Difference between revisions of "Staging page"

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[[#top|Back to Top]]
 
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{{#lst:Section editor transclusions|gi}}
 
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<big>Note: there is significant overlap between regimens for gastric cancer and '''[[esophageal cancer]]''', if you can't find the regimen you're looking for here, please try the esophageal cancer page. If you still can't find it, it is possible that we've moved it to the [[Gastric_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Gastric cancer - null regimens|this page]].
 
−
*'''Note: this page contains regimens which were not tested in biomarker-specific populations. The following links will take you to biomarker-specific subpages:'''
 
−
*Regimens for [[Gastric_cancer,_HER2-positive|'''HER2 positive gastric cancer are here''']]</big>.
 
−
{| class="wikitable" style="float:right; margin-right: 5px;"
 
−
|-
 
−
|<div style="background-color: #fee0d1; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}" align="right"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Regimen |limit=10000|format=sum}} [[Tutorial#Regimens|regimens]] on this page</b></font></div>
 
−
<div style="background-color: #deebf6; border: 1px solid #808000; padding: 5px; {{border-radius|16px}}"><font size="4"><b>{{#ask: [[-Has subobject::{{FULLPAGENAME}}]] |?Variant |limit=10000|format=sum}} [[Tutorial#Variants|variants]] on this page</b></font></div>
 
−
|}
 
−
{{TOC limit|limit=3}}
 
−
=Guidelines=
 
−
==[http://www.esmo.org/ ESMO]==
 
−
*'''2019:''' Stjepanovic et al. [https://academic.oup.com/annonc/article/30/10/1558/5543095 Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
 
−
*'''2016:''' Smyth et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Gastric-Cancer Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27664260 PubMed]
 
−
==ESMO/ESSO/ESTRO==
 
−
*'''2013:''' Waddell et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdt344 Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/24078663 PubMed]
 
−
==[https://www.nccn.org/ NCCN]==
 
−
*[https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf NCCN Guidelines - Gastric Cancer]
 
−
=Perioperative therapy=
 
−
''This section contains protocols with a pre-planned neoadjuvant (preoperative) and adjuvant (postoperative) component.''
 
−
==Capecitabine & Cisplatin (CX) {{#subobject:tr26bc|Regimen=1}}==
 
−
CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:cz7085|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (KEYNOTE-585)
 
−
|2017-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab_66|Perioperative CX & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab_66|Perioperative CF & Pembrolizumab]]<br>3. [[#FLOT_.26_Pembrolizumab_66|FLOT & Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |To be determined
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant CX portion====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgical resection]]
 
−
====Chemotherapy, adjuvant CX portion====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''KEYNOTE-585:''' '''contains dosing details on CT.gov''' NCT03221426
 
−
==Cisplatin & Fluorouracil (CF) {{#subobject:7b88be|Regimen=1}}==
 
−
CF: '''<u>C</u>'''isplatin & '''<u>F</u>'''luorouracil
 
−
<br>FP: '''<u>F</u>'''luorouracil & '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #1, 80/4000 {{#subobject:c2yy1e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (KEYNOTE-585)
 
−
|2017-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab_66|Perioperative CX & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab_66|Perioperative CF & Pembrolizumab]]<br>3. [[#FLOT_.26_Pembrolizumab_66|FLOT & Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |To be determined
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant CF portion====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgical resection]]
 
−
====Chemotherapy, adjuvant CF portion====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #2, 100/4000 {{#subobject:c2dc1e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2010.33.0597 Ychou et al. 2011 (ACCORD 07)]
 
−
|1995-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Surgery#Gastrectomy|Surgery alone]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS60: 38% vs 24%<br>(HR 0.69, 95% CI 0.50-0.95)
 
−
|-
 
−
|}
 
−
''Note: ACCORD 07 included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant CF portion====
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''28-day cycle for 2 to 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgical resection]]
 
−
====Chemotherapy, adjuvant CF portion====
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 28
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''28-day cycle for 3 to 4 cycles, for a total of 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ACCORD 07:''' Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P; FNCLCC; FFCD. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. [https://doi.org/10.1200/jco.2010.33.0597 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21444866 PubMed] NCT00002883
 
−
#'''KEYNOTE-585:''' '''contains dosing details on CT.gov''' NCT03221426
 
−
==ECF {{#subobject:f0281c|Regimen=1}}==
 
−
ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:66f602|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)]
 
−
|1994-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Surgery#Gastrectomy|Surgery alone]]
 
−
| style="background-color:#1a9850" |Superior OS<br>OS60: 36% vs 23%<br>(HR 0.75, 95% CI 0.60-0.93)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
 
−
|2007-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 
−
|-
 
−
|}
 
−
''Note: MAGIC included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction). CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction. In CRITICS, only patients with trouble swallowing pills were assigned to this treatment arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant ECF portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*MAGIC, suggested as thrombosis prophylaxis:
 
−
**[[Warfarin (Coumadin)]] 1 mg PO once per day
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*MAGIC: [[Surgery#Gastrectomy|Surgical resection]] is performed 3 to 6 weeks after the completion of cycle 3
 
−
*CRITICS: [[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
 
−
'''Followed in 6 to 12 weeks by:'''
 
−
====Chemotherapy, adjuvant ECF portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*MAGIC, suggested as thrombosis prophylaxis:
 
−
**[[Warfarin (Coumadin)]] 1 mg PO once per day
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://doi.org/10.1056/NEJMoa055531 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16822992 PubMed] NCT00002615
 
−
#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
 
−
==ECX {{#subobject:c8ab0e|Regimen=1}}==
 
−
ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:27f848|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
 
−
|2007-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 
−
|-
 
−
|}
 
−
''Note: CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant ECX portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
 
−
====Chemotherapy, adjuvant ECX portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
 
−
==EOF {{#subobject:139705|Regimen=1}}==
 
−
EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luourouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:bf7464|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
 
−
|2007-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 
−
|-
 
−
|}
 
−
''Note: CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction. Only patients with trouble swallowing pills were assigned to this treatment arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neodjuvant EOF portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
 
−
====Chemotherapy, adjuvant EOF portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
 
−
==EOX {{#subobject:86ee8e|Regimen=1}}==
 
−
EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:edae45|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
 
−
|2007-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 
−
|-
 
−
|}
 
−
''Note: CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant EOX portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
 
−
====Chemotherapy, adjuvant EOX portion====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
 
−
==FLOT {{#subobject:aa7f4f|Regimen=1}}==
 
−
FLOT: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin, '''<u>T</u>'''axotere (Docetaxel)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #1, 3 + 3 {{#subobject:16408e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (KEYNOTE-585)
 
−
|2017-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab_66|Perioperative CX & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab_66|Perioperative CF & Pembrolizumab]]<br>3. [[#FLOT_.26_Pembrolizumab_66|FLOT & Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |To be determined
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant FLOT portion====
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycle 1: 200 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
−
**Cycle 2: 200 mg/m<sup>2</sup> IV once on day 8
 
−
**Cycle 3: 200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 3 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgery]]
 
−
====Chemotherapy, adjuvant FLOT portion====
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
*[[Folinic acid (Leucovorin)]] as follows:
 
−
**Cycle 1: 200 mg/m<sup>2</sup> IV once per day on days 1 & 15
 
−
**Cycle 2: 200 mg/m<sup>2</sup> IV once on day 8
 
−
**Cycle 3: 200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol variant #2, 4 + 4 {{#subobject:16408e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(16)30531-9 Al-Batran et al. 2016 (FLOT4-AIO)]
 
−
|2010-2015
 
−
| style="background-color:#1a9851" |Phase 2/3 (E-switch-ic)
 
−
|1. [[#ECF|Perioperative ECF]]<br>2. [[#ECX|Perioperative ECX]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 50 vs 35 mo<br>(HR 0.77, 95% CI 0.63-0.94)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2019 update.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant FLOT portion====
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycle for 4 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Surgery]]
 
−
====Chemotherapy, adjuvant FLOT portion====
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycle for 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''FLOT4-AIO:''' Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://doi.org/10.1016/S1470-2045(16)30531-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27776843 PubMed] NCT01216644
 
−
##'''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. [https://doi.org/10.1016/s0140-6736(18)32557-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30982686 PubMed]
 
−
#'''KEYNOTE-585:''' '''contains dosing details on CT.gov''' NCT03221426
 
−
#'''MATTERHORN:''' NCT04592913
 
−
#'''RAMSES:''' NCT02661971
 
−
==SOX {{#subobject:ecig8a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:5guz13|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8886520/ Yu et al. 2022 (FOCUS<sub>gastric</sub>)]
 
−
|2011-2016
 
−
|style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#mFOLFOX6_88|Perioperative mFOLFOX6]]
 
−
| style="background-color:#eeee01" |Non-inferior OS<br>OS36: 75.2% vs 67.8%
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, neoadjuvant SOX portion====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
 
−
**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
'''21-day cycle for 2 to 4 cycles'''
 
−
====Surgery====
 
−
*[[Surgery#Gastrectomy|Gastrectomy]] with at least D2 dissection
 
−
====Chemotherapy, adjuvant SOX portion====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
 
−
**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
'''21-day cycle for 2 to 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''RESOLVE<sub>gastric</sub>:''' Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. [https://doi.org/10.1016/s1470-2045(21)00297-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34252374/ PubMed] NCT01534546
 
−
#'''FOCUS<sub>gastric</sub>:''' Yu J, Gao Y, Chen L, Wu D, Shen Q, Zhao Z, Liu W, Yang H, Zhang Q, Wang X, Hu P, Zheng Z, Wang X, Liu H, Xu Z, Yan Z, Wu Y, Jin M, Zhang Q, Liu X, Zhu K, Shou C. Effect of S-1 Plus Oxaliplatin Compared With Fluorouracil, Leucovorin Plus Oxaliplatin as Perioperative Chemotherapy for Locally Advanced, Resectable Gastric Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e220426. [https://doi.org/10.1001/jamanetworkopen.2022.0426 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8886520/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35226081/ PubMed] NCT01364376
 
−
=Neoadjuvant chemotherapy=
 
−
==DOS {{#subobject:a2ug18|Regimen=1}}==
 
−
DOS: '''<u>D</u>'''ocetaxel, '''<u>O</u>'''xaliplatin, '''<u>S</u>'''-1
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:gu1503|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425847/ Kang et al. 2021 (PRODIGY)]
 
−
|2012-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant therapy]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>PFS36: 66% vs 60%<br>(aHR 0.70, 95% CI 0.52-0.95)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Tegafur, gimeracil, oteracil (S-1)|S-1]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 3 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[Surgery#Gastrectomy|Surgery]], then adjuvant [[#S-1_monotherapy|S-1]]
 
−
</div></div>
 
−
===References===
 
−
#'''PRODIGY:''' Kang YK, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, Ryu MH, Rha SY, Chung IJ, Kim IH, Oh SC, Park YS, Son T, Jung MR, Heo MH, Kim HK, Park C, Yoo CH, Choi JH, Zang DY, Jang YJ, Sul JY, Kim JG, Kim BS, Beom SH, Cho SH, Ryu SW, Kook MC, Ryoo BY, Kim HK, Yoo MW, Lee NS, Lee SH, Kim G, Lee Y, Lee JH, Noh SH. PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. J Clin Oncol. 2021 Sep 10;39(26):2903-2913. Epub 2021 Jun 16. [https://doi.org/10.1200/jco.20.02914 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425847/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34133211/ PubMed] NCT01515748
 
−
==ECF {{#subobject:f0281c|Regimen=1}}==
 
−
ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:66f602|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (TOPGEAR)
 
−
|2009-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ECF.2FFluorouracil_.26_RT_66|ECF/5-FU & RT]]<br>2. [[#ECX.2FCapecitabine_.26_RT|ECX/Capecitabine & RT]]<br>3. [[#EOX.2FCapecitabine_.26_RT|EOX/Capecitabine & RT]]<br>4. [[#FLOT.2FCapecitabine_.26_RT|FLOT/Capecitabine & RT]]
 
−
|Awaiting results
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''TOPGEAR:''' NCT01924819
 
−
=Adjuvant therapy=
 
−
==CapeOx {{#subobject:cf9acc|Regimen=1}}==
 
−
CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1ef938|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(11)61873-4 Bang et al. 2012 (CLASSIC)]
 
−
|2006-2009
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Observation|Surgery alone]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 78% vs 69%<br>(HR 0.66, 95% CI 0.51-0.85)
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s1470-2045(21)00297-7 Zhang et al. 2021 (RESOLVE<sub>gastric</sub>)]
 
−
|rowspan=2|2012-2017
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#SOX|Perioperative SOX]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS36
 
−
|-
 
−
|2. [[#SOX_2|Adjuvant SOX]]
 
−
| style="background-color:#eeee01" |Non-inferior DFS36
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for CLASSIC is based on the 2014 update.''<br>
 
−
''Note: RESOLVE should not be confused for the trial by the same name in pancreatic cancer.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Gastrectomy|Gastrectomy]] with D2 dissection
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CLASSIC:''' Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012 Jan 28;379(9813):315-21. Epub 2012 Jan 7. [https://doi.org/10.1016/S0140-6736(11)61873-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22226517 PubMed] NCT00411229
 
−
##'''Update:''' Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. Epub 2014 Oct 15. [https://doi.org/10.1016/S1470-2045(14)70473-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25439693 PubMed]
 
−
#'''RESOLVE<sub>gastric</sub>:''' Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. [https://doi.org/10.1016/s1470-2045(21)00297-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34252374/ PubMed] NCT01534546
 
−
==Carboplatin & Docetaxel {{#subobject:7263b8|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cd8hbq|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s00280-010-1256-6 Bamias et al. 2010]
 
−
|2002-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Carboplatin.2C_Docetaxel.2C_RT_99|Carboplatin, Docetaxel, RT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: the original protocol was for cisplatin & docetaxel but was changed due to excess CINV. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Gastrectomy|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, Samantas E, Christodoulou Ch, Pentheroudakis G, Pectasides D, Dimopoulos MA, Fountzilas G. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010 May;65(6):1009-21. Epub 2010 Feb 4. [https://doi.org/10.1007/s00280-010-1256-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20130877 PubMed]
 
−
==Capecitabine & Cisplatin (CX) {{#subobject:4896bc|Regimen=1}}==
 
−
CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:877085|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.39.1953 Lee et al. 2011 (ARTIST<sub>gastric</sub>)]
 
−
|2004-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Cisplatin_.28CX.29_2|XP]], then [[#Radiation_therapy_88|RT]], then [[#Capecitabine_.26_Cisplatin_.28CX.29_2|XP]]
 
−
| style="background-color:#fee08b" |Might have inferior DFS
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. This trial should not be confused for the one by the same name in colorectal cancer.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*R0 [[Surgery#Gastrectomy|gastrectomy]] and at least D2 dissection
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ARTIST:''' Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. [https://doi.org/10.1200/jco.2011.39.1953 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22184384 PubMed] NCT00323830
 
−
##'''Update:''' Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. [https://doi.org/10.1200/jco.2014.58.3930 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25559811 PubMed]
 
−
==Docetaxel & S-1 {{#subobject:a22c2a|Regimen=1}}==
 
−
DS: '''<u>D</u>'''ocetaxel & '''<u>S</u>'''-1
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:82ca03|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6333977/ Lee et al. 2018 (POST)]
 
−
|2010-2013
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cisplatin_.26_S-1_88|SP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Gastrectomy|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV once per day on days 1 & 8
 
−
*[[Tegafur, gimeracil, oteracil (S-1)|S-1]] 35 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:82ca03|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524985/ Yoshida et al. 2019 (JACCRO GC-07)]
 
−
|2013-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#S-1 monotherapy_2|S-1]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS36: 77.7% vs 71.2%<br>(HR 0.74, 95% CI 0.60-0.925)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update; primary endpoint was RFS.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Gastrectomy|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] as follows:
 
−
**Cycles 1 to 7: 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Tegafur, gimeracil, oteracil (S-1)|S-1]] as follows:
 
−
**Cycles 1 to 7: 80 to 120 mg/m<sup>2</sup> PO on days 1 to 14
 
−
**Cycles 8 to 11: 80 to 120 mg/m<sup>2</sup> PO on days 1 to 28
 
−
'''21-day cycle for 1 cycle, then 42-day cycle for 10 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''POST:''' Lee CK, Jung M, Kim HS, Jung I, Shin DB, Kang SY, Zang DY, Kim KH, Lee MH, Kim BS, Lee KH, Cheong JH, Hyung WJ, Noh SH, Chung HC, Rha SY. S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial. Cancer Res Treat. 2019 Jan;51(1):1-11. Epub 2018 Feb 5. [https://doi.org/10.4143/crt.2018.028 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6333977/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29397659/ PubMed] NCT01283217
 
−
<!-- #'''Abstract:''' Kodera Y, Yoshida K, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Nakamura M, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matssuyama J, Yamada M, Ito Y, Takeuchi M, Fujii M; JACCRO. A randomized phase III study comparing S-1 plus docetaxel with S-1 alone as a postoperative adjuvant chemotherapy for curatively resected stage III gastric cancer (JACCRO GC-07 trial). 2019 American Society of Clinical Oncology annual meeting. DOI: 10.1200/JCO.2018.36.15_suppl.4007  36, no. 15_suppl (May 20, 2018) 4007-4007. [https://doi.org/10.1200/JCO.2018.36.15_suppl.4007 link to abstract] -->
 
−
#'''JACCRO GC-07:''' Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matsuyama J, Yamada M, Ito S, Takeuchi M, Fujii M. Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol. 2019 May 20;37(15):1296-1304. Epub 2019 Mar 29. [https://doi.org/10.1200/jco.18.01138 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524985/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30925125/ PubMed] UMIN000010337
 
−
##'''Update:''' Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022 Jan;25(1):188-196. Epub 2021 Aug 5. [https://doi.org/10.1007/s10120-021-01224-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34351555/ PubMed]
 
−
==FP/Capecitabine & RT {{#subobject:778727|Regimen=1}}==
 
−
FP/Capecitabine & RT: '''<u>F</u>'''luorouracil & '''<u>P</u>'''latinol (Cisplatin) alternating with Capecitabine & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:20ea7f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066094/ Lee et al. 2006]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: In contrast to the primary reference, some guidelines list this regimen without FP cycles 1, 3, 4, 5. Dosage of [[Capecitabine (Xeloda)]] was listed as 625 to 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5 or 1 to 7 while radiation is being given.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Gastrectomy|Surgery]], 3 weeks prior
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, part 1====
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 5000 mg/m<sup>2</sup>)
 
−
'''21-day cycle, followed immediately by:'''
 
−
====Chemotherapy, part 2====
 
−
*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.8 Gy fractions x 25 fractions (total dose of 45 Gy)
 
−
'''5-week course, followed 4 weeks later by:'''
 
−
====Chemotherapy, part 3====
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m<sup>2</sup>)
 
−
'''21-day cycle for 3 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. [http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16489675 PubMed]
 
−
==FULV {{#subobject:5bbh1e|Regimen=1}}==
 
−
FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1tzi01|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdu146 Bajetta et al. 2014 (ITACA-S)]
 
−
|2005-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FOLFIRI_99|FOLFIRI]], then [[#Cisplatin_.26_Docetaxel_.28DC.29_99|Cisplatin & Docetaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*[[Surgery#Gastrectomy|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2
 
−
'''14-day cycle for 9 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ITACA-S:''' Bajetta E, Floriani I, Di Bartolomeo M, Labianca R, Falcone A, Di Costanzo F, Comella G, Amadori D, Pinto C, Carlomagno C, Nitti D, Daniele B, Mini E, Poli D, Santoro A, Mosconi S, Casaretti R, Boni C, Pinotti G, Bidoli P, Landi L, Rosati G, Ravaioli A, Cantore M, Di Fabio F, Aitini E, Marchet A; ITACA-S (Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach Trial) Study Group. Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer. Ann Oncol. 2014 Jul;25(7):1373-1378. Epub 2014 Apr 12. [https://doi.org/10.1093/annonc/mdu146 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24728035/ PubMed] NCT01640782
 
−
==FULV/FULV & RT {{#subobject:2cd29|Regimen=1}}==
 
−
FULV/FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid) alternating with '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid) & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Protocol {{#subobject:dfd3ec|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa010187 Macdonald et al. 2001 (INT-0116)]
 
−
|1991-1998
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Observation|Surgery alone]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678342/ Fuchs et al. 2017 (CALGB 80101)]
 
−
|2002-2009
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#ECF_2|ECF]], then [[#FULV_.26_RT_99|FULV & RT]], then [[#ECF_2|ECF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Treatment is to start 20 to 40 days after surgery.''
 
−
''Note: Study included patients with GE junction malignancy as well (20% GE junction) and included patients with a performance status of 2.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*INT-0116: [[Surgery#Gastrectomy|Surgery]] with R0 resection (10% underwent D2 dissection, 36% underwent D1 dissection and 54% underwent D0 dissection)
 
−
*CALGB 80101: [[Surgery#Gastrectomy|Surgery]]
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy, part 1====
 
−
*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 
−
*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 
−
'''28-day cycle for 1 cycle, followed by:'''
 
−
====Chemotherapy, part 2====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
 
−
*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
 
−
====Radiotherapy====
 
−
*Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy x 25 fractions (total of 45 Gy)
 
−
'''35-day course, followed in 1 month by:'''
 
−
====Chemotherapy, part 3====
 
−
*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 
−
*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
 
−
'''28-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''INT-0116:''' Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [https://doi.org/10.1056/NEJMoa010187 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11547741 PubMed]
 
−
##'''Update:''' Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. [https://doi.org/10.1200/JCO.2011.36.7136 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517071/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22585691 PubMed]
 
−
#'''CALGB 80101:''' Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, Mayer RJ. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10;35(32):3671-3677. Epub 2017 Oct 4. [https://doi.org/10.1200/JCO.2017.74.2130 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678342/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28976791 PubMed] NCT00052910
 
−
==S-1 monotherapy {{#subobject:ec10ef|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 21-day cycles {{#subobject:5dbc53|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(14)70025-7 Tsuburaya et al. 2014 (SAMIT)]
 
−
| rowspan="2" |2004-2009
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Paclitaxel_monotherapy_99|Paclitaxel]], then [[#S-1_monotherapy|S-1]]<br> 2. [[#Paclitaxel_monotherapy_99|Paclitaxel]], then [[#UFT_monotherapy_99|UFT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|3. [[#UFT_monotherapy_99|UFT]]
 
−
| style="background-color:#1a9850" |Superior DFS<br>DFS36: 58.2% vs 53%<br>(HR 0.81, 95% CI 0.70-0.93)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*R0 or R1 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 2 to 8 weeks
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] 80 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for 16 cycles (1 year)'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 42-day cycles {{#subobject:0ee98c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1056/NEJMoa072252 Sakuramoto et al. 2007 (ACTS-GC)]
 
−
|2001-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Observation|Observation]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 72% vs 61%<br>(HR 0.67, 95% CI 0.54-0.83)
 
−
|-
 
−
|[https://doi.org/10.1016/S2468-1253(18)30383-2 Yoshikawa et al. 2019 (OPAS-1)]
 
−
|2012-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#S-1_monotherapy|S-1]] x 6 mo
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/j.annonc.2020.11.017 Park et al. 2020 (ARTIST 2)]
 
−
|rowspan=2|2013-2018
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#SOX|SOX]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DFS
 
−
|-
 
−
|2. [[#SOX_.26_RT_88|SOXRT]]
 
−
| style="background-color:#fee08b" |Might have inferior DFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy for ACTS-GC is based on the 2011 update.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*R0 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 6 weeks
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
 
−
**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
 
−
'''42-day cycle for 8 cycles (1 year)'''
 
−
</div></div>
 
−
===References===
 
−
#'''ACTS-GC:''' Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. [https://doi.org/10.1056/NEJMoa072252 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17978289 PubMed] NCT00152217
 
−
##'''Update:''' Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. [https://doi.org/10.1200/JCO.2011.36.5908 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22010012 PubMed]
 
−
#'''SAMIT:''' Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. [https://doi.org/10.1016/S1470-2045(14)70025-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24954805 PubMed] UMIN C000000082
 
−
#'''OPAS-1:''' Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, Yabusaki H, Yoshida K, Ito S, Takeno A, Yasuda T, Kawachi Y, Katayama H, Fukuda H, Boku N, Sano T, Sasako M. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104[OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019 Mar;4(3):208-216. Epub 2019 Jan 22. Erratum in: Lancet Gastroenterol Hepatol. 2019 Apr;4(4):e3. [https://doi.org/10.1016/S2468-1253(18)30383-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30679107 PubMed] UMIN000007306
 
−
#'''JACCRO GC-07:''' Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matsuyama J, Yamada M, Ito S, Takeuchi M, Fujii M. Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol. 2019 May 20;37(15):1296-1304. Epub 2019 Mar 29. [https://doi.org/10.1200/jco.18.01138 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524985/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30925125/ PubMed] UMIN000010337
 
−
##'''Update:''' Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022 Jan;25(1):188-196. Epub 2021 Aug 5. [https://doi.org/10.1007/s10120-021-01224-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34351555/ PubMed]
 
−
#'''ARTIST 2:''' Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, Kang JH, Oh SY, Hwang IG, Ji JH, Shin DB, Yu JI, Kim KM, An JY, Choi MG, Lee JH, Kim S, Hong JY, Park JO, Park YS, Lim HY, Bae JM, Kang WK; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-374. Epub 2020 Dec 3. [https://doi.org/10.1016/j.annonc.2020.11.017 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33278599/ PubMed] NCT0176146
 
−
#'''HKIT-GC:''' NCT00216034
 
−
==SOX {{#subobject:ecig8a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5guz13|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/j.annonc.2020.11.017 Park et al. 2020 (ARTIST 2)]
 
−
|rowspan=2|2013-2018
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#S-1_monotherapy|S-1]]
 
−
| style="background-color:#91cf60" |Seems to have superior DFS<br>DFS36: 74.3% vs 64.8%<br>(HR 0.69, 95% CI 0.41-0.99)
 
−
|-
 
−
|2. [[#SOX_.26_RT_88|SOXRT]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*R0 or R1 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
 
−
**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
'''21-day cycle for up to 8 cycles (6 months)'''
 
−
</div></div>
 
−
===References===
 
−
#'''ARTIST 2:''' Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, Kang JH, Oh SY, Hwang IG, Ji JH, Shin DB, Yu JI, Kim KM, An JY, Choi MG, Lee JH, Kim S, Hong JY, Park JO, Park YS, Lim HY, Bae JM, Kang WK; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-374. Epub 2020 Dec 3. [https://doi.org/10.1016/j.annonc.2020.11.017 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33278599/ PubMed] NCT0176146
 
−
#'''TOTTG030103:''' Zhao Q, Lian C, Huo Z, Li M, Liu Y, Fan L, Tan B, Zhao X, Zhang Z, Wang D, Liu Y, Guo H, Yang P, Tian Y, Li Y. The efficacy and safety of neoadjuvant chemotherapy on patients with advanced gastric cancer: A multicenter randomized clinical trial. Cancer Med. 2020 Aug;9(16):5731-5745. Epub 2020 Jun 24. [https://doi.org/10.1002/cam4.3224 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7433829/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32583567/ PubMed] NCT01516944
 
−
=Metastatic or locally advanced disease, first-line=
 
−
==Capecitabine monotherapy {{#subobject:a9eb0b|Regimen=1}}==
 
−
X: '''<u>X</u>'''eloda (Capecitabine)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 2000 mg/m<sup>2</sup>/day {{#subobject:b6ba4c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.geriatriconcology.net/article/S1879-4068(17)30022-X Hwang et al. 2017 (SMC 2010-04-118)]
 
−
|2010-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CapeOx_2|XELOX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 2500 mg/m<sup>2</sup>/day {{#subobject:b6ba4c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdh343 Hong et al. 2004]
 
−
|NR
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Eligibility criteria====
 
−
*Karnofsky status of at least 70%
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. [https://doi.org/10.1093/annonc/mdh343 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15319239 PubMed]
 
−
#'''SMC 2010-04-118:''' Hwang IG, Ji JH, Kang JH, Lee HR, Lee HY, Chi KC, Park SW, Lee SJ, Kim ST, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol. 2017 May;8(3):170-175. Epub 2017 Jan 21. [https://www.geriatriconcology.net/article/S1879-4068(17)30022-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28119041 PubMed] NCT01470742
 
−
==Capecitabine & Cisplatin (CX) {{#subobject:2bd34d|Regimen=1}}==
 
−
CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:82b184|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdn717 Kang et al. 2009 (ML17032)]
 
−
|2003-2005
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.36.2236 Ohtsu et al. 2011 (AVAGAST)]
 
−
|2007-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Capecitabine_.26_Cisplatin_.28CX.29_.26_Bevacizumab|CX & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70102-5 Lordick et al. 2013 (EXPAND)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Cetuximab_99|CX & Cetuximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544634/ Shen et al. 2014 (AVATAR)]
 
−
|2009-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Capecitabine_.26_Cisplatin_.28CX.29_.26_Bevacizumab|CX & Bevacizumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(14)00884-3 Kim et al. 2014 (SMC 2008-12-019)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Simvastatin_99|CX & Simvastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097104/ Lu et al. 2018 (PAC-C)]
 
−
|2009-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Paclitaxel_99|Capecitabine & Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30791-5 Fuchs et al. 2019 (RAINFALL)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[Stub#Capecitabine_.26_Cisplatin_.28CX.29_.26_Ramucirumab|CX & Ramucirumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup>
 
−
|-
 
−
|}
 
−
''<sup>1</sup>while the primary analysis of RAINFALL showed that this arm seemed to have inferior PFS, independent central review did not confirm this finding.''<br>
 
−
The following studies included patients with GE junction malignancy as well:
 
−
*''AVAGAST patients: 86% gastric and 14% GE junction. 5.4% of patients had an ECOG of 2.''
 
−
*''EXPAND patients: 83% gastric, 5% GE junction and 16% unknown''
 
−
*''SMC 2008-12-019 patients: 79% gastric, 16% GE junction and 5% unknown''
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
**EXPAND: 1000 mg/m<sup>2</sup> PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)
 
−
====Supportive therapy====
 
−
*Some protocols: [[:Category:Hydration|"Hyperhydration"]] for cisplatin
 
−
'''21-day cycles, varied duration (see below)'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*AVAGAST & AVATAR: after 6 cycles, [[#Capecitabine_monotherapy_2|capecitabine]] maintenance
 
−
*SMC 2008-12-019: after 8 cycles, [[#Capecitabine_monotherapy_2|capecitabine]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''ML17032:''' Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [https://doi.org/10.1093/annonc/mdn717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19153121 PubMed] content property of [http://hemonc.org HemOnc.org] NCT02563054
 
−
#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://doi.org/10.1200/JCO.2011.36.2236 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21844504 PubMed] NCT00548548
 
−
#'''EXPAND:''' Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [https://doi.org/10.1016/S1470-2045(13)70102-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23594786 PubMed] NCT00678535
 
−
#'''AVATAR:''' Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, Xu R, Chen L, Liu Y, Yu S, Bu L, Piao Y. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015 Jan;18(1):168-76. Epub 2014 Feb 21. [https://doi.org/10.1007/s10120-014-0351-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544634/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24557418 PubMed] NCT00887822
 
−
#'''SMC 2008-12-019:''' Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25218337 PubMed] NCT01099085
 
−
#'''PAC-C:''' Lu Z, Zhang X, Liu W, Liu T, Hu B, Li W, Fan Q, Xu J, Xu N, Bai Y, Pan Y, Xu Q, Bai W, Xia L, Gao Y, Wang W, Shu Y, Shen L. A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer. Gastric Cancer. 2018 Sep;21(5):782-791. Epub 2018 Feb 27. [https://doi.org/10.1007/s10120-018-0809-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097104/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29488121 PubMed] NCT01015339
 
−
#'''RAINFALL:''' Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):420-435. Epub 2019 Feb 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. [https://doi.org/10.1016/S1470-2045(18)30791-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30718072 PubMed] NCT02314117
 
−
==Capecitabine & Cisplatin (CX) & Pembrolizumab {{#subobject:ahg7ab|Regimen=1}}==
 
−
CX & Pembrolizumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Pembrolizumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1yt34c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
 
−
|rowspan=2|2015-2017
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]<br> 2. [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 12.5 vs 11.1 mo<br>(HR 0.85, 95% CI 0.70-1.03)
 
−
|-
 
−
|3. [[#Pembrolizumab_monotherapy|Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|}
 
−
''KEYNOTE-062 included patients with GEJ malignancy''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
PD-L1 Combined Positive Score (CPS) of 1 or more as determined by an FDA-approved test
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
 
−
#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
 
−
==CapeOx {{#subobject:4e3bb4|Regimen=1}}==
 
−
CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 750/78 {{#subobject:4faj81|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ Hall et al. 2021 (GO2)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#CapeOx_2|CapeOx]]; 130/1250
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 375 mg/m<sup>2</sup> PO twice per day
 
−
*[[Oxaliplatin (Eloxatin)]] 78 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 1000/104 {{#subobject:4faj65|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ Hall et al. 2021 (GO2)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#CapeOx_2|CapeOx]]; 130/1250
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 500 mg/m<sup>2</sup> PO twice per day
 
−
*[[Oxaliplatin (Eloxatin)]] 104 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 1250/130 {{#subobject:guzj65|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ Hall et al. 2021 (GO2)]
 
−
|2014-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_2|CapeOx]]; 750/78<br>2. [[#CapeOx_2|CapeOx]]; 1000/104
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 1700/130 {{#subobject:4faee3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdj063 Jatoi et al. 2006]
 
−
|2002-2004
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 850 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
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 2000/130 {{#subobject:4fagg3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.00892 Moehler et al. 2020 (JAVELIN Gastric 100)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_2|CapeOx]] x 4, then [[#Avelumab_monotherapy_99|Avelumab]]<br> 2. [[#mFOLFOX4_88|mFOLFOX4]] x 4, then [[#Avelumab_monotherapy_99|Avelumab]]<br> 3. [[#mFOLFOX6|mFOLFOX6]] x 4, then [[#Avelumab_monotherapy_99|Avelumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|Awaiting publication (ARMANI)
 
−
|2016-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_2|CapeOx]] x 3 mo, then [[#Paclitaxel_.26_Ramucirumab_88|Paclitaxel & Ramucirumab]]<br> 2. [[#FOLFOX4_88|FOLFOX4]] x 3 mo, then [[#Paclitaxel_.26_Ramucirumab_88|Paclitaxel & Ramucirumab]]<br> 3. [[#mFOLFOX6|mFOLFOX6]] x 3 mo, then [[#Paclitaxel_.26_Ramucirumab_88|Paclitaxel & Ramucirumab]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00692-6 Kang et al. 2022 (ATTRACTION-4)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Nivolumab|CapeOx & Nivolumab]]<br>2. [[#SOX_.26_Nivolumab_77|SOX & Nivolumab]]
 
−
| style="background-color:#d73027" |Inferior PFS
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
 
−
|rowspan=2|2017-2019
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Nivolumab|CapeOx & Nivolumab]]<br> 2. [[#mFOLFOX6_.26_Nivolumab|mFOLFOX6 & Nivolumab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|Awaiting publication (BGB-A317-305)
 
−
|2018-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Tislelizumab_77|CapeOx & Tislelizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Tislelizumab_77|CF & Tislelizumab]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|Awaiting publication (KEYNOTE-859)
 
−
|2018-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Pembrolizumab_66|CapeOx & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 2000/130, limited oxaliplatin {{#subobject:4hazb3|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ Zhu et al. 2022 (EXELOX)]
 
−
|2015-2020
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|[[#EOX_2|EOX]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS<br>Median PFS: 5 vs 5.5 mo<br>(HR 0.989, 95% CI 0.81-1.20)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
*[[Oxaliplatin (Eloxatin)]] as follows:
 
−
**Cycles 1 up to 8: 130 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr; North Central Cancer Treatment Group. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006 Jan;17(1):29-34. Epub 2005 Nov 22. [https://doi.org/10.1093/annonc/mdj063 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16303863 PubMed]
 
−
#'''JAVELIN Gastric 100:''' Moehler M, Dvorkin M, Boku N, Özgüroğlu M, Ryu MH, Muntean AS, Lonardi S, Nechaeva M, Bragagnoli AC, Coşkun HS, Cubillo Gracian A, Takano T, Wong R, Safran H, Vaccaro GM, Wainberg ZA, Silver MR, Xiong H, Hong J, Taieb J, Bang YJ. Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100. J Clin Oncol. 2021 Mar 20;39(9):966-977. Epub 2020 Nov 16. [https://doi.org/10.1200/jco.20.00892 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33197226/ PubMed] NCT02625610
 
−
#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
 
−
#'''GO2:''' Hall PS, Swinson D, Cairns DA, Waters JS, Petty R, Allmark C, Ruddock S, Falk S, Wadsley J, Roy R, Tillett T, Nicoll J, Cummins S, Mano J, Grumett S, Stokes Z, Kamposioras KV, Chatterjee A, Garcia A, Waddell T, Guptal K, Maisey N, Khan M, Dent J, Lord S, Crossley A, Katona E, Marshall H, Grabsch HI, Velikova G, Ow PL, Handforth C, Howard H, Seymour MT; GO2 Trial Investigators. Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):869-877. Erratum in: JAMA Oncol. 2021 Aug 1;7(8):1249. [https://doi.org/10.1001/jamaoncol.2021.0848 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33983395/ PubMed] ISRCTN44687907
 
−
#'''ATTRACTION-4:''' Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. Epub 2022 Jan 11. [https://doi.org/10.1016/s1470-2045(21)00692-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35030335/ PubMed] NCT02746796
 
−
#'''EXELOX:''' Zhu XD, Huang MZ, Wang YS, Feng WJ, Chen ZY, He YF, Zhang XW, Liu X, Wang CC, Zhang W, Ying JE, Wu J, Yang L, Qin YR, Luo JF, Zhao XY, Li WH, Zhang Z, Qiu LX, Geng QR, Zou JL, Zhang JY, Zheng H, Song XF, Wu SS, Zhang CY, Gong Z, Liu QQ, Wang XF, Xu Q, Wang Q, Ji JM, Zhao J, Guo WJ. XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX). Cancer Commun (Lond). 2022 Apr;42(4):314-326. Epub 2022 Feb 25. [https://doi.org/10.1002/cac2.12278 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35212487/ PubMed] NCT02395640
 
−
#'''ARMANI:''' NCT02934464
 
−
#'''BGB-A317-305:''' '''contains dosing details on CT.gov''' NCT03777657
 
−
#'''KEYNOTE-859:''' '''contains dosing details on CT.gov''' NCT03675737
 
−
#'''ORIENT-16:''' NCT03745170
 
−
==CapeOx & Nivolumab {{#subobject:1ybz18|Regimen=1}}==
 
−
CapeOx & Nivolumab: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin, Nivolumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1bja1f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(21)00692-6 Kang et al. 2022 (ATTRACTION-4)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#CapeOx_2|CapeOx]]<br>2. [[#SOX_88|SOX]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.45 vs 8.3 mo<br>(HR 0.68, 98.51% 0.51-0.90)
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
 
−
|rowspan=2|2017-2019
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#CapeOx_2|CapeOx]]<br> 2. [[#mFOLFOX6|mFOLFOX6]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 14.4 vs 11.1 mo<br>(HR 0.71, 98.4% CI 0.59-0.86)
 
−
|-
 
−
|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is for the group with PD-L1 CPS of 5 or more.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[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
 
−
====Immunotherapy====
 
−
*[[Nivolumab (Opdivo)]] 360 mg IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
 
−
#'''ATTRACTION-4:''' Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. Epub 2022 Jan 11. [https://doi.org/10.1016/s1470-2045(21)00692-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35030335/ PubMed] NCT02746796
 
−
==Carboplatin & Paclitaxel (CP) {{#subobject:4df570|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9725d8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://pubmed.ncbi.nlm.nih.gov/9427274 Philip et al. 1997]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract Gadgeel et al. 2003]
 
−
|1996-2000
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: In contrast to the original reference, some guidelines list the dosage of carboplatin as AUC 6.''
 
−
''Philip et al. included patients with locally advanced metastatic or recurrent esophageal or gastric cancer''
 
−
''Gadgeel et al. study showed an ORR of 35%'' 
 
−
====Chemotherapy====
 
−
*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1, '''given second'''
 
−
*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9427274 PubMed]
 
−
#Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12576922 PubMed]
 
−
==Cisplatin & Docetaxel (DC) {{#subobject:724868|Regimen=1}}==
 
−
DC: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin
 
−
<br>TC: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 75/75 {{#subobject:cd0910|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2006.08.0135 Roth et al. 2007]
 
−
| rowspan="2" |1999-2003
 
−
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|1. [[#ECF_3|ECF]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#DCF|TCF]]
 
−
| style="background-color:#fee08b" |Might have inferior ORR
 
−
|-
 
−
|}
 
−
''Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
====Supportive therapy====
 
−
*3 liters per day [[:Category:Hydration|"hyperhydration"]]
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO twice per day for 4 days after [[Docetaxel (Taxotere)]]
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
 
−
*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 75/85 {{#subobject:f1913d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.17.376 Ajani et al. 2005 (V-325)]
 
−
|1998-1999
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#DCF|DCF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior ORR
 
−
|-
 
−
|}
 
−
''Patients: 100% adenocarcinoma histology (32% esophagogastric junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.''
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
 
−
*[[Docetaxel (Taxotere)]] 85 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
====Supportive therapy====
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (total dose per cycle: 48 mg)
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
 
−
*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
 
−
*"[[:Category:Hydration|Hydration]] was administered in a standard manner"
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [https://doi.org/10.1200/jco.2005.17.376 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16110025 PubMed]
 
−
#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [https://doi.org/10.1200/jco.2006.08.0135 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17664469 PubMed]
 
−
==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}==
 
−
CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 60/5000 {{#subobject:9yt155|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2699097/ Lee et al. 2009a]
 
−
|2000-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fluorouracil_.26_Heptaplatin_.28FH.29_77|Fluorouracil & Heptaplatin (FH)]]
 
−
| style="background-color:#eeee01" |Equivalent OS
 
−
|-
 
−
|}
 
−
''Note: this is reported to be an equivalence study but the statistical analysis does not provide details on the definition of equivalence.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
 
−
*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 5, '''given second'''
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 80/4000 x 8 {{#subobject:9abe95|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdx275 Ajani et al. 2017 (DIGEST)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_S-1|CS]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*Some protocols: [[:Category:Hydration|"Hyperhydration"]] for cisplatin
 
−
'''21-day cycle for 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 80/4000, indefinite {{#subobject:69c795|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdn717 Kang et al. 2009 (ML17032)]
 
−
|2003-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
 
−
|rowspan=2|2015-2017
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab|CX & Pembrolizumab]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[[#Pembrolizumab_monotherapy|Pembrolizumab]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|Awaiting publication (BGB-A317-305)
 
−
|2018-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Tislelizumab_77|CapeOx & Tislelizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Tislelizumab_77|CF & Tislelizumab]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|Awaiting publication (KEYNOTE-859)
 
−
|2018-ongoing
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Pembrolizumab_66|CapeOx & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |TBD
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*Some protocols: [[:Category:Hydration|"Hyperhydration"]] for cisplatin
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 100/4000 {{#subobject:16f88f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[http://ar.iiarjournals.org/content/26/5B/3877.long Duffour et al. 2006 (FFCD 9404)]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CLF|FLP]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on either day 1 or 2
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #5, 100/4000, split-dose cisplatin {{#subobject:16f18e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2003.04.130 Ohtsu et al. 2003 (JCOG 9205)]
 
−
| rowspan="2" |1992-1997
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Fluorouracil_monotherapy|Fluorouracil]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#UFTM|UFTM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: this study included patients with ECOG PS of 2 (9.6%)''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''28-day cycle for up to 6 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #6, 100/5000 {{#subobject:10f0c6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.06.8429 Van Cutsem et al. 2006 (TAX 325)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DCF|DCF]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdn166 Dank et al. 2008]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#FOLFIRI|IF]]
 
−
| style="background-color:#fee08b" |Might have inferior TTP
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.25.4706 Ajani et al. 2010 (FLAGS)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_S-1|CS]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Van Cutsem et al Patients: 100% adenocarcinoma histology (22% Esophagogastric junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70.''
 
−
''Dank et al Patients: 100% adenocarcinoma histology (20% Esophagogastric junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.''
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
 
−
*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 5000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*As described in Dank et al. 2008:
 
−
*[[:Category:Hydration|"Hyperhydration"]] for 2 to 3 days with each infusion
 
−
*[[Ondansetron (Zofran)]] IV for antiemetic prophylaxis
 
−
*[[Dexamethasone (Decadron)]] IV for antiemetic prophylaxis, then PO for 2 to 3 days
 
−
*[[Metoclopramide (Reglan)]] for antiemetic prophylaxis
 
−
*[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
 
−
*[[Atropine (Atropen)]] prn cholinergic symptoms
 
−
*[[Loperamide (Imodium)]] prn delayed diarrhea
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; [[Study_Groups#JCOG|JCOG]]. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [https://doi.org/10.1200/jco.2003.04.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506170 PubMed]
 
−
#'''FFCD 9404:''' Duffour J, Bouché O, Rougier P, Milan C, Bedenne L, Seitz JF, Buecher B, Legoux JL, Ducreux M, Vetter D, Raoul JL, François E, Ychou M. Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Anticancer Res. 2006 Sep-Oct;26(5B):3877-83. [http://ar.iiarjournals.org/content/26/5B/3877.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17094417 PubMed]
 
−
#'''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [https://doi.org/10.1200/jco.2006.06.8429 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17075117 PubMed]
 
−
#Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [https://doi.org/10.1093/annonc/mdn166 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18558665 PubMed]
 
−
#'''ML17032:''' Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [https://doi.org/10.1093/annonc/mdn717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19153121 PubMed] NCT02563054
 
−
#Lee KH, Hyun MS, Kim HK, Jin HM, Yang J, Song HS, Do YR, Ryoo HM, Chung JS, Zang DY, Lim HY, Jin JY, Yim CY, Park HS, Kim JS, Sohn CH, Lee SN. Randomized, multicenter, phase III trial of heptaplatin 1-hour infusion and 5-fluorouracil combination chemotherapy comparing with cisplatin and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. Cancer Res Treat. 2009 Mar;41(1):12-8. Epub 2009 Mar 31. [https://doi.org/10.4143/crt.2009.41.1.12 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2699097/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19688066/ PubMed]
 
−
#'''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://doi.org/10.1200/JCO.2009.25.4706 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20159816 PubMed] NCT00400179
 
−
#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://doi.org/10.1200/JCO.2011.36.2236 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21844504 PubMed] NCT00548548
 
−
#'''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://doi.org/10.1093/annonc/mdx275 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911091 PubMed] NCT01285557
 
−
<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
 
−
#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
 
−
#'''BGB-A317-305:''' '''contains dosing details on CT.gov''' NCT03777657
 
−
#'''KEYNOTE-859:''' '''contains dosing details on CT.gov''' NCT03675737
 
−
==Cisplatin & Fluorouracil (CF) & Pembrolizumab==
 
−
CF & Pembrolizumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Pembrolizumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
 
−
|rowspan=2|2015-2017
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]<br> 2. [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 12.5 vs 11.1 mo<br>(HR 0.85, 95% CI 0.70-1.03)
 
−
|-
 
−
|3. [[#Pembrolizumab_monotherapy|Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|}
 
−
''KEYNOTE-062 included patients with GEJ malignancy''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
PD-L1 Combined Positive Score (CPS) of 1 or more as determined by an FDA-approved test
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
 
−
#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
 
−
==Cisplatin & S-1 {{#subobject:252c51|Regimen=1}}==
 
−
CS: '''<u>C</u>'''isplatin & '''<u>S</u>'''-1
 
−
<br>SP: '''<u>S</u>'''-1 & '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, q3wk ("SP3") {{#subobject:4ff7cf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdv316 Ryu et al. 2015 (SOS)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]; SP5
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 5.5 vs 4.9 mo<br>(HR 0.82, 95% CI 0.68-0.99)
 
−
|-
 
−
|[https://doi.org/10.1007/s10120-020-01101-4 Lee et al. 2020 (SOPP)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#SOX_88|SOX]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, q4wk {{#subobject:03b3c4|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2009.25.4706 Ajani et al. 2010 (FLAGS)]
 
−
|2005-2007
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdx275 Ajani et al. 2017 (DIGEST)]
 
−
|2011-2014
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm of a study where the primary endpoint was not met. Included because CS has been shown to be superior in comparison to other regimens (see above).''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] 25 mg/m<sup>2</sup> PO twice per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, q5wk ("SP5") {{#subobject:cdcc15|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(08)70035-4 Koizumi et al. 2008 (SPIRITS)]
 
−
|2002-2004
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#S-1_monotherapy_2|S-1]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 13 vs 11 mo<br>(HR 0.77, 95% CI 0.61-0.98)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(15)00553-7 Fujitani et al. 2016 (REGATTA)]
 
−
|2008-2013
 
−
| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdv316 Ryu et al. 2015 (SOS)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]; SP3
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdu472 Yamada et al. 2014 (G-SOX)]
 
−
|2010-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#SOX_88|SOX]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.77.8613 Ishigami et al. 2018 (PHOENIX-GC)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_.26_S-1|IV/IP Paclitaxel & S-1]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/s2468-1253(19)30083-4 Yamada et al. 2019 (JCOG1013)]
 
−
|2012-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Docetaxel_.28DC.29_.26_S-1_99|Cisplatin, Docetaxel, S-1]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1016/s1470-2045(20)30315-6 Kang et al. 2020 (SOLAR)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Oxaliplatin_.26_TAS-118_77|Oxaliplatin & TAS-118]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
''Note: in REGATTA, there was no difference in outcome amongst patients who did or did not undergo surgery.''
 
−
''Inclusion criteria for REGATTA included the presence of a single non-curable factor (ex: hepatic, peritoneal, and para-aortic mets), see link for further details''
 
−
''SPIRITS trial included patients with ECOG of 2 (3% of patients)''
 
−
''Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*REGATTA: Non-laparoscopic [[Surgery#Gastrectomy|gastrectomy]] with D1 [[Surgery#Lymphadenectomy|lymphadenectomy]] versus [[Surgery#No_surgery|no surgery]]; chemotherapy began within 8 weeks of surgery
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 8
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 21
 
−
**BSA at least 1.25 m<sup>2</sup> and less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 21
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 21
 
−
'''35-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://doi.org/10.1016/S1470-2045(08)70035-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18282805 PubMed] NCT00150670
 
−
#'''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://doi.org/10.1200/JCO.2009.25.4706 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20159816 PubMed] NCT00400179
 
−
#'''G-SOX:''' Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015 Jan;26(1):141-8. Epub 2014 Oct 14. [https://doi.org/10.1093/annonc/mdu472 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25316259 PubMed] JapicCTI-101021
 
−
#'''SOS:''' Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, Kang YK; SOS study investigators. Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol. 2015 Oct;26(10):2097-101. Epub 2015 Jul 27. [https://doi.org/10.1093/annonc/mdv316 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26216386 PubMed] NCT00915382
 
−
#'''REGATTA:''' Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. [https://doi.org/10.1016/S1470-2045(15)00553-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26822397 PubMed] UMIN000001012
 
−
#'''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://doi.org/10.1093/annonc/mdx275 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911091 PubMed] NCT01285557
 
−
#'''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.77.8613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29746229 PubMed] UMIN000005930
 
−
#'''JCOG1013:''' Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jul;4(7):501-510. Epub 2019 May 14. [https://doi.org/10.1016/s2468-1253(19)30083-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31101534 PubMed] UMIN000007652
 
−
#'''SOPP:''' Lee KW, Chung IJ, Ryu MH, Park YI, Nam BH, Oh HS, Lee KH, Han HS, Seo BG, Jo JC, Lee HR, Kim JW, Park SR, Cho SH, Kang YK; SOPP study investigators. Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial). Gastric Cancer. 2021 Jan;24(1):156-167. Epub 2020 Jun 28. [https://doi.org/10.1007/s10120-020-01101-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32596783/ PubMed] NCT01671449
 
−
#'''SOLAR:''' Kang YK, Chin K, Chung HC, Kadowaki S, Oh SC, Nakayama N, Lee KW, Hara H, Chung IJ, Tsuda M, Park SH, Hosaka H, Hironaka S, Miyata Y, Ryu MH, Baba H, Hyodo I, Bang YJ, Boku N. S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer (SOLAR): a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 Aug;21(8):1045-1056. Epub 2020 Jul 16. [https://doi.org/10.1016/s1470-2045(20)30315-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32682457 PubMed] NCT02322593
 
−
==CLF {{#subobject:b913d6|Regimen=1}}==
 
−
CLF: '''<u>C</u>'''isplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
 
−
<br>FLP: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>P</u>'''latinol (Cisplatin)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:beef19|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.13.9378 Al-Batran et al. 2008]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#OLF|FLO]]
 
−
| style="background-color:#fee08b" |Might have inferior PFS
 
−
|-
 
−
|}
 
−
''Note: In contrast to the original reference, some guidelines list 5-FU as being given every 2 weeks rather than the schedule below.''
 
−
''Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric'').
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
 
−
*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*Up to 3 liters [[normal saline]] as hydration with cisplatin
 
−
*[[Category:Emesis prevention|Antiemetic medications]] per "local protocols"
 
−
'''8-week cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:34890|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.01.140 Bouché et al. 2004 (FFCD 9803)]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#FULV_2|LV5FU2]]<br> 2. [[#FOLFIRI|LV5FU2 & Irinotecan]]
 
−
| style="background-color:#d3d3d3" |Not powered to draw conclusions
 
−
|-
 
−
|}
 
−
''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on either day 1 or 2
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours 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> IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*1 liter [[:Category:Hydration|hydration]] over 3 hours before and after [[Cisplatin (Platinol)]]
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV before [[Cisplatin (Platinol)]]
 
−
*[[Methylprednisolone (Solumedrol)]] 120 mg IV 10 minutes before [[Cisplatin (Platinol)]]
 
−
*Oral [[Category:Emesis prevention|antiemetics]] and [[Category:Steroids|corticosteroids]] from days 2 to 5
 
−
'''14-day cycle for at least 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [https://doi.org/10.1200/jco.2004.01.140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15514373 PubMed]
 
−
#Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [https://doi.org/10.1200/jco.2007.13.9378 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18349393 PubMed]
 
−
==DCF {{#subobject:efbdc5|Regimen=1}}==
 
−
DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<br>TCF: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:5aba07|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2005.17.376 Ajani et al. 2005 (V-325)]
 
−
|1998-1999
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[#Cisplatin_.26_Docetaxel_.28DC.29|DC]]
 
−
| style="background-color:#91cf60" |Seems to have superior ORR
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.06.8429 Van Cutsem et al. 2006 (TAX 325)]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS
 
−
|-
 
−
|}
 
−
''Note: In contrast to the original references, some guidelines list each cycle as lasting 28 days.''
 
−
''Anjani et al. Patients: 100% adenocarcinoma histology (32% gastroesophageal junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.''
 
−
''Van Cutsem et al Patients: 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS score of 70.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
 
−
*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*(varied depending on reference):
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO once the night before chemotherapy, then 8 mg PO once on day 1; 1 hour prior to chemotherapy, then 8 mg PO twice per day until day 2 (total dose per cycle: 48 mg)
 
−
*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
 
−
*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
 
−
*"[[:Category:Hydration|Hydration]] (was) administered in a standard manner"
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2 {{#subobject:baa015|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2006.08.0135 Roth et al. 2007]
 
−
| rowspan="2" |1999-2003
 
−
| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#ECF_3|ECF]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#Cisplatin_.26_Docetaxel_.28DC.29|TC]]
 
−
| style="background-color:#d9ef8b" |Might have superior ORR
 
−
|-
 
−
|}
 
−
''Note: the protocol was amended to change the original dose of ''docetaxel from'' 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
 
−
*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion over 14 days, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*3 liters per day [[:Category:Hydration|"hyperhydration"]]
 
−
*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO twice per day for 4 days after [[Docetaxel (Taxotere)]]
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
 
−
*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [https://doi.org/10.1200/jco.2005.17.376 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16110025 PubMed]
 
−
#'''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [https://doi.org/10.1200/jco.2006.06.8429 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17075117 PubMed]
 
−
#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [https://doi.org/10.1200/jco.2006.08.0135 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17664469 PubMed]
 
−
==mDCF {{#subobject:70e20f|Regimen=1}}==
 
−
mDCF: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 40/40/2800 {{#subobject:372f9c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ Shah et al. 2010 (MSK 06-096)]
 
−
|2006-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: In contrast to the primary reference, some guidelines list this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab.''
 
−
''Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 3
 
−
*[[Folinic acid (Leucovorin)]] 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>)
 
−
====Supportive therapy====
 
−
*"Standard premedication and delayed emesis regimens"
 
−
'''14-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 60/60/3000, 4-day 5-FU infusion {{#subobject:323b13|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ Wang et al. 2015 (DOCET L 02195)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 10.2 vs 8.5 mo<br>(HR 0.71, 95% CI 0.52-0.97)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 3000 mg/m<sup>2</sup>)
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 60/60/3000, 5-day 5-FU infusion {{#subobject:323bug|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ Wang et al. 2015 (DOCET L 02195)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 10.2 vs 8.5 mo<br>(HR 0.71, 95% CI 0.52-0.97)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3000 mg/m<sup>2</sup>)
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MSK 06-096:''' Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [https://doi.org/10.1200/jco.2010.32.0770 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21189380 PubMed] NCT00390416
 
−
#'''DOCET L 02195:''' Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-44. Epub 2015 Jan 21. [https://doi.org/10.1007/s10120-015-0457-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25604851 PubMed] NCT00811447
 
−
==mDCF & Bevacizumab {{#subobject:30ea9e|Regimen=1}}==
 
−
mDCF & Bevacizumab: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil & Bevacizumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5485f9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ Shah et al. 2010 (MSK 06-096)]
 
−
|2006-2008
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.''
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
 
−
*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 3
 
−
*[[Folinic acid (Leucovorin)]] 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>)
 
−
====Targeted therapy====
 
−
*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
 
−
====Supportive therapy====
 
−
*"Standard premedication and delayed emesis regimens"
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''MSK 06-096:''' Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [https://doi.org/10.1200/jco.2010.32.0770 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21189380 PubMed] NCT00390416
 
−
==Docetaxel & S-1 {{#subobject:a22c2a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:82ca03|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ Koizumi et al. 2013 (START<sub>gastric</sub>)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#S-1_monotherapy_2|S-1]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 12.5 vs 10.8 mo<br>(HR 0.84, 95% CI 0.71-0.99)
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
 
−
**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO; KCSG. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://doi.org/10.1007/s00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24366758 PubMed] NCT00287768
 
−
==ECF {{#subobject:6325cb|Regimen=1}}==
 
−
ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:e5ede0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/oxfordjournals.annonc.a058932 Findlay et al. 1994]
 
−
|1988-1992
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.1997.15.1.261 Webb et al. 1997]
 
−
|1992-1995
 
−
| style="background-color:#1a9851" |Randomized (E-switch-ic)
 
−
|[[Gastric_cancer_-_historical#FAMTX|FAMTX]]
 
−
| style="background-color:#1a9850" |Superior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2002.08.105 Ross et al. 2002]
 
−
|1995-1998
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#MCF|MCF]]
 
−
| style="background-color:#eeee01" |Seems to have non-inferior OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2006.08.0135 Roth et al. 2007]
 
−
|1999-2003
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|1. [[#Cisplatin_.26_Docetaxel_.28DC.29|TC]]<br> 2. [[#DCF|TCF]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
| rowspan="3" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
 
−
| rowspan="3" |2000-2005
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#ECX_2|ECX]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|2. [[#EOF_2|EOF]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|3. [[#EOX_2|EOX]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|}
 
−
''Findlay et al. Patients: all metastatic gastric cancer''
 
−
''Ross et al. Patients: adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma histology, all advanced esophagogastric cancer.''
 
−
''Roth et al.  Patients: all metastatic gastric cancer''
 
−
''REAL-2 Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*(varied depending on reference):
 
−
*3 liters per day [[:Category:Hydration|"hyperhydration"]]
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
 
−
*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
 
−
*Ross et al. 2002 & Cunningham et al. 2008 used [[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. [https://doi.org/10.1093/oxfordjournals.annonc.a058932 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7993836 PubMed]
 
−
#Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7. [https://doi.org/10.1200/JCO.1997.15.1.261 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8996151 PubMed]
 
−
##'''Update:''' Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer. 1999 Apr;80(1-2):269-72. [https://www.nature.com/articles/6690350 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363002/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/10390007 PubMed]
 
−
#Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. [https://doi.org/10.1200/jco.2002.08.105 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11956258 PubMed]
 
−
#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [https://doi.org/10.1200/jco.2006.08.0135 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17664469 PubMed]
 
−
#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] ISRCTN51678883
 
−
==ECX {{#subobject:36cac7|Regimen=1}}==
 
−
ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>ECC: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>C</u>'''apecitabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, continuous capecitabine {{#subobject:f0efc0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
 
−
|rowspan=2|2000-2005
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#ECF_2|ECF]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|2. [[#EOF_2|EOF]]<br> 3. [[#EOX_2|EOX]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30566-1 Catenacci et al. 2017 (RILOMET-1)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#ECX_.26_Rilotumumab_77|ECX & Rilotumumab]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.7 vs 8.8 mo<br>(HR 0.75, 95% CI 0.61-0.91)
 
−
|-
 
−
|}
 
−
''REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
 
−
''RILOMET-1 patients had unresectable or metastatic MET-positive gastric or gastro-esophageal junction cancer.''
 
−
''RILOMET-1 patients: ~80% gastric, 20% GE junction and 10% distal esophageal''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
 
−
'''21-day cycle for up to 10 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, intermittent capecitabine {{#subobject:f0efc0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(10)00731-8 Konings et al. 2010]
 
−
|2005-2009
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|[[#ECX_.26_Pravastatin_99|ECC & Pravastatin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS6
 
−
|-
 
−
|}
 
−
''Patients: 6.6% of  patients had an ECOG of 2''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1, '''given first'''
 
−
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] ISRCTN51678883
 
−
#Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. [https://www.ejcancer.com/article/S0959-8049(10)00731-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20727735 PubMed]
 
−
#'''RILOMET-1:''' Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. [https://doi.org/10.1016/S1470-2045(17)30566-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28958504 PubMed] NCT01697072
 
−
==EOF {{#subobject:a6390c|Regimen=1}}==
 
−
EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:abf19f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
 
−
|rowspan=2|2000-2005
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#ECF_2|ECF]]<br> 2. [[#ECX_2|ECX]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|3. [[#EOX_2|EOX]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|}
 
−
''Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] ISRCTN51678883
 
−
==EOX {{#subobject:438182|Regimen=1}}==
 
−
EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
 
−
<br>EOC: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>C</u>'''apecitabine
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1 {{#subobject:339609|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="3" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
 
−
|rowspan=3|2000-2005
 
−
| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#ECF_2|ECF]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 11.2 vs 9.9 mo<br>(HR 0.80, 95% CI 0.66-0.97)
 
−
|-
 
−
|2. [[#ECX_2|ECX]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|3. [[#EOF_2|EOF]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ Waddell et al. 2013 (REAL3)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#mEOC.2BP_99|mEOC+P]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 11.3 vs 8.3 mo<br>(HR 0.73, 95% CI 0.57-0.93)
 
−
|-
 
−
|}
 
−
''REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
 
−
''REAL3 patients: 99% adenocarcinoma, 1% undifferentiated histology. 39% esophagus, 31% ''gastroesophageal'' junction, 30% gastric. 6% ECOF PS of 2. 89% metastatic disease.''
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 21
 
−
'''21-day cycle for up to 8 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, with maintenance capecitabine {{#subobject:3gacn9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ Zhu et al. 2022 (EXELOX)]
 
−
|2015-2020
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#CapeOx_2|CapeOx]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Epirubicin (Ellence)]] as follows:
 
−
**Cycles 1 up to 8: 50 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] as follows:
 
−
**Cycles 1 up to 8: 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] content property of [http://hemonc.org HemOnc.org] ISRCTN51678883
 
−
#'''REAL3:''' Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. Epub 2013 Apr 15. [https://doi.org/10.1016/s1470-2045(13)70096-2 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23594787 PubMed] NCT00824785
 
−
#'''EXELOX:''' Zhu XD, Huang MZ, Wang YS, Feng WJ, Chen ZY, He YF, Zhang XW, Liu X, Wang CC, Zhang W, Ying JE, Wu J, Yang L, Qin YR, Luo JF, Zhao XY, Li WH, Zhang Z, Qiu LX, Geng QR, Zou JL, Zhang JY, Zheng H, Song XF, Wu SS, Zhang CY, Gong Z, Liu QQ, Wang XF, Xu Q, Wang Q, Ji JM, Zhao J, Guo WJ. XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX). Cancer Commun (Lond). 2022 Apr;42(4):314-326. Epub 2022 Feb 25. [https://doi.org/10.1002/cac2.12278 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35212487/ PubMed] NCT02395640
 
−
==Fluorouracil monotherapy {{#subobject:588907|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, CI {{#subobject:3289d8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2003.04.130 Ohtsu et al. 2003 (JCOG 9205)]
 
−
| rowspan="2" |1992-1997
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|FP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#UFTM|UFTM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(09)70259-1 Boku et al. 2009 (JCOG 9912)]
 
−
| rowspan="2" |2000-2006
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#Cisplatin_.26_Irinotecan_88|Cisplatin & Irinotecan]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|2. [[#S-1_monotherapy_2|S-1]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|[https://academic.oup.com/jjco/article/43/10/972/851849 Shirao et al. 2013 (JCOG 0106)]
 
−
|2002-2007
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fluorouracil_.26_Methotrexate_.28MF.29_99|MF]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
 
−
|-
 
−
|}
 
−
''JCOG 9205 included patients with PFS of 2 (9.6%)''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, intermittent, BSA-based {{#subobject:27a992|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://jamanetwork.com/journals/jama/fullarticle/397816 Cullinan et al. 1985]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (E-de-esc)
 
−
|1. [[#Doxorubicin_.26_Fluorouracil_.28FA.29_88|FA]]<br> 2. [[Gastric_cancer_-_historical#FAM|FAM]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
 
−
'''28-day cycle for 2 cycles, then 35-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, intermittent, weight-based {{#subobject:27jb82|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.karger.com/Article/Abstract/226337 Kolarić et al. 1986]
 
−
|NR
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Epirubicin_.26_Fluorouracil_88|Epirubicin & Fluorouracil]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior DOR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 12 mg/kg IV once per day on days 1 to 5
 
−
'''21- to 28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, PVI {{#subobject:d98c9f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdf273 Tebbutt et al. 2002]
 
−
|1994-2001
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Fluorouracil_.26_Mitomycin_99|5-FU & Mitomycin]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion
 
−
'''Up to 24-week course'''
 
−
</div></div>
 
−
===References===
 
−
#Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. [https://jamanetwork.com/journals/jama/fullarticle/397816 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2579257 PubMed]
 
−
#Kolarić K, Potrebica V, Stanovnik M. Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer. Oncology. 1986;43(2):73-7. [https://www.karger.com/Article/Abstract/226337 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3513075 PubMed]
 
−
#Tebbutt NC, Norman A, Cunningham D, Iveson T, Seymour M, Hickish T, Harper P, Maisey N, Mochlinski K, Prior Y, Hill M. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002 Oct;13(10):1568-75. [https://doi.org/10.1093/annonc/mdf273 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12377644 PubMed]
 
−
#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; [[Study_Groups#JCOG|JCOG]]. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [https://doi.org/10.1200/jco.2003.04.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506170 PubMed]
 
−
#'''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://doi.org/10.1016/S1470-2045(09)70259-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19818685 PubMed] NCT00142350
 
−
#'''JCOG 0106:''' Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Randomized Phase III study of 5-fluorouracil continuous infusion vs sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol. 2013 Oct;43(10):972-80. Epub 2013 Sep 7. [https://academic.oup.com/jjco/article/43/10/972/851849 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24014884 PubMed] NCT00149201
 
−
==Fluorouracil, Folinic acid, Mitomycin {{#subobject:a4ca9d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:672a28|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/64319 Hofheinz et al. 2002]
 
−
|1998-2000
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 15,600 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
 
−
*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 22
 
−
'''56-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12119460 PubMed]
 
−
==FOLFIRI {{#subobject:ba35aa|Regimen=1}}==
 
−
FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
 
−
<br>IF: '''<u>I</u>'''rinotecan & 5-'''<u>F</u>'''luorouracil
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 6 out of 7 weeks ("AIO regimen") {{#subobject:cec083|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdn166 Dank et al. 2008]
 
−
|2000-2002
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]
 
−
| style="background-color:#d9ef8b" |Might have superior TTP
 
−
|-
 
−
|}
 
−
''Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric origin). 96% with metastatic disease.''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous infusion over 22 hours, started on days 1, 8, 15, 22, 29, 36, '''given third''' (total dose per cycle: 12,000 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given second'''
 
−
*[[Irinotecan (Camptosar)]] 80 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
 
−
====Supportive therapy====
 
−
*[[Ondansetron (Zofran)]] for antiemetic prophylaxis
 
−
*[[Dexamethasone (Decadron)]] for antiemetic prophylaxis
 
−
*[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
 
−
*[[Atropine (Atropen)]] prn cholinergic symptoms
 
−
*[[Loperamide (Imodium)]] prn delayed diarrhea
 
−
'''7-week cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, LV5FU2 & Irinotecan (200/1600/180) {{#subobject:56018a|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.01.140 Bouché et al. 2004 (FFCD 9803)]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|1. [[#FULV_2|LV5FU2]]<br> 2. [[#CLF|LV5FU2 & Cisplatin]]
 
−
| style="background-color:#d3d3d3" |Not powered to draw conclusions
 
−
|-
 
−
|}
 
−
''Patients: 100% adenocarcinoma (70% gastric origin, 30% cardia).''
 
−
''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours 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> IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
 
−
'''14-day cycle for at least 4 cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 400/2800/180 {{#subobject:6526d0|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2013.54.1011 Guimbaud et al. 2014 (FFCD 03-07)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#ECX_2|ECX]]
 
−
| style="background-color:#1a9850" |Superior TTF
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [https://doi.org/10.1200/jco.2004.01.140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15514373 PubMed]
 
−
#Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [https://doi.org/10.1093/annonc/mdn166 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18558665 PubMed]
 
−
#'''FFCD 03-07:''' Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. [https://doi.org/10.1200/JCO.2013.54.1011 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25287828 PubMed] NCT00374036
 
−
==mFOLFOX6 {{#subobject:328g5a|Regimen=1}}==
 
−
mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, limited duration {{#subobject:2057uf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.02755 Shah et al. 2021 (GAMMA-1)]
 
−
|2015-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#mFOLFOX6_.26_Andecaliximab_77|mFOLFOX6 & Andecaliximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 400 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 12 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#FULV_2|FULV]] maintenance
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, indefinite {{#subobject:2057uf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
 
−
|rowspan=2|2017-2019
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#CapeOx_.26_Nivolumab|CapeOx & Nivolumab]]<br> 2. [[#mFOLFOX6_.26_Nivolumab|mFOLFOX6 & Nivolumab]]
 
−
| style="background-color:#d73027" |Inferior OS
 
−
|-
 
−
|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 400 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 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''GAMMA-1:''' Shah MA, Bodoky G, Starodub A, Cunningham D, Yip D, Wainberg ZA, Bendell J, Thai D, He J, Bhargava P, Ajani JA. Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1). J Clin Oncol. 2021 Mar 20;39(9):990-1000. Epub 2021 Feb 12. [https://doi.org/10.1200/jco.20.02755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33577358/ PubMed] NCT02545504
 
−
#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
 
−
==mFOLFOX6 (L-Leucovorin) {{#subobject:32hyaa|Regimen=1}}==
 
−
mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:21jxuf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.20.02755 Shah et al. 2021 (GAMMA-1)]
 
−
|2015-2019
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#mFOLFOX6_.26_Andecaliximab_77|mFOLFOX6 & Andecaliximab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Levoleucovorin (Fusilev)]] 200 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 12 cycles'''
 
−
</div>
 
−
<div class="toccolours" style="background-color:#cbd5e7">
 
−
====Subsequent treatment====
 
−
*[[#FULV_2|FULV]] maintenance
 
−
</div></div>
 
−
===References===
 
−
#'''GAMMA-1:''' Shah MA, Bodoky G, Starodub A, Cunningham D, Yip D, Wainberg ZA, Bendell J, Thai D, He J, Bhargava P, Ajani JA. Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1). J Clin Oncol. 2021 Mar 20;39(9):990-1000. Epub 2021 Feb 12. [https://doi.org/10.1200/jco.20.02755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33577358/ PubMed] NCT02545504
 
−
#'''ARMANI:''' NCT02934464
 
−
==mFOLFOX6 & Nivolumab {{#subobject:32ug18|Regimen=1}}==
 
−
mFOLFOX6 & Nivolumab: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Nivolumab
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:1gh7uf|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
!style="width: 20%"|Study
 
−
!style="width: 20%"|Years of enrollment
 
−
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
!style="width: 20%"|Comparator
 
−
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
 
−
|rowspan=2|2017-2019
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|1. [[#CapeOx_2|CapeOx]]<br> 2. [[#mFOLFOX6|mFOLFOX6]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 14.4 vs 11.1 mo<br>(HR 0.71, 98.4% CI 0.59-0.86)
 
−
|-
 
−
|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is for the group with PD-L1 CPS of 5 or more.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
 
−
====Immunotherapy====
 
−
*[[Nivolumab (Opdivo)]] 240 mg IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
 
−
==FULV {{#subobject:5aad1e|Regimen=1}}==
 
−
FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2d601|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2004.01.140 Bouché et al. 2004 (FFCD 9803)]
 
−
|1999-2001
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
 
−
|1. [[#CLF_2|LV5FU2 & Cisplatin]]<br> 2. [[#FOLFIRI|LV5FU2 & Irinotecan]]
 
−
| style="background-color:#d3d3d3" |Not powered to draw conclusions
 
−
|-
 
−
|}
 
−
''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.''
 
−
''Patients: 100% adenocarcinoma (70% gastric origin, 30% cardia)''
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup> IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
 
−
'''14-day cycle for at least 4 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [https://doi.org/10.1200/jco.2004.01.140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15514373 PubMed]
 
−
==FULV (L-leucovorin) {{#subobject:5ga11e|Regimen=1}}==
 
−
FULV: 5-'''<u>FU</u>''' & Levo-'''<u>L</u>'''euco'''<u>V</u>'''orin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:2gahc1|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10120-020-01043-x Nakajima et al. 2020 (JCOG1108)]
 
−
|2013-2017
 
−
| style="background-color:#1a9851" |Phase 2/3 (C)
 
−
|[[#CLF|FLTAX]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 60 minutes after levoleucovorin'''
 
−
*[[Levoleucovorin (Fusilev)]] 250 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
 
−
'''8-week cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''JCOG1108:''' Nakajima TE, Yamaguchi K, Boku N, Hyodo I, Mizusawa J, Hara H, Nishina T, Sakamoto T, Shitara K, Shinozaki K, Katayama H, Nakamura S, Muro K, Terashima M. Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G). Gastric Cancer. 2020 Jul;23(4):677-688. Epub 2020 Feb 8. [https://doi.org/10.1007/s10120-020-01043-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32036492/ PubMed] UMIN000010949
 
−
==Irinotecan monotherapy {{#subobject:41e063|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:9fb427|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s10620-005-3038-2 Enzinger et al. 2005]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m<sup>2</sup> IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable." This study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GEJ and 33% distal esophagus). The results showed a 14% response rate and 53% disease control rate.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
 
−
'''42-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007/s10620-005-3038-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16416165 PubMed]
 
−
==OLF {{#subobject:98b4fa|Regimen=1}}==
 
−
OLF: '''<u>O</u>'''xaliplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
 
−
<br>FLO: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3d7273|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2007.13.9378 Al-Batran et al. 2008]
 
−
|2003-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#CLF|FLP]]
 
−
| style="background-color:#d9ef8b" |Might have superior PFS<br>Median PFS: 5.8 vs 3.9 mo
 
−
|-
 
−
|}
 
−
''Patients: 100% adenocarcinoma histology (20% esophagogastric junction, 80% gastric'').
 
−
====Chemotherapy====
 
−
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
 
−
*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 15, 29, 43 (total dose per cycle: 10,400 mg/m<sup>2</sup>)
 
−
====Supportive therapy====
 
−
*[[Category:Emesis prevention|Antiemetic medications]] per "local protocols"
 
−
'''8-week cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [https://doi.org/10.1200/jco.2007.13.9378 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18349393 PubMed]
 
−
==Paclitaxel & S-1 {{#subobject:a88c2a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:82ca09|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2018.77.8613 Ishigami et al. 2018 (PHOENIX-GC)]
 
−
|2011-2013
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]
 
−
| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 17.7 vs 15.2 mo<br>(HR 0.72, 95% CI 0.49-1.04)
 
−
|}
 
−
''Note: Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 and 8
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
 
−
**BSA 1.25 to less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
 
−
**BSA more than 1.5 m<sup>2</sup>: 60 mg PO twice per day on days 1 to 14
 
−
*[[Paclitaxel (Taxol)]] 20 mg/m<sup>2</sup> IP once per day over 1 hour on days 1 and 8
 
−
====Supportive therapy====
 
−
*500 mL of normal saline was given prior to intraperitoneal [[Paclitaxel (Taxol)]]
 
−
'''35-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.77.8613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29746229 PubMed] UMIN000005930
 
−
==Pembrolizumab monotherapy==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
 
−
|rowspan=2|2015-2017
 
−
|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
 
−
| style="background-color:#eeee01" |Non-inferior OS<sup>1</sup>
 
−
|-
 
−
|3. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]<br>4. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Prembrolizumab_99|CX & Pembrolizumab]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is for patients with PD-L1 CPS score of 1 or more. Improved OS was seen in patients with PD-L1 CPS score of 10 or more (HR: 0.62) but was not tested per analysis plan.''<br>
 
−
''KEYNOTE-062 included patients with GEJ malignancy.''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
PD-L1 CPS score of 1 or more
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
 
−
#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
 
−
==S-1 monotherapy {{#subobject:a12a2a|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, BSA-based {{#subobject:86c009|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S1470-2045(09)70259-1 Boku et al. 2009 (JCOG 9912)]
 
−
| rowspan="2" |2000-2006
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Cisplatin_.26_Irinotecan_88|Cisplatin & Irinotecan]]
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|2. [[#Fluorouracil_monotherapy|5-FU]]
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 28
 
−
'''42-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, weight-based {{#subobject:f90b1b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(08)70035-4 Koizumi et al. 2008 (SPIRITS)]
 
−
|2002-2004
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056989/ Narahara et al. 2011 (TOP-002)]
 
−
|2004-2005
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#IRIS_99|IRIS]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ Koizumi et al. 2013 (START<sub>gastric</sub>)]
 
−
|2005-2008
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Docetaxel_.26_S-1|Docetaxel & S-1]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(16)32267-5 Yoshino et al. 2016 (JFMC36-0701)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Lentinan_.26_S-1_77|Lentinan & S-1]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: there is another trial named START in NSCLC.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
 
−
**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
 
−
**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
 
−
**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
 
−
'''42-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://doi.org/10.1016/S1470-2045(08)70035-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18282805 PubMed] NCT00150670
 
−
#'''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://doi.org/10.1016/S1470-2045(09)70259-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19818685 PubMed] NCT00142350
 
−
#'''TOP-002:''' Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011 Mar;14(1):72-80. Epub 2011 Feb 23. [https://doi.org/10.1007/s10120-011-0009-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056989/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21340666 PubMed] JapicCTI-050083
 
−
#'''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO; KCSG. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://doi.org/10.1007/s00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24366758 PubMed] NCT00287768
 
−
#'''JFMC36-0701:''' Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, Shimizu R, Yoshikawa T, Osanai H, Imano M, Naitoh H, Tanaka A, Tajiri T, Gochi A, Suzuki M, Sakamoto J, Saji S, Oka M. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016 Sep;65:164-71. Epub 2016 Aug 5. [https://www.ejcancer.com/article/S0959-8049(16)32267-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27501505 PubMed] UMIN000000574
 
−
#'''RESCUE-GC:''' NCT02867839
 
−
==UFTM {{#subobject:96e8bf|Regimen=1}}==
 
−
UFTM: '''<u>UFT</u>''' (Tegafur and uracil) & '''<u>M</u>'''itomycin
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:3a603b|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1200/jco.2003.04.130 Ohtsu et al. 2003 (JCOG 9205)]
 
−
| rowspan="2" |1992-1995
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|1. [[#Fluorouracil_monotherapy|Fluorouracil]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|FP]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Note: this arm of the study was terminated early. Study included patients with PFS of 2 (9.6%). Mitomycin was interrupted for 1 month after patients received a total cumulative dose of 60 mg.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Tegafur and uracil (UFT)]] 187.5 mg/m<sup>2</sup> PO twice per day
 
−
*[[Mitomycin (Mutamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 
−
'''28-day cycles (see note)'''
 
−
</div></div>
 
−
===References===
 
−
#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; [[Study_Groups#JCOG|JCOG]]. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [https://doi.org/10.1200/jco.2003.04.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506170 PubMed]
 
−
=Maintenance after first-line therapy=
 
−
==Capecitabine monotherapy {{#subobject:c6df5d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:878a56|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2011.36.2236 Ohtsu et al. 2011 (AVAGAST)]
 
−
|2007-2008
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(14)00884-3 Kim et al. 2014 (SMC 2008-12-019)]
 
−
|2009-2012
 
−
| style="background-color:#91cf61" |Non-randomized portion of RCT
 
−
|-
 
−
|}
 
−
''AVAGAST patients: 86% gastric and 14% GEJ.  5.4% of patients had an ECOG of 2.''
 
−
''SMC 2008-12-019 patients: 79% gastric, 5% GEJ, and 16% unknown. 2% of patients had an ECOG of 2.''
 
−
<div class="toccolours" style="background-color:#cbd5e8">
 
−
====Preceding treatment====
 
−
*AVAGAST: [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]] x 6
 
−
*SMC 2008-12-019: [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]] x 8
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://doi.org/10.1200/JCO.2011.36.2236 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21844504 PubMed] NCT00548548
 
−
#'''SMC 2008-12-019:''' Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25218337 PubMed] NCT01099085
 
−
=Metastatic or locally advanced disease, subsequent lines of therapy=
 
−
==Apatinib monotherapy {{#subobject:ao594c|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:913ap2|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|Awaiting publication (ANGEL)
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior PFS
 
−
|}
 
−
''ANGEL included patients with GEJ malignancy''
 
−
====Targeted therapy====
 
−
*[[Apatinib (Aitan)]] 700 mg once per day
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ANGEL:''' NCT03042611
 
−
##'''Abstract:''' Kang Y, Kang WK, Di Bartolomeo M, Chau I, Yoon HH, Cascinu S, Ryu M, Kim JG, Lee K, Oh SC, Takashima A, Kryzhanivska A, Chao Y, Vladimirov V, Evesque L, Schenker M, McGinn A, Sankar N, Wyrwicz L, Boku N. Randomized Phase 3 ANGEL study of rivoceranib (apatinib) + best supportive care (BSC) vs placebo + BSC in patients with advanced/metastatic gastric cancer. 2019 European Society of Medical Oncology annual meeting. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394 [https://doi.org/10.1093/annonc/mdz394.034 link to abstract]
 
−
==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 60 mg/m<sup>2</sup> {{#subobject:577cd6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.39.4585 Kang et al. 2012 (SMC 2008-08-055)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.3 vs 3.8 mo<br>(HR 0.66, 95% CI 0.485-0.89)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 75 mg/m<sup>2</sup> x 6 {{#subobject:3b4816|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(13)70549-7 Ford et al. 2014 (COUGAR-02)]
 
−
|2008-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.2 vs 3.6 mo<br>(HR 0.67, 95% CI 0.49-0.92)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycle for up to 6 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''SMC 2008-08-055:''' Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [https://doi.org/10.1200/jco.2011.39.4585 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22412140 PubMed] NCT00821990
 
−
#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://doi.org/10.1093/annonc/mdt002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23406728 PubMed] NCT00813072
 
−
#'''COUGAR-02:''' Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [https://doi.org/10.1016/S1470-2045(13)70549-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24332238 PubMed] NCT00978549
 
−
#'''INTEGRATEIIb:''' NCT04879368
 
−
==Fluorouracil, Folinic acid, Mitomycin {{#subobject:b4ca9d|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:672b28|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://www.karger.com/Article/Abstract/64319 Hofheinz et al. 2002]
 
−
|1998-2000
 
−
| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 15,600 mg/m<sup>2</sup>)
 
−
*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
 
−
*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 22
 
−
'''56-day cycle for 2 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12119460 PubMed]
 
−
==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 125 mg/m<sup>2</sup>, 4 weeks out of 6 {{#subobject:9fb427|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://link.springer.com/article/10.1007/s10620-005-3038-2 Enzinger et al. 2005]
 
−
|NR in abstract
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
''Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m<sup>2</sup> IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable." This study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GE junction and 33% distal esophagus), and showed a 14% response rate and 53% disease control rate.''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
 
−
'''42-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 150 mg/m<sup>2</sup> q2wk {{#subobject:fa1ef9|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.48.5805 Hironaka et al. 2013 (WJOG 4007)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Paclitaxel_monotherapy|Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(15)00209-9 Nishikawa et al. 2015 (TRICS)]
 
−
|2007-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1200/jco.2011.39.4585 Kang et al. 2012 (SMC 2008-08-055)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.3 vs 3.8 mo<br>(HR 0.66, 95% CI 0.485-0.89)
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(14)00093-8 Higuchi et al. 2014 (BIRIP)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdv265 Tanabe et al. 2015 (JACCRO GC-05)]
 
−
|2008-2011
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Irinotecan_.26_S-1_77|Irinotecan & S-1]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ Bang et al. 2018 (JAVELIN Gastric 300)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Avelumab_monotherapy_99|Avelumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|}
 
−
''Hironaka et al patients: 3.7% patients with an ECOG PS of 2''
 
−
====Chemotherapy====
 
−
*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 300 mg/m<sup>2</sup> q3wk {{#subobject:c410d|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (C)
 
−
|1. [[#Docetaxel_monotherapy|Docetaxel]]<br> 2. [[#Irinotecan_liposomal_monotherapy|Irinotecan liposomal]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
''Note: this study included patients with GE junction malignancy (77% gastric, 23% GE junction) and included patients with ECOG of 2''
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 350 mg/m<sup>2</sup> q3wk {{#subobject:160f2f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ejcancer.com/article/S0959-8049(11)00396-0 Thuss-Patience et al. 2011]
 
−
|2002-2006
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 4 vs 2.4 mo<br>(HR 0.48, 95% CI 0.25-0.92)
 
−
|-
 
−
|}
 
−
''Thuss-Patience et al. 2011 included patients with GE junction malignancy (~58% gastric, 43% GE junction) and included patients with ECOG of 2''
 
−
====Chemotherapy====
 
−
*[[Irinotecan (Camptosar)]] as follows:
 
−
**Cycle 1: 250 mg/m<sup>2</sup> (maximum dose of 500 mg) IV over 30 minutes once on day 1
 
−
**Cycles 2 to 10 (depending on toxicity): 350 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 
−
====Supportive therapy====
 
−
*[[Atropine (Atropen)]] 0.25 mg SC once on day 1, given prior to [[Irinotecan (Camptosar)]]
 
−
*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]]
 
−
*[[Dexamethasone (Decadron)]]
 
−
'''21-day cycle for up to 10 cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007/s10620-005-3038-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16416165 PubMed]
 
−
#Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [https://www.ejcancer.com/article/S0959-8049(11)00396-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21742485 PubMed] NCT00144378
 
−
#'''SMC 2008-08-055:''' Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [https://doi.org/10.1200/jco.2011.39.4585 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22412140 PubMed] NCT00821990
 
−
#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://doi.org/10.1093/annonc/mdt002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23406728 PubMed] NCT00813072
 
−
#'''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://doi.org/10.1200/JCO.2012.48.5805 link to original artile] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24190112 PubMed] UMIN000001252
 
−
#'''BIRIP:''' Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W; Tokyo Cooperative Oncology Group. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014 May;50(8):1437-45. Epub 2014 Feb 20. [https://www.ejcancer.com/article/S0959-8049(14)00093-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24560487 PubMed] UMIN000001028
 
−
#'''TRICS:''' Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M, Tamura S, Sugimoto N, Shigematsu T, Yoshikawa T, Ishiguro T, Nakamura M, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J, Tsujinaka T. Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer. 2015 May;51(7):808-16. Epub 2015 Mar 18. [https://www.ejcancer.com/article/S0959-8049(15)00209-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25797356 PubMed] UMIN000002571
 
−
#'''JACCRO GC-05:''' Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. Epub 2015 Jun 24. [https://doi.org/10.1093/annonc/mdv265 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26109630 PubMed] NCT00639327
 
−
#'''JAVELIN Gastric 300:''' Bang YJ, Yanez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://doi.org/10.1093/annonc/mdy264 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30052729 PubMed] NCT02625623
 
−
#'''INTEGRATEIIb:''' NCT04879368
 
−
==Irinotecan liposomal monotherapy {{#subobject:9a99c8|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:c50e15|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)]
 
−
|2008-2010
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
 
−
|1. [[#Docetaxel_monotherapy|Docetaxel]]<br> 2. [[#Irinotecan_monotherapy|Irinotecan]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Irinotecan liposome (Onivyde)]] 120 mg/m<sup>2</sup> IV over 90 minutes once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://doi.org/10.1093/annonc/mdt002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23406728 PubMed] NCT00813072
 
−
==Nivolumab monotherapy {{#subobject:7011e1|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:#f2fd8e|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ Janjigian et al. 2018 (CheckMate 032)]
 
−
|2013-2015
 
−
| style="background-color:#91cf61" |Phase 2
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(17)31827-5 Kang et al. 2017 (ATTRACTION-2)]
 
−
|2014-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 5.3 vs 4.1 mo<br>(HR 0.62, 95% CI 0.50-0.75)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
 
−
''ATTRACTION-2 included patients with GE junction malignancy (82.6% gastric, 8.5% GE junction) and 12.3% of patients had a PD-L1 CPS score of at least 1''
 
−
====Immunotherapy====
 
−
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ATTRACTION-2:''' Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. [https://doi.org/10.1016/S0140-6736(17)31827-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28993052 PubMed] NCT02267343
 
−
##'''Subgroup analysis:''' Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Nakajima TE, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer. 2019 Mar;22(2):344-354. Epub 2018 Dec 1. [https://doi.org/10.1007/s10120-018-0899-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6394726/ link to original article] [https://pubmed.ncbi.nlm.nih.gov/30506519 PubMed]
 
−
##'''Update:''' Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Sameshima H, Kang YK, Boku N. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020 May;23(3):510-519. Epub 2019 Dec 20. [https://doi.org/10.1007/s10120-019-01034-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7165140/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31863227/ PubMed]
 
−
##'''Update:''' Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Nishiyama T, Chen LT, Kang YK. Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab. Gastric Cancer. 2021 Jul;24(4):946-958. Epub 2021 Mar 20. [https://doi.org/10.1007/s10120-021-01173-w link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8205916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33743112/ PubMed]
 
−
#'''CheckMate 032:''' Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate 032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. Epub 2018 Aug 15. [https://doi.org/10.1200/JCO.2017.76.6212 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30110194 PubMed] NCT01928394
 
−
==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #1, 70 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:gg21e8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324622/ Lee et al. 2018 (KCSG ST10-01)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Irinotecan_monotherapy_2|Irinotecan]]
 
−
| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #2, 80 mg/m<sup>2</sup> weekly {{#subobject:0e8f41|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 60%; text-align:center;"
 
−
!style="width: 33%"|Study
 
−
!style="width: 33%"|Years of enrollment
 
−
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 
−
|-
 
−
|[http://ar.iiarjournals.org/content/27/4C/2667.long Kodera et al. 2007 (CCOG0302)]
 
−
|2003-2006
 
−
| style="background-color:#91cf61" |Phase 2
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''21-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #3, 80 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:dd21e8|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1007/s10120-005-0351-6 Hironaka et al. 2006]
 
−
|2002-2004
 
−
| style="background-color:#91cf61" |Non-randomized
 
−
| style="background-color:#d3d3d3" |
 
−
| style="background-color:#d3d3d3" |
 
−
|-
 
−
|[https://doi.org/10.1200/JCO.2012.48.5805 Hironaka et al. 2013 (WJOG 4007)]
 
−
|2007-2010
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|[[#Irinotecan_monotherapy_2|Irinotecan]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS <br>(HR 0.88, 95% CI 0.67-1.16)
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2814%2970420-6 Wilke et al. 2014 (RAINBOW)]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_.26_Ramucirumab|Paclitaxel & Ramucirumab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1002/ijc.33025 Lorenzen et al. 2020 (RADPAC)]
 
−
|2011-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Everolimus_.26_Paclitaxel_99|Everolimus & Paclitaxel]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S2468-1253(16)30219-9 Shitara et al. 2017 (ABSOLUTE)]
 
−
| rowspan="2" |2013-2015
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
 
−
|1. [[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]] weekly
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|2. [[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]] q3wk
 
−
| style="background-color:#d9ef8b" |Might have superior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(17)30682-4 Bang et al. 2017 (GOLD)]
 
−
|2013-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Olaparib_.26_Paclitaxel_88|Olaparib & Paclitaxel]]
 
−
| style="background-color:#fee08b" |Might have inferior OS
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(18)31257-1 Shitara et al. 2018 (KEYNOTE-061)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pembrolizumab_monotherapy|Pembrolizumab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ Bang et al. 2018 (JAVELIN Gastric 300)]
 
−
|2015-2017
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Avelumab_monotherapy_99|Avelumab]]
 
−
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 
−
|-
 
−
|[https://doi.org/10.1002/cncr.34019 Chung et al. 2021 (KEYNOTE-063)]
 
−
|2017-2018
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Pembrolizumab_monotherapy|Pembrolizumab]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 4 vs 2 mo<br>(HR 0.62, 95% CI 0.40-0.96)
 
−
|-
 
−
|[https://doi.org/10.1016/s2468-1253(21)00313-7 Xu et al. 2021 (RAINBOW-Asia)]
 
−
|2017-2020
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#Paclitaxel_.26_Ramucirumab|Paclitaxel & Ramucirumab]]
 
−
| style="background-color:#fc8d59" |Seems to have inferior PFS
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update, for the CPS ≥ 1 group.''<br>
 
−
''Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."''
 
−
''RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction)''
 
−
''Satoh et al. patients: 98.5% gastric. 1.5 other''
 
−
''Hironaka et al patients: 3.7% patients with a PFS of 2''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
 
−
'''28-day cycles'''
 
−
</div></div><br>
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen variant #4, 175 mg/m<sup>2</sup> q3wk {{#subobject:a4bdf6|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1093/annonc/mdy055 Kang et al. 2018 (DREAM)]
 
−
|2013-2015
 
−
| style="background-color:#1a9851" |Phase 3 (C)
 
−
|[[#DHP107_monotherapy_77|DHP107]]
 
−
| style="background-color:#eeee01" |Non-inferior PFS
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
 
−
'''21-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2006;9(1):14-8. [https://doi.org/10.1007/s10120-005-0351-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16557431 PubMed]
 
−
#'''CCOG0302:''' Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, Matsui T, Kojima H, Takase T, Ohashi N, Fujiwara M, Sakamoto J, Akimasa N; Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007 Jul-Aug;27(4C):2667-71. [http://ar.iiarjournals.org/content/27/4C/2667.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17695430 PubMed]
 
−
#'''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://doi.org/10.1200/JCO.2012.48.5805 link to original artile] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24190112 PubMed] UMIN000001252
 
−
#'''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. Epub 2014 Sep 17. [https://doi.org/10.1016/S1470-2045%2814%2970420-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25240821 PubMed] NCT01170663
 
−
#'''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://doi.org/10.1016/S2468-1253(16)30219-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28404157 PubMed] JapicCTI-132059
 
−
#'''GOLD:''' Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. [https://doi.org/10.1016/S1470-2045(17)30682-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29103871 PubMed] NCT01924533
 
−
#'''DREAM:''' Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Park YI, Park SR, Rha SY, Kang MJ, Cho JY, Kang SY, Roh SY, Ryoo BY, Nam BH, Jo YW, Yoon KE, Oh SC. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol. 2018 May 1;29(5):1220-1226. [https://doi.org/10.1093/annonc/mdy055 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29438463 PubMed] NCT01839773
 
−
#'''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://doi.org/10.1016/S0140-6736(18)31257-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29880231 PubMed] NCT02370498
 
−
##'''Update:''' Fuchs CS, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. Epub 2021 Sep 1. [https://doi.org/10.1007/s10120-021-01227-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8732941/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34468869/ PubMed]
 
−
#'''KCSG ST10-01:''' Lee KW, Maeng CH, Kim TY, Zang DY, Kim YH, Hwang IG, Oh SC, Chung JS, Song HS, Kim JW, Jeong SJ, Cho JY. A phase III study to compare the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer who failed in first-line therapy (KCSG ST10-01). Oncologist. 2019 Jan;24(1):18-e24. Epub 2018 Aug 20. [http://theoncologist.alphamedpress.org/content/24/1/18.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324622/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30126861 PubMed] NCT01224652
 
−
#'''JAVELIN Gastric 300:''' Bang YJ, Yanez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://doi.org/10.1093/annonc/mdy264 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30052729 PubMed] NCT02625623
 
−
#'''RADPAC:''' Lorenzen S, Knorrenschild JR, Pauligk C, Hegewisch-Becker S, Seraphin J, Thuss-Patience P, Kopp HG, Dechow T, Vogel A, Luley KB, Pink D, Stahl M, Kullmann F, Hebart H, Siveke J, Egger M, Homann N, Probst S, Goetze TO, Al-Batran SE. Phase III randomized, double-blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC). Int J Cancer. 2020 Nov 1;147(9):2493-2502. Epub 2020 May 7. [https://doi.org/10.1002/ijc.33025 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32339253/ PubMed] NCT01248403
 
−
#'''RAINBOW-Asia:''' Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. Epub 2021 Oct 6. Epub ahead of print. [https://doi.org/10.1016/s2468-1253(21)00313-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34626550/ PubMed] NCT02898077
 
−
#'''KEYNOTE-063:''' Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, Park YL, Koo DH, Lu J, Xu J, Chon HJ, Bai LY, Zeng S, Yuan Y, Chen YY, Gu K, Zhong WY, Kuang S, Shih CS, Qin SK. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer. 2022 Mar 1;128(5):995-1003. Epub 2021 Dec 8. [https://doi.org/10.1002/cncr.34019 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34878659/ PubMed] NCT03019588
 
−
#'''INTEGRATEIIb:''' NCT04879368
 
−
==nab-Paclitaxel monotherapy {{#subobject:8f6227|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:fe2978|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
| rowspan="2" |[https://doi.org/10.1016/S2468-1253(16)30219-9 Shitara et al. 2017 (ABSOLUTE)]
 
−
| rowspan="2" |2013-2015
 
−
| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
 
−
|1. [[#Paclitaxel_monotherapy|Paclitaxel]]; weekly
 
−
| style="background-color:#eeee01" |Non-inferior OS
 
−
|-
 
−
|2. [[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]]; q3wk
 
−
| style="background-color:#d3d3d3" |Not reported
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://doi.org/10.1016/S2468-1253(16)30219-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28404157 PubMed] JapicCTI-132059
 
−
==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:f66446|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045%2814%2970420-6 Wilke et al. 2014 (RAINBOW)]
 
−
|2010-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[#Paclitaxel_monotherapy|Paclitaxel]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 9.6 vs 7.4 mo<br>(HR 0.81, 95% CI 0.68-0.96)
 
−
|-
 
−
|[https://doi.org/10.1016/s2468-1253(21)00313-7 Xu et al. 2021 (RAINBOW-Asia)]
 
−
|2017-2020
 
−
| style="background-color:#1a9851" |Phase 3 (E-esc)
 
−
|[[#Paclitaxel_monotherapy|Paclitaxel]]
 
−
| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 4.1 vs 3.15 mo <br>(HR 0.77, 95% CI 0.61-0.955)
 
−
|-
 
−
|}
 
−
''Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."''
 
−
''RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction).''
 
−
====Targeted therapy====
 
−
*[[Ramucirumab (Cyramza)]] 8 mg/kg IV over 60 minutes once per day on days 1 & 15, '''given first'''
 
−
====Chemotherapy====
 
−
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, '''given second'''
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. Epub 2014 Sep 17. [https://doi.org/10.1016/S1470-2045%2814%2970420-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25240821 PubMed] NCT01170663
 
−
#'''RAINBOW-Asia:''' Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. Epub 2021 Oct 6. [https://doi.org/10.1016/s2468-1253(21)00313-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34626550/ PubMed] NCT02898077
 
−
#'''RAMIRIS:''' NCT03081143
 
−
==Pembrolizumab monotherapy {{#subobject:88c665|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:ac7d94|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885175/ Fuchs et al. 2018 (KEYNOTE-059)]
 
−
|2015-2016
 
−
| style="background-color:#91cf61" |Phase 2 (RT)
 
−
| style="background-color:#d3d3d3" |
 
−
|ORR: 12% (95% CI 8-16)
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(18)31257-1 Shitara et al. 2018 (KEYNOTE-061)]
 
−
|2015-2016
 
−
| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
 
−
|[[#Paclitaxel_monotherapy|Paclitaxel]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 9.1 vs 8.3 mo<br>(HR 0.81, 95% CI 0.66-1.00)
 
−
|-
 
−
|}
 
−
''<sup>1</sup>Reported efficacy is based on the 2021 update, for the CPS ≥ 1 group.''<br>
 
−
''Both studies included patients with GE junction malignancy:''
 
−
*''KEYNOTE-059: 48.3% gastric, 51.4% GE junction and 57.1% of patients had a PD-L1 CPS score of at least 1''
 
−
*''KEYNOTE-061: 68.8% gastric, 31.2% GE junction and 66% of all patients receiving pembrolizumab had a PD-L1 CPS score of at least 1''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Biomarker eligibility criteria====
 
−
PD-L1 (combined positive score > 1%) as determined by an FDA-approved test.
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Immunotherapy====
 
−
*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
 
−
'''21-day cycle for up to 35 cycles (2 years)'''
 
−
</div></div>
 
−
===References===
 
−
<!-- # '''Abstract:''' Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, ...Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Philippe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V.T. Catenacci, Yung-Jue Bang, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Harry H. Yoon (2017). KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4003-4003. [https://doi.org/10.1200/JCO.2017.35.15_suppl.4003 link to abstract] -->
 
−
#'''KEYNOTE-059:''' Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013. Epub 2018 May 10. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2675013 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885175/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29543932 PubMed] NCT02335411
 
−
#'''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://doi.org/10.1016/S0140-6736(18)31257-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29880231 PubMed] NCT02370498
 
−
##'''Update:''' Fuchs CS, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. Epub 2021 Sep 1. [https://doi.org/10.1007/s10120-021-01227-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8732941/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34468869/ PubMed]
 
−
==Ramucirumab monotherapy {{#subobject:425b15|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:813cff|Variant=1}}===
 
−
{| class="wikitable" style="color:white; background-color:#404040"
 
−
|<small>'''FDA-recommended dose'''</small>
 
−
|-
 
−
|}
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S0140-6736(13)61719-5 Fuchs et al. 2013 (REGARD)]
 
−
|2009-2012
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 5.2 vs 3.8 mo<br>(HR 0.78, 95% CI 0.60-0.998)
 
−
|-
 
−
|}
 
−
''Note: this study included patients with GE junction malignancy (75% gastric, 25% GE junction).''
 
−
<div class="toccolours" style="background-color:#fdcdac">
 
−
====Prior treatment criteria====
 
−
*REGARD: Disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment
 
−
</div>
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Targeted therapy====
 
−
*[[Ramucirumab (Cyramza)]] 8 mg/kg IV over 60 minutes once on day 1
 
−
'''14-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''REGARD:''' Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. [https://doi.org/10.1016/S0140-6736(13)61719-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24094768 PubMed] NCT00917384
 
−
==Regorafenib monotherapy {{#subobject:022ef0|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:5f203f|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ Pavlakis et al. 2016 (INTEGRATE)]
 
−
|2012-2014
 
−
| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 2.6 vs 0.9 mo<br>(HR 0.40, 95% CI 0.28-0.59)
 
−
|-
 
−
|}
 
−
''INTEGRATE included patients with GEJ malignancy: 62% stomach or other, 38% GEJ''
 
−
====Targeted therapy====
 
−
*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''INTEGRATE:''' Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. [https://doi.org/10.1200/JCO.2015.65.1901 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27325864 PubMed] ANZCTR12612000239864
 
−
==Trifluridine and tipiracil monotherapy {{#subobject:938bf3|Regimen=1}}==
 
−
<div class="toccolours" style="background-color:#eeeeee">
 
−
===Regimen {{#subobject:cfc20c|Variant=1}}===
 
−
{| class="wikitable sortable" style="width: 100%; text-align:center;"
 
−
! style="width: 20%" |Study
 
−
! style="width: 20%" |Years of enrollment
 
−
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
 
−
! style="width: 20%" |Comparator
 
−
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 
−
|-
 
−
|[https://doi.org/10.1016/S1470-2045(18)30739-3 Shitara et al. 2018 (TAGS)]
 
−
|2016-2018
 
−
| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
 
−
|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
 
−
| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.7 vs 3.6 mo<br>(HR 0.69, 95% CI 0.56-0.85)
 
−
|-
 
−
|}
 
−
<div class="toccolours" style="background-color:#b3e2cd">
 
−
====Chemotherapy====
 
−
*[[Trifluridine and tipiracil (Lonsurf)]] 35 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12
 
−
'''28-day cycles'''
 
−
</div></div>
 
−
===References===
 
−
#'''TAGS:''' Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. [https://doi.org/10.1016/S1470-2045(18)30739-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30355453 PubMed] NCT02500043
 
−
#'''INTEGRATEIIb:''' NCT04879368
 
−
[[Category:Gastric cancer regimens]]
 
−
[[Category:Disease-specific pages]]
 
−
[[Category:Gastroesophageal cancers]]
 

Latest revision as of 00:13, 18 June 2023

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