Martel-Lafay I, Artru P, Clavere P, Vendrely V, Boige V, Gargot D, Lemanski C, De Sousa Carvalho N, Gal J, Pernot M, Magné N. Comparison of short course radiotherapy with chemoradiotherapy for locally advanced rectal cancers in the elderly: A multicentre, randomised, non-blinded, phase 3 trial. Eur J Cancer. 2023 Feb;180:62-70. Epub 2022 Nov 28. [https://doi.org/10.1016/j.ejca.2022.11.020 link to original article] [https://pubmed.ncbi.nlm.nih.gov/36535196/ PubMed] | ||
+ | #'''PROSPECT<sub>rectal</sub>:''' Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. [https://doi.org/10.1056/nejmoa2303269 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775881/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37272534/ PubMed] [https://clinicaltrials.gov/study/NCT01515787 NCT01515787] | ||
+ | ##'''PRO analysis:''' Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. [https://doi.org/10.1200/jco.23.00903 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37270691/ PubMed] | ||
==Capecitabine, Sorafenib, RT {{#subobject:1812b9|Regimen=1}}== | ==Capecitabine, Sorafenib, RT {{#subobject:1812b9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Capecitabine, Sorafenib, RT: Capecitabine, Sorafenib, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Capecitabine, Sorafenib, RT: Capecitabine, Sorafenib, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a01232|Variant=1}}=== | ===Regimen {{#subobject:a01232|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.ejca.2017.11.005 von Moos et al. 2017 (SAKK 41/08)] |
− | | style="background-color:#91cf61" |Phase | + | |2009-03 to 2013-05 |
+ | | style="background-color:#91cf61" |Phase 1/2 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Biomarker eligibility criteria==== | ||
+ | *KRAS-mutation | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 33 | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on days 1 to 33 | ||
Line 242: | Line 283: | ||
*[[Sorafenib (Nexavar)]] 400 mg PO once per day | *[[Sorafenib (Nexavar)]] 400 mg PO once per day | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 4500 cGy total |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''SAKK 41/08:''' von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bärtschi D, Zaugg K; Swiss Group for Clinical Cancer Research. Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08). Eur J Cancer. 2018 Jan;89:82-89. Epub 2017 Dec 11. [https:// | + | # '''SAKK 41/08:''' von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bärtschi D, Zaugg K; Swiss Group for Clinical Cancer Research. Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08). Eur J Cancer. 2018 Jan;89:82-89. Epub 2017 Dec 11. [https://doi.org/10.1016/j.ejca.2017.11.005 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29241084/ PubMed] |
==CapeOx {{#subobject:cf9acc|Regimen=1}}== | ==CapeOx {{#subobject:cf9acc|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin | CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 4 cycles {{#subobject:205ad6|Variant=1}}=== | ===Regimen variant #1, 4 cycles {{#subobject:205ad6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 60%; text-align:center;" | {| class="wikitable sortable" style="width: 60%; text-align:center;" | ||
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1016/s1470-2045(09)70381-x Chua et al. 2010] | |[https://doi.org/10.1016/s1470-2045(09)70381-x Chua et al. 2010] | ||
|2001-2005 | |2001-2005 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1 | *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 4 cycles''' | '''21-day cycle for 4 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#Capecitabine_.26_RT|Capecitabine & RT]], then [[Surgery#Total_mesorectal_excision|TME]] | + | *Neoadjuvant [[#Capecitabine_.26_RT|Capecitabine & RT]], then [[Surgery#Total_mesorectal_excision|TME]] |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 6 cycles {{#subobject:9a1iog|Variant=1}}=== | ===Regimen variant #2, 6 cycles {{#subobject:9a1iog|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 290: | Line 333: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Radiation_therapy|RT]]; 5 x | + | *Neoadjuvant [[#Radiation_therapy|RT]]; 5 x 500 cGy |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1 | *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*[[Surgery#Total_mesorectal_excision|TME]] | *[[Surgery#Total_mesorectal_excision|TME]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. Epub 2010 Jan 25. [https://doi.org/10.1016/s1470-2045(09)70381-x link to original article] ''' | + | # Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. Epub 2010 Jan 25. [https://doi.org/10.1016/s1470-2045(09)70381-x link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20106720/ PubMed] [https://clinicaltrials.gov/study/NCT00220051 NCT00220051] |
− | #'''RAPIDO:''' Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. [https://doi.org/10.1016/s1470-2045(20)30555-6 link to original article] ''' | + | #'''RAPIDO:''' Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. [https://doi.org/10.1016/s1470-2045(20)30555-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33301740/ PubMed] [https://clinicaltrials.gov/study/NCT01558921 NCT01558921] |
− | |||
==CapeOx, Cetuximab, RT {{#subobject:2d68ed|Regimen=1}}== | ==CapeOx, Cetuximab, RT {{#subobject:2d68ed|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CapeOX, Cetuximab, RT: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin, Cetuximab, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CapeOX, Cetuximab, RT: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin, Cetuximab, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:5a3ef0|Variant=1}}=== | ===Regimen {{#subobject:5a3ef0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6598683/ Leichman et al. 2017 (SWOG S0713)] |
− | | style="background-color:#91cf61" |Phase | + | |2009-02 to 2013-04 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on Monday to Friday | *[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day on Monday to Friday | ||
Line 329: | Line 374: | ||
**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29 | **Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1, then 250 mg/m<sup>2</sup> IV once per day on days 8, 15, 22, 29 | ||
**Cycle 2: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 | **Cycle 2: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 | ||
+ | ====Radiotherapy==== | ||
+ | *[[External_beam_radiotherapy|RT]] as follows: | ||
+ | **Cycle 2: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions) | ||
'''35-day cycle for 2 cycles''' | '''35-day cycle for 2 cycles''' | ||
− | == | + | </div> |
− | + | <div class="toccolours" style="background-color:#cbd5e7"> | |
− | |||
− | |||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
*[[Surgery#Total_mesorectal_excision|TME]] | *[[Surgery#Total_mesorectal_excision|TME]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''SWOG S0713:''' Leichman CG, McDonough SL, Smalley SR, Billingsley KG, Lenz HJ, Beldner MA, Hezel AF, Velasco MR, Guthrie KA, Blanke CD, Hochster HS. Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713. Clin Colorectal Cancer. 2018 Mar;17(1):e121-e125. Epub 2017 Oct 24. [https:// | + | # '''SWOG S0713:''' Leichman CG, McDonough SL, Smalley SR, Billingsley KG, Lenz HJ, Beldner MA, Hezel AF, Velasco MR, Guthrie KA, Blanke CD, Hochster HS. Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713. Clin Colorectal Cancer. 2018 Mar;17(1):e121-e125. Epub 2017 Oct 24. [https://doi.org/10.1016/j.clcc.2017.10.008 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6598683/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/29233486/ PubMed] [https://clinicaltrials.gov/study/NCT00686166 NCT00686166] |
− | |||
==CapIriRT {{#subobject:115th9|Regimen=1}}== | ==CapIriRT {{#subobject:115th9|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CapIriRT: '''<u>Cap</u>'''ecitabine, '''<u>Iri</u>'''notecan, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CapIriRT: '''<u>Cap</u>'''ecitabine, '''<u>Iri</u>'''notecan, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 65 mg/m<sup>2</sup> {{#subobject:19ugak|Variant=1}}=== | ===Regimen variant #1, 65 mg/m<sup>2</sup> {{#subobject:19ugak|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 356: | Line 398: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ Zhu et al. 2020 (CinClare)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ Zhu et al. 2020 (CinClare)] | ||
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase 3 ( | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[Complex_multipart_regimens#CinClare|See link]] | |[[Complex_multipart_regimens#CinClare|See link]] | ||
| style="background-color:#1a9850" |[[Complex_multipart_regimens#CinClare|See link]] | | style="background-color:#1a9850" |[[Complex_multipart_regimens#CinClare|See link]] | ||
Line 362: | Line 404: | ||
|} | |} | ||
''Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.'' | ''Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*''UGT1A1*1*28'' genotype | *''UGT1A1*1*28'' genotype | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once on | + | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *CAPIRI x 1, then [[Surgery# | + | *Neoadjuvant [[#CAPIRI_888|CAPIRI]] x 1, then [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[#CapeOx|CapeOx]] x 5 |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:t81bak|Variant=1}}=== | ===Regimen variant #2, 80 mg/m<sup>2</sup> {{#subobject:t81bak|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 385: | Line 431: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ Zhu et al. 2020 (CinClare)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ Zhu et al. 2020 (CinClare)] | ||
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase 3 ( | + | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) |
|[[Complex_multipart_regimens#CinClare|See link]] | |[[Complex_multipart_regimens#CinClare|See link]] | ||
| style="background-color:#1a9850" |[[Complex_multipart_regimens#CinClare|See link]] | | style="background-color:#1a9850" |[[Complex_multipart_regimens#CinClare|See link]] | ||
Line 391: | Line 437: | ||
|} | |} | ||
''Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.'' | ''Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.'' | ||
+ | <div class="toccolours" style="background-color:#fdcdac"> | ||
====Biomarker eligibility criteria==== | ====Biomarker eligibility criteria==== | ||
*''UGT1A1*1*1'' genotype | *''UGT1A1*1*1'' genotype | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 5 | + | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 |
− | *[[Irinotecan (Camptosar)]] 80 mg/m<sup>2</sup> IV once on | + | *[[Irinotecan (Camptosar)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *CAPIRI x 1, then [[Surgery# | + | *Neoadjuvant [[#CAPIRI_888|CAPIRI]] x 1, then [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[#CapeOx|CapeOx]] x 5 |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #'''CinClare:''' Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. [https://doi.org/10.1200/jco.20.01932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ link to PMC article] ''' | + | #'''CinClare:''' Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. [https://doi.org/10.1200/jco.20.01932 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7768334/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33119477/ PubMed] [https://clinicaltrials.gov/study/NCT02605265 NCT02605265] |
− | |||
==Fluorouracil & RT {{#subobject:bffc7f|Regimen=1}}== | ==Fluorouracil & RT {{#subobject:bffc7f|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Fluorouracil & RT: Fluorouracil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Fluorouracil & RT: Fluorouracil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, continuous {{#subobject:5801b6|Variant=1}}=== | ===Regimen variant #1, continuous {{#subobject:5801b6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 442: | Line 488: | ||
| style="background-color:#eeee01" |Similar toxicity | | style="background-color:#eeee01" |Similar toxicity | ||
|- | |- | ||
− | |2. CapeOx & RT<br> 3. [[#FUOX_.26_RT|FUOX & RT]] | + | |2. [[#CapeOx_.26_RT_999|CapeOx & RT]]<br> 3. [[#FUOX_.26_RT|FUOX & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | | style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | ||
| style="background-color:#1a9850" |Superior toxicity | | style="background-color:#1a9850" |Superior toxicity | ||
Line 448: | Line 494: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy for STAR-01 is based on the 2016 update.'' | ''<sup>1</sup>Reported efficacy for STAR-01 is based on the 2016 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion until the end of radiation, started on day 1 | *[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion until the end of radiation, started on day 1 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 180 cGy for 25 fractions (4500 cGy), with boost depending on stage |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *STAR-01: [[Surgery# | + | *STAR-01: [[Surgery#Rectal_cancer_surgery|Surgery]], preferably [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[Regimen_classes#5-FU-based_regimen|fluourouracil-based therapy]] |
− | *NSABP R-04: [[Surgery# | + | *NSABP R-04: [[Surgery#Rectal_cancer_surgery|Surgery]] |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, intermittent {{#subobject:3c5452|Variant=1}}=== | ===Regimen variant #2, intermittent {{#subobject:3c5452|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa040694 Sauer et al. 2004 (CAO/ARO/AIO-94)] |
|1995-2002 | |1995-2002 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#Fluorouracil_.26_RT_2|5-FU & RT]]; adjuvant | |[[#Fluorouracil_.26_RT_2|5-FU & RT]]; adjuvant | ||
− | | style="background-color:#1a9850" |Superior five-year cumulative incidence of local relapse | + | | style="background-color:#1a9850" |Superior five-year cumulative incidence of local relapse (secondary endpoint) |
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2812%2970116-X Hofheinz et al. 2012 (Rektum-III)] |
|2002-2007 | |2002-2007 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 478: | Line 527: | ||
| style="background-color:#eeee01" |Non-inferior OS | | style="background-color:#eeee01" |Non-inferior OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70187-0 Rödel et al. 2012 (CAO/ARO/AIO-04)] |
|2006-2010 | |2006-2010 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 485: | Line 534: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on | + | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on days 1 & 29 (total dose: 10,000 mg/m<sup>2</sup>) |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 5040 cGy total |
− | |||
'''One course''' | '''One course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *CAO/ARO/AIO-94: [[Surgery#Total_mesorectal_excision|TME]], then [[#Fluorouracil_monotherapy| | + | *CAO/ARO/AIO-94: [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[#Fluorouracil_monotherapy|5-FU]] |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''CAO/ARO/AIO-94:''' Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. [https:// | + | # '''CAO/ARO/AIO-94:''' Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. [https://doi.org/10.1056/NEJMoa040694 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/15496622/ PubMed] |
− | ## '''Update:''' Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. Epub 2012 Apr 23. [https://doi.org/10.1200/jco.2011.40.1836 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22529255 PubMed] | + | ## '''Update:''' Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. Epub 2012 Apr 23. [https://doi.org/10.1200/jco.2011.40.1836 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22529255/ PubMed] |
− | # '''STAR-01:''' Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.34.4911 link to original article] ''' | + | # '''STAR-01:''' Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.34.4911 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21606427/ PubMed] |
## '''Update: Abstract:''' Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 [https://doi.org/10.1200/JCO.2016.34.15_suppl.3521 link to abstract] | ## '''Update: Abstract:''' Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 [https://doi.org/10.1200/JCO.2016.34.15_suppl.3521 link to abstract] | ||
− | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https:// | + | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https://doi.org/10.1016/S1470-2045%2812%2970116-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22503032/ PubMed] [https://clinicaltrials.gov/study/NCT01500993 NCT01500993] |
− | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https:// | + | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https://doi.org/10.1016/S1470-2045(12)70187-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22627104/ PubMed] [https://clinicaltrials.gov/study/NCT00349076 NCT00349076] |
− | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https:// | + | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https://doi.org/10.1016/S1470-2045(15)00159-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26189067/ PubMed] |
− | # '''TROG 01.014:''' Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. [https://doi.org/10.1200/JCO.2012.42.9597 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23008301 PubMed] NCT00351598 | + | # '''TROG 01.014:''' Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. [https://doi.org/10.1200/JCO.2012.42.9597 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23008301/ PubMed] [https://clinicaltrials.gov/study/NCT00351598 NCT00351598] |
− | # '''NSABP R-04:''' O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. [https://doi.org/10.1200/JCO.2013.53.7753 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050205/ link to PMC article] ''' | + | # '''NSABP R-04:''' O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. [https://doi.org/10.1200/JCO.2013.53.7753 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050205/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24799484/ PubMed] [https://clinicaltrials.gov/study/NCT00058474 NCT00058474] |
− | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). [https:// | + | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). [https://doi.org/10.1093/jnci/djv248 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849360/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26374429/ PubMed] |
− | + | #'''PROSPECT<sub>rectal</sub>:''' Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. [https://doi.org/10.1056/nejmoa2303269 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775881/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37272534/ PubMed] [https://clinicaltrials.gov/study/NCT01515787 NCT01515787] | |
+ | ##'''PRO analysis:''' Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. [https://doi.org/10.1200/jco.23.00903 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37270691/ PubMed] | ||
==FOLFIRINOX {{#subobject:aaa3c4|Regimen=1}}== | ==FOLFIRINOX {{#subobject:aaa3c4|Regimen=1}}== | ||
− | + | FOLFIRINOX: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>IRIN</u>'''otecan, '''<u>OX</u>'''aliplatin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | FOLFIRINOX: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRIN</u>'''otecan, '''<u>OX</u>'''aliplatin | ||
===Regimen {{#subobject:e140cb|Variant=1}}=== | ===Regimen {{#subobject:e140cb|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 524: | Line 572: | ||
|2012-2017 | |2012-2017 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |No neoadjuvant chemotherapy | + | |[[Rectal_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant chemotherapy]] |
− | | style="background-color:#91cf60" |Seems to have superior | + | | style="background-color:#91cf60" |Seems to have superior DFS36 (primary endpoint)<br>DFS36: 76% vs 69%<br>(sHR 0.69, 95% CI 0.49-0.97) |
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first''' | ||
+ | *[[Fluorouracil (5-FU)]] 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, started on day 1, '''given third''' | ||
+ | *[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given second''' | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first''' | ||
+ | '''14-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
+ | ====Subsequent treatment==== | ||
+ | *Neoadjuvant [[#Capecitabine_.26_RT|Capecitabine & RT]] | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | # '''UNICANCER-PRODIGE 23:''' Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. Epub 2021 Apr 13. [https://doi.org/10.1016/s1470-2045(21)00079-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33862000/ PubMed] [https://clinicaltrials.gov/study/NCT01804790 NCT01804790] | ||
+ | ==mFOLFOX6 {{#subobject:faig8v|Regimen=1}}== | ||
+ | mFOLFOX6: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:ckvfc0|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/PMC10775881/ Schrag et al. 2023 (PROSPECT<sub>rectal</sub>)] | ||
+ | |2012-06 to 2018-12 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-switch-ooc) | ||
+ | |1a. [[#Capecitabine_.26_RT|Capecitabine & RT]]<br>1b. [[#Fluorouracil_.26_RT|5-FU & RT]] | ||
+ | | style="background-color:#eeee01" |Non-inferior DFS (primary endpoint)<br>DFS60: 80.8% vs 78.6%<br>(HR 0.92, 90.2% CI 0.74-1.14) | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: this trial (PROSPECT) is labeled as PROSPECT<sub>rectal</sub> to avoid confusion with the one by the same name in prostate cancer.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once on day 1 |
− | |||
− | *[[ | ||
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''14-day cycle for 6 cycles''' | '''14-day cycle for 6 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then optional adjuvant [[#mFOLFOX6_2|mFOLFOX6]] x 6 |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # ''' | + | #'''PROSPECT<sub>rectal</sub>:''' Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. [https://doi.org/10.1056/nejmoa2303269 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10775881/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37272534/ PubMed] [https://clinicaltrials.gov/study/NCT01515787 NCT01515787] |
− | + | ##'''PRO analysis:''' Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. [https://doi.org/10.1200/jco.23.00903 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10351948/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37270691/ PubMed] | |
==FULV & RT {{#subobject:fbe1a7|Regimen=1}}== | ==FULV & RT {{#subobject:fbe1a7|Regimen=1}}== | ||
− | + | FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>L</u>'''euco'''<u>V</u>'''orin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>L</u>'''euco'''<u>V</u>'''orin | ||
===Regimen variant #1, 800/200 ("Nordic schedule") {{#subobject:3780c0|Variant=1}}=== | ===Regimen variant #1, 800/200 ("Nordic schedule") {{#subobject:3780c0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 559: | Line 638: | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Radiation_therapy|Radiotherapy]] | |[[#Radiation_therapy|Radiotherapy]] | ||
− | | style="background-color:#d9ef8b" |Might have superior OS60 | + | | style="background-color:#d9ef8b" |Might have superior OS60 (primary endpoint)<br>OS60: 66% vs 53% |
|- | |- | ||
|} | |} | ||
''Note: reported efficacy is based on the 2018 update.'' | ''Note: reported efficacy is based on the 2018 update.'' | ||
+ | <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 | + | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1, 2, 15, 16, 29, 30 '''given first, prior to RT''' |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 100 mg IV once per day on days 1 & 2, '''given second''' |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, total of 5000 cGy) |
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#FULV|FULV]] x 8 |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 1625/100 {{#subobject:0160e1|Variant=1}}=== | ===Regimen variant #2, 1625/100 {{#subobject:0160e1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 584: | Line 666: | ||
|1993-1999 | |1993-1999 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |[[# | + | |Adjuvant [[#Fluorouracil_.26_RT_2|5-FU & RT]] |
− | | style="background-color:#d9ef8b" |Might have superior OS | + | | style="background-color:#d9ef8b" |Might have superior OS (co-primary endpoint)<br>OS60: 74.5% vs 65.6%<br>(HR 0.69, 95% CI 0.47-1.03) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *FULV x 1 | + | *Neoadjuvant [[#FULV_888|FULV]] x 1 |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 325 mg/m<sup>2</sup> IV once per day on days 1 to 5 | + | *[[Fluorouracil (5-FU)]] 325 mg/m<sup>2</sup> IV once per day on days 1 to 5, 29 to 33 |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5, 29 to 33 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 5040 cGy |
'''5-week course''' | '''5-week course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#FULV|FULV]] x 4 |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1750/100 {{#subobject:7d3ec1|Variant=1}}=== | ===Regimen variant #3, 1750/100 {{#subobject:7d3ec1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.radonc.2014.10.006 Sainato et al. 2014 (I-CNR-RT)] |
|1992-2001 | |1992-2001 | ||
− | | style="background-color:#91cf61" |Non-randomized | + | | style="background-color:#91cf61" |Non-randomized part of phase 3 RCT |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa060829 Bosset et al. 2006 (EORTC 22921)] |
|1993-2003 | |1993-2003 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 629: | Line 715: | ||
|} | |} | ||
''<sup>1</sup>These trials were negative for the primary endpoint of overall survival, but had much improved local control for the experimental arm.'' | ''<sup>1</sup>These trials were negative for the primary endpoint of overall survival, but had much improved local control for the experimental arm.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 350 mg/m<sup>2</sup> IV once per day on days 1 to 5 | + | *[[Fluorouracil (5-FU)]] 350 mg/m<sup>2</sup> IV once per day on days 1 to 5, 29 to 33 |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5, 29 to 33 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 4500 cGy |
'''5-week course''' | '''5-week course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *FFCD 9203 & EORTC 22921: [[Surgery# | + | *FFCD 9203 & EORTC 22921: [[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#FULV|FULV]] x 2 |
− | *I-CNR-RT: [[Surgery# | + | *I-CNR-RT: [[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#FULV|FULV]] versus [[Rectal_cancer_-_null_regimens#Observation|no further treatment]] |
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 2800/400 {{#subobject:98d3ca|Variant=1}}=== | ===Regimen variant #4, 2800/400 {{#subobject:98d3ca|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 652: | Line 741: | ||
|rowspan=2|2010-2015 | |rowspan=2|2010-2015 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (C) | ||
− | |1. mFOLFOX6 | + | |1. [[#mFOLFOX6|mFOLFOX6]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36<sup>1</sup> | ||
|- | |- | ||
Line 661: | Line 750: | ||
''<sup>1</sup>Reported efficacy is based on the 2019 update.''<br> | ''<sup>1</sup>Reported efficacy is based on the 2019 update.''<br> | ||
''Note: this regimen is stated to be based on the de Gramont regimen in the manuscript, although the details are different than those in de Gramont et al. 2000.'' | ''Note: this regimen is stated to be based on the de Gramont regimen in the manuscript, although the details are different than those in de Gramont et al. 2000.'' | ||
+ | <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 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV once on day 1 |
'''14-day cycle for 5 cycles''' | '''14-day cycle for 5 cycles''' | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] given during cycles 2 to 4: 1.8 to | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] given during cycles 2 to 4: 1.8 to 200 cGy once per day Monday through Friday for a total of 23 to 28 fractions over 5 to 6 weeks and a total dose of 4600 to 5040 cGy |
− | |||
'''6-week course''' | '''6-week course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#FULV|FULV]] x 7 |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''FFCD 9203:''' Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. [https://doi.org/10.1200/JCO.2006.06.7629 link to original article] ''' | + | # '''FFCD 9203:''' Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. [https://doi.org/10.1200/JCO.2006.06.7629 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17008704/ PubMed] [https://clinicaltrials.gov/study/NCT00296608 NCT00296608] |
− | # '''EORTC 22921:''' Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; [[Study_Groups#EORTC|EORTC]] Radiotherapy Group. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. Erratum in: N Engl J Med. 2007 Aug 16;357(7):728. [https:// | + | # '''EORTC 22921:''' Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; [[Study_Groups#EORTC|EORTC]] Radiotherapy Group. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. Erratum in: N Engl J Med. 2007 Aug 16;357(7):728. [https://doi.org/10.1056/NEJMoa060829 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16971718/ PubMed] [https://clinicaltrials.gov/study/NCT00002523 NCT00002523] |
− | ## '''Update:''' Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. Epub 2014 Jan 17. [https:// | + | ## '''Update:''' Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. Epub 2014 Jan 17. [https://doi.org/10.1016/S1470-2045(13)70599-0 link to original article] [https://pubmed.ncbi.nlm.nih.gov/24440473/ PubMed] |
− | # '''LARCS:''' Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. [https://doi.org/10.1200/JCO.2007.15.3858 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18669453 PubMed] | + | # '''LARCS:''' Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. [https://doi.org/10.1200/JCO.2007.15.3858 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18669453/ PubMed] |
− | ## '''Update:''' Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. [https:// | + | ## '''Update:''' Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. [https://doi.org/10.1016/j.radonc.2018.05.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29778486/ PubMed] |
− | # '''NSABP R-03:''' Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009 Nov 1;27(31):5124-30. Epub 2009 Sep 21. [https://doi.org/10.1200/JCO.2009.22.0467 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773471/ link to PMC article] ''' | + | # '''NSABP R-03:''' Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009 Nov 1;27(31):5124-30. Epub 2009 Sep 21. [https://doi.org/10.1200/JCO.2009.22.0467 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2773471/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19770376/ PubMed] |
− | # '''I-CNR-RT:''' Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, Aristei C, Vidali C, Conti M, Galardi A, Ponticelli P, Friso ML, Iannone T, Osti FM, Manfredi B, Coppola M, Orlandini C, Cionini L. No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014 Nov;113(2):223-9. Epub 2014 Nov 14. [https:// | + | # '''I-CNR-RT:''' Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, Aristei C, Vidali C, Conti M, Galardi A, Ponticelli P, Friso ML, Iannone T, Osti FM, Manfredi B, Coppola M, Orlandini C, Cionini L. No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014 Nov;113(2):223-9. Epub 2014 Nov 14. [https://doi.org/10.1016/j.radonc.2014.10.006 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25454175/ PubMed] |
<!-- Presented at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015, and 18th Annual Meeting of the Chinese Society of Clinical Oncology, Xiamen, China, September 16-20, 2015. --> | <!-- Presented at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015, and 18th Annual Meeting of the Chinese Society of Clinical Oncology, Xiamen, China, September 16-20, 2015. --> | ||
− | # '''FOWARC:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. Epub 2016 Aug 1. [https://doi.org/10.1200/jco.2016.66.6198 link to original article] ''' | + | # '''FOWARC:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. Epub 2016 Aug 1. [https://doi.org/10.1200/jco.2016.66.6198 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27480145/ PubMed] [https://clinicaltrials.gov/study/NCT01211210 NCT01211210] |
− | ## '''Update:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. [https://doi.org/10.1200/JCO.18.02309 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31557064 PubMed] | + | ## '''Update:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. [https://doi.org/10.1200/JCO.18.02309 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6881102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31557064/ PubMed] |
− | |||
==FUOX & RT {{#subobject:b3761c|Regimen=1}}== | ==FUOX & RT {{#subobject:b3761c|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FUOX & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>OX</u>'''aliplatin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | FUOX & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>OX</u>'''aliplatin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 225/50 {{#subobject:66269c|Variant=1}}=== | ===Regimen variant #1, 225/50 {{#subobject:66269c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 703: | Line 789: | ||
|rowspan=2|2004-2010 | |rowspan=2|2004-2010 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |1. [[#Fluorouracil_.26_RT|5-FU & RT]]<br> 2. [[#Capecitabine_.26_RT|Capecitabine & RT]] | + | |1. [[#Fluorouracil_.26_RT|5-FU & RT]]<br>2. [[#Capecitabine_.26_RT|Capecitabine & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | | style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | ||
| style="background-color:#d73027" |Inferior toxicity | | style="background-color:#d73027" |Inferior toxicity | ||
|- | |- | ||
− | |3. CapeOx & RT | + | |3. [[#CapeOx_.26_RT_999|CapeOx & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | | style="background-color:#ffffbf" |Did not meet primary endpoint of LRC | ||
| style="background-color:#eeee01" |Similar toxicity | | style="background-color:#eeee01" |Similar toxicity | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on | + | *[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 5625 mg/m<sup>2</sup>) |
− | *[[Oxaliplatin (Eloxatin)]] 50 mg/m<sup>2</sup> IV once on | + | *[[Oxaliplatin (Eloxatin)]] 50 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 5040 cGy total |
− | |||
'''5.5-week course''' | '''5.5-week course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 225/60 {{#subobject:0b1c02|Variant=1}}=== | ===Regimen variant #2, 225/60 {{#subobject:0b1c02|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 17%"|Study | !style="width: 17%"|Study | ||
− | !style="width: 15%"| | + | !style="width: 15%"|Dates of enrollment |
!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 17%"|Comparator | !style="width: 17%"|Comparator | ||
Line 743: | Line 830: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2016 update.''<br> | ''<sup>1</sup>Reported efficacy is based on the 2016 update.''<br> | ||
− | ''This | + | ''Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.'' |
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over approximately 6 weeks, started on day 1 | *[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over approximately 6 weeks, started on day 1 | ||
*[[Oxaliplatin (Eloxatin)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36 | *[[Oxaliplatin (Eloxatin)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 5040 cGy total |
− | |||
'''6-week course''' | '''6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], preferably [[Surgery#Total_mesorectal_excision|TME]], then adjuvant [[Regimen_classes#5-FU-based_regimen|fluourouracil-based therapy]] |
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 250/50 {{#subobject:858489|Variant=1}}=== | ===Regimen variant #3, 250/50 {{#subobject:858489|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70187-0 Rödel et al. 2012 (CAO/ARO/AIO-04)] |
|2006-2010 | |2006-2010 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Fluorouracil_.26_RT|Fluorouracil & RT]] | |[[#Fluorouracil_.26_RT|Fluorouracil & RT]] | ||
− | | style="background-color:#91cf60" |Seems to have superior pCR rate | + | | style="background-color:#91cf60" |Seems to have superior pCR rate (secondary endpoint) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 250 mg/m<sup>2</sup>/day IV continuous infusion over 14 days, started on | + | *[[Fluorouracil (5-FU)]] 250 mg/m<sup>2</sup>/day IV continuous infusion over 14 days, started on days 1 & 22 (total dose: 7000 mg/m<sup>2</sup>) |
− | *[[Oxaliplatin (Eloxatin)]] 50 mg/m<sup>2</sup> IV once per day on days 1 | + | *[[Oxaliplatin (Eloxatin)]] 50 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 22, 29 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 5040 cGy total |
'''One course''' | '''One course''' | ||
− | + | </div> | |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#FOLFOX|FOLFOX]] |
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''STAR-01:''' Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.34.4911 link to original article] ''' | + | # '''STAR-01:''' Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 23. [https://doi.org/10.1200/JCO.2010.34.4911 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21606427/ PubMed] |
## '''Update: Abstract:''' Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 [https://doi.org/10.1200/JCO.2016.34.15_suppl.3521 link to abstract] | ## '''Update: Abstract:''' Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 [https://doi.org/10.1200/JCO.2016.34.15_suppl.3521 link to abstract] | ||
− | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https:// | + | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https://doi.org/10.1016/S1470-2045(12)70187-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22627104/ PubMed] [https://clinicaltrials.gov/study/NCT00349076 NCT00349076] |
− | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https:// | + | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https://doi.org/10.1016/S1470-2045(15)00159-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26189067/ PubMed] |
− | # '''NSABP R-04:''' O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. [https://doi.org/10.1200/JCO.2013.53.7753 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050205/ link to PMC article] ''' | + | # '''NSABP R-04:''' O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. [https://doi.org/10.1200/JCO.2013.53.7753 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4050205/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24799484/ PubMed] [https://clinicaltrials.gov/study/NCT00058474 NCT00058474] |
− | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). [https:// | + | ## '''Update:''' Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). [https://doi.org/10.1093/jnci/djv248 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4849360/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26374429/ PubMed] |
− | |||
==mFOLFOX6 & RT {{#subobject:4ffffc|Regimen=1}}== | ==mFOLFOX6 & RT {{#subobject:4ffffc|Regimen=1}}== | ||
− | + | mFOLFOX6 & RT: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin and '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | mFOLFOX6 & RT: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin and '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
===Regimen {{#subobject:9bf2ab|Variant=1}}=== | ===Regimen {{#subobject:9bf2ab|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 808: | Line 895: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36<sup>1</sup> | ||
|- | |- | ||
− | |2. mFOLFOX6 | + | |2. [[#mFOLFOX6|mFOLFOX6]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36<sup>1</sup> | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36<sup>1</sup> | ||
|- | |- | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2019 update.'' | ''<sup>1</sup>Reported efficacy is based on the 2019 update.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV once on day 1 |
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | ||
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
'''14-day cycle for 4 to 6 cycles''' | '''14-day cycle for 4 to 6 cycles''' | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] given before or after surgery at physician discretion: | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] given before or after surgery at physician discretion: 180 to 200 cGy once per day Monday through Friday for a total of 23 to 28 fractions, for a total dose of 4600 to 5040 cGy |
'''5- to 6-week course''' | '''5- to 6-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]], then adjuvant [[#mFOLFOX6_2|mFOLFOX6]] x 6 to 8 |
− | + | </div></div> | |
===References=== | ===References=== | ||
<!-- Presented at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015, and 18th Annual Meeting of the Chinese Society of Clinical Oncology, Xiamen, China, September 16-20, 2015. --> | <!-- Presented at the 51st Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 29-June 2, 2015, and 18th Annual Meeting of the Chinese Society of Clinical Oncology, Xiamen, China, September 16-20, 2015. --> | ||
− | # '''FOWARC:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. Epub 2016 Aug 1. [https://doi.org/10.1200/jco.2016.66.6198 link to original article] ''' | + | # '''FOWARC:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. Epub 2016 Aug 1. [https://doi.org/10.1200/jco.2016.66.6198 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27480145/ PubMed] [https://clinicaltrials.gov/study/NCT01211210 NCT01211210] |
− | ## '''Update:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. [https://doi.org/10.1200/JCO.18.02309 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31557064 PubMed] | + | ## '''Update:''' Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. [https://doi.org/10.1200/JCO.18.02309 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6881102/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31557064/ PubMed] |
− | |||
==Radiation therapy {{#subobject:41234c|Regimen=1}}== | ==Radiation therapy {{#subobject:41234c|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy | RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | ===Regimen variant #1, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, 2500 cGy {{#subobject:9abcab|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199704033361402 Cedermark et al. 1997 (Swedish Rectal Cancer Trial)] |
|1987-1990 | |1987-1990 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 849: | Line 935: | ||
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa010580 Kapiteijn et al. 2001] |
|1996-1999 | |1996-1999 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 858: | Line 944: | ||
|1998-2005 | |1998-2005 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |Selective postoperative 5-FU & RT | + | |Selective postoperative [[#Fluorouracil_.26_RT_2|5-FU & RT]] |
| style="background-color:#91cf60" |Seems to have superior DFS | | style="background-color:#91cf60" |Seems to have superior DFS | ||
|- | |- | ||
Line 864: | Line 950: | ||
|2008-2014 | |2008-2014 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | | | + | |[[#FULV_.26_RT|FULV & RT]] |
− | | style="background-color:#d9ef8b" |Might have superior R0 resection rate | + | | style="background-color:#d9ef8b" |Might have superior R0 resection rate (primary endpoint) |
|- | |- | ||
|[https://doi.org/10.1016/s1470-2045(20)30555-6 Bahadoer et al. 2020 (RAPIDO)] | |[https://doi.org/10.1016/s1470-2045(20)30555-6 Bahadoer et al. 2020 (RAPIDO)] | ||
Line 874: | Line 960: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Radiation therapy]], | + | *[[External_beam_radiotherapy|Radiation therapy]], 500 cGy once per day for a total of 5 fractions (total dose: 2500 cGy) |
− | |||
'''5-day course''' | '''5-day course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *Swedish Rectal Cancer Trial, Kapiteijn et al. 2001, NCIC-CTG CO.16: [[Surgery# | + | *Swedish Rectal Cancer Trial, Kapiteijn et al. 2001, NCIC-CTG CO.16: [[Surgery#Rectal_cancer_surgery|Surgery]] |
− | *Polish II: FOLFOX4 x 3, then [[Surgery# | + | *Polish II: Neoadjuvant [[#FOLFOX4_888|FOLFOX4]] x 3, then [[Surgery#Rectal_cancer_surgery|Surgery]] |
− | *RAPIDO: [[#CapeOx|CapeOx]] x 6 or FOLFOX4 x 9, then [[Surgery# | + | *RAPIDO: Neoadjuvant [[#CapeOx|CapeOx]] x 6 or [[#FOLFOX4_888|FOLFOX4]] x 9, then [[Surgery#Rectal_cancer_surgery|Surgery]] |
− | + | </div></div><br> | |
− | ===Regimen variant #2, | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #2, 4000 cGy {{#subobject:8b0799|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#f01e2c" | ||
+ | |<small><span style="color:white;">'''Historic variant'''</span></small> | ||
+ | |- | ||
+ | |} | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(96)05348-2 Oates et al. 1996] |
|1981-1989 | |1981-1989 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 898: | Line 991: | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Radiation therapy]], | + | *[[External_beam_radiotherapy|Radiation therapy]], 200 cGy x 20 fractions (total dose: 4000 cGy) |
− | |||
'''4-week course''' | '''4-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | + | </div></div><br> | |
− | ===Regimen variant #3, | + | <div class="toccolours" style="background-color:#ee6b6e"> |
+ | ===Regimen variant #3, 5000 cGy {{#subobject:159853|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#f01e2c" | ||
+ | |<small><span style="color:white;">'''Historic variant'''</span></small> | ||
+ | |- | ||
+ | |} | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 917: | Line 1,016: | ||
|1996-2003 | |1996-2003 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#FULV.2FFULV_.26_RT|FULV/FULV & RT]] |
| style="background-color:#fee08b" |Might have inferior OS60 | | style="background-color:#fee08b" |Might have inferior OS60 | ||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Radiation therapy]], | + | *[[External_beam_radiotherapy|Radiation therapy]], 200 cGy x 25 fractions (total dose: 5000 cGy) |
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # Oates GD, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet. 1996 Dec 14;348(9042):1605-10. [https:// | + | # Oates GD, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet. 1996 Dec 14;348(9042):1605-10. [https://doi.org/10.1016/S0140-6736(96)05348-2 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8961989/ PubMed] |
− | # '''Swedish Rectal Cancer Trial:''' Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N; Swedish Rectal Cancer Trial investigators. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539. [https:// | + | # '''Swedish Rectal Cancer Trial:''' Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N; Swedish Rectal Cancer Trial investigators. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539. [https://doi.org/10.1056/NEJM199704033361402 link to original article] [https://pubmed.ncbi.nlm.nih.gov/9091798/ PubMed] |
− | ## '''Update:''' Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. [https://doi.org/10.1200/JCO.2005.08.144 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16110023 PubMed] | + | ## '''Update:''' Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. [https://doi.org/10.1200/JCO.2005.08.144 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16110023/ PubMed] |
− | # Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. [https:// | + | # Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. [https://doi.org/10.1056/NEJMoa010580 link to original article] [https://pubmed.ncbi.nlm.nih.gov/11547717/ PubMed] |
− | # '''LARCS:''' Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. [https://doi.org/10.1200/JCO.2007.15.3858 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18669453 PubMed] | + | # '''LARCS:''' Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. [https://doi.org/10.1200/JCO.2007.15.3858 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18669453/ PubMed] |
− | ## '''Update:''' Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. [https:// | + | ## '''Update:''' Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. [https://doi.org/10.1016/j.radonc.2018.05.004 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29778486/ PubMed] |
− | # '''MRC CR07; NCIC-CTG CO.16:''' Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. [https:// | + | # '''MRC CR07; NCIC-CTG CO.16:''' Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. [https://doi.org/10.1016/s0140-6736(09)60484-0 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2668947/ link to PMC article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19269519/ PubMed] [https://clinicaltrials.gov/study/NCT00003422 NCT00003422] |
− | # '''Polish II:''' Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 | + | # '''Polish II:''' Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016 May;27(5):834-42. Epub 2016 Feb 15. [https://doi.org/10.1093/annonc/mdw062 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26884592/ PubMed] [https://clinicaltrials.gov/study/NCT00833131 NCT00833131] |
− | ## '''Update:''' Ciseł B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E, Cencelewicz A, Spałek M, Polkowski W, Jankiewicz M, Styliński R, Bębenek M, Kapturkiewicz B, Maciejczyk A, Sadowski J, Zygulska J, Zegarski W, Jankowski M, Las-Jankowska M, Toczko Z, Żelazowska-Omiotek U, Kępka L, Socha J, Wasilewska-Tesluk E, Markiewicz W, Kładny J, Majewski A, Kapuściński W, Suwiński R, Bujko K; Polish Colorectal Study Group. Long-course preoperative chemoradiation vs 5 x 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann Oncol. 2019 Aug 1;30(8):1298-1303. Epub 2019 Jun 13. [https://doi.org/10.1093/annonc/mdz186 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31192355 PubMed] | + | ## '''Update:''' Ciseł B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E, Cencelewicz A, Spałek M, Polkowski W, Jankiewicz M, Styliński R, Bębenek M, Kapturkiewicz B, Maciejczyk A, Sadowski J, Zygulska J, Zegarski W, Jankowski M, Las-Jankowska M, Toczko Z, Żelazowska-Omiotek U, Kępka L, Socha J, Wasilewska-Tesluk E, Markiewicz W, Kładny J, Majewski A, Kapuściński W, Suwiński R, Bujko K; Polish Colorectal Study Group. Long-course preoperative chemoradiation vs 5 x 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann Oncol. 2019 Aug 1;30(8):1298-1303. Epub 2019 Jun 13. [https://doi.org/10.1093/annonc/mdz186 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31192355/ PubMed] |
− | #'''RAPIDO:''' Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. [https://doi.org/10.1016/s1470-2045(20)30555-6 link to original article] ''' | + | #'''RAPIDO:''' Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. [https://doi.org/10.1016/s1470-2045(20)30555-6 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33301740/ PubMed] [https://clinicaltrials.gov/study/NCT01558921 NCT01558921] |
=Adjuvant chemotherapy= | =Adjuvant chemotherapy= | ||
==Capecitabine monotherapy {{#subobject:38d595|Regimen=1}}== | ==Capecitabine monotherapy {{#subobject:38d595|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 2000 mg/m<sup>2</sup>/day x 6 {{#subobject:48gua4|Variant=1}}=== | ===Regimen variant #1, 2000 mg/m<sup>2</sup>/day x 6 {{#subobject:48gua4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 957: | Line 1,055: | ||
|2008-2011 | |2008-2011 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CapeOx | + | |[[#CapeOx_999|CapeOx]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Capecitabine_.26_RT| | + | *Neoadjuvant [[#Capecitabine_.26_RT|capecitabine & RT]], then [[Surgery#Rectal_cancer_surgery|surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 15 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 15 | ||
− | |||
'''21-day cycle for 6 cycles''' | '''21-day cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 2500 mg/m<sup>2</sup>/day x 5 {{#subobject:4e5ce4|Variant=1}}=== | ===Regimen variant #2, 2500 mg/m<sup>2</sup>/day x 5 {{#subobject:4e5ce4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2812%2970116-X Hofheinz et al. 2012 (Rektum-III)] |
|2002-2007 | |2002-2007 | ||
− | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) |
|[[#Fluorouracil_monotherapy|Fluorouracil]] | |[[#Fluorouracil_monotherapy|Fluorouracil]] | ||
− | | style="background-color:#eeee01" |Non-inferior OS | + | | style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>OS60: 76% vs 67% |
|- | |- | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Capecitabine_.26_RT| | + | *Neoadjuvant [[#Capecitabine_.26_RT|capecitabine & RT]], then [[Surgery#Rectal_cancer_surgery|surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
− | |||
'''21-day cycle for 5 cycles''' | '''21-day cycle for 5 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 2500 mg/m<sup>2</sup>/day x 8 {{#subobject:4e9jn4|Variant=1}}=== | ===Regimen variant #3, 2500 mg/m<sup>2</sup>/day x 8 {{#subobject:4e9jn4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,008: | Line 1,112: | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *5-FU-based chemoradiotherapy or [[#Radiation_therapy|RT]], then [[Surgery# | + | *Neoadjuvant [[Regimen_classes#5-FU-based_chemoradiotherapy|5-FU-based chemoradiotherapy]] or [[#Radiation_therapy|RT]], then [[Surgery#Rectal_cancer_surgery|surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | *[[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=== | ||
− | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https:// | + | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https://doi.org/10.1016/S1470-2045%2812%2970116-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22503032/ PubMed] [https://clinicaltrials.gov/study/NCT01500993 NCT01500993] |
− | # '''SCRIPT:''' Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. [https://doi.org/10.1093/annonc/mdu560 link to original article] ''' | + | # '''SCRIPT:''' Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. [https://doi.org/10.1093/annonc/mdu560 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25480874/ PubMed] ISRCTN36266738 |
− | # '''PETACC 6:''' Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. [https://doi.org/10.1200/jco.20.01740 link to original article] ''' | + | # '''PETACC 6:''' Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. [https://doi.org/10.1200/jco.20.01740 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/33001764/ PubMed] [https://clinicaltrials.gov/study/NCT00766155 NCT00766155] |
− | |||
==Fluorouracil monotherapy {{#subobject:adc56e|Regimen=1}}== | ==Fluorouracil monotherapy {{#subobject:adc56e|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1 {{#subobject:66d35a|Variant=1}}=== | ===Regimen variant #1 {{#subobject:66d35a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2812%2970116-X Hofheinz et al. 2012 (Rektum-III)] |
|2002-2007 | |2002-2007 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 1,040: | Line 1,142: | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Fluorouracil_.26_RT| | + | *Neoadjuvant [[#Fluorouracil_.26_RT|5-FU & RT]], then [[Surgery#Rectal_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 to 5 | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | ||
− | |||
'''28-day cycle for 4 cycles''' | '''28-day cycle for 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2 {{#subobject:38a90a|Variant=1}}=== | ===Regimen variant #2 {{#subobject:38a90a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70187-0 Rödel et al. 2012 (CAO/ARO/AIO-04)] |
|2006-2010 | |2006-2010 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
Line 1,063: | Line 1,168: | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2015 update.'' | ''<sup>1</sup>Reported efficacy is based on the 2015 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#Fluorouracil_.26_RT| | + | *Neoadjuvant [[#Fluorouracil_.26_RT|5-FU & RT]], then [[Surgery#Rectal_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 to 5, 29 | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, 29 | ||
− | + | '''1-month cycle for 4 cycles''' | |
− | '''4 cycles | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https:// | + | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https://doi.org/10.1016/S1470-2045%2812%2970116-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22503032/ PubMed] [https://clinicaltrials.gov/study/NCT01500993 NCT01500993] |
− | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https:// | + | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https://doi.org/10.1016/S1470-2045(12)70187-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22627104/ PubMed] [https://clinicaltrials.gov/study/NCT00349076 NCT00349076] |
− | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https:// | + | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https://doi.org/10.1016/S1470-2045(15)00159-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26189067/ PubMed] |
− | |||
==FULV {{#subobject:d6c3bd|Regimen=1}}== | ==FULV {{#subobject:d6c3bd|Regimen=1}}== | ||
− | {| class="wikitable" style=" | + | FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin |
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
+ | ===Regimen variant #1, 500/500 {{#subobject:cc7508|Variant=1}}=== | ||
+ | {| class="wikitable" style="color:white; background-color:#f01e2c" | ||
+ | |<small><span style="color:white;">'''Historic variant'''</span></small> | ||
|- | |- | ||
− | |||
|} | |} | ||
− | |||
− | |||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1093/jnci/92.5.388 Wolmark et al. 2000 (NSABP R-02)] |
|1987-1992 | |1987-1992 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |[[#FULV_.26_RT_999|FULV & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS60 | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS60 | ||
|- | |- | ||
|} | |} | ||
+ | ''Note: male patients were also randomized to MOF or MOF & RT.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_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, '''given 1 hour after leucovorin''' | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36, '''given 1 hour after leucovorin''' | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29, 36, '''given first''' |
− | |||
'''8-week cycle for 6 cycles''' | '''8-week cycle for 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 1000/120 ("Nordic regimen") {{#subobject:9df33b|Variant=1}}=== | ===Regimen variant #2, 1000/120 ("Nordic regimen") {{#subobject:9df33b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,119: | Line 1,230: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have been used as a standard comparator. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *5-FU-based chemoradiotherapy or [[#Radiation_therapy|RT]], then [[Surgery# | + | *Neoadjuvant [[Regimen_classes#5-FU-based_chemoradiotherapy|5-FU-based chemoradiotherapy]] or [[#Radiation_therapy|RT]], then [[Surgery#Rectal_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 & 2, '''given first''' (total dose per cycle: 1000 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given first''' (total dose per cycle: 1000 mg/m<sup>2</sup>) | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 2, '''given second''' (total dose per cycle: 120 mg/m<sup>2</sup>) |
− | |||
'''14-day cycle for 12 cycles''' | '''14-day cycle for 12 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #3, 1900/100 {{#subobject:9df33b|Variant=1}}=== | ===Regimen variant #3, 1900/100 {{#subobject:9df33b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70377-8 Hong et al. 2014 (ADORE)] |
|2008-2012 | |2008-2012 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
|[[#FOLFOX|FOLFOX]] | |[[#FOLFOX|FOLFOX]] | ||
− | | style="background-color:#fc8d59" |Seems to have inferior | + | | style="background-color:#fc8d59" |Seems to have inferior DFS36 |
|- | |- | ||
|} | |} | ||
''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ''Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Fluoropyrimidine-based chemoradiation, then [[Surgery#Total_mesorectal_excision|TME]] | + | *Neoadjuvant [[Regimen_classes#Fluoropyrimidine-based_chemoradiotherapy|fluoropyrimidine-based chemoradiation]], then [[Surgery#Total_mesorectal_excision|TME]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 380 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 1900 mg/m<sup>2</sup>) | + | *[[Fluorouracil (5-FU)]] 380 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 (total dose per cycle: 1900 mg/m<sup>2</sup>) |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 100 mg/m<sup>2</sup>) |
− | |||
'''28-day cycle for 4 cycles''' | '''28-day cycle for 4 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #4, 2125/100 ("Mayo regimen") {{#subobject:9df33b|Variant=1}}=== | ===Regimen variant #4, 2125/100 ("Mayo regimen") {{#subobject:9df33b|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,163: | Line 1,280: | ||
|1999-2005 | |1999-2005 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |FOLFIRI | + | |[[#FOLFIRI_999|FOLFIRI]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS | ||
|- | |- | ||
Line 1,173: | Line 1,290: | ||
|- | |- | ||
|} | |} | ||
− | ''Note: | + | ''Note: This was an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *PROCTOR: 5-FU-based chemoradiotherapy or [[#Radiation_therapy|RT]], then [[Surgery# | + | *PROCTOR: Neoadjuvant [[Regimen_classes#5-FU-based_chemoradiotherapy|5-FU-based chemoradiotherapy]] or [[#Radiation_therapy|RT]], then [[Surgery#Rectal_cancer_surgery|surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 2125 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 2125 mg/m<sup>2</sup>) | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5 (total dose per cycle: 100 mg/m<sup>2</sup>) |
− | |||
'''4- to 5-week cycle for 6 cycles''' | '''4- to 5-week cycle for 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''NSABP R-02:''' Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000 Mar 1;92(5):388-96. [https:// | + | # '''NSABP R-02:''' Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000 Mar 1;92(5):388-96. [https://doi.org/10.1093/jnci/92.5.388 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/10699069/ PubMed] |
− | # '''ADORE:''' Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. Epub 2014 Sep 4. [https:// | + | # '''ADORE:''' Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. Epub 2014 Sep 4. [https://doi.org/10.1016/S1470-2045(14)70377-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25201358/ PubMed] [https://clinicaltrials.gov/study/NCT00807911 NCT00807911] |
− | ## '''Update:''' Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. [https://doi.org/10.1200/JCO.19.00016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31593484 PubMed] | + | ## '''Update:''' Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. [https://doi.org/10.1200/JCO.19.00016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31593484/ PubMed] |
− | # '''PROCTOR:''' Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. [https://doi.org/10.1093/annonc/mdu560 link to original article] ''' | + | # '''PROCTOR:''' Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. [https://doi.org/10.1093/annonc/mdu560 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25480874/ PubMed] ISRCTN36266738 |
− | # '''R98:''' Delbaldo C, Ychou M, Zawadi A, Douillard JY, André T, Guerin-Meyer V, Rougier P, Dupuis O, Faroux R, Jouhaud A, Quinaux E, Buyse M, Piedbois P; AERO; GERCOR; FNCLCC; FFCD. Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial. Ann Oncol. 2015 Jun;26(6):1208-15. Epub 2015 Mar 3. [https://doi.org/10.1093/annonc/mdv135 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25739671 PubMed] | + | # '''R98:''' Delbaldo C, Ychou M, Zawadi A, Douillard JY, André T, Guerin-Meyer V, Rougier P, Dupuis O, Faroux R, Jouhaud A, Quinaux E, Buyse M, Piedbois P; AERO; GERCOR; FNCLCC; FFCD. Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial. Ann Oncol. 2015 Jun;26(6):1208-15. Epub 2015 Mar 3. [https://doi.org/10.1093/annonc/mdv135 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25739671/ PubMed] |
− | |||
==mFOLFOX6 {{#subobject:fad3f|Regimen=1}}== | ==mFOLFOX6 {{#subobject:fad3f|Regimen=1}}== | ||
− | + | mFOLFOX6: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, with 5-FU bolus, 8 cycles {{#subobject:f31fc0|Variant=1}}=== | |
− | |||
− | mFOLFOX6: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | ||
− | |||
− | ===Regimen variant #1, | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70377-8 Hong et al. 2014 (ADORE)] |
|2008-2012 | |2008-2012 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
|[[#FULV|FULV]] | |[[#FULV|FULV]] | ||
− | | style="background-color:#91cf60" |Seems to have superior | + | | style="background-color:#91cf60" |Seems to have superior DFS36 (primary endpoint)<br>DFS36: 71.6% vs 62.9%<br>(HR 0.66, 95% CI 0.43-0.994) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Fluoropyrimidine-based chemoradiation, then [[Surgery#Total_mesorectal_excision|TME]] | + | *Neoadjuvant [[Regimen_classes#Fluoropyrimidine-based_chemoradiotherapy|fluoropyrimidine-based chemoradiation]], then [[Surgery#Total_mesorectal_excision|TME]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first''' |
− | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | + | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first''' |
− | |||
'''14-day cycle for 8 cycles''' | '''14-day cycle for 8 cycles''' | ||
− | + | </div></div><br> | |
− | ===Regimen variant #2, | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #2, no 5-FU bolus, 8 cycles {{#subobject:f3300f|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(12)70187-0 Rödel et al. 2012 (CAO/ARO/AIO-04)] |
|2006-2010 | |2006-2010 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[#Fluorouracil_monotherapy|Fluorouracil]] | |[[#Fluorouracil_monotherapy|Fluorouracil]] | ||
− | | style="background-color:#91cf60" |Seems to have superior DFS<sup>1</sup> <br>(HR 0.79, 95% CI 0.64-0.98) | + | | style="background-color:#91cf60" |Seems to have superior DFS<sup>1</sup> (primary endpoint)<br>DFS36: 75.95% vs 71.2%<br>(HR 0.79, 95% CI 0.64-0.98) |
|- | |- | ||
|} | |} | ||
''<sup>1</sup>Reported efficacy is based on the 2015 update.'' | ''<sup>1</sup>Reported efficacy is based on the 2015 update.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[#FUOX_.26_RT| | + | *Neoadjuvant [[#FUOX_.26_RT|FUOX & RT]], then [[Surgery#Rectal_cancer_surgery|surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Fluorouracil (5-FU)]] 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, started on | + | *[[Fluorouracil (5-FU)]] 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, started on day 1, '''given third''' (total dose per cycle: 2400 mg/m<sup>2</sup>) |
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second''' |
− | *[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV over 2 hours once | + | *[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given first''' |
− | + | '''14-day cycle for 8 cycles''' | |
− | ''' | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
+ | ===Regimen variant #3, 12 cycles {{#subobject:f3hg10|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/pmc7216434/ Chakravarthy et al. 2019 (ECOG E5204)] | ||
+ | |2006-2009 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#mFOLFOX6-B_999|mFOLFOX6-B]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>OS60: 88.3% vs 83.7% | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *Neoadjuvant [[Regimen_classes#Fluoropyrimidine-based_chemoradiotherapy|fluoropyrimidine-based chemoradiation]], then [[Surgery#Total_mesorectal_excision|TME]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (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 | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1 | ||
+ | '''14-day cycle for 12 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''ADORE:''' Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. Epub 2014 Sep 4. [https:// | + | # '''ADORE:''' Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. Epub 2014 Sep 4. [https://doi.org/10.1016/S1470-2045(14)70377-8 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25201358/ PubMed] [https://clinicaltrials.gov/study/NCT00807911 NCT00807911] |
− | ## '''Update:''' Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. [https://doi.org/10.1200/JCO.19.00016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31593484 PubMed] | + | ## '''Update:''' Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. [https://doi.org/10.1200/JCO.19.00016 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31593484/ PubMed] |
− | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https:// | + | # '''CAO/ARO/AIO-04:''' Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. [https://doi.org/10.1016/S1470-2045(12)70187-0 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22627104/ PubMed] [https://clinicaltrials.gov/study/NCT00349076 NCT00349076] |
− | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https:// | + | ## '''Update:''' Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. [https://doi.org/10.1016/S1470-2045(15)00159-X link to original article] [https://pubmed.ncbi.nlm.nih.gov/26189067/ PubMed] |
− | #'''ECOG E5204:''' NCT00303628 | + | #'''ECOG E5204:''' Chakravarthy AB, Zhao F, Meropol NJ, Flynn PJ, Wagner LI, Sloan J, Diasio RB, Mitchell EP, Catalano P, Giantonio BJ, Catalano RB, Haller DG, Awan RA, Mulcahy MF, O'Brien TE, Santala R, Cripps C, Weis JR, Atkins JN, Leichman CG, Petrelli NJ, Sinicrope FA, Brierley JD, Tepper JE, O'Dwyer PJ, Sigurdson ER, Hamilton SR, Cella D, Benson AB 3rd. Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204). Oncologist. 2020 May;25(5):e798-e807. Epub 2019 Dec 18. [https://doi.org/10.1634/theoncologist.2019-0437 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7216434/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/31852811/ PubMed] [https://clinicaltrials.gov/study/NCT00303628 NCT00303628] |
− | |||
==S-1 monotherapy {{#subobject:ec10ef|Regimen=1}}== | ==S-1 monotherapy {{#subobject:ec10ef|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:0ee98c|Variant=1}}=== | ===Regimen {{#subobject:0ee98c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,269: | Line 1,411: | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
|[[#UFT_monotherapy|UFT]] | |[[#UFT_monotherapy|UFT]] | ||
− | | style="background-color:#91cf60" |Seems to have superior RFS | + | | style="background-color:#91cf60" |Seems to have superior RFS (primary endpoint)<br>RFS60: 66.4% vs 61.7%<br>(HR 0.77, 95% CI 0.63-0.96) |
|- | |- | ||
|} | |} | ||
''Note: these patients did not receive preoperative therapy.'' | ''Note: these patients did not receive preoperative therapy.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Curative [[Surgery# | + | *Curative [[Surgery#Rectal_cancer_surgery|resection]] for stage II or stage III rectal cancer, within 49 days |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Tegafur, gimeracil, oteracil (S-1)]] | + | *[[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 1.25 to 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28 | **BSA 1.25 to 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28 | ||
**BSA 1.5 or greater m<sup>2</sup>: 60 mg PO twice per day on days 1 to 28 | **BSA 1.5 or greater m<sup>2</sup>: 60 mg PO twice per day on days 1 to 28 | ||
− | |||
'''42-day cycle for 9 cycles (1 year)''' | '''42-day cycle for 9 cycles (1 year)''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''ACTS-RC:''' Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. [https://doi.org/10.1093/annonc/mdw162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922318/ link to PMC article] ''' | + | # '''ACTS-RC:''' Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. [https://doi.org/10.1093/annonc/mdw162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922318/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27056996/ PubMed] UMIN C000000385 |
− | |||
==UFT monotherapy {{#subobject:0c1194|Regimen=1}}== | ==UFT monotherapy {{#subobject:0c1194|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:7dc55c|Variant=1}}=== | ===Regimen {{#subobject:7dc55c|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1007/s00280-010-1358-1 Hamaguchi et al. 2010 (NSAS-CC)] |
|1996-2001 | |1996-2001 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
|[[Rectal_cancer_-_null_regimens#Observation|Observation]] | |[[Rectal_cancer_-_null_regimens#Observation|Observation]] | ||
− | | style="background-color:#91cf60" |Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS (secondary endpoint) |
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922318/ Oki et al. 2016 (ACTS-RC)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922318/ Oki et al. 2016 (ACTS-RC)] | ||
Line 1,312: | Line 1,453: | ||
|} | |} | ||
''Note: these patients did not receive preoperative therapy.'' | ''Note: these patients did not receive preoperative therapy.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *Curative [[Surgery# | + | *Curative [[Surgery#Rectal_cancer_surgery|resection]] for stage II or stage III rectal cancer, within 49 days |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Tegafur and uracil (UFT)]] | + | *[[Tegafur and uracil (UFT)]] by the following BSA-based criteria: |
− | ** | + | **Less than 1.25 m<sup>2</sup>: 250 mg PO twice per day on days 1 to 5 |
− | ** | + | **1.25 m<sup>2</sup> or more: 300 mg PO twice per day on days 1 to 5 |
− | |||
'''7-day cycle for 52 cycles''' | '''7-day cycle for 52 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | # '''NSAS-CC:''' Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y; NSAS-CC Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011 Mar;67(3):587-96. Epub 2010 May 19. [https:// | + | # '''NSAS-CC:''' Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y; NSAS-CC Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011 Mar;67(3):587-96. Epub 2010 May 19. [https://doi.org/10.1007/s00280-010-1358-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/20490797/ PubMed] [https://clinicaltrials.gov/study/NCT00152230 NCT00152230] |
− | # '''ACTS-RC:''' Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. [https://doi.org/10.1093/annonc/mdw162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922318/ link to PMC article] ''' | + | # '''ACTS-RC:''' Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. [https://doi.org/10.1093/annonc/mdw162 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4922318/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27056996/ PubMed] UMIN C000000385 |
=Adjuvant chemoradiotherapy= | =Adjuvant chemoradiotherapy= | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
==Capecitabine & RT {{#subobject:3cec7f|Regimen=1}}== | ==Capecitabine & RT {{#subobject:3cec7f|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Capecitabine & RT: Capecitabine & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Capecitabine & RT: Capecitabine & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | ===Regimen {{#subobject:5ea375|Variant=1}}=== | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen variant #1, fully concurrent {{#subobject:5ea375|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,387: | Line 1,484: | ||
|2008-2014 | |2008-2014 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |CapeOx & RT | + | |[[#CapeOx_.26_RT_999|CapeOx & RT]] |
− | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | + | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS<br>DFS36: 71.6% vs 73.9% |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | + | *[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO twice per day on days 1 to 14, 22 to 36 |
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]], 4500 to 5040 cGy total in 25 to 28 fractions |
− | |||
'''5- to 5.5-week course''' | '''5- to 5.5-week course''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
− | === | + | ===Regimen variant #2, sandwich {{#subobject:2028c1|Variant=1}}=== |
− | # | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://doi.org/10. | + | |[https://doi.org/10.1016/S1470-2045%2812%2970116-X Hofheinz et al. 2012 (Rektum-III)] |
− | | | + | |2002-2007 |
− | | style="background-color:#1a9851" |Phase 3 ( | + | | style="background-color:#1a9851" |Phase 3 (E-RT-switch-ic) |
− | | | + | |[[#Fluorouracil_.26_RT_2|5-FU & RT]] |
− | | style="background-color:# | + | | style="background-color:#eeee01" |Non-inferior OS (primary endpoint)<br>OS60: 76% vs 67% |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
+ | ====Preceding treatment==== | ||
+ | *[[Surgery#Rectal_cancer_surgery|Surgery]] | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | *[[ | + | *[[Capecitabine (Xeloda)]] as follows: |
+ | **Cycles 1 & 2: 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
+ | **Cycle 3 (chemoradiation): 825 mg/m<sup>2</sup> PO twice per day on days 1 to 38 | ||
+ | **Cycles 4 to 6: 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy| | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: |
− | + | **Cycle 3: 5040 cGy total | |
+ | '''21-day cycle for 2 cycles, then 38-day course, then 21-day cycle for 3 cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # | + | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. [https://doi.org/10.1016/S1470-2045%2812%2970116-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22503032/ PubMed] [https://clinicaltrials.gov/study/NCT01500993 NCT01500993] |
+ | # '''CAMS rectal cancer 01:''' Feng YR, Zhu Y, Liu LY, Wang WH, Wang SL, Song YW, Wang X, Tang Y, Liu YP, Ren H, Fang H, Zhang SP, Liu XF, Yu ZH, Li YX, Jin J. Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial. Oncotarget. 2016 May 3;7(18):25576-84. [https://doi.org/10.18632/oncotarget.8226 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5041927/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/27014909/ PubMed] [https://clinicaltrials.gov/study/NCT00714077 NCT00714077] | ||
− | == | + | ==Fluorouracil & RT {{#subobject:25293e|Regimen=1}}== |
− | + | Fluorouracil & RT: Fluorouracil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #1, Bolus 5-FU (500 mg/m<sup>2</sup>), then CI 5-FU & RT, then Bolus 5-FU (450 mg/m<sup>2</sup>) {{#subobject:d06581|Variant=1}}=== | |
− | |||
− | |||
− | |||
− | === | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199408253310803 O'Connell et al. 1994 (INT 864751)] |
|1986-1990 | |1986-1990 | ||
| style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | | | + | |[[#Fluorouracil_.26_RT_2|5-FU & RT]]; bolus |
| style="background-color:#1a9850" |Superior OS | | style="background-color:#1a9850" |Superior OS | ||
|- | |- | ||
Line 1,457: | Line 1,555: | ||
|rowspan=2|1994-2000 | |rowspan=2|1994-2000 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |1. | + | |1. [[#Fluorouracil_.26_RT_2|5-FU & RT]]; bolus |
| style="background-color:#d3d3d3" |Not compared | | style="background-color:#d3d3d3" |Not compared | ||
|- | |- | ||
− | |2. | + | |2. [[#Fluorouracil_.26_RT_2|5-FU & RT]]; CI |
− | | style="background-color:#ffffbf" |Did not meet primary endpoints of OS/DFS | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of OS/DFS |
|- | |- | ||
|} | |} | ||
''Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.'' | ''Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | ====Chemotherapy | + | </div> |
− | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | + | *[[Fluorouracil (5-FU)]] as follows: | |
− | + | **Cycles 1 & 2: 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | |
− | + | **Cycle 3 (chemoradiation): 225 mg/m<sup>2</sup>/day IV continuous infusion while radiation is being given | |
− | * | + | **Cycles 4 & 5: 450 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: |
− | + | **Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided | |
− | ''' | + | '''28-day cycle for 2 cycles, then 8-week course, then 28-day cycle for 2 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #2, Bolus 5-FU (500 mg/m<sup>2</sup>), then CI 5-FU & RT, then Bolus 5-FU (500 mg/m<sup>2</sup>) {{#subobject:23bcde|Variant=1}}=== | |
− | |||
− | |||
− | |||
− | === | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2812%2970116-X Hofheinz et al. 2012 (Rektum-III)] |
|2002-2007 | |2002-2007 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |[[# | + | |[[#Capecitabine_.26_RT_2|Capecitabine & RT]] |
| style="background-color:#eeee01" |Non-inferior OS | | style="background-color:#eeee01" |Non-inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | ====Chemotherapy | + | </div> |
− | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | + | *[[Fluorouracil (5-FU)]] as follows: | |
− | + | **Cycles 1, 2, 4, 5: 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | |
− | + | **Cycle 3 (chemoradiation): 225 mg/m<sup>2</sup>/day IV continuous infusion while radiation is being given | |
− | * | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: |
− | + | **Cycle 3: 5040 cGy total | |
− | ''' | + | '''28-day cycle for 2 cycles, then one course, then 28-day cycle for 2 cycles''' |
− | + | </div></div><br> | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen variant #3, CI 5-FU, then CI 5-FU & RT, then CI 5-FU {{#subobject:da8c0d|Variant=1}}=== | |
− | |||
− | |||
− | |||
− | === | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,529: | Line 1,620: | ||
|rowspan=2|1994-2000 | |rowspan=2|1994-2000 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic) | ||
− | |1. | + | |1. [[#Fluorouracil_.26_RT_2|5-FU & RT]]; bolus |
− | | style="background-color:#ffffbf" |Did not meet primary endpoints of DFS/OS | + | | style="background-color:#ffffbf" |Did not meet co-primary endpoints of DFS/OS |
|- | |- | ||
− | |2. | + | |2. [[#Fluorouracil_.26_RT_2|5-FU & RT]]; fully concurrent |
| style="background-color:#d3d3d3" |Not compared | | style="background-color:#d3d3d3" |Not compared | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | ====Chemotherapy | + | </div> |
− | *[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion over 42 days, started on day 1 (total dose: 12,600 mg/m<sup>2</sup>) | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | + | *[[Fluorouracil (5-FU)]] as follows: | |
− | + | **Cycle 1: 300 mg/m<sup>2</sup>/day IV continuous infusion over 42 days, started on day 1 (total dose: 12,600 mg/m<sup>2</sup>) | |
− | + | **Cycle 2 (chemoradiation): 225 mg/m<sup>2</sup>/day IV continuous infusion while radiation is being given | |
− | + | **Cycle 3: 300 mg/m<sup>2</sup>/day IV continuous infusion over 56 days, started on day 1 (total dose: 16,800 mg/m<sup>2</sup>) | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: |
− | + | **Cycle 2: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided | |
− | ''' | + | '''10-week cycle for 3 cycles''' |
− | + | </div></div><br> | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | |||
− | + | ===Regimen variant #4, bolus 5-FU, then bolus 5-FU & RT, then bolus 5-FU {{#subobject:3d1b7b|Variant=1}}=== | |
− | |||
− | === | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199408253310803 O'Connell et al. 1994 (INT 864751)] |
|1986-1990 | |1986-1990 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | | | + | |[[#Fluorouracil_.26_RT_2|5-FU & RT]]; bolus/CI |
| style="background-color:#d73027" |Inferior OS | | style="background-color:#d73027" |Inferior OS | ||
|- | |- | ||
Line 1,572: | Line 1,661: | ||
|rowspan=3|1990-1992 | |rowspan=3|1990-1992 | ||
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C) | | rowspan="3" style="background-color:#1a9851" |Phase 3 (C) | ||
− | |1. [[#FULV.2FFULV_. | + | |1. [[#FULV.2FFULV_.26_RT_2|FULV/FULV & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
Line 1,583: | Line 1,672: | ||
|} | |} | ||
''Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.'' | ''Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.'' | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | ====Chemotherapy | + | </div> |
− | *[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | + | *[[Fluorouracil (5-FU)]] as follows: | |
− | + | **Cycles 1 & 2: 500 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | |
− | + | **Cycle 3 (chemoradiation): 500 mg/m<sup>2</sup> IV bolus 3 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation | |
− | * | + | **Cycles 4 & 5: 450 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 |
+ | ====Radiotherapy==== | ||
+ | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: | ||
+ | **Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided | ||
+ | '''28-day cycle for 2 cycles, then 10-week course, then 28-day cycle for 2 cycles''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen variant #5, fully concurrent {{#subobject:e903ad|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://doi.org/10.1023/a:1008357609434 Fountzilas et al. 1999] | ||
+ | |1989-1997 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#FULV.2FFluorouracil_.26_RT_999|FULV/5-FU & RT]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS36 | ||
+ | |- | ||
+ | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fluorouracil (5-FU)]] | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | * | + | *[[External_beam_radiotherapy|Radiation therapy]] |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # '''INT 864751:''' O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. [https:// | + | # '''INT 864751:''' O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. [https://doi.org/10.1056/NEJM199408253310803 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8041415/ PubMed] |
− | # '''GI INT 0114:''' Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. [https://doi.org/10.1200/jco.1997.15.5.2030 link to original article] ''' | + | # '''GI INT 0114:''' Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. [https://doi.org/10.1200/jco.1997.15.5.2030 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9164215/ PubMed] |
− | ## '''Update:''' Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. [https://doi.org/10.1200/jco.2002.07.132 link to original article] ''' | + | ## '''Update:''' Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. [https://doi.org/10.1200/jco.2002.07.132 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11919230/ PubMed] content property of [https://hemonc.org HemOnc.org] |
− | # '''GI INT 0144:''' Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, Fisher B, Rich TA, Martenson JA, Kugler JW, Benson AB 3rd, Haller DG, Mayer RJ, Atkins JN, Cripps C, Pedersen J, Periman PO, Tanaka MS Jr, Leichman CG, Macdonald JS. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. 2006 Aug 1;24(22):3542-7. [https://doi.org/10.1200/jco.2005.04.9544 link to original article] ''' | + | # Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Liaros A, Athanassiou E, Dombros N, Dervenis C, Basdanis G, Gamvros O, Souparis A, Briasoulis E, Samantas E, Kappas A, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 1999 Jun;10(6):671-6. [https://doi.org/10.1023/a:1008357609434 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10442189/ PubMed] |
− | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 13. [https:// | + | # '''GI INT 0144:''' Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, Fisher B, Rich TA, Martenson JA, Kugler JW, Benson AB 3rd, Haller DG, Mayer RJ, Atkins JN, Cripps C, Pedersen J, Periman PO, Tanaka MS Jr, Leichman CG, Macdonald JS. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. 2006 Aug 1;24(22):3542-7. [https://doi.org/10.1200/jco.2005.04.9544 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16877719/ PubMed] [https://clinicaltrials.gov/study/NCT00002551 NCT00002551] |
+ | # '''Rektum-III:''' Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 13. [https://doi.org/10.1016/S1470-2045%2812%2970116-X link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/22503032/ PubMed] [https://clinicaltrials.gov/study/NCT01500993 NCT01500993] | ||
==FULV/FULV & RT {{#subobject:e9de02|Regimen=1}}== | ==FULV/FULV & RT {{#subobject:e9de02|Regimen=1}}== | ||
− | + | FULV/FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil & '''<u>L</u>'''euco'''<u>V</u>'''orin alternating with '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>L</u>'''euco'''<u>V</u>'''orin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:cd06ac|Variant=1}}=== | |
− | |||
− | FULV/FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil & '''<u>L</u>'''euco'''<u>V</u>'''orin | ||
− | === | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,626: | Line 1,731: | ||
|rowspan=3|1990-1992 | |rowspan=3|1990-1992 | ||
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc) | | rowspan="3" style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |1. [[# | + | |1. [[#Fluorouracil_.26_RT_2|5-FU & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
Line 1,635: | Line 1,740: | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36 | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/j.ejca.2008.05.025 Kalofonos et al. 2008] |
|1999-2004 | |1999-2004 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |IFL & RT | + | |[[#IFL_.26_RT_999|IFL & RT]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS36 | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS36 | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
− | ====Chemotherapy | + | </div> |
− | *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second''' | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | * | + | ====Chemotherapy==== |
− | + | *[[Fluorouracil (5-FU)]] as follows: | |
− | + | **Cycles 1 & 2: 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second''' | |
− | + | **Cycle 3 (chemoradiation): 400 mg/m<sup>2</sup> IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation | |
− | + | **Cycles 4 & 5: 380 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given second''' | |
− | *[[ | + | *[[Leucovorin (Folinic acid)]] as follows: |
− | * | + | **Cycles 1, 2, 4, 5: 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5, '''given first''' |
+ | **Cycle 3 (chemoradiation): 20 mg/m<sup>2</sup> IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: |
− | + | **Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided | |
− | ''' | + | '''28-day cycle for 2 cycles, then 10-week course, then 28-day cycles for 2 cycles''' |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | # '''GI INT 0114:''' Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. [https://doi.org/10.1200/jco.1997.15.5.2030 link to original article] ''' | + | # '''GI INT 0114:''' Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. [https://doi.org/10.1200/jco.1997.15.5.2030 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/9164215/ PubMed] |
− | ## '''Update:''' Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. [https://doi.org/10.1200/jco.2002.07.132 link to original article] ''' | + | ## '''Update:''' Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. [https://doi.org/10.1200/jco.2002.07.132 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11919230/ PubMed] |
− | # Kalofonos HP, Bamias A, Koutras A, Papakostas P, Basdanis G, Samantas E, Karina M, Misailidou D, Pisanidis N, Pentheroudakis G, Economopoulos T, Papadimitriou C, Skarlos DV, Pectasides D, Stavropoulos M, Bafaloukos D, Kardamakis D, Karanikiotis C, Vourli G, Fountzilas G; Hellenic Cooperative Oncology Group. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study. Eur J Cancer. 2008 Aug;44(12):1693-700. Epub 2008 Jul 17. [https:// | + | # Kalofonos HP, Bamias A, Koutras A, Papakostas P, Basdanis G, Samantas E, Karina M, Misailidou D, Pisanidis N, Pentheroudakis G, Economopoulos T, Papadimitriou C, Skarlos DV, Pectasides D, Stavropoulos M, Bafaloukos D, Kardamakis D, Karanikiotis C, Vourli G, Fountzilas G; Hellenic Cooperative Oncology Group. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study. Eur J Cancer. 2008 Aug;44(12):1693-700. Epub 2008 Jul 17. [https://doi.org/10.1016/j.ejca.2008.05.025 link to original article] [https://pubmed.ncbi.nlm.nih.gov/18639450/ PubMed] |
==Radiation therapy {{#subobject:3f3b45|Regimen=1}}== | ==Radiation therapy {{#subobject:3f3b45|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy | RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:f7cd24|Variant=1}}=== | ===Regimen {{#subobject:f7cd24|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | | rowspan="2" |[https:// | + | | rowspan="2" |[https://doi.org/10.1093/jnci/80.1.21 Fisher et al. 1988 (NSABP R-01)] |
|rowspan=2|1977-1986 | |rowspan=2|1977-1986 | ||
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | | rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc) | ||
− | |1. MOF | + | |1. [[#MOF_888|MOF]] |
| style="background-color:#d3d3d3" |Not reported | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
Line 1,692: | Line 1,790: | ||
| style="background-color:#ffffbf" |Did not meet efficacy endpoints of DFS/OS | | style="background-color:#ffffbf" |Did not meet efficacy endpoints of DFS/OS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199103143241101 Krook et al. 1991] |
|1980-1986 | |1980-1986 | ||
| style="background-color:#1a9851" |Phase 3 (C) | | style="background-color:#1a9851" |Phase 3 (C) | ||
− | |Fluorouracil & RT | + | |[[#Fluorouracil_.26_RT_2|Fluorouracil & RT]] |
| style="background-color:#d73027" |Inferior RFS | | style="background-color:#d73027" |Inferior RFS | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(96)05349-4 Amott et al. 1996] |
|1984-1989 | |1984-1989 | ||
| style="background-color:#1a9851" |Phase 3 (E-esc) | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
Line 1,705: | Line 1,803: | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: this regimen in this context is of historic interest.'' |
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | *[[Surgery# | + | *[[Surgery#Rectal_cancer_surgery|Surgery]] |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | *[[External_beam_radiotherapy|Radiation therapy]], | + | *[[External_beam_radiotherapy|Radiation therapy]], 4000 to 5040 cGy |
− | |||
'''4-week course''' | '''4-week course''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | # '''NSABP R-01:''' Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, Gordon P, Feldman M, Cruz A, Legault-Poisson S, Wexler M, Lawrence W, Robidoux A. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. [https:// | + | # '''NSABP R-01:''' Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, Gordon P, Feldman M, Cruz A, Legault-Poisson S, Wexler M, Lawrence W, Robidoux A. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. [https://doi.org/10.1093/jnci/80.1.21 link to original article] [https://pubmed.ncbi.nlm.nih.gov/3276900/ PubMed] |
− | # Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991 Mar 14;324(11):709-15. [https:// | + | # Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991 Mar 14;324(11):709-15. [https://doi.org/10.1056/NEJM199103143241101 link to original article] [https://pubmed.ncbi.nlm.nih.gov/1997835/ PubMed] |
− | # Amott SJ, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet. 1996 Dec 14;348(9042):1610-4. [https:// | + | # Amott SJ, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet. 1996 Dec 14;348(9042):1610-4. [https://doi.org/10.1016/S0140-6736(96)05349-4 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8961990/ PubMed] |
− | # '''TROG 01.014:''' Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. [https://doi.org/10.1200/JCO.2012.42.9597 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23008301 PubMed] NCT00351598 | + | # '''TROG 01.014:''' Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. [https://doi.org/10.1200/JCO.2012.42.9597 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23008301/ PubMed] [https://clinicaltrials.gov/study/NCT00351598 NCT00351598] |
=Advanced or metastatic disease= | =Advanced or metastatic disease= | ||
− | ''See the [[ | + | ''See the [[Colorectal cancer|colorectal cancer page]] for colorectal cancer regimens.'' |
− | |||
[[Category:Rectal cancer regimens]] | [[Category:Rectal cancer regimens]] | ||
[[Category:Disease-specific pages]] | [[Category:Disease-specific pages]] | ||
[[Category:Colorectal cancers]] | [[Category:Colorectal cancers]] |
Latest revision as of 23:47, 20 July 2024
Section editor | |
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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? 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!
22 regimens on this page
48 variants on this page
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Note: the page has (neo-)adjuvant regimens specific to rectal cancer. Please see the colon cancer page for adjuvant regimens specific to colon cancer (e.g., adjuvant CapeOx) and the colorectal cancer page for regimens intended more generically for colorectal cancer.
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.
ESMO
- 2018: Glynne-Jones et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2017: Glynne-Jones et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2013: Glimelius et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2010: Glimelius et al. Rectal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed
- 2009: Glimelius & Oliveira. Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2008: Glimelius & Oliveira. Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2007: Glimelius. Rectal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up PubMed
- 2005: Tveit & Kataja. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer PubMed
- 2003: Tveit. ESMO Minimum Clinical Recommendations for diagnosis, treatment and follow-up of rectal cancer PubMed
French Intergroup
- 2017: Gérard et al. Rectal cancer: French Intergroup clinical practice guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO) PubMed
NCCN
- NCCN Guidelines - Rectal Cancer
- 2015: Benson et al. Rectal Cancer, Version 2.2015 PubMed
- 2009: Engstrom et al. NCCN Clinical Practice Guidelines in Oncology: rectal cancer. PubMed
SIOG
- 2018: Montroni et al. Personalized management of elderly patients with rectal cancer: Expert recommendations of the European Society of Surgical Oncology, European Society of Coloproctology, International Society of Geriatric Oncology, and American College of Surgeons Commission on Cancer PubMed
Neoadjuvant therapy
Capecitabine & RT
Capecitabine & RT: Capecitabine & Radiation Therapy
Regimen variant #1, interrupted capecitabine, 1600 mg/m2/day, 4500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Gérard et al. 2010 (ACCORD 12/0405 PRODIGE 2) | 2005-2008 | Phase 3 (C) | CapeOx & RT | Might have inferior pCR rate |
Note: adjuvant therapy was not specified. Treatment is assumed to start on a Monday.
Chemotherapy
- Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)
5-week course
Subsequent treatment
Regimen variant #2, interrupted capecitabine, 1600 mg/m2/day, 5000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Conroy et al. 2021 (UNICANCER-PRODIGE 23) | 2012-2017 | Non-randomized part of phase 3 RCT | ||
François et al. 2022 | 2016-2019 | Phase 3 (C) | RT; 5 x 5 | Inconclusive whether non-inferior R0 resection rate |
Note: Treatment is assumed to start on a Monday.
Preceding treatment
- UNICANCER-PRODIGE 23: Neoadjuvant FOLFIRINOX versus no neoadjuvant chemotherapy
Chemotherapy
- Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Radiotherapy
- Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
Regimen variant #3, interrupted capecitabine, 1650 mg/m2/day, 4500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmoll et al. 2020 (PETACC 6) | 2008-2011 | Phase 3 (C) | CapeOx & RT | Did not meet primary endpoint of DFS36 |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (4500 cGy total in 25 fractions)
5-week course
Subsequent treatment
- Surgery, then adjuvant capecitabine
Regimen variant #4, continuous capecitabine, 1650 mg/m2/day, 4500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Hofheinz et al. 2012 (Rektum-III) | 2002-2007 | Phase 3 (E-RT-switch-ic) | 5-FU & RT | Non-inferior OS (primary endpoint) OS60: 76% vs 67% |
|
Park et al. 2011 (AMC Rectal Pre Vs Post 2004) | 2004-2006 | Phase 3 (E-switch-ic) | Capecitabine & RT; adjuvant | Did not meet primary endpoint of DFS36 | Superior sphincter preservation |
O'Connell et al. 2014 (NSABP R-04) | 2004-2010 | Phase 3 (E-switch-ic) | 1. 5-FU & RT | Did not meet primary endpoint of LRC | Similar toxicity |
2. CapeOx & RT 3. FUOX & RT |
Did not meet primary endpoint of LRC | Superior toxicity | |||
Valentini et al. 2016 (INTERACT) | 2005-2013 | Phase 3 (C) | CapeOx & RT | Did not meet efficacy endpoints | Superior toxicity |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 38
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions/4500 cGy), with boost depending on stage
5.5-week course
Subsequent treatment
- Surgery, then adjuvant capecitabine
Regimen variant #5, interrupted capecitabine, 1650 mg/m2/day, 5000 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhu et al. 2020 (CinClare) | 2015-2017 | Phase 3 (C) | See link | See link |
Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Radiotherapy
- Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
Regimen variant #6, interrupted capecitabine, 1650 mg/m2/day, 5040 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmoll et al. 2020 (PETACC 6) | 2008-2011 | Phase 3 (C) | CapeOx & RT | Did not meet primary endpoint of DFS36 |
Note: Treatment starts on a Monday.
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (5040 cGy total in 28 fractions)
5.5-week course
Subsequent treatment
- Surgery, then adjuvant capecitabine
References
- ACCORD 12: Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Laffay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Montoto-Grillot C, Conroy T. Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-PRODIGE 2. J Clin Oncol. 2010 Apr 1;28(10):1638-44. Epub 2010 Mar 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00227747
- Update: Gérard JP, Azria D, Gourgou-Bourgade S, Martel-Lafay I, Hennequin C, Etienne PL, Vendrely V, François E, de La Roche G, Bouché O, Mirabel X, Denis B, Mineur L, Berdah JF, Mahé MA, Bécouarn Y, Dupuis O, Lledo G, Seitz JF, Bedenne L, Juzyna B, Conroy T. Clinical outcome of the ACCORD 12/0405 PRODIGE 2 randomized trial in rectal cancer. J Clin Oncol. 2012 Dec 20;30(36):4558-65. Epub 2012 Oct 29. link to original article PubMed
- AMC Rectal Pre Vs Post 2004: Park JH, Yoon SM, Yu CS, Kim JH, Kim TW, Kim JC. Randomized phase 3 trial comparing preoperative and postoperative chemoradiotherapy with capecitabine for locally advanced rectal cancer. Cancer. 2011 Aug 15;117(16):3703-12. Epub 2011 Feb 15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01186081
- Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01500993
- NSABP R-04: O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00058474
- Update: Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). link to original article link to PMC article PubMed
- INTERACT: Valentini V, Gambacorta MA, Cellini F, Aristei C, Coco C, Barbaro B, Alfieri S, D'Ugo D, Persiani R, Deodato F, Crucitti A, Lupattelli M, Mantello G, Navarria F, Belluco C, Buonadonna A, Boso C, Lonardi S, Caravatta L, Barba MC, Vecchio FM, Maranzano E, Genovesi D, Doglietto GB, Morganti AG, La Torre G, Pucciarelli S, De Paoli A. The INTERACT Trial: Long-term results of a randomised trial on preoperative capecitabine-based radiochemotherapy intensified by concomitant boost or oxaliplatin, for cT2 (distal)-cT3 rectal cancer. Radiother Oncol. 2019 May;134:110-118. Epub 2019 Feb 7. link to original article PubMed NCT01653301
- CinClare: Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02605265
- PETACC 6: Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00766155
- UNICANCER-PRODIGE 23: Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. Epub 2021 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01804790
- STELLARrectal: Jin J, Tang Y, Hu C, Jiang LM, Jiang J, Li N, Liu WY, Chen SL, Li S, Lu NN, Cai Y, Li YH, Zhu Y, Cheng GH, Zhang HY, Wang X, Zhu SY, Wang J, Li GF, Yang JL, Zhang K, Chi Y, Yang L, Zhou HT, Zhou AP, Zou SM, Fang H, Wang SL, Zhang HZ, Wang XS, Wei LC, Wang WL, Liu SX, Gao YH, Li YX. Multicenter, Randomized, Phase III Trial of Short-Term Radiotherapy Plus Chemotherapy Versus Long-Term Chemoradiotherapy in Locally Advanced Rectal Cancer (STELLAR). J Clin Oncol. 2022 May 20;40(15):1681-1692. Epub 2022 Mar 9. link to original article link to PMC article NCT02533271 PubMed
- CONVERTrectal: Mei WJ, Wang XZ, Li YF, Sun YM, Yang CK, Lin JZ, Wu ZG, Zhang R, Wang W, Li Y, Zhuang YZ, Lei J, Wan XB, Ren YK, Cheng Y, Li WL, Wang ZQ, Xu DB, Mo XW, Ju HX, Ye SW, Zhao JL, Zhang H, Gao YH, Zeng ZF, Xiao WW, Zhang XP, Zhang X, Xie E, Feng YF, Tang JH, Wu XJ, Chen G, Li LR, Lu ZH, Wan DS, Bei JX, Pan ZZ, Ding PR. Neoadjuvant Chemotherapy With CAPOX Versus Chemoradiation for Locally Advanced Rectal Cancer With Uninvolved Mesorectal Fascia (CONVERT): Initial Results of a Phase III Trial. Ann Surg. 2023 Apr 1;277(4):557-564. Epub 2022 Dec 20. link to original article link to PMC article PubMed NCT02288195
- François E, De Bari B, Ronchin P, Nouhaud E, Martel-Lafay I, Artru P, Clavere P, Vendrely V, Boige V, Gargot D, Lemanski C, De Sousa Carvalho N, Gal J, Pernot M, Magné N. Comparison of short course radiotherapy with chemoradiotherapy for locally advanced rectal cancers in the elderly: A multicentre, randomised, non-blinded, phase 3 trial. Eur J Cancer. 2023 Feb;180:62-70. Epub 2022 Nov 28. link to original article PubMed
- PROSPECTrectal: Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. link to original article link to PMC article PubMed NCT01515787
- PRO analysis: Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. link to original article link to PMC article PubMed
Capecitabine, Sorafenib, RT
Capecitabine, Sorafenib, RT: Capecitabine, Sorafenib, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
von Moos et al. 2017 (SAKK 41/08) | 2009-03 to 2013-05 | Phase 1/2 |
Biomarker eligibility criteria
- KRAS-mutation
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on days 1 to 33
Targeted therapy
- Sorafenib (Nexavar) 400 mg PO once per day
Radiotherapy
- Concurrent radiation therapy, 4500 cGy total
5-week course
Subsequent treatment
References
- SAKK 41/08: von Moos R, Koeberle D, Schacher S, Hayoz S, Winterhalder RC, Roth A, Bodoky G, Samaras P, Berger MD, Rauch D, Saletti P, Plasswilm L, Zwahlen D, Meier UR, Yan P, Izzo P, Klingbiel D, Bärtschi D, Zaugg K; Swiss Group for Clinical Cancer Research. Neoadjuvant radiotherapy combined with capecitabine and sorafenib in patients with advanced KRAS-mutated rectal cancer: A phase I/II trial (SAKK 41/08). Eur J Cancer. 2018 Jan;89:82-89. Epub 2017 Dec 11. link to original article PubMed
CapeOx
CapeOX: Capecitabine & OXaliplatin
Regimen variant #1, 4 cycles
Study | Dates of enrollment | Evidence |
---|---|---|
Chua et al. 2010 | 2001-2005 | Phase 2 |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for 4 cycles
Subsequent treatment
- Neoadjuvant Capecitabine & RT, then TME
Regimen variant #2, 6 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Bahadoer et al. 2020 (RAPIDO) | 2011-2016 | Phase 3 (E-switch-ic) | See link | See link |
Preceding treatment
- Neoadjuvant RT; 5 x 500 cGy
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycle for 6 cycles
Subsequent treatment
References
- Chua YJ, Barbachano Y, Cunningham D, Oates JR, Brown G, Wotherspoon A, Tait D, Massey A, Tebbutt NC, Chau I. Neoadjuvant capecitabine and oxaliplatin before chemoradiotherapy and total mesorectal excision in MRI-defined poor-risk rectal cancer: a phase 2 trial. Lancet Oncol. 2010 Mar;11(3):241-8. Epub 2010 Jan 25. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00220051
- RAPIDO: Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01558921
CapeOx, Cetuximab, RT
CapeOX, Cetuximab, RT: Capecitabine, OXaliplatin, Cetuximab, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Leichman et al. 2017 (SWOG S0713) | 2009-02 to 2013-04 | Phase 2 |
Chemotherapy
- Capecitabine (Xeloda) 825 mg/m2 PO twice per day on Monday to Friday
- Oxaliplatin (Eloxatin) as follows:
- Cycle 1: 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Cycle 2: 50 mg/m2 IV once per day on days 1, 8, 22, 29
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV once on day 1, then 250 mg/m2 IV once per day on days 8, 15, 22, 29
- Cycle 2: 250 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- RT as follows:
- Cycle 2: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions)
35-day cycle for 2 cycles
Subsequent treatment
References
- SWOG S0713: Leichman CG, McDonough SL, Smalley SR, Billingsley KG, Lenz HJ, Beldner MA, Hezel AF, Velasco MR, Guthrie KA, Blanke CD, Hochster HS. Cetuximab Combined With Induction Oxaliplatin and Capecitabine, Followed by Neoadjuvant Chemoradiation for Locally Advanced Rectal Cancer: SWOG 0713. Clin Colorectal Cancer. 2018 Mar;17(1):e121-e125. Epub 2017 Oct 24. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00686166
CapIriRT
CapIriRT: Capecitabine, Irinotecan, Radiation Therapy
Regimen variant #1, 65 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhu et al. 2020 (CinClare) | 2015-2017 | Phase 3 (E-switch-ic) | See link | See link |
Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.
Biomarker eligibility criteria
- UGT1A1*1*28 genotype
Chemotherapy
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
Regimen variant #2, 80 mg/m2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Zhu et al. 2020 (CinClare) | 2015-2017 | Phase 3 (E-switch-ic) | See link | See link |
Note: Treatment is assumed to start on a Monday. Surgery is to take place 8 weeks after completion of chemoradiotherapy.
Biomarker eligibility criteria
- UGT1A1*1*1 genotype
Chemotherapy
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
- Irinotecan (Camptosar) 80 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5000 cGy total in 25 fractions)
5-week course
References
- CinClare: Zhu J, Liu A, Sun X, Liu L, Zhu Y, Zhang T, Jia J, Tan S, Wu J, Wang X, Zhou J, Yang J, Zhang C, Zhang H, Zhao Y, Cai G, Zhang W, Xia F, Wan J, Zhang H, Shen L, Cai S, Zhang Z. Multicenter, Randomized, Phase III Trial of Neoadjuvant Chemoradiation With Capecitabine and Irinotecan Guided by UGT1A1 Status in Patients With Locally Advanced Rectal Cancer. J Clin Oncol. 2020 Dec 20;38(36):4231-4239. Epub 2020 Oct 29. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT02605265
Fluorouracil & RT
Fluorouracil & RT: Fluorouracil & Radiation Therapy
Regimen variant #1, continuous
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Ngan et al. 2012 (TROG 01.014) | 2001-2006 | Phase 3 (C) | Short-course RT | Did not meet primary endpoint of LR rate at 36 mo | Similar toxicity |
Aschele et al. 2011 (STAR-01) | 2003-2008 | Phase 3 (C) | FUOX & RT | Did not meet primary endpoint of OS1 | Less toxic |
O'Connell et al. 2014 (NSABP R-04) | 2004-2010 | Phase 3 (C) | 1. Capecitabine & RT | Did not meet primary endpoint of LRC | Similar toxicity |
2. CapeOx & RT 3. FUOX & RT |
Did not meet primary endpoint of LRC | Superior toxicity |
1Reported efficacy for STAR-01 is based on the 2016 update.
Chemotherapy
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion until the end of radiation, started on day 1
Radiotherapy
- Concurrent radiation therapy, 180 cGy for 25 fractions (4500 cGy), with boost depending on stage
5-week course
Subsequent treatment
- STAR-01: Surgery, preferably TME, then adjuvant fluourouracil-based therapy
- NSABP R-04: Surgery
Regimen variant #2, intermittent
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sauer et al. 2004 (CAO/ARO/AIO-94) | 1995-2002 | Phase 3 (E-switch-ic) | 5-FU & RT; adjuvant | Superior five-year cumulative incidence of local relapse (secondary endpoint) |
Hofheinz et al. 2012 (Rektum-III) | 2002-2007 | Phase 3 (C) | Capecitabine & RT | Non-inferior OS |
Rödel et al. 2012 (CAO/ARO/AIO-04) | 2006-2010 | Phase 3 (C) | FUOX & RT | Seems to have inferior pCR rate |
Chemotherapy
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on days 1 & 29 (total dose: 10,000 mg/m2)
Radiotherapy
- Concurrent radiation therapy, 5040 cGy total
One course
References
- CAO/ARO/AIO-94: Sauer R, Becker H, Hohenberger W, Rödel C, Wittekind C, Fietkau R, Martus P, Tschmelitsch J, Hager E, Hess CF, Karstens JH, Liersch T, Schmidberger H, Raab R; German Rectal Cancer Study Group. Preoperative versus postoperative chemoradiotherapy for rectal cancer. N Engl J Med. 2004 Oct 21;351(17):1731-40. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Sauer R, Liersch T, Merkel S, Fietkau R, Hohenberger W, Hess C, Becker H, Raab HR, Villanueva MT, Witzigmann H, Wittekind C, Beissbarth T, Rödel C. Preoperative versus postoperative chemoradiotherapy for locally advanced rectal cancer: results of the German CAO/ARO/AIO-94 randomized phase III trial after a median follow-up of 11 years. J Clin Oncol. 2012 Jun 1;30(16):1926-33. Epub 2012 Apr 23. link to original article PubMed
- STAR-01: Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Abstract: Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 link to abstract
- Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01500993
- CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349076
- Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article PubMed
- TROG 01.014: Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00351598
- NSABP R-04: O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00058474
- Update: Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). link to original article link to PMC article PubMed
- PROSPECTrectal: Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. link to original article link to PMC article PubMed NCT01515787
- PRO analysis: Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. link to original article link to PMC article PubMed
FOLFIRINOX
FOLFIRINOX: FOLinic acid (Leucovorin), Fluorouracil, IRINotecan, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Conroy et al. 2021 (UNICANCER-PRODIGE 23) | 2012-2017 | Phase 3 (E-esc) | No neoadjuvant chemotherapy | Seems to have superior DFS36 (primary endpoint) DFS36: 76% vs 69% (sHR 0.69, 95% CI 0.49-0.97) |
Chemotherapy
- Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given first
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given third
- Irinotecan (Camptosar) 180 mg/m2 IV over 90 minutes once on day 1, given second
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 6 cycles
Subsequent treatment
- Neoadjuvant Capecitabine & RT
References
- UNICANCER-PRODIGE 23: Conroy T, Bosset JF, Etienne PL, Rio E, François É, Mesgouez-Nebout N, Vendrely V, Artignan X, Bouché O, Gargot D, Boige V, Bonichon-Lamichhane N, Louvet C, Morand C, de la Fouchardière C, Lamfichekh N, Juzyna B, Jouffroy-Zeller C, Rullier E, Marchal F, Gourgou S, Castan F, Borg C; Unicancer Gastrointestinal Group and Partenariat de Recherche en Oncologie Digestive (PRODIGE) Group. Neoadjuvant chemotherapy with FOLFIRINOX and preoperative chemoradiotherapy for patients with locally advanced rectal cancer (UNICANCER-PRODIGE 23): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2021 May;22(5):702-715. Epub 2021 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01804790
mFOLFOX6
mFOLFOX6: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schrag et al. 2023 (PROSPECTrectal) | 2012-06 to 2018-12 | Phase 3 (E-switch-ooc) | 1a. Capecitabine & RT 1b. 5-FU & RT |
Non-inferior DFS (primary endpoint) DFS60: 80.8% vs 78.6% (HR 0.92, 90.2% CI 0.74-1.14) |
Note: this trial (PROSPECT) is labeled as PROSPECTrectal to avoid confusion with the one by the same name in prostate cancer.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 6 cycles
References
- PROSPECTrectal: Schrag D, Shi Q, Weiser MR, Gollub MJ, Saltz LB, Musher BL, Goldberg J, Al Baghdadi T, Goodman KA, McWilliams RR, Farma JM, George TJ, Kennecke HF, Shergill A, Montemurro M, Nelson GD, Colgrove B, Gordon V, Venook AP, O'Reilly EM, Meyerhardt JA, Dueck AC, Basch E, Chang GJ, Mamon HJ. Preoperative Treatment of Locally Advanced Rectal Cancer. N Engl J Med. 2023 Jul 27;389(4):322-334. Epub 2023 Jun 4. link to original article link to PMC article PubMed NCT01515787
- PRO analysis: Basch E, Dueck AC, Mitchell SA, Mamon H, Weiser M, Saltz L, Gollub M, Rogak L, Ginos B, Mazza GL, Colgrove B, Chang G, Minasian L, Denicoff A, Thanarajasingam G, Musher B, George T, Venook A, Farma J, O'Reilly E, Meyerhardt JA, Shi Q, Schrag D. Patient-Reported Outcomes During and After Treatment for Locally Advanced Rectal Cancer in the PROSPECT Trial (Alliance N1048). J Clin Oncol. 2023 Jul 20;41(21):3724-3734. Epub 2023 Jun 4. link to original article link to PMC article PubMed
FULV & RT
FULV & RT: FluoroUracil, LeucoVorin, Radiation Therapy
Regimen variant #1, 800/200 ("Nordic schedule")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Braendengen et al. 2008 (LARCS) | 1996-2003 | Phase 3 (E-esc) | Radiotherapy | Might have superior OS60 (primary endpoint) OS60: 66% vs 53% |
Note: reported efficacy is based on the 2018 update.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1, 2, 15, 16, 29, 30 given first, prior to RT
- Leucovorin (Folinic acid) 100 mg IV once per day on days 1 & 2, given second
Radiotherapy
- Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, total of 5000 cGy)
5-week course
Regimen variant #2, 1625/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roh et al. 2009 (NSABP R-03) | 1993-1999 | Phase 3 (E-esc) | Adjuvant 5-FU & RT | Might have superior OS (co-primary endpoint) OS60: 74.5% vs 65.6% (HR 0.69, 95% CI 0.47-1.03) |
Preceding treatment
- Neoadjuvant FULV x 1
Chemotherapy
- Fluorouracil (5-FU) 325 mg/m2 IV once per day on days 1 to 5, 29 to 33
- Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5, 29 to 33
Radiotherapy
- Concurrent radiation therapy, 5040 cGy
5-week course
Regimen variant #3, 1750/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Sainato et al. 2014 (I-CNR-RT) | 1992-2001 | Non-randomized part of phase 3 RCT | ||
Bosset et al. 2006 (EORTC 22921) | 1993-2003 | Phase 3 (E-esc) | Radiotherapy | Did not meet primary endpoint of OS1 |
Gérard et al. 2006 (FFCD 9203) | 1993-2003 | Phase 3 (E-esc) | Radiotherapy | Did not meet primary endpoint of OS1 |
1These trials were negative for the primary endpoint of overall survival, but had much improved local control for the experimental arm.
Chemotherapy
- Fluorouracil (5-FU) 350 mg/m2 IV once per day on days 1 to 5, 29 to 33
- Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5, 29 to 33
Radiotherapy
- Concurrent radiation therapy, 4500 cGy
5-week course
Subsequent treatment
- FFCD 9203 & EORTC 22921: Surgery, then adjuvant FULV x 2
- I-CNR-RT: Surgery, then adjuvant FULV versus no further treatment
Regimen variant #4, 2800/400
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Deng et al. 2016 (FOWARC) | 2010-2015 | Phase 3 (C) | 1. mFOLFOX6 | Did not meet primary endpoint of DFS361 |
2. mFOLFOX6 & RT | Did not meet primary endpoint of DFS361 |
1Reported efficacy is based on the 2019 update.
Note: this regimen is stated to be based on the de Gramont regimen in the manuscript, although the details are different than those in de Gramont et al. 2000.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
14-day cycle for 5 cycles
Radiotherapy
- Concurrent radiation therapy given during cycles 2 to 4: 1.8 to 200 cGy once per day Monday through Friday for a total of 23 to 28 fractions over 5 to 6 weeks and a total dose of 4600 to 5040 cGy
6-week course
References
- FFCD 9203: Gérard JP, Conroy T, Bonnetain F, Bouché O, Chapet O, Closon-Dejardin MT, Untereiner M, Leduc B, Francois E, Maurel J, Seitz JF, Buecher B, Mackiewicz R, Ducreux M, Bedenne L. Preoperative radiotherapy with or without concurrent fluorouracil and leucovorin in T3-4 rectal cancers: results of FFCD 9203. J Clin Oncol. 2006 Oct 1;24(28):4620-5. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00296608
- EORTC 22921: Bosset JF, Collette L, Calais G, Mineur L, Maingon P, Radosevic-Jelic L, Daban A, Bardet E, Beny A, Ollier JC; EORTC Radiotherapy Group. Chemotherapy with preoperative radiotherapy in rectal cancer. N Engl J Med. 2006 Sep 14;355(11):1114-23. Erratum in: N Engl J Med. 2007 Aug 16;357(7):728. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002523
- Update: Bosset JF, Calais G, Mineur L, Maingon P, Stojanovic-Rundic S, Bensadoun RJ, Bardet E, Beny A, Ollier JC, Bolla M, Marchal D, Van Laethem JL, Klein V, Giralt J, Clavère P, Glanzmann C, Cellier P, Collette L; EORTC Radiation Oncology Group. Fluorouracil-based adjuvant chemotherapy after preoperative chemoradiotherapy in rectal cancer: long-term results of the EORTC 22921 randomised study. Lancet Oncol. 2014 Feb;15(2):184-90. Epub 2014 Jan 17. link to original article PubMed
- LARCS: Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. link to original article PubMed
- NSABP R-03: Roh MS, Colangelo LH, O'Connell MJ, Yothers G, Deutsch M, Allegra CJ, Kahlenberg MS, Baez-Diaz L, Ursiny CS, Petrelli NJ, Wolmark N. Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03. J Clin Oncol. 2009 Nov 1;27(31):5124-30. Epub 2009 Sep 21. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed
- I-CNR-RT: Sainato A, Cernusco Luna Nunzia V, Valentini V, De Paoli A, Maurizi ER, Lupattelli M, Aristei C, Vidali C, Conti M, Galardi A, Ponticelli P, Friso ML, Iannone T, Osti FM, Manfredi B, Coppola M, Orlandini C, Cionini L. No benefit of adjuvant Fluorouracil Leucovorin chemotherapy after neoadjuvant chemoradiotherapy in locally advanced cancer of the rectum (LARC): Long term results of a randomized trial (I-CNR-RT). Radiother Oncol. 2014 Nov;113(2):223-9. Epub 2014 Nov 14. link to original article dosing details in abstract have been reviewed by our editors PubMed
- FOWARC: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. Epub 2016 Aug 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01211210
- Update: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. link to original article link to PMC article PubMed
FUOX & RT
FUOX & RT: FluoroUracil, OXaliplatin, Radiation Therapy
Regimen variant #1, 225/50
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
O'Connell et al. 2014 (NSABP R-04) | 2004-2010 | Phase 3 (E-esc) | 1. 5-FU & RT 2. Capecitabine & RT |
Did not meet primary endpoint of LRC | Inferior toxicity |
3. CapeOx & RT | Did not meet primary endpoint of LRC | Similar toxicity |
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Chemotherapy
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 5625 mg/m2)
- Oxaliplatin (Eloxatin) 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy, 5040 cGy total
5.5-week course
Subsequent treatment
Regimen variant #2, 225/60
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy | Comparative Toxicity |
---|---|---|---|---|---|
Aschele et al. 2011 (STAR-01) | 2003-2008 | Phase 3 (E-esc) | Fluorouracil & RT | Did not meet primary endpoint of OS1 | More toxic |
1Reported efficacy is based on the 2016 update.
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
Chemotherapy
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over approximately 6 weeks, started on day 1
- Oxaliplatin (Eloxatin) 60 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36
Radiotherapy
- Concurrent radiation therapy, 5040 cGy total
6-week course
Subsequent treatment
- Surgery, preferably TME, then adjuvant fluourouracil-based therapy
Regimen variant #3, 250/50
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rödel et al. 2012 (CAO/ARO/AIO-04) | 2006-2010 | Phase 3 (E-esc) | Fluorouracil & RT | Seems to have superior pCR rate (secondary endpoint) |
Chemotherapy
- Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 14 days, started on days 1 & 22 (total dose: 7000 mg/m2)
- Oxaliplatin (Eloxatin) 50 mg/m2 IV over 2 hours once per day on days 1, 8, 22, 29
Radiotherapy
- Concurrent radiation therapy, 5040 cGy total
One course
References
- STAR-01: Aschele C, Cionini L, Lonardi S, Pinto C, Cordio S, Rosati G, Artale S, Tagliagambe A, Ambrosini G, Rosetti P, Bonetti A, Negru ME, Tronconi MC, Luppi G, Silvano G, Corsi DC, Bochicchio AM, Chiaulon G, Gallo M, Boni L. Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial. J Clin Oncol. 2011 Jul 10;29(20):2773-80. Epub 2011 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Abstract: Carlo Aschele, Sara Lonardi, Luca Cionini, Carmine Pinto, Stefano Sergio Cordio, Gerardo Rosati, Andrea Sartore Bianchi, Angiolo Tagliagambe, Michela Frisinghelli, Vittorina Zagonel, Paola Rosetti, Maria Emanuela Negru, Andrea Bonetti, Maria Chiara Tronconi, Gabriele Luppi, Anna Rita Marsella, Domenico C. Corsi, Anna Maria Bochicchio, Nicoletta Pella, and Luca Boni. Final results of STAR-01: A randomized phase III trial comparing preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer. Journal of Clinical Oncology 2016 34:15_suppl, 3521-3521 link to abstract
- CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349076
- Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article PubMed
- NSABP R-04: O'Connell MJ, Colangelo LH, Beart RW, Petrelli NJ, Allegra CJ, Sharif S, Pitot HC, Shields AF, Landry JC, Ryan DP, Parda DS, Mohiuddin M, Arora A, Evans LS, Bahary N, Soori GS, Eakle J, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Wozniak TF, Roh MS, Yothers G, Wolmark N. Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04. J Clin Oncol. 2014 Jun 20;32(18):1927-34. Epub 2014 May 5. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00058474
- Update: Allegra CJ, Yothers G, O'Connell MJ, Beart RW, Wozniak TF, Pitot HC, Shields AF, Landry JC, Ryan DP, Arora A, Evans LS, Bahary N, Soori G, Eakle JF, Robertson JM, Moore DF Jr, Mullane MR, Marchello BT, Ward PJ, Sharif S, Roh MS, Wolmark N. Neoadjuvant 5-FU or capecitabine plus radiation with or without oxaliplatin in rectal cancer patients: a phase III randomized clinical trial. J Natl Cancer Inst. 2015 Sep 14;107(11). Erratum in: J Natl Cancer Inst. 2016 Apr;108(4). link to original article link to PMC article PubMed
mFOLFOX6 & RT
mFOLFOX6 & RT: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin and Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Deng et al. 2016 (FOWARC) | 2010-2015 | Phase 3 (E-esc) | 1. FULV & RT | Did not meet primary endpoint of DFS361 |
2. mFOLFOX6 | Did not meet primary endpoint of DFS361 |
1Reported efficacy is based on the 2019 update.
Chemotherapy
- Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1200 mg/m2/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m2)
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 4 to 6 cycles
Radiotherapy
- Concurrent radiation therapy given before or after surgery at physician discretion: 180 to 200 cGy once per day Monday through Friday for a total of 23 to 28 fractions, for a total dose of 4600 to 5040 cGy
5- to 6-week course
References
- FOWARC: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Peng J, Ren D, Wang J. Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-arm phase III trial. J Clin Oncol. 2016 Sep 20;34(27):3300-7. Epub 2016 Aug 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01211210
- Update: Deng Y, Chi P, Lan P, Wang L, Chen W, Cui L, Chen D, Cao J, Wei H, Peng X, Huang Z, Cai G, Zhao R, Huang Z, Xu L, Zhou H, Wei Y, Zhang H, Zheng J, Huang Y, Zhou Z, Cai Y, Kang L, Huang M, Wu X, Peng J, Ren D, Wang J. Neoadjuvant Modified FOLFOX6 With or Without Radiation Versus Fluorouracil Plus Radiation for Locally Advanced Rectal Cancer: Final Results of the Chinese FOWARC Trial. J Clin Oncol. 2019 Dec 1;37(34):3223-3233. Epub 2019 Sep 26. link to original article link to PMC article PubMed
Radiation therapy
RT: Radiation Therapy
Regimen variant #1, 2500 cGy
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cedermark et al. 1997 (Swedish Rectal Cancer Trial) | 1987-1990 | Phase 3 (E-esc) | Surgery alone | Superior OS |
Kapiteijn et al. 2001 | 1996-1999 | Phase 3 (E-esc) | Surgery alone | Superior local recurrence rate |
Sebag-Montefiore et al. 2009 (MRC CR07; NCIC-CTG CO.16) | 1998-2005 | Phase 3 (C) | Selective postoperative 5-FU & RT | Seems to have superior DFS |
Bujko et al. 2016 (Polish II) | 2008-2014 | Phase 3 (E-switch-ic) | FULV & RT | Might have superior R0 resection rate (primary endpoint) |
Bahadoer et al. 2020 (RAPIDO) | 2011-2016 | Phase 3 (E-switch-ic) | See link | See link |
Radiotherapy
- Radiation therapy, 500 cGy once per day for a total of 5 fractions (total dose: 2500 cGy)
5-day course
Regimen variant #2, 4000 cGy
Historic variant |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oates et al. 1996 | 1981-1989 | Phase 3 (E-esc) | Surgery alone | Seems to have superior DFS |
Subsequent treatment
Regimen variant #3, 5000 cGy
Historic variant |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Braendengen et al. 2008 (LARCS) | 1996-2003 | Phase 3 (C) | FULV/FULV & RT | Might have inferior OS60 |
Subsequent treatment
References
- Oates GD, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus radiotherapy followed by surgery for potentially operable locally advanced rectal cancer. Lancet. 1996 Dec 14;348(9042):1605-10. link to original article dosing details in abstract have been reviewed by our editors PubMed
- Swedish Rectal Cancer Trial: Cedermark B, Dahlberg M, Glimelius B, Påhlman L, Rutqvist LE, Wilking N; Swedish Rectal Cancer Trial investigators. Improved survival with preoperative radiotherapy in resectable rectal cancer. N Engl J Med. 1997 Apr 3;336(14):980-7. Erratum in: N Engl J Med 1997 May 22;336(21):1539. link to original article PubMed
- Update: Folkesson J, Birgisson H, Pahlman L, Cedermark B, Glimelius B, Gunnarsson U. Swedish Rectal Cancer Trial: long lasting benefits from radiotherapy on survival and local recurrence rate. J Clin Oncol. 2005 Aug 20;23(24):5644-50. link to original article PubMed
- Kapiteijn E, Marijnen CA, Nagtegaal ID, Putter H, Steup WH, Wiggers T, Rutten HJ, Pahlman L, Glimelius B, van Krieken JH, Leer JW, van de Velde CJ; Dutch Colorectal Cancer Group. Preoperative radiotherapy combined with total mesorectal excision for resectable rectal cancer. N Engl J Med. 2001 Aug 30;345(9):638-46. link to original article PubMed
- LARCS: Braendengen M, Tveit KM, Berglund A, Birkemeyer E, Frykholm G, Påhlman L, Wiig JN, Byström P, Bujko K, Glimelius B. Randomized phase III study comparing preoperative radiotherapy with chemoradiotherapy in nonresectable rectal cancer. J Clin Oncol. 2008 Aug 1;26(22):3687-94. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Brændengen M, Glimelius B. Preoperative radiotherapy or chemoradiotherapy in rectal cancer - Is survival improved? An update of the "Nordic" LARC study in non-resectable cancers. Radiother Oncol. 2018 Jun;127(3):392-395. Epub 2018 May 16. link to original article PubMed
- MRC CR07; NCIC-CTG CO.16: Sebag-Montefiore D, Stephens RJ, Steele R, Monson J, Grieve R, Khanna S, Quirke P, Couture J, de Metz C, Myint AS, Bessell E, Griffiths G, Thompson LC, Parmar M. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial. Lancet. 2009 Mar 7;373(9666):811-20. link to original article link to PMC article dosing details in abstract have been reviewed by our editors PubMed NCT00003422
- Polish II: Bujko K, Wyrwicz L, Rutkowski A, Malinowska M, Pietrzak L, Kryński J, Michalski W, Olędzki J, Kuśnierz J, Zając L, Bednarczyk M, Szczepkowski M, Tarnowski W, Kosakowska E, Zwoliński J, Winiarek M, Wiśniowska K, Partycki M, Bęczkowska K, Polkowski W, Styliński R, Wierzbicki R, Bury P, Jankiewicz M, Paprota K, Lewicka M, Ciseł B, Skórzewska M, Mielko J, Bębenek M, Maciejczyk A, Kapturkiewicz B, Dybko A, Hajac Ł, Wojnar A, Leśniak T, Zygulska J, Jantner D, Chudyba E, Zegarski W, Las-Jankowska M, Jankowski M, Kołodziejski L, Radkowski A, Żelazowska-Omiotek U, Czeremszyńska B, Kępka L, Kolb-Sielecki J, Toczko Z, Fedorowicz Z, Dziki A, Danek A, Nawrocki G, Sopyło R, Markiewicz W, Kędzierawski P, Wydmański J; Polish Colorectal Study Group. Long-course oxaliplatin-based preoperative chemoradiation versus 5 x 5 Gy and consolidation chemotherapy for cT4 or fixed cT3 rectal cancer: results of a randomized phase III study. Ann Oncol. 2016 May;27(5):834-42. Epub 2016 Feb 15. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00833131
- Update: Ciseł B, Pietrzak L, Michalski W, Wyrwicz L, Rutkowski A, Kosakowska E, Cencelewicz A, Spałek M, Polkowski W, Jankiewicz M, Styliński R, Bębenek M, Kapturkiewicz B, Maciejczyk A, Sadowski J, Zygulska J, Zegarski W, Jankowski M, Las-Jankowska M, Toczko Z, Żelazowska-Omiotek U, Kępka L, Socha J, Wasilewska-Tesluk E, Markiewicz W, Kładny J, Majewski A, Kapuściński W, Suwiński R, Bujko K; Polish Colorectal Study Group. Long-course preoperative chemoradiation vs 5 x 5 Gy and consolidation chemotherapy for clinical T4 and fixed clinical T3 rectal cancer: long-term results of the randomized Polish II study. Ann Oncol. 2019 Aug 1;30(8):1298-1303. Epub 2019 Jun 13. link to original article PubMed
- RAPIDO: Bahadoer RR, Dijkstra EA, van Etten B, Marijnen CAM, Putter H, Kranenbarg EM, Roodvoets AGH, Nagtegaal ID, Beets-Tan RGH, Blomqvist LK, Fokstuen T, Ten Tije AJ, Capdevila J, Hendriks MP, Edhemovic I, Cervantes A, Nilsson PJ, Glimelius B, van de Velde CJH, Hospers GAP; RAPIDO collaborative investigators. Short-course radiotherapy followed by chemotherapy before total mesorectal excision (TME) versus preoperative chemoradiotherapy, TME, and optional adjuvant chemotherapy in locally advanced rectal cancer (RAPIDO): a randomised, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):29-42. Epub 2020 Dec 7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01558921
Adjuvant chemotherapy
Capecitabine monotherapy
Regimen variant #1, 2000 mg/m2/day x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Schmoll et al. 2020 (PETACC 6) | 2008-2011 | Phase 3 (C) | CapeOx | Did not meet primary endpoint of DFS36 |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant capecitabine & RT, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 15
21-day cycle for 6 cycles
Regimen variant #2, 2500 mg/m2/day x 5
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hofheinz et al. 2012 (Rektum-III) | 2002-2007 | Phase 3 (E-RT-switch-ic) | Fluorouracil | Non-inferior OS (primary endpoint) OS60: 76% vs 67% |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant capecitabine & RT, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 5 cycles
Regimen variant #3, 2500 mg/m2/day x 8
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Breugom et al. 2014 (SCRIPT) | 2000-2013 | Phase 3 (E-esc) | Observation | Did not meet primary endpoint of OS |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
Chemotherapy
- Capecitabine (Xeloda) 1250 mg/m2 PO twice per day on days 1 to 14
21-day cycle for 8 cycles
References
- Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01500993
- SCRIPT: Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN36266738
- PETACC 6: Schmoll HJ, Stein A, Van Cutsem E, Price T, Hofheinz RD, Nordlinger B, Daisne JF, Janssens J, Brenner B, Reinel H, Hollerbach S, Caca K, Fauth F, Hannig CV, Zalcberg J, Tebbutt N, Mauer ME, Marreaud S, Lutz MP, Haustermans K. Pre- and Postoperative Capecitabine Without or With Oxaliplatin in Locally Advanced Rectal Cancer: PETACC 6 Trial by EORTC GITCG and ROG, AIO, AGITG, BGDO, and FFCD. J Clin Oncol. 2021 Jan 1;39(1):17-29. Epub 2020 Oct 1. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00766155
Fluorouracil monotherapy
Regimen variant #1
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hofheinz et al. 2012 (Rektum-III) | 2002-2007 | Phase 3 (C) | Capecitabine | Non-inferior OS |
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1 to 5
28-day cycle for 4 cycles
Regimen variant #2
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rödel et al. 2012 (CAO/ARO/AIO-04) | 2006-2010 | Phase 3 (C) | FOLFOX | Seems to have inferior DFS1 |
1Reported efficacy is based on the 2015 update.
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV bolus once per day on days 1 to 5, 29
1-month cycle for 4 cycles
References
- Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01500993
- CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349076
- Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article PubMed
FULV
FULV: 5-FU & LeucoVorin
Regimen variant #1, 500/500
Historic variant |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wolmark et al. 2000 (NSABP R-02) | 1987-1992 | Phase 3 (C) | FULV & RT | Did not meet primary endpoint of OS60 |
Note: male patients were also randomized to MOF or MOF & RT.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, given 1 hour after leucovorin
- Leucovorin (Folinic acid) 500 mg/m2 IV once per day on days 1, 8, 15, 22, 29, 36, given first
8-week cycle for 6 cycles
Regimen variant #2, 1000/120 ("Nordic regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Breugom et al. 2014 (PROCTOR) | 2000-2013 | Phase 3 (E-esc) | Observation | Did not meet primary endpoint of OS |
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have been used as a standard comparator. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
Chemotherapy
- Fluorouracil (5-FU) 500 mg/m2 IV once per day on days 1 & 2, given first (total dose per cycle: 1000 mg/m2)
- Leucovorin (Folinic acid) 60 mg/m2 IV once per day on days 1 & 2, given second (total dose per cycle: 120 mg/m2)
14-day cycle for 12 cycles
Regimen variant #3, 1900/100
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hong et al. 2014 (ADORE) | 2008-2012 | Randomized Phase 2 (C) | FOLFOX | Seems to have inferior DFS36 |
Note: this is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- Neoadjuvant fluoropyrimidine-based chemoradiation, then TME
Chemotherapy
- Fluorouracil (5-FU) 380 mg/m2 IV bolus once per day on days 1 to 5 (total dose per cycle: 1900 mg/m2)
- Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5 (total dose per cycle: 100 mg/m2)
28-day cycle for 4 cycles
Regimen variant #4, 2125/100 ("Mayo regimen")
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Delbaldo et al. 2015 (R98) | 1999-2005 | Phase 3 (C) | FOLFIRI | Did not meet primary endpoint of DFS |
Breugom et al. 2014 (PROCTOR) | 2000-2013 | Phase 3 (E-esc) | Observation | Did not meet primary endpoint of OS |
Note: This was an experimental arm that did not meet its primary endpoint; included here because it was eventually used to establish this regimen as a standard comparator. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Preceding treatment
- PROCTOR: Neoadjuvant 5-FU-based chemoradiotherapy or RT, then surgery
Chemotherapy
- Fluorouracil (5-FU) 425 mg/m2 IV once per day on days 1 to 5 (total dose per cycle: 2125 mg/m2)
- Leucovorin (Folinic acid) 20 mg/m2 IV once per day on days 1 to 5 (total dose per cycle: 100 mg/m2)
4- to 5-week cycle for 6 cycles
References
- NSABP R-02: Wolmark N, Wieand HS, Hyams DM, Colangelo L, Dimitrov NV, Romond EH, Wexler M, Prager D, Cruz AB Jr, Gordon PH, Petrelli NJ, Deutsch M, Mamounas E, Wickerham DL, Fisher ER, Rockette H, Fisher B. Randomized trial of postoperative adjuvant chemotherapy with or without radiotherapy for carcinoma of the rectum: National Surgical Adjuvant Breast and Bowel Project Protocol R-02. J Natl Cancer Inst. 2000 Mar 1;92(5):388-96. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ADORE: Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. Epub 2014 Sep 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00807911
- Update: Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. link to original article PubMed
- PROCTOR: Breugom AJ, van Gijn W, Muller EW, Berglund Å, van den Broek CB, Fokstuen T, Gelderblom H, Kapiteijn E, Leer JW, Marijnen CA, Martijn H, Meershoek-Klein Kranenbarg E, Nagtegaal ID, Påhlman L, Punt CJ, Putter H, Roodvoets AG, Rutten HJ, Steup WH, Glimelius B, van de Velde CJ; Dutch Colorectal Cancer Group; Nordic Gastrointestinal Tumour Adjuvant Therapy Group. Adjuvant chemotherapy for rectal cancer patients treated with preoperative (chemo)radiotherapy and total mesorectal excision: a Dutch Colorectal Cancer Group (DCCG) randomized phase III trial. Ann Oncol. 2015 Apr;26(4):696-701. Epub 2014 Dec 5. link to original article dosing details in manuscript have been reviewed by our editors PubMed ISRCTN36266738
- R98: Delbaldo C, Ychou M, Zawadi A, Douillard JY, André T, Guerin-Meyer V, Rougier P, Dupuis O, Faroux R, Jouhaud A, Quinaux E, Buyse M, Piedbois P; AERO; GERCOR; FNCLCC; FFCD. Postoperative irinotecan in resected stage II-III rectal cancer: final analysis of the French R98 Intergroup trial. Ann Oncol. 2015 Jun;26(6):1208-15. Epub 2015 Mar 3. link to original article PubMed
mFOLFOX6
mFOLFOX6: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen variant #1, with 5-FU bolus, 8 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hong et al. 2014 (ADORE) | 2008-2012 | Randomized Phase 2 (E-esc) | FULV | Seems to have superior DFS36 (primary endpoint) DFS36: 71.6% vs 62.9% (HR 0.66, 95% CI 0.43-0.994) |
Preceding treatment
- Neoadjuvant fluoropyrimidine-based chemoradiation, then TME
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once on day 1, given first
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 8 cycles
Regimen variant #2, no 5-FU bolus, 8 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Rödel et al. 2012 (CAO/ARO/AIO-04) | 2006-2010 | Phase 3 (E-esc) | Fluorouracil | Seems to have superior DFS1 (primary endpoint) DFS36: 75.95% vs 71.2% (HR 0.79, 95% CI 0.64-0.98) |
1Reported efficacy is based on the 2015 update.
Chemotherapy
- Fluorouracil (5-FU) 2400 mg/m2 IV continuous infusion over 46 hours, started on day 1, given third (total dose per cycle: 2400 mg/m2)
- Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second
- Oxaliplatin (Eloxatin) 100 mg/m2 IV over 2 hours once on day 1, given first
14-day cycle for 8 cycles
Regimen variant #3, 12 cycles
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Chakravarthy et al. 2019 (ECOG E5204) | 2006-2009 | Phase 3 (C) | mFOLFOX6-B | Did not meet primary endpoint of OS OS60: 88.3% vs 83.7% |
Preceding treatment
- Neoadjuvant fluoropyrimidine-based chemoradiation, then TME
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for 12 cycles
References
- ADORE: Hong YS, Nam BH, Kim KP, Kim JE, Park SJ, Park YS, Park JO, Kim SY, Kim TY, Kim JH, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin, fluorouracil, and leucovorin versus fluorouracil and leucovorin as adjuvant chemotherapy for locally advanced rectal cancer after preoperative chemoradiotherapy (ADORE): an open-label, multicentre, phase 2, randomised controlled trial. Lancet Oncol. 2014 Oct;15(11):1245-53. Epub 2014 Sep 4. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00807911
- Update: Hong YS, Kim SY, Lee JS, Nam BH, Kim KP, Kim JE, Park YS, Park JO, Baek JY, Kim TY, Lee KW, Ahn JB, Lim SB, Yu CS, Kim JC, Yun SH, Kim JH, Park JH, Park HC, Jung KH, Kim TW. Oxaliplatin-Based Adjuvant Chemotherapy for Rectal Cancer After Preoperative Chemoradiotherapy (ADORE): Long-Term Results of a Randomized Controlled Trial. J Clin Oncol. 2019 Nov 20;37(33):3111-3123. Epub 2019 Oct 8. link to original article PubMed
- CAO/ARO/AIO-04: Rödel C, Liersch T, Becker H, Fietkau R, Hohenberger W, Hothorn T, Graeven U, Arnold D, Lang-Welzenbach M, Raab HR, Sülberg H, Wittekind C, Potapov S, Staib L, Hess C, Weigang-Köhler K, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R; German Rectal Cancer Study Group. Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial. Lancet Oncol. 2012 Jul;13(7):679-87. Epub 2012 May 23. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00349076
- Update: Rödel C, Graeven U, Fietkau R, Hohenberger W, Hothorn T, Arnold D, Hofheinz RD, Ghadimi M, Wolff HA, Lang-Welzenbach M, Raab HR, Wittekind C, Ströbel P, Staib L, Wilhelm M, Grabenbauer GG, Hoffmanns H, Lindemann F, Schlenska-Lange A, Folprecht G, Sauer R, Liersch T; German Rectal Cancer Study Group. Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial. Lancet Oncol. 2015 Aug;16(8):979-89. Epub 2015 Jul 15. link to original article PubMed
- ECOG E5204: Chakravarthy AB, Zhao F, Meropol NJ, Flynn PJ, Wagner LI, Sloan J, Diasio RB, Mitchell EP, Catalano P, Giantonio BJ, Catalano RB, Haller DG, Awan RA, Mulcahy MF, O'Brien TE, Santala R, Cripps C, Weis JR, Atkins JN, Leichman CG, Petrelli NJ, Sinicrope FA, Brierley JD, Tepper JE, O'Dwyer PJ, Sigurdson ER, Hamilton SR, Cella D, Benson AB 3rd. Intergroup Randomized Phase III Study of Postoperative Oxaliplatin, 5-Fluorouracil, and Leucovorin Versus Oxaliplatin, 5-Fluorouracil, Leucovorin, and Bevacizumab for Patients with Stage II or III Rectal Cancer Receiving Preoperative Chemoradiation: A Trial of the ECOG-ACRIN Research Group (E5204). Oncologist. 2020 May;25(5):e798-e807. Epub 2019 Dec 18. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00303628
S-1 monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Oki et al. 2016 (ACTS-RC) | 2006-2009 | Phase 3 (E-switch-ic) | UFT | Seems to have superior RFS (primary endpoint) RFS60: 66.4% vs 61.7% (HR 0.77, 95% CI 0.63-0.96) |
Note: these patients did not receive preoperative therapy.
Preceding treatment
- Curative resection for stage II or stage III rectal cancer, within 49 days
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 1.25 to 1.5 m2: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 or greater m2: 60 mg PO twice per day on days 1 to 28
42-day cycle for 9 cycles (1 year)
References
- ACTS-RC: Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed UMIN C000000385
UFT monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hamaguchi et al. 2010 (NSAS-CC) | 1996-2001 | Phase 3 (E-esc) | Observation | Seems to have superior OS (secondary endpoint) |
Oki et al. 2016 (ACTS-RC) | 2006-2009 | Phase 3 (C) | S-1 | Seems to have inferior RFS |
Note: these patients did not receive preoperative therapy.
Preceding treatment
- Curative resection for stage II or stage III rectal cancer, within 49 days
Chemotherapy
- Tegafur and uracil (UFT) by the following BSA-based criteria:
- Less than 1.25 m2: 250 mg PO twice per day on days 1 to 5
- 1.25 m2 or more: 300 mg PO twice per day on days 1 to 5
7-day cycle for 52 cycles
References
- NSAS-CC: Hamaguchi T, Shirao K, Moriya Y, Yoshida S, Kodaira S, Ohashi Y; NSAS-CC Group. Final results of randomized trials by the National Surgical Adjuvant Study of Colorectal Cancer (NSAS-CC). Cancer Chemother Pharmacol. 2011 Mar;67(3):587-96. Epub 2010 May 19. link to original article PubMed NCT00152230
- ACTS-RC: Oki E, Murata A, Yoshida K, Maeda K, Ikejiri K, Munemoto Y, Sasaki K, Matsuda C, Kotake M, Suenaga T, Matsuda H, Emi Y, Kakeji Y, Baba H, Hamada C, Saji S, Maehara Y. A randomized phase III trial comparing S-1 versus UFT as adjuvant chemotherapy for stage II/III rectal cancer (JFMC35-C1: ACTS-RC). Ann Oncol. 2016 Jul;27(7):1266-72. Epub 2016 Apr 7. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed UMIN C000000385
Adjuvant chemoradiotherapy
Capecitabine & RT
Capecitabine & RT: Capecitabine & Radiation Therapy
Regimen variant #1, fully concurrent
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Feng et al. 2016 (CAMS rectal cancer 01) | 2008-2014 | Phase 3 (C) | CapeOx & RT | Did not meet primary endpoint of DFS DFS36: 71.6% vs 73.9% |
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 14, 22 to 36
Radiotherapy
- Concurrent radiation therapy, 4500 to 5040 cGy total in 25 to 28 fractions
5- to 5.5-week course
Regimen variant #2, sandwich
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hofheinz et al. 2012 (Rektum-III) | 2002-2007 | Phase 3 (E-RT-switch-ic) | 5-FU & RT | Non-inferior OS (primary endpoint) OS60: 76% vs 67% |
Preceding treatment
Chemotherapy
- Capecitabine (Xeloda) as follows:
- Cycles 1 & 2: 1250 mg/m2 PO twice per day on days 1 to 14
- Cycle 3 (chemoradiation): 825 mg/m2 PO twice per day on days 1 to 38
- Cycles 4 to 6: 1250 mg/m2 PO twice per day on days 1 to 14
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 3: 5040 cGy total
21-day cycle for 2 cycles, then 38-day course, then 21-day cycle for 3 cycles
References
- Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01500993
- CAMS rectal cancer 01: Feng YR, Zhu Y, Liu LY, Wang WH, Wang SL, Song YW, Wang X, Tang Y, Liu YP, Ren H, Fang H, Zhang SP, Liu XF, Yu ZH, Li YX, Jin J. Interim analysis of postoperative chemoradiotherapy with capecitabine and oxaliplatin versus capecitabine alone for pathological stage II and III rectal cancer: a randomized multicenter phase III trial. Oncotarget. 2016 May 3;7(18):25576-84. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00714077
Fluorouracil & RT
Fluorouracil & RT: Fluorouracil & Radiation Therapy
Regimen variant #1, Bolus 5-FU (500 mg/m2), then CI 5-FU & RT, then Bolus 5-FU (450 mg/m2)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Connell et al. 1994 (INT 864751) | 1986-1990 | Phase 3 (E-switch-ic) | 5-FU & RT; bolus | Superior OS |
Smalley et al. 2006 (GI INT 0144) | 1994-2000 | Phase 3 (E-switch-ic) | 1. 5-FU & RT; bolus | Not compared |
2. 5-FU & RT; CI | Did not meet co-primary endpoints of OS/DFS |
Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1 & 2: 500 mg/m2 IV bolus once per day on days 1 to 5
- Cycle 3 (chemoradiation): 225 mg/m2/day IV continuous infusion while radiation is being given
- Cycles 4 & 5: 450 mg/m2 IV bolus once per day on days 1 to 5
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
28-day cycle for 2 cycles, then 8-week course, then 28-day cycle for 2 cycles
Regimen variant #2, Bolus 5-FU (500 mg/m2), then CI 5-FU & RT, then Bolus 5-FU (500 mg/m2)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Hofheinz et al. 2012 (Rektum-III) | 2002-2007 | Phase 3 (C) | Capecitabine & RT | Non-inferior OS |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1, 2, 4, 5: 500 mg/m2 IV bolus once per day on days 1 to 5
- Cycle 3 (chemoradiation): 225 mg/m2/day IV continuous infusion while radiation is being given
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 3: 5040 cGy total
28-day cycle for 2 cycles, then one course, then 28-day cycle for 2 cycles
Regimen variant #3, CI 5-FU, then CI 5-FU & RT, then CI 5-FU
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Smalley et al. 2006 (GI INT 0144) | 1994-2000 | Phase 3 (E-switch-ic) | 1. 5-FU & RT; bolus | Did not meet co-primary endpoints of DFS/OS |
2. 5-FU & RT; fully concurrent | Not compared |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycle 1: 300 mg/m2/day IV continuous infusion over 42 days, started on day 1 (total dose: 12,600 mg/m2)
- Cycle 2 (chemoradiation): 225 mg/m2/day IV continuous infusion while radiation is being given
- Cycle 3: 300 mg/m2/day IV continuous infusion over 56 days, started on day 1 (total dose: 16,800 mg/m2)
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 2: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
10-week cycle for 3 cycles
Regimen variant #4, bolus 5-FU, then bolus 5-FU & RT, then bolus 5-FU
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
O'Connell et al. 1994 (INT 864751) | 1986-1990 | Phase 3 (C) | 5-FU & RT; bolus/CI | Inferior OS |
Tepper et al. 1997 (GI INT 0114) | 1990-1992 | Phase 3 (C) | 1. FULV/FULV & RT | Did not meet primary endpoint of DFS36 |
2. Levamisole combination #1 | Did not meet primary endpoint of DFS36 | |||
3. Levamisole combination #2 | Did not meet primary endpoint of DFS36 |
Note: INT 864751 also included a randomization to add semustine, which is only of historic interest.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1 & 2: 500 mg/m2 IV bolus once per day on days 1 to 5
- Cycle 3 (chemoradiation): 500 mg/m2 IV bolus 3 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
- Cycles 4 & 5: 450 mg/m2 IV bolus once per day on days 1 to 5
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
28-day cycle for 2 cycles, then 10-week course, then 28-day cycle for 2 cycles
Regimen variant #5, fully concurrent
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fountzilas et al. 1999 | 1989-1997 | Phase 3 (C) | FULV/5-FU & RT | Did not meet primary endpoint of OS36 |
References
- INT 864751: O'Connell MJ, Martenson JA, Wieand HS, Krook JE, Macdonald JS, Haller DG, Mayer RJ, Gunderson LL, Rich TA. Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med. 1994 Aug 25;331(8):502-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- GI INT 0114: Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. link to original article dosing details in manuscript have been reviewed by our editors PubMed content property of HemOnc.org
- Fountzilas G, Zisiadis A, Dafni U, Konstantaras C, Hatzitheoharis G, Liaros A, Athanassiou E, Dombros N, Dervenis C, Basdanis G, Gamvros O, Souparis A, Briasoulis E, Samantas E, Kappas A, Kosmidis P, Skarlos D, Pavlidis N; Hellenic Cooperative Oncology Group. Postoperative radiation and concomitant bolus fluorouracil with or without additional chemotherapy with fluorouracil and high-dose leucovorin in patients with high-risk rectal cancer: a randomized phase III study conducted by the Hellenic Cooperative Oncology Group. Ann Oncol. 1999 Jun;10(6):671-6. link to original article PubMed
- GI INT 0144: Smalley SR, Benedetti JK, Williamson SK, Robertson JM, Estes NC, Maher T, Fisher B, Rich TA, Martenson JA, Kugler JW, Benson AB 3rd, Haller DG, Mayer RJ, Atkins JN, Cripps C, Pedersen J, Periman PO, Tanaka MS Jr, Leichman CG, Macdonald JS. Phase III trial of fluorouracil-based chemotherapy regimens plus radiotherapy in postoperative adjuvant rectal cancer: GI INT 0144. J Clin Oncol. 2006 Aug 1;24(22):3542-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002551
- Rektum-III: Hofheinz RD, Wenz F, Post S, Matzdorff A, Laechelt S, Hartmann JT, Müller L, Link H, Moehler M, Kettner E, Fritz E, Hieber U, Lindemann HW, Grunewald M, Kremers S, Constantin C, Hipp M, Hartung G, Gencer D, Kienle P, Burkholder I, Hochhaus A. Chemoradiotherapy with capecitabine versus fluorouracil for locally advanced rectal cancer: a randomised, multicentre, non-inferiority, phase 3 trial. Lancet Oncol. 2012 Jun;13(6):579-88. Epub 2012 Apr 13. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01500993
FULV/FULV & RT
FULV/FULV & RT: FluoroUracil & LeucoVorin alternating with FluoroUracil, LeucoVorin, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Tepper et al. 1997 (GI INT 0114) | 1990-1992 | Phase 3 (E-esc) | 1. 5-FU & RT | Did not meet primary endpoint of DFS36 |
2. Levamisole combination #1 | Did not meet primary endpoint of DFS36 | |||
3. Levamisole combination #2 | Did not meet primary endpoint of DFS36 | |||
Kalofonos et al. 2008 | 1999-2004 | Phase 3 (C) | IFL & RT | Did not meet primary endpoint of OS36 |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1 & 2: 425 mg/m2 IV bolus once per day on days 1 to 5, given second
- Cycle 3 (chemoradiation): 400 mg/m2 IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
- Cycles 4 & 5: 380 mg/m2 IV bolus once per day on days 1 to 5, given second
- Leucovorin (Folinic acid) as follows:
- Cycles 1, 2, 4, 5: 20 mg/m2 IV bolus once per day on days 1 to 5, given first
- Cycle 3 (chemoradiation): 20 mg/m2 IV bolus 4 days per week during weeks 1 & 5 of radiation, preferably within 2 hours after the day's radiation
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 3: 180 cGy fractions x 25 fractions for an initial dose of 4500 cGy, which is followed by a 180 cGy x 3 fraction (540 cGy total) boost to the tumor bed and adjacent lymph nodes, and then optionally a 180 cGy x 2 fraction (360 cGy total) boost to the tumor bed and a 2 cm margin if the small bowel could be avoided
28-day cycle for 2 cycles, then 10-week course, then 28-day cycles for 2 cycles
References
- GI INT 0114: Tepper JE, O'Connell MJ, Petroni GR, Hollis D, Cooke E, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA. Adjuvant postoperative fluorouracil-modulated chemotherapy combined with pelvic radiation therapy for rectal cancer: initial results of intergroup 0114. J Clin Oncol. 1997 May;15(5):2030-9. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Tepper JE, O'Connell M, Niedzwiecki D, Hollis DR, Benson AB 3rd, Cummings B, Gunderson LL, Macdonald JS, Martenson JA, Mayer RJ. Adjuvant therapy in rectal cancer: analysis of stage, sex, and local control--final report of intergroup 0114. J Clin Oncol. 2002 Apr 1;20(7):1744-50. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Kalofonos HP, Bamias A, Koutras A, Papakostas P, Basdanis G, Samantas E, Karina M, Misailidou D, Pisanidis N, Pentheroudakis G, Economopoulos T, Papadimitriou C, Skarlos DV, Pectasides D, Stavropoulos M, Bafaloukos D, Kardamakis D, Karanikiotis C, Vourli G, Fountzilas G; Hellenic Cooperative Oncology Group. A randomised phase III trial of adjuvant radio-chemotherapy comparing Irinotecan, 5FU and Leucovorin to 5FU and Leucovorin in patients with rectal cancer: a Hellenic Cooperative Oncology Group Study. Eur J Cancer. 2008 Aug;44(12):1693-700. Epub 2008 Jul 17. link to original article PubMed
Radiation therapy
RT: Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fisher et al. 1988 (NSABP R-01) | 1977-1986 | Phase 3 (E-esc) | 1. MOF | Not reported |
2. Observation | Did not meet efficacy endpoints of DFS/OS | |||
Krook et al. 1991 | 1980-1986 | Phase 3 (C) | Fluorouracil & RT | Inferior RFS |
Amott et al. 1996 | 1984-1989 | Phase 3 (E-esc) | Observation | Superior local recurrence rate |
Note: this regimen in this context is of historic interest.
Preceding treatment
References
- NSABP R-01: Fisher B, Wolmark N, Rockette H, Redmond C, Deutsch M, Wickerham DL, Fisher ER, Caplan R, Jones J, Lerner H, Gordon P, Feldman M, Cruz A, Legault-Poisson S, Wexler M, Lawrence W, Robidoux A. Postoperative adjuvant chemotherapy or radiation therapy for rectal cancer: results from NSABP protocol R-01. J Natl Cancer Inst. 1988 Mar 2;80(1):21-9. link to original article PubMed
- Krook JE, Moertel CG, Gunderson LL, Wieand HS, Collins RT, Beart RW, Kubista TP, Poon MA, Meyers WC, Mailliard JA, Twito DI, Morton RF, Veeder MH, Witzig TE, Cha S, Vidyarthi SC. Effective surgical adjuvant therapy for high-risk rectal carcinoma. N Engl J Med. 1991 Mar 14;324(11):709-15. link to original article PubMed
- Amott SJ, Stenning SP, Hardcastle JD; Medical Research Council Rectal Cancer Working Party. Randomised trial of surgery alone versus surgery followed by radiotherapy for mobile cancer of the rectum. Lancet. 1996 Dec 14;348(9042):1610-4. link to original article dosing details in abstract have been reviewed by our editors PubMed
- TROG 01.014: Ngan SY, Burmeister B, Fisher RJ, Solomon M, Goldstein D, Joseph D, Ackland SP, Schache D, McClure B, McLachlan SA, McKendrick J, Leong T, Hartopeanu C, Zalcberg J, Mackay J. Randomized trial of short-course radiotherapy versus long-course chemoradiation comparing rates of local recurrence in patients with T3 rectal cancer: Trans-Tasman Radiation Oncology Group trial 01.04. J Clin Oncol. 2012 Nov 1;30(31):3827-33. Epub 2012 Sep 24. Erratum in: J Clin Oncol. 2013 Jan 20;31(3):399. link to original article PubMed NCT00351598
Advanced or metastatic disease
See the colorectal cancer page for colorectal cancer regimens.