Difference between revisions of "Esophageal adenocarcinoma"
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− | + | [[#top|Back to Top]] | |
− | + | </div> | |
− | + | {{#lst:Editorial board transclusions|gi}} | |
− | + | ''Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit [[Esophageal adenocarcinoma - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.<br> | |
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Note: these are regimens tested in histology-specific populations, please see the '''[[Esophageal cancer|main esophageal cancer page]]''' for other regimens. | Note: these are regimens tested in histology-specific populations, please see the '''[[Esophageal cancer|main esophageal cancer page]]''' for other regimens. | ||
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+ | =Guidelines= | ||
+ | '''Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.''' | ||
+ | ==NCCN== | ||
+ | *''NCCN does not currently have guidelines at this granular level; please see [https://www.nccn.org/guidelines/guidelines-detail?category=1&id=1433 NCCN Guidelines - Esophageal and Esophagogastric Junction Cancers].'' | ||
+ | =Perioperative therapy= | ||
+ | ''This section contains protocols with a pre-planned neoadjuvant (preoperative) and adjuvant (postoperative) component.'' | ||
+ | ==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:#c8a2c8"> | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1200/jco.2010.33.0597 Ychou et al. 2011 (ACCORD 07)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-30-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |1995-2003 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Surgery#Esophagectomy|Surgery alone]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>OS60: 38% vs 24%<br>(HR 0.69, 95% CI 0.50-0.95) | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: Study included patients with gastric malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).'' | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Neoadjuvant {{#subobject:c2dc1e|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[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, followed by:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | |||
+ | ===Definitive=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Local therapy==== | ||
+ | *[[Surgery#Gastrectomy|Surgical resection]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Adjuvant=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[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></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. Epub 2011 Mar 28. [https://doi.org/10.1200/jco.2010.33.0597 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/21444866/ PubMed] [https://clinicaltrials.gov/study/NCT00002883 NCT00002883] | ||
+ | |||
+ | ==ECF {{#subobject:87a09a|Regimen=1}}== | ||
+ | ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | ||
+ | <div class="toccolours" style="background-color:#c8a2c8"> | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-29-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |1994-2002 | ||
+ | | style="background-color:#1a9851" |Phase 3 (E-esc) | ||
+ | |[[Surgery#Gastrectomy|Surgery alone]] | ||
+ | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>OS60: 36% vs 23%<br>(HR 0.75, 95% CI 0.60-0.93) | ||
+ | |- | ||
+ | |[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 (C) | ||
+ | |[[#FLOT|Perioperative FLOT]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: MAGIC patients had 100% adenocarcinoma histology. 75% gastric adenocarcinoma, 15% lower esophagus, 11% gastroesophageal junction.'' | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Neoadjuvant {{#subobject:d40982|Variant=1}}=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus 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: 4200 mg/m<sup>2</sup>) | ||
+ | '''21-day cycle for 3 cycles, followed by:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Local therapy==== | ||
+ | *[[Surgery#Esophageal_cancer_surgery|Surgery]] occurs 3 to 6 weeks after completing cycle 3 | ||
+ | '''Adjuvant chemotherapy is started 6 to 12 weeks after surgery:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Adjuvant=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus 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: 4200 mg/m<sup>2</sup>) | ||
+ | ====Supportive therapy==== | ||
+ | *MAGIC: [[Warfarin (Coumadin)]] 1 mg PO once per day recommended for thrombosis prophylaxis | ||
+ | '''21-day cycle for 3 cycles''' | ||
+ | </div></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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16822992/ PubMed] [https://clinicaltrials.gov/study/NCT00002615 NCT00002615] | ||
+ | #'''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] [https://clinicaltrials.gov/study/NCT01216644 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, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter 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] | ||
+ | |||
+ | ==ECX {{#subobject:c8agj39|Regimen=1}}== | ||
+ | ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine) | ||
+ | <div class="toccolours" style="background-color:#c8a2c8"> | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(17)30043-8 Cunningham et al. 2017 (UK MRC ST03)] | ||
+ | |2007-2014 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |[[#ECX_.26_Bevacizumab_999|Perioperative ECX & Bevacizumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
+ | |- | ||
+ | |[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 (C) | ||
+ | |[[#FLOT|Perioperative FLOT]] | ||
+ | | style="background-color:#d73027" |Inferior OS | ||
+ | |- | ||
+ | |} | ||
+ | ''Note: UK MRC ST03 patients had 100% adenocarcinoma histology (36% gastric, 14% lower esophageal, 50% gastroesophageal junction). FLOT4-AIO patients had 100% adenocarcinoma histology including gastroesophageal junction (AEG I-III) or the stomach.'' | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Neoadjuvant {{#subobject:2gajj48|Variant=1}}=== | ||
+ | <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 | ||
+ | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day | ||
+ | '''21-day cycle for 3 cycles, followed by:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Local therapy==== | ||
+ | *[[Surgery#Esophageal_cancer_surgery|Surgery]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Adjuvant=== | ||
+ | <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 | ||
+ | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day | ||
+ | '''21-day cycle for 3 cycles''' | ||
+ | </div></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] [https://clinicaltrials.gov/study/NCT01216644 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, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter 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] | ||
+ | #'''UK MRC ST03:''' Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. [https://doi.org/10.1016/S1470-2045(17)30043-8 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5337626/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28163000/ PubMed] [https://clinicaltrials.gov/study/NCT00450203 NCT00450203] | ||
+ | |||
+ | ==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:#c8a2c8"> | ||
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | ! style="width: 20%" |Study | ||
+ | ! style="width: 20%" |Dates of enrollment | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | ! style="width: 20%" |Comparator | ||
+ | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://doi.org/10.1016/S1470-2045(16)30531-9 Al-Batran et al. 2016 (FLOT4-AIO)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-119-1 <span style="color:white;">ESMO-MCBS (A)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |2010-2015 | ||
+ | | style="background-color:#1a9851" |Phase 2/3 (E-switch-ic) | ||
+ | |1a. [[#ECF|Perioperative ECF]]<br>1b. [[#ECX|Perioperative ECX]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (primary endpoint)<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.''<br> | ||
+ | ''Note: FLOT4-AIO patients had 100% adenocarcinoma histology of the gastroesophageal junction (AEG I-III) or the stomach.'' | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Neoadjuvant {{#subobject:16408e|Variant=1}}=== | ||
+ | <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 day 1 | ||
+ | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles, followed by:''' | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Definitive=== | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Local therapy==== | ||
+ | *[[Surgery#Gastrectomy|Surgery]] | ||
+ | </div></div><br> | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Adjuvant=== | ||
+ | <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 day 1 | ||
+ | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''14-day cycle for 4 cycles''' | ||
+ | </div></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] [https://clinicaltrials.gov/study/NCT01216644 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] | ||
=Neoadjuvant induction therapy= | =Neoadjuvant induction therapy= | ||
==Cisplatin & Fluorouracil (CF) {{#subobject:37e6ba|Regimen=1}}== | ==Cisplatin & Fluorouracil (CF) {{#subobject:37e6ba|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | ||
<br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol (Cisplatin) | <br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 40/4200 {{#subobject:034277|Variant=1}}=== | ===Regimen variant #1, 40/4200 {{#subobject:034277|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2006.06.4840 Ajani et al. 2006 (RTOG 9904)] | |[https://doi.org/10.1200/jco.2006.06.4840 Ajani et al. 2006 (RTOG 9904)] | ||
− | | style="background-color:#91cf61" |Phase | + | |1999-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma histology. The majority of patients had gastric adenocarcinoma. Although gastroesophageal junction was involved, percentages were not included.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 & 5 | *[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 & 5 | ||
*[[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>) | *[[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>) | ||
− | |||
'''28-day cycle for 2 cycles''' | '''28-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *Neoadjuvant [[#Fluorouracil.2C_Paclitaxel.2C_RT|fluorouracil, paclitaxel, RT]], then [[Surgery#Esophageal_cancer_surgery|surgery]] | |
− | *[[#Fluorouracil.2C_Paclitaxel.2C_RT| | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #2, 80/4000, 4 day 5-FU infusion {{#subobject:2335c3|Variant=1}}=== | ===Regimen variant #2, 80/4000, 4 day 5-FU infusion {{#subobject:2335c3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 56: | Line 271: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585417/ Alderson et al. 2017 (UK MRC OE05)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585417/ Alderson et al. 2017 (UK MRC OE05)] | ||
|2005-2011 | |2005-2011 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |[[# | + | |[[#ECX_2|ECX]] |
− | | style="background-color:# | + | | style="background-color:#fee08b" |Might have inferior OS |
|- | |- | ||
|} | |} | ||
− | ''UK MRC OE05 patients | + | ''Note: UK MRC OE05 patients had 100% adenocarcinoma of the esophagus (including Siewert types 1 and 2 gastroesophageal junction tumors)'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>) | *[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>) | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Surgery#Esophageal_cancer_surgery|Surgery]] | *[[Surgery#Esophageal_cancer_surgery|Surgery]] | ||
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
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− | |||
− | |||
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− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | #'''RTOG 9904:''' Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. [https://doi.org/10.1200/jco.2006.06.4840 link to original article] ''' | + | #'''RTOG 9904:''' Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. [https://doi.org/10.1200/jco.2006.06.4840 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16921048/ PubMed] |
− | + | #'''UK MRC OE05:''' Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, Grabsch HI, Langer R, Pritchard S, Okines A, Krysztopik R, Coxon F, Thompson J, Falk S, Robb C, Stenning S, Langley RE. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1249-1260. Epub 2017 Aug 4. [https://doi.org/10.1016/S1470-2045(17)30447-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585417/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28784312/ PubMed] [https://clinicaltrials.gov/study/NCT00041262 NCT00041262] | |
− | #'''UK MRC OE05:''' Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, Grabsch HI, Langer R, Pritchard S, Okines A, Krysztopik R, Coxon F, Thompson J, Falk S, Robb C, Stenning S, Langley RE. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1249-1260. Epub 2017 Aug 4. [https:// | ||
− | |||
==Cisplatin & Irinotecan (IC) {{#subobject:500b44|Regimen=1}}== | ==Cisplatin & Irinotecan (IC) {{#subobject:500b44|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
IC: '''<u>I</u>'''rinotecan & '''<u>C</u>'''isplatin | IC: '''<u>I</u>'''rinotecan & '''<u>C</u>'''isplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:927613|Variant=1}}=== | ===Regimen {{#subobject:927613|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ijrobp.2008.12.087 Rivera et al. 2009] |
− | | style="background-color:#91cf61" |Phase | + | |2003-12 to 2004-10 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Rivera et al. patients | + | ''Note: Rivera et al. patients had 100% adenocarcinoma histology (43% gastroesophageal junction, 57% gastric adenocarcinoma)'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given first''' | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given first''' | ||
*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given second''' | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given second''' | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1 & 8, prior to chemotherapy | *[[Dexamethasone (Decadron)]] 20 mg IV or PO once per day on days 1 & 8, prior to chemotherapy | ||
*One of the following: | *One of the following: | ||
Line 136: | Line 316: | ||
*At least 500 mL D5NS or NS as supportive hydration | *At least 500 mL D5NS or NS as supportive hydration | ||
*[[Atropine (Atropen)]] 0.5 to 1 mg IV prn cholinergic symptoms | *[[Atropine (Atropen)]] 0.5 to 1 mg IV prn cholinergic symptoms | ||
− | |||
'''21-day cycle for 2 cycles''' | '''21-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *Neoadjuvant [[#Cisplatin.2C_Irinotecan.2C_RT|cisplatin, irinotecan, RT]], then [[Surgery#Esophageal_cancer_surgery|surgery]] | |
− | *[[#Cisplatin.2C_Irinotecan.2C_RT| | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | + | #Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. [https://doi.org/10.1016/j.ijrobp.2008.12.087 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19540072/ PubMed] | |
− | #Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. [ | ||
− | |||
==CLF {{#subobject:74dca8|Regimen=1}}== | ==CLF {{#subobject:74dca8|Regimen=1}}== | ||
− | + | CLF: '''<u>C</u>'''isplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil | |
− | + | <br>PLF: '''<u>P</u>'''latinol (Cisplatin), '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | CLF: '''<u>C</u>'''isplatin, '''<u>L</u>'''eucovorin | ||
− | <br>PLF: '''<u>P</u>'''latinol (Cisplatin), '''<u>L</u>'''eucovorin | ||
===Regimen variant #1, 12 weeks {{#subobject:e3d573|Variant=1}}=== | ===Regimen variant #1, 12 weeks {{#subobject:e3d573|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 163: | Line 338: | ||
|[https://doi.org/10.1200/JCO.2008.17.0506 Stahl et al. 2009 (POET)] | |[https://doi.org/10.1200/JCO.2008.17.0506 Stahl et al. 2009 (POET)] | ||
|2000-2005 | |2000-2005 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-de-esc) |
|[[Complex_multipart_regimens#POET|See link]] | |[[Complex_multipart_regimens#POET|See link]] | ||
|[[Complex_multipart_regimens#POET|See link]] | |[[Complex_multipart_regimens#POET|See link]] | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 15, 29 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 15, 29 | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36 |
− | *[[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> ) | + | *[[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>) |
− | |||
'''42-day cycle for 2 cycles''' | '''42-day cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *Neoadjuvant [[#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]], then [[Surgery#Esophageal_cancer_surgery|surgery]] | |
− | *[[#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]], then [[Surgery#Esophageal_cancer_surgery|surgery]] | + | </div></div><br> |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 15 weeks {{#subobject:cf9923|Variant=1}}=== | ===Regimen variant #2, 15 weeks {{#subobject:cf9923|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 191: | Line 367: | ||
|[https://doi.org/10.1200/JCO.2008.17.0506 Stahl et al. 2009 (POET)] | |[https://doi.org/10.1200/JCO.2008.17.0506 Stahl et al. 2009 (POET)] | ||
|2000-2005 | |2000-2005 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |PLF x 12 wk, then [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]] | + | |[[#CLF|PLF]] x 12 wk, then [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]] |
| style="background-color:#fee08b" |Might have inferior OS | | style="background-color:#fee08b" |Might have inferior OS | ||
|- | |- | ||
|} | |} | ||
− | ''Note: this regimen is given for 2.5 cycles, which is a highly unusual instruction; total duration of treatment is 15 weeks. | + | ''Note: this regimen is given for 2.5 cycles, which is a highly unusual instruction; total duration of treatment is 15 weeks. Patients had 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 15, 29 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 15, 29 | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36 |
− | *[[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> ) | + | *[[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>) |
− | |||
'''42-day cycle for 2.5 cycles''' | '''42-day cycle for 2.5 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Surgery#Esophageal_cancer_surgery|Surgery]], in 3 to 4 weeks | *[[Surgery#Esophageal_cancer_surgery|Surgery]], in 3 to 4 weeks | ||
− | + | </div></div> | |
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===References=== | ===References=== | ||
− | + | #'''POET:''' Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [https://doi.org/10.1200/JCO.2008.17.0506 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19139439/ PubMed] | |
− | #''' | + | ##'''Update:''' Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. [https://doi.org/10.1016/j.ejca.2017.04.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28628843/ PubMed] |
− | |||
− | ##'''Update:''' | ||
− | |||
==ECX {{#subobject:c8ab0e|Regimen=1}}== | ==ECX {{#subobject:c8ab0e|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine) | ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine) | ||
− | ===Regimen {{#subobject: | + | <div class="toccolours" style="background-color:#eeeeee"> |
+ | ===Regimen {{#subobject:24u848|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www. | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585417/ Alderson et al. 2017 (UK MRC OE05)] |
− | | | + | |2005-2011 |
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | | | + | |[[#Cisplatin_.26_Fluorouracil_.28CF.29_2|CF]] |
− | | style="background-color:# | + | | style="background-color:#d9ef8b" |Might have superior OS (primary endpoint)<br>Median OS: 26.1 vs 23.4 mo<br>(HR 0.90, 95% CI 0.77-1.05) |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
− | |||
− | |||
− | |||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1 | *[[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 | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | ||
− | *[[Capecitabine (Xeloda)]] | + | *[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup>/day PO on days 1 to 21 |
− | + | '''21-day cycle for 4 cycles''' | |
− | '''21-day cycle for | + | </div> |
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *[[Surgery#Esophageal_cancer_surgery|Surgery]] | |
− | *[[Surgery#Esophageal_cancer_surgery|Surgery]] | + | </div></div> |
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
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− | |||
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− | |||
− | |||
− | |||
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− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===References=== | ||
− | #''' | + | #'''UK MRC OE05:''' Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, Grabsch HI, Langer R, Pritchard S, Okines A, Krysztopik R, Coxon F, Thompson J, Falk S, Robb C, Stenning S, Langley RE. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1249-1260. Epub 2017 Aug 4. [https://doi.org/10.1016/S1470-2045(17)30447-3 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5585417/ link to PMC article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28784312/ PubMed] [https://clinicaltrials.gov/study/NCT00041262 NCT00041262] |
− | |||
− | |||
=Neoadjuvant chemoradiotherapy= | =Neoadjuvant chemoradiotherapy= | ||
''Note: while these regimens are listed as neoadjuvant (pre-operative), in some cases they are also used as definitive therapy in patients that are not surgical candidates.'' | ''Note: while these regimens are listed as neoadjuvant (pre-operative), in some cases they are also used as definitive therapy in patients that are not surgical candidates.'' | ||
− | |||
==Cisplatin, Etoposide, RT {{#subobject:88cc36|Regimen=1}}== | ==Cisplatin, Etoposide, RT {{#subobject:88cc36|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy | EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:a9fc90|Variant=1}}=== | ===Regimen {{#subobject:a9fc90|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 377: | Line 434: | ||
|[https://doi.org/10.1200/JCO.2008.17.0506 Stahl et al. 2009 (POET)] | |[https://doi.org/10.1200/JCO.2008.17.0506 Stahl et al. 2009 (POET)] | ||
|2000-2005 | |2000-2005 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[Complex_multipart_regimens#POET|See link]] | |[[Complex_multipart_regimens#POET|See link]] | ||
| style="background-color:#d9ef8b" |[[Complex_multipart_regimens#POET|See link]] | | style="background-color:#d9ef8b" |[[Complex_multipart_regimens#POET|See link]] | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III. Chemoradiation is to start 2 weeks after the last day of PLF.'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[#CLF|PLF]] induction x 12 wk | |
− | *[[#CLF|PLF]] x 12 wk | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | ====Chemotherapy | + | ====Chemotherapy==== |
− | |||
*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8 | *[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 & 8 | ||
*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 3 to 5 | *[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 3 to 5 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19 (15 fractions; target dose of 3000 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | ||
− | |||
'''3-week course''' | '''3-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Surgery#Esophagectomy|Surgery]], in 3 to 4 weeks | *[[Surgery#Esophagectomy|Surgery]], in 3 to 4 weeks | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''POET:''' Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [https://doi.org/10.1200/JCO.2008.17.0506 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19139439/ PubMed] | |
− | #'''POET:''' Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [https://doi.org/10.1200/JCO.2008.17.0506 link to original article] ''' | + | ##'''Update:''' Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. [https://doi.org/10.1016/j.ejca.2017.04.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28628843/ PubMed] |
− | ##'''Update:''' Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. [https://doi.org/10.1016/j.ejca.2017.04.027 link to original article] [https://pubmed.ncbi.nlm.nih.gov/28628843 PubMed] | + | ==Cisplatin & Fluorouracil (CF) & RT {{#subobject:17919|Regimen=1}}== |
− | |||
− | ==Cisplatin | ||
− | |||
− | |||
− | |||
− | |||
CF & RT: '''C'''isplatin, '''<u>F</u>'''luourouracil, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | CF & RT: '''C'''isplatin, '''<u>F</u>'''luourouracil, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#ee6b6e"> | ||
===Regimen {{#subobject:213574|Variant=1}}=== | ===Regimen {{#subobject:213574|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJM199608153350702 Walsh et al. 1996] |
|1990-1995 | |1990-1995 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-esc) |
− | |[[ | + | |[[Esophageal_adenocarcinoma_-_null_regimens#No_neoadjuvant_therapy|Surgery alone]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint) |
|- | |- | ||
|} | |} | ||
''Note: of historic interest only.'' | ''Note: of historic interest only.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Cisplatin (Platinol)]] 15 mg/kg IV over 16 hours once per day on days 1 to 5 | |
− | *[[Cisplatin (Platinol)]] | + | *[[Fluorouracil (5-FU)]] 75 mg/m<sup>2</sup> IV over 8 hours once on day 7 |
− | *[[Fluorouracil (5-FU)]] | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | **Cycle 1: 267 cGy per fraction on days 1 to 5, 8 to 12, 15 to 19 |
+ | '''5-week cycle for 2 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Surgery#Esophagectomy|Surgery]] | *[[Surgery#Esophagectomy|Surgery]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. [https://doi.org/10.1056/NEJM199608153350702 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/8672151/ PubMed] | |
− | #Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. [https:// | ||
==Cisplatin, Irinotecan, RT {{#subobject:4932b1|Regimen=1}}== | ==Cisplatin, Irinotecan, RT {{#subobject:4932b1|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Cisplatin, Irinotecan, RT: Cisplatin, Irinotecan, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Cisplatin, Irinotecan, RT: Cisplatin, Irinotecan, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
− | ===Regimen variant #1, 60/130 x 2 + | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style="width: | + | ===Regimen variant #1, 60/130 x 2 + 4500 cGy {{#subobject:eac274|Variant=1}}=== |
− | ! style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
+ | !style="width: 33%"|Dates of enrollment | ||
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011 (ECOG E1201)] |
− | | style="background-color:#91cf61" |Phase | + | |2002-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29 | |
− | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 | + | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29 |
− | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 | ||
− | |||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | ||
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *[[Surgery#Esophagectomy|surgery]] no earlier than 28 days after finishing chemoradiation, then adjuvant [[#Cisplatin_.26_Irinotecan_.28IC.29_2|IC]], beginning no earlier than 28 days after surgical resection | |
− | * | + | </div></div><br> |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
===Regimen variant #2 {{#subobject:1a3475|Variant=1}}=== | ===Regimen variant #2 {{#subobject:1a3475|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ijrobp.2008.12.087 Rivera et al. 2009] |
− | | style="background-color:#91cf61" |Phase | + | |2003-12 to 2004-10 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma histology (43% gastroesophageal junction, 57% gastric adenocarcinoma)'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[#Cisplatin_.26_Irinotecan_.28IC.29|IC]] induction x 2 | |
− | *[[#Cisplatin_.26_Irinotecan_.28IC.29|IC | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | ||
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Surgery#Esophagectomy|Surgery]], 5 to 8 weeks after finishing chemoradiation | *[[Surgery#Esophagectomy|Surgery]], 5 to 8 weeks after finishing chemoradiation | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. [https://doi.org/10.1016/j.ijrobp.2008.12.087 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19540072/ PubMed] | |
− | #Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. [ | + | #'''ECOG E1201:''' Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21286719/ PubMed] |
− | #Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] ''' | ||
− | |||
==Cisplatin, Paclitaxel, RT {{#subobject:3d8eaa|Regimen=1}}== | ==Cisplatin, Paclitaxel, RT {{#subobject:3d8eaa|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Cisplatin, Paclitaxel, RT: Cisplatin, Paclitaxel, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Cisplatin, Paclitaxel, RT: Cisplatin, Paclitaxel, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, weekly cisplatin {{#subobject:5a433d|Variant=1}}=== | ===Regimen variant #1, weekly cisplatin {{#subobject:5a433d|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011 (ECOG E1201)] |
− | | style="background-color:#91cf61" |Phase | + | |2002-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 | ||
*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29 | *[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]]: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | ||
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | + | *[[Surgery#Esophagectomy|Surgery]] no earlier than 28 days after finishing chemoradiation, then adjuvant [[#Cisplatin_.26_Paclitaxel|cisplatin & paclitaxel]] no earlier than 28 days after surgical resection | |
− | *[[Surgery#Esophagectomy|Surgery]] | + | </div></div> |
− | |||
===References=== | ===References=== | ||
− | #Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] ''' | + | #'''ECOG E1201:''' Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21286719/ PubMed] |
− | |||
==Fluorouracil, Paclitaxel, RT {{#subobject:52e768|Regimen=1}}== | ==Fluorouracil, Paclitaxel, RT {{#subobject:52e768|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
Fluorouracil, Paclitaxel, RT: Fluorouracil, Paclitaxel, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | Fluorouracil, Paclitaxel, RT: Fluorouracil, Paclitaxel, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:f8576f|Variant=1}}=== | ===Regimen {{#subobject:f8576f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2006.06.4840 Ajani et al. 2006 (RTOG 9904)] | |[https://doi.org/10.1200/jco.2006.06.4840 Ajani et al. 2006 (RTOG 9904)] | ||
− | | style="background-color:#91cf61" |Phase | + | |1999-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma histology. The majority of patients had gastric adenocarcinoma. Although gastroesophageal junction was involved, percentages were not included.'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *[[#Cisplatin_.26_Fluorouracil_.28CF.29_2|CF]] induction x 2 | |
− | *[[#Cisplatin_.26_Fluorouracil_.28CF. | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 7500 mg/m<sup>2</sup>) | |
− | *[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on | + | *[[Paclitaxel (Taxol)]] 45 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29 |
− | *[[Paclitaxel (Taxol)]] 45 mg/m<sup>2</sup> IV once on | ||
− | |||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy) | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]], | ||
− | |||
'''5-week course''' | '''5-week course''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | |||
*[[Surgery#Esophagectomy|Surgery]] | *[[Surgery#Esophagectomy|Surgery]] | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''RTOG 9904:''' Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. [https://doi.org/10.1200/jco.2006.06.4840 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16921048/ PubMed] | |
− | #'''RTOG 9904:''' Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. [https://doi.org/10.1200/jco.2006.06.4840 link to original article] ''' | ||
− | |||
=Adjuvant therapy= | =Adjuvant therapy= | ||
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==Cisplatin & Irinotecan (IC) {{#subobject:308dd0|Regimen=1}}== | ==Cisplatin & Irinotecan (IC) {{#subobject:308dd0|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:507e9f|Variant=1}}=== | ===Regimen {{#subobject:507e9f|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011 (ECOG E1201)] |
− | | style="background-color:#91cf61" |Phase | + | |2002-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *Neoadjuvant [[#Cisplatin.2C_Irinotecan.2C_RT|cisplatin, irinotecan, RT]], then [[Surgery#Esophageal_cancer_surgery|surgery]] | |
− | *[[#Cisplatin.2C_Irinotecan.2C_RT| | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8 | *[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8 | ||
− | |||
'''21-day cycle for 3 cycles''' | '''21-day cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''ECOG E1201:''' Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21286719/ PubMed] | |
− | #Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] ''' | ||
− | |||
==Cisplatin & Paclitaxel {{#subobject:b40afb|Regimen=1}}== | ==Cisplatin & Paclitaxel {{#subobject:b40afb|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:c15e56|Variant=1}}=== | ===Regimen {{#subobject:c15e56|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011] | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ Yoon et al. 2011 (ECOG E1201)] |
− | | style="background-color:#91cf61" |Phase | + | |2002-2004 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
====Preceding treatment==== | ====Preceding treatment==== | ||
− | + | *Neoadjuvant [[#Cisplatin.2C_Paclitaxel.2C_RT|cisplatin, paclitaxel, RT]], then [[Surgery#Esophageal_cancer_surgery|surgery]] | |
− | *[[#Cisplatin.2C_Paclitaxel.2C_RT| | + | </div> |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | *[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1 | ||
*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | *[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1 | ||
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'''21-day cycle for 3 cycles''' | '''21-day cycle for 3 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''ECOG E1201:''' Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; [[Study_Groups#ECOG|ECOG]]. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [https://doi.org/10.1007/s00280-011-1556-5 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3563156/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21286719/ PubMed] | |
− | #''' | ||
− | |||
− | |||
− | |||
==ECF/5-FU & RT {{#subobject:7f3e93|Regimen=1}}== | ==ECF/5-FU & RT {{#subobject:7f3e93|Regimen=1}}== | ||
− | + | ECF/5-FU & RT: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil alternating with '''<u>5</u>'''-'''<u>F</u>'''luoro'''<u>U</u>'''racil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy sandwich | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:53c380|Variant=1}}=== | |
− | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" | |
− | ECF/5-FU & RT: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil alternating with '''<u>5</u>'''-'''<u>F</u>'''luoro'''<u>U</u>'''racil & '''<u>R</u>'''adiation '''<u>T</u>'''herapy | + | !style="width: 33%"|Study |
− | === | + | !style="width: 33%"|Dates of enrollment |
− | {| class="wikitable" style="width: | + | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] |
− | ! style="width: | ||
− | ! style="width: | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1016/j.ijrobp.2009.11.042 Leong et al. 2010] |
− | | style="background-color:#91cf61" |Phase | + | |2003-07 to 2006-10 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Note: In contrast to the primary reference, some guidelines list this regimen without ECF cycles 1, 3, 4. | + | ''Note: In contrast to the primary reference, some guidelines list this regimen without ECF cycles 1, 3, 4. Patients had 100% adenocarcinoma (6% gastroesophageal junction, 94% gastric origin).'' |
− | + | <div class="toccolours" style="background-color:#cbd5e8"> | |
− | |||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#Esophageal_cancer_surgery|Surgery]], within 10 weeks | *[[Surgery#Esophageal_cancer_surgery|Surgery]], within 10 weeks | ||
− | + | </div> | |
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1 | + | *[[Epirubicin (Ellence)]] as follows: |
− | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1 | + | **Cycle 1: 50 mg/m<sup>2</sup> IV bolus once on day 1 |
− | *[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion, started on day 1 (total dose: 4200 mg/m<sup>2</sup>) | + | **Cycles 3 & 4: 50 mg/m<sup>2</sup> IV bolus once on day 1 |
− | + | *[[Cisplatin (Platinol)]] as follows: | |
− | + | **Cycle 1: 60 mg/m<sup>2</sup> IV once on day 1 | |
− | + | **Cycles 3 & 4: 60 mg/m<sup>2</sup> IV once on day 1 | |
− | + | *[[Fluorouracil (5-FU)]] as follows: | |
− | + | **Cycle 1: 200 mg/m<sup>2</sup>/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>) | |
− | * | + | **Cycle 2 (chemoradiation): 225 mg/m<sup>2</sup>/day IV continuous infusion over 35 days, started on day 1 (total dose: 7875 mg/m<sup>2</sup>) |
− | + | **Cycles 3 & 4: 200 mg/m<sup>2</sup>/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>) | |
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | **Cycle 2 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy) |
− | + | '''4- to 6-week course, then 9-week course, then 21-day cycle for 2 cycles''' | |
− | + | </div></div> | |
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===References=== | ===References=== | ||
− | # | + | #Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M; Trans-Tasman Radiation Oncology Group. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):690-5. Epub 2010 May 14. [https://doi.org/10.1016/j.ijrobp.2009.11.042 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/20472363/ PubMed] |
− | |||
− | == | + | ==FULV & RT {{#subobject:f6b345|Regimen=1}}== |
− | + | FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>L</u>'''euco'''<u>V</u>'''orin, '''<u>R</u>'''adiation '''<u>T</u>'''herapy | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | + | ===Regimen {{#subobject:5cd826|Variant=1}}=== | |
− | |||
− | |||
− | === | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1056/NEJMoa010187 Macdonald et al. 2001 (INT-0116)] |
|1991-1998 | |1991-1998 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |[[ | + | |[[Esophageal_adenocarcinoma_-_null_regimens#Observation|Observation]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 36 vs 27 mo<br>(HR 0.74, 95% CI 0.60-0.92) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#cbd5e8"> | ||
====Preceding treatment==== | ====Preceding treatment==== | ||
− | |||
*[[Surgery#Esophageal_cancer_surgery|Surgery]] | *[[Surgery#Esophageal_cancer_surgery|Surgery]] | ||
− | + | </div> | |
− | ====Chemotherapy | + | <div class="toccolours" style="background-color:#b3e2cd"> |
− | + | ====Chemotherapy==== | |
− | *[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 (total dose per cycle: 2125 mg/m<sup>2</sup>) | + | *[[Fluorouracil (5-FU)]] as follows: |
− | * | + | **Cycles 1, 3, 4: 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 (total dose per cycle: 2125 mg/m<sup>2</sup>) |
− | + | **Cycle 2 (chemoradiation): 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy (total dose: 2800 mg/m<sup>2</sup>) | |
− | + | *[[Leucovorin (Folinic acid)]] as follows: | |
− | + | **Cycles 1, 3, 4: 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5 | |
− | + | **Cycle 2 (chemoradiation): 20 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 | ||
− | |||
====Radiotherapy==== | ====Radiotherapy==== | ||
− | + | *Concurrent [[External_beam_radiotherapy|radiation therapy]] as follows: | |
− | *Concurrent [[External_beam_radiotherapy|radiation therapy]] | + | **Cycle 2 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy) |
− | + | '''28-day course, then 9-week course, then 28-day cycle for 2 cycles''' | |
− | + | </div></div> | |
− | |||
− | |||
− | |||
− | * | ||
− | |||
− | |||
− | '''28-day cycle for 2 cycles''' | ||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
− | |||
===References=== | ===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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/11547741/ PubMed] | |
− | #'''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:// | ||
=Metastatic or locally advanced disease, first-line= | =Metastatic or locally advanced disease, first-line= | ||
==Capecitabine & Cisplatin (CX) {{#subobject:c58325|Regimen=1}}== | ==Capecitabine & Cisplatin (CX) {{#subobject:c58325|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CX: '''<u>C</u>'''isplatin & '''<u>X</u>'''eloda (Capecitabine) | CX: '''<u>C</u>'''isplatin & '''<u>X</u>'''eloda (Capecitabine) | ||
<br>XP: '''<u>X</u>'''eloda (Capecitabine) & '''<u>P</u>'''latinol (Cisplatin) | <br>XP: '''<u>X</u>'''eloda (Capecitabine) & '''<u>P</u>'''latinol (Cisplatin) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:130681|Variant=1}}=== | ===Regimen {{#subobject:130681|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 972: | Line 761: | ||
|[https://doi.org/10.1093/annonc/mdp269 Moehler et al. 2009] | |[https://doi.org/10.1093/annonc/mdp269 Moehler et al. 2009] | ||
|2003-2006 | |2003-2006 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
|[[#CAPIRI|XI]] | |[[#CAPIRI|XI]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70102-5 Lordick et al. 2013 (EXPAND)] |
|2008-2010 | |2008-2010 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Cetuximab|CX & Cetuximab]] | |[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Cetuximab|CX & Cetuximab]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
− | ''EXPAND patients | + | ''Note: EXPAND patients had 100% adenocarcinoma (stomach or gastroesophageal junction) locally advanced unresectable (M0) or metastatic (M1).'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1 | *[[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 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
− | **Lordick et al. 2013: 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) | + | **Alternative dosing in Lordick et al. 2013: 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) |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. [https://doi.org/10.1093/annonc/mdp269 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19605504/ PubMed] | |
− | #Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. [https://doi.org/10.1093/annonc/mdp269 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19605504 PubMed] | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23594786/ PubMed] [https://clinicaltrials.gov/study/NCT00678535 NCT00678535] |
− | #'''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:// | ||
− | |||
==Capecitabine & Cisplatin (CX) & Cetuximab {{#subobject:318959|Regimen=1}}== | ==Capecitabine & Cisplatin (CX) & Cetuximab {{#subobject:318959|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CX-C: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), '''<u>C</u>'''etuximab | CX-C: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), '''<u>C</u>'''etuximab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:afe6a1|Variant=1}}=== | ===Regimen {{#subobject:afe6a1|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70102-5 Lordick et al. 2013 (EXPAND)] |
|2008-2010 | |2008-2010 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Capecitabine_.26_Cisplatin_.28CX.29_2|CX]] | |[[#Capecitabine_.26_Cisplatin_.28CX.29_2|CX]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | | style="background-color:#ffffbf" |Did not meet primary endpoint of PFS | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma (stomach or gastroesophageal junction) locally advanced unresectable (M0) or metastatic (M1).'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1 | *[[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 from the evening of day 1 to the morning of day 15 (28 doses per cycle) | *[[Capecitabine (Xeloda)]] 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) | ||
Line 1,028: | Line 809: | ||
*[[Cetuximab (Erbitux)]] as follows: | *[[Cetuximab (Erbitux)]] as follows: | ||
**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1 | **Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1 | ||
− | ** | + | **Cycle 2 onwards: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 |
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23594786/ PubMed] [https://clinicaltrials.gov/study/NCT00678535 NCT00678535] | |
− | #'''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:// | ||
− | |||
==CapeOx {{#subobject:4e3bb4|Regimen=1}}== | ==CapeOx {{#subobject:4e3bb4|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin | CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:4fagg3|Variant=1}}=== | ===Regimen {{#subobject:4fagg3|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078426/ Moehler et al. 2020 (JAVELIN Gastric 100)] |
|2015-2017 | |2015-2017 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | | | + | |1a. [[#CapeOx-Avelumab_999|CapeOx-Avelumab]]<br>1b. [[#FOLFOX6-Avelumab_999|FOLFOX6-Avelumab]]<br>1c. [[#mFOLFOX6-Avelumab_999|mFOLFOX6-Avelumab]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1 | *[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #'''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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078426/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33197226/ PubMed] [https://clinicaltrials.gov/study/NCT02625610 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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8436782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] [https://clinicaltrials.gov/study/NCT02872116 NCT02872116] | |
− | == | + | ##'''Update:''' Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. [https://doi.org/10.1038/s41586-022-04508-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967713/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35322232/ PubMed] |
− | {| class="wikitable" style=" | + | ##'''HRQoL analysis:''' Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. [https://doi.org/10.1200/jco.23.00170 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10713185/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37713657/ PubMed] |
+ | ##'''Update:''' Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. [https://doi.org/10.1200/jco.23.01601 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11185916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38382001/ PubMed] | ||
+ | ==CapeOx & Nivolumab {{#subobject:c798a3|Regimen=1}}== | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d18acj2|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%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8436782/ Janjigian et al. 2021 (CheckMate 649)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-290-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |rowspan=2|2017-03 to 2019-04 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |1a. [[#CapeOx_2|CapeOx]]<br>1b. [[#mFOLFOX6|mFOLFOX6]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 14.4 vs 11.1 mo<br>(HR 0.70, 95% CI 0.61-0.81)<br><br>Superior PFS (co-primary endpoint)<br>Median PFS: 7.7 vs 6.05 mo<br>(HR 0.68, 98% CI 0.56-0.81) | ||
+ | |- | ||
+ | |2. [[#Ipilimumab_.26_Nivolumab_999|Ipilimumab & Nivolumab]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
|- | |- | ||
− | |||
|} | |} | ||
+ | ''<sup>1</sup>Reported efficacy and MCBS score are for the group with PD-L1 CPS of 5 or more; reported efficacy is based on the 2022 update.''<br> | ||
+ | ''Note: CheckMate 649 included patients on both 21-day (Nivo/CapeOx) and 14-day (Nivo/FOLFOX) regimens in the immunotherapy + chemo arm. 60% PD-L1 CPS >5, 82% PD-L1 CPS >1.'' | ||
+ | <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)|Nivolumab]] 360 mg IV once on day 1 | ||
+ | '''21-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- #'''Abstract:''' Moehler et al. LBA6_PR - Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325. [https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/nivolumab-nivo-plus-chemotherapy-chemo-versus-chemo-as-first-line-1l-treatment-for-advanced-gastric-cancer-gastroesophageal-junction-cancer link to abstract] [https://clinicaltrials.gov/study/NCT02872116 NCT02872116]. --> | ||
+ | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8436782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] [https://clinicaltrials.gov/study/NCT02872116 NCT02872116] | ||
+ | ##'''Update:''' Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. [https://doi.org/10.1038/s41586-022-04508-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967713/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35322232/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. [https://doi.org/10.1200/jco.23.00170 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10713185/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37713657/ PubMed] | ||
+ | ##'''Update:''' Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. [https://doi.org/10.1200/jco.23.01601 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11185916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38382001/ PubMed] | ||
+ | ==CAPIRI {{#subobject:c701c3|Regimen=1}}== | ||
CapeIRI: '''<u>Cape</u>'''citabine and '''<u>IRI</u>'''notecan | CapeIRI: '''<u>Cape</u>'''citabine and '''<u>IRI</u>'''notecan | ||
<br>CAPIRI: '''<u>CAP</u>'''ecitabine and '''<u>IRI</u>'''notecan | <br>CAPIRI: '''<u>CAP</u>'''ecitabine and '''<u>IRI</u>'''notecan | ||
<br>XELIRI: '''<u>XEL</u>'''ox (Capecitabine) and '''<u>IRI</u>'''notecan | <br>XELIRI: '''<u>XEL</u>'''ox (Capecitabine) and '''<u>IRI</u>'''notecan | ||
<br>XI: '''<u>X</u>'''eloda (Capecitabine) and '''<u>I</u>'''rinotecan | <br>XI: '''<u>X</u>'''eloda (Capecitabine) and '''<u>I</u>'''rinotecan | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:d62c90|Variant=1}}=== | ===Regimen {{#subobject:d62c90|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,086: | Line 905: | ||
|[https://doi.org/10.1093/annonc/mdp269 Moehler et al. 2009] | |[https://doi.org/10.1093/annonc/mdp269 Moehler et al. 2009] | ||
|2003-2006 | |2003-2006 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
|[[#Capecitabine_.26_Cisplatin_.28CX.29_2|XP]] | |[[#Capecitabine_.26_Cisplatin_.28CX.29_2|XP]] | ||
| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | | style="background-color:#ffffbf" |Did not meet primary endpoint of ORR | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 45% esophageal, 38% gastroesophageal junction, 17% gastric origin. 93% adenocarcinoma, 7% squamous cell histology. 86% metastatic disease. 14% ECOG PS of 2.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14 | ||
*[[Irinotecan (Camptosar)]] 250 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1 | *[[Irinotecan (Camptosar)]] 250 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Atropine (Atropen)]] 0.25 mg SC once on day 1, given prior to irinotecan |
− | |||
− | *[[Atropine (Atropen)]] 0.25 mg SC once on day 1, given | ||
*[[Loperamide (Imodium)]] 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool | *[[Loperamide (Imodium)]] 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool | ||
*[[Ciprofloxacin (Cipro)]] 250 mg PO twice per day prn diarrhea lasting longer than 24 hours despite loperamide | *[[Ciprofloxacin (Cipro)]] 250 mg PO twice per day prn diarrhea lasting longer than 24 hours despite loperamide | ||
'''21-day cycles''' | '''21-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | + | #Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. [https://doi.org/10.1093/annonc/mdp269 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19605504/ PubMed] | |
− | #Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. [https://doi.org/10.1093/annonc/mdp269 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19605504 PubMed] | ||
− | |||
==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}== | ==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil | ||
<br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol | <br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:10f0c6|Variant=1}}=== | ===Regimen {{#subobject:10f0c6|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,126: | Line 938: | ||
|[https://doi.org/10.1200/jco.2006.06.8429 Van Cutsem et al. 2006 (TAX 325)] | |[https://doi.org/10.1200/jco.2006.06.8429 Van Cutsem et al. 2006 (TAX 325)] | ||
|1999-2003 | |1999-2003 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#DCF|DCF]] | |[[#DCF|DCF]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
Line 1,132: | Line 944: | ||
|[https://doi.org/10.1093/annonc/mdn166 Dank et al. 2008] | |[https://doi.org/10.1093/annonc/mdn166 Dank et al. 2008] | ||
|2000-2002 | |2000-2002 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#FOLFIRI|IF]] | |[[#FOLFIRI|IF]] | ||
| style="background-color:#fee08b" |Might have inferior TTP | | style="background-color:#fee08b" |Might have inferior TTP | ||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: TAX 325 patients had 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70. Dank et al. patients had 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first''' | *[[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> ) | + | *[[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==== | |
− | ====Supportive | ||
− | |||
*As described in Dank et al. 2008: | *As described in Dank et al. 2008: | ||
*"Hyperhydration" for 2 to 3 days with each infusion | *"Hyperhydration" for 2 to 3 days with each infusion | ||
Line 1,153: | Line 960: | ||
*[[Dexamethasone (Decadron)]] IV for antiemetic prophylaxis, then PO for 2 to 3 days | *[[Dexamethasone (Decadron)]] IV for antiemetic prophylaxis, then PO for 2 to 3 days | ||
*[[Metoclopramide (Reglan)]] for antiemetic prophylaxis | *[[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/ | + | *[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/μL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection |
*[[Atropine (Atropen)]] prn cholinergic symptoms | *[[Atropine (Atropen)]] prn cholinergic symptoms | ||
*[[Loperamide (Imodium)]] prn delayed diarrhea | *[[Loperamide (Imodium)]] prn delayed diarrhea | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
+ | </div></div> | ||
===References=== | ===References=== | ||
− | #'''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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [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] ''' | + | #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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18558665/ PubMed] |
− | |||
==ECX {{#subobject:bb95b5|Regimen=1}}== | ==ECX {{#subobject:bb95b5|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine) | ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine) | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #1, 50/60/1250 {{#subobject:eab855|Variant=1}}=== | ===Regimen variant #1, 50/60/1250 {{#subobject:eab855|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(14)70023-3 Iveson et al. 2014 (Amgen 20060317)] |
|2009 | |2009 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
− | |ECX & Rilotumumab | + | |[[#ECX_.26_Rilotumumab_777|ECX & Rilotumumab]] |
| style="background-color:#fc8d59" |Seems to have inferior PFS | | style="background-color:#fc8d59" |Seems to have inferior PFS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1 | *[[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 | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1 | ||
*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 21 | *[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 21 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 50/60/2000 {{#subobject:2f83d2|Variant=1}}=== | ===Regimen variant #2, 50/60/2000 {{#subobject:2f83d2|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,201: | Line 1,004: | ||
|[https://doi.org/10.1200/JCO.2013.54.1011 Guimbaud et al. 2014 (FFCD 03-07)] | |[https://doi.org/10.1200/JCO.2013.54.1011 Guimbaud et al. 2014 (FFCD 03-07)] | ||
|2005-2008 | |2005-2008 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#FOLFIRI|FOLFIRI]] | |[[#FOLFIRI|FOLFIRI]] | ||
| style="background-color:#d73027" |Inferior TTF | | style="background-color:#d73027" |Inferior TTF | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | + | *[[Epirubicin (Ellence)]] as follows: | |
− | *[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1 | + | **Cycles 1 up to 18: 50 mg/m<sup>2</sup> IV over 15 minutes once on day 1 (maximum cumulative dose of 900 mg/m<sup>2</sup>) |
− | |||
*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 2 to 15 | *[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 2 to 15 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #'''Amgen 20060317:''' Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. Epub 2014 Jun 22. [https:// | + | #'''Amgen 20060317:''' Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. Epub 2014 Jun 22. [https://doi.org/10.1016/S1470-2045(14)70023-3 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24965569/ PubMed] [https://clinicaltrials.gov/study/NCT00719550 NCT00719550] |
− | #'''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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25287828/ PubMed] [https://clinicaltrials.gov/study/NCT00374036 NCT00374036] |
− | |||
==Erlotinib monotherapy {{#subobject:50cjcd|Regimen=1}}== | ==Erlotinib monotherapy {{#subobject:50cjcd|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:yac7de|Variant=1}}=== | ===Regimen {{#subobject:yac7de|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1200/jco.2006.07.1316 Dragovich et al. 2006 (SWOG 0127)] | |[https://doi.org/10.1200/jco.2006.07.1316 Dragovich et al. 2006 (SWOG 0127)] | ||
− | | style="background-color:#91cf61" |Phase | + | |2002-2003 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma (63% gastroesophageal junction, 37% gastric origin). All with ECOG PS of 0 or 1.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Targeted therapy==== | ====Targeted therapy==== | ||
− | + | *[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28, taken at least 1 hour before a meal or 2 hours after a meal | |
− | *[[Erlotinib (Tarceva)]] 150 mg PO once per day, at least 1 hour before a meal | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''SWOG 0127:''' Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. [https://doi.org/10.1200/jco.2006.07.1316 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/17050876/ PubMed] [https://clinicaltrials.gov/study/NCT00032123 NCT00032123] | |
− | #'''SWOG 0127:''' Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. [https://doi.org/10.1200/jco.2006.07.1316 link to original article] ''' | ||
==FLOT {{#subobject:b427b1|Regimen=1}}== | ==FLOT {{#subobject:b427b1|Regimen=1}}== | ||
− | |||
− | |||
− | |||
− | |||
FLOT: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin, '''<u>T</u>'''axotere (Docetaxel) | 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"> | ||
===Regimen {{#subobject:bb5eb6|Variant=1}}=== | ===Regimen {{#subobject:bb5eb6|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://doi.org/10.1093/annonc/mdn403 Al-Batran et al. 2008a] | |[https://doi.org/10.1093/annonc/mdn403 Al-Batran et al. 2008a] | ||
− | | style="background-color:#91cf61" |Phase | + | |2006 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% adenocarcinoma histology (44% gastroesophageal junction, 56% gastric origin). 93% metastatic disease. 15% with ECOG 2-3.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, '''given fourth''' | *[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, '''given fourth''' | ||
− | *[[Folinic acid | + | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1 |
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1 | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1 | ||
*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1 | *[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*[[Dexamethasone (Decadron)]] 8 mg PO once per day on days 0 to 3 | *[[Dexamethasone (Decadron)]] 8 mg PO once per day on days 0 to 3 | ||
− | |||
'''14-day cycle for up to 8 (or more) cycles''' | '''14-day cycle for up to 8 (or more) cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. [https://doi.org/10.1093/annonc/mdn403 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/18669868/ PubMed] | |
− | #Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. [https://doi.org/10.1093/annonc/mdn403 link to original article] ''' | ||
− | |||
==FOLFIRI {{#subobject:ba35aa|Regimen=1}}== | ==FOLFIRI {{#subobject:ba35aa|Regimen=1}}== | ||
− | + | FOLFIRI: '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan | |
− | |||
− | |||
− | |||
− | 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 | <br>IF: '''<u>I</u>'''rinotecan & 5-'''<u>F</u>'''luorouracil | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:cec083|Variant=1}}=== | ===Regimen {{#subobject:cec083|Variant=1}}=== | ||
− | {| class="wikitable sortable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
!style="width: 33%"|Study | !style="width: 33%"|Study | ||
− | !style="width: 33%"| | + | !style="width: 33%"|Dates of enrollment |
!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2009&issue=03000&article=00002&type=abstract Wolff et al. 2009] | |[http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2009&issue=03000&article=00002&type=abstract Wolff et al. 2009] | ||
|2002-2006 | |2002-2006 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 2 |
|- | |- | ||
|} | |} | ||
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====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>) | *[[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 (Folinic acid)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given second''' |
*[[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''' | *[[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==== | |
− | ====Supportive | ||
− | |||
*[[Ondansetron (Zofran)]] for antiemetic prophylaxis | *[[Ondansetron (Zofran)]] for antiemetic prophylaxis | ||
*[[Dexamethasone (Decadron)]] 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/ | + | *[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/μL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection |
*[[Atropine (Atropen)]] prn cholinergic symptoms | *[[Atropine (Atropen)]] prn cholinergic symptoms | ||
*[[Loperamide (Imodium)]] prn delayed diarrhea | *[[Loperamide (Imodium)]] prn delayed diarrhea | ||
− | |||
'''7-week cycles''' | '''7-week cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. [http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2009&issue=03000&article=00002&type=abstract link to original article] ''' | + | #Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. [http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2009&issue=03000&article=00002&type=abstract link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/19125117/ PubMed] |
− | |||
==Irinotecan monotherapy {{#subobject:69cjc0|Regimen=1}}== | ==Irinotecan monotherapy {{#subobject:69cjc0|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:9fb982|Variant=1}}=== | ===Regimen {{#subobject:9fb982|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1007/s10620-005-3038-2 Enzinger et al. 2005] |
− | | style="background-color:#91cf61" |Phase | + | |1997-12 to 2000-08 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Note: In contrast to the primary reference, 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. | + | ''Note: In contrast to the primary reference, 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. Patients had 100% adenocarcinoma histology, both gastric and esophageal.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
− | |||
− | |||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22 | *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22 | ||
− | |||
'''42-day cycles''' | '''42-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https://doi.org/10.1007/s10620-005-3038-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16416165/ PubMed] | |
− | #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. [ | ||
− | |||
==Irinotecan & Mitomycin {{#subobject:dfcjc2|Regimen=1}}== | ==Irinotecan & Mitomycin {{#subobject:dfcjc2|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:87100a|Variant=1}}=== | ===Regimen {{#subobject:87100a|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,360: | Line 1,132: | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641556/ Lustberg et al. 2010] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641556/ Lustberg et al. 2010] | ||
|2002-2006 | |2002-2006 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
− | |[[#Irinotecan_.26_Mitomycin|Irinotecan & Mitomycin | + | |[[#Irinotecan_.26_Mitomycin|Irinotecan & Mitomycin]]; alternate schedule |
| style="background-color:#d3d3d3" |No statistical comparison | | style="background-color:#d3d3d3" |No statistical comparison | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 56% lower esophageal, 44% gastroesophageal junction. 100% adenocarcinoma histology. 100% previously untreated 6% with ECOG PS = 2. 77% stage four disease.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 2 & 9 | *[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 2 & 9 | ||
*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1 | *[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1 | ||
− | + | ====Supportive therapy==== | |
− | ====Supportive | ||
− | |||
*[[Ondansetron (Zofran)]] or [[Granisetron]] and [[Dexamethasone (Decadron)]] premedication | *[[Ondansetron (Zofran)]] or [[Granisetron]] and [[Dexamethasone (Decadron)]] premedication | ||
*[[Loperamide (Imodium)]] started with first episode of diarrhea | *[[Loperamide (Imodium)]] started with first episode of diarrhea | ||
*Erythropoietin for hemoglobin less than 10 g/dL permitted | *Erythropoietin for hemoglobin less than 10 g/dL permitted | ||
− | |||
'''28-day cycle for up to 6 cycles''' | '''28-day cycle for up to 6 cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. [https://doi.org/10.1097/JTO.0b013e3181d7776d link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3641556/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20354452/ PubMed] | |
− | #Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. [https:// | + | ==FOLFOX6 {{#subobject:7239a0|Regimen=1}}== |
− | + | FOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | |
− | == | + | <div class="toccolours" style="background-color:#eeeeee"> |
− | {| class="wikitable" style=" | + | ===Regimen {{#subobject:4uvvg3|Variant=1}}=== |
+ | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
+ | !style="width: 20%"|Study | ||
+ | !style="width: 20%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078426/ Moehler et al. 2020 (JAVELIN Gastric 100)] | ||
+ | |2015-2017 | ||
+ | | style="background-color:#1a9851" |Phase 3 (C) | ||
+ | |1a. [[#CapeOx-Avelumab_999|CapeOx-Avelumab]]<br>1b. [[#FOLFOX6-Avelumab_999|FOLFOX6-Avelumab]]<br>1c. [[#mFOLFOX6-Avelumab_999|mFOLFOX6-Avelumab]] | ||
+ | | style="background-color:#ffffbf" |Did not meet primary endpoint of OS | ||
|- | |- | ||
− | |||
|} | |} | ||
− | mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | + | <div class="toccolours" style="background-color:#b3e2cd"> |
+ | ====Chemotherapy==== | ||
+ | *[[Leucovorin (Folinic acid)]] 200 mg/m<sup>2</sup> IV once on day 1 | ||
+ | *[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1, '''given last''' | ||
+ | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
+ | '''14-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078426/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33197226/ PubMed] [https://clinicaltrials.gov/study/NCT02625610 NCT02625610] | ||
+ | ==mFOLFOX6 {{#subobject:328g5a|Regimen=1}}== | ||
+ | mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen {{#subobject:2057uf|Variant=1}}=== | ===Regimen {{#subobject:2057uf|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078292/ Shah et al. 2021 (GAMMA-1)] |
|2015-2019 | |2015-2019 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |mFOLFOX6 & Andecaliximab | + | |[[#mFOLFOX6_.26_Andecaliximab_999|mFOLFOX6 & Andecaliximab]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | 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 prior to becoming a standard comparator arm.'' | + | ''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==== | ====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>) | *[[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 (Folinic acid)]] 400 mg/m<sup>2</sup> IV once on day 1 |
*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''14-day cycle for 12 cycles''' | '''14-day cycle for 12 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#FULV|FULV | + | *[[#FULV|FULV]] maintenance |
+ | </div></div> | ||
===References=== | ===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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078292/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33577358/ PubMed] [https://clinicaltrials.gov/study/NCT02545504 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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8436782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] [https://clinicaltrials.gov/study/NCT02872116 NCT02872116] | |
+ | ##'''Update:''' Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. [https://doi.org/10.1038/s41586-022-04508-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967713/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35322232/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. [https://doi.org/10.1200/jco.23.00170 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10713185/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37713657/ PubMed] | ||
+ | ##'''Update:''' Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. [https://doi.org/10.1200/jco.23.01601 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11185916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38382001/ PubMed] | ||
==mFOLFOX6 (L-Leucovorin) {{#subobject:32hyaa|Regimen=1}}== | ==mFOLFOX6 (L-Leucovorin) {{#subobject:32hyaa|Regimen=1}}== | ||
− | + | mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | |
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin | ||
===Regimen {{#subobject:21jxuf|Variant=1}}=== | ===Regimen {{#subobject:21jxuf|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078292/ Shah et al. 2021 (GAMMA-1)] |
|2015-2019 | |2015-2019 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
− | |mFOLFOX6 & Andecaliximab | + | |[[#mFOLFOX6_.26_Andecaliximab_999|mFOLFOX6 & Andecaliximab]] |
| style="background-color:#ffffbf" |Did not meet primary endpoint of OS | | 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 prior to becoming a standard comparator arm.'' | + | ''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==== | ====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>) | *[[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 | *[[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 | *[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''14-day cycle for 12 cycles''' | '''14-day cycle for 12 cycles''' | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#cbd5e7"> | ||
====Subsequent treatment==== | ====Subsequent treatment==== | ||
− | *[[#FULV|FULV | + | *[[#FULV|FULV]] maintenance |
+ | </div></div> | ||
===References=== | ===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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8078292/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33577358/ PubMed] [https://clinicaltrials.gov/study/NCT02545504 NCT02545504] |
+ | ==mFOLFOX6 & Nivolumab {{#subobject:c79uyg|Regimen=1}}== | ||
+ | mFOLFOX6 & Nivolumab: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid (Leucovorin), '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Nivolumab | ||
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
+ | ===Regimen {{#subobject:d18acj2|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%"|Dates of enrollment | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
+ | !style="width: 20%"|Comparator | ||
+ | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
+ | |- | ||
+ | |rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8436782/ Janjigian et al. 2021 (CheckMate 649)] | ||
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-290-1 <span style="color:white;">ESMO-MCBS (4)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
+ | |rowspan=2|2017-03 to 2019-04 | ||
+ | |rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc) | ||
+ | |1a. [[#CapeOx_2|CapeOx]]<br>1b. [[#mFOLFOX6|mFOLFOX6]] | ||
+ | | style="background-color:#1a9850" |Superior OS<sup>1</sup> (co-primary endpoint)<br>Median OS: 14.4 vs 11.1 mo<br>(HR 0.70, 95% CI 0.61-0.81)<br><br>Superior PFS (co-primary endpoint)<br>Median PFS: 7.7 vs 6.05 mo<br>(HR 0.68, 98% CI 0.56-0.81) | ||
+ | |- | ||
+ | |2. [[#Ipilimumab_.26_Nivolumab_999|Ipilimumab & Nivolumab]] | ||
+ | | style="background-color:#d3d3d3" |Not reported | ||
+ | |- | ||
+ | |} | ||
+ | ''<sup>1</sup>Reported efficacy and MCBS score are for the group with PD-L1 CPS of 5 or more; reported efficacy is based on the 2022 update.''<br> | ||
+ | ''Note: CheckMate 649 included patients on both 21-day (Nivo/CapeOx) and 14-day (Nivo/FOLFOX) regimens in the immunotherapy + chemo arm. 60% PD-L1 CPS >5, 82% PD-L1 CPS >1.'' | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
+ | ====Chemotherapy==== | ||
+ | *[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>) | ||
+ | *[[Leucovorin (Folinic acid)]] 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)|Nivolumab]] 240 mg IV once on day 1 | ||
+ | '''14-day cycles''' | ||
+ | </div></div> | ||
+ | ===References=== | ||
+ | <!-- #'''Abstract:''' Moehler et al. LBA6_PR - Nivolumab (nivo) plus chemotherapy (chemo) versus chemo as first-line (1L) treatment for advanced gastric cancer/gastroesophageal junction cancer (GC/GEJC)/esophageal adenocarcinoma (EAC): First results of the CheckMate 649 study. Annals of Oncology (2020) 31 (suppl_4): S1142-S1215. 10.1016/annonc/annonc325. [https://oncologypro.esmo.org/meeting-resources/esmo-virtual-congress-2020/nivolumab-nivo-plus-chemotherapy-chemo-versus-chemo-as-first-line-1l-treatment-for-advanced-gastric-cancer-gastroesophageal-junction-cancer link to abstract] [https://clinicaltrials.gov/study/NCT02872116 NCT02872116]. --> | ||
+ | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8436782/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] [https://clinicaltrials.gov/study/NCT02872116 NCT02872116] | ||
+ | ##'''Update:''' Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. [https://doi.org/10.1038/s41586-022-04508-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8967713/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/35322232/ PubMed] | ||
+ | ##'''HRQoL analysis:''' Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. [https://doi.org/10.1200/jco.23.00170 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc10713185/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/37713657/ PubMed] | ||
+ | ##'''Update:''' Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. [https://doi.org/10.1200/jco.23.01601 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc11185916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/38382001/ PubMed] | ||
=Metastatic or locally advanced disease, subsequent lines of therapy= | =Metastatic or locally advanced disease, subsequent lines of therapy= | ||
==Apatinib monotherapy {{#subobject:c701c3|Regimen=1}}== | ==Apatinib monotherapy {{#subobject:c701c3|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:d1dde0|Variant=1}}=== | ===Regimen {{#subobject:d1dde0|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://doi.org/10.1200/jco.2015.63.5995 Li et al. 2016] | + | |[https://doi.org/10.1200/jco.2015.63.5995 Li et al. 2016 (HENGRUI 20101208)] |
− | |2011-2012 | + | |2011-01 to 2012-11 |
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |[[ | + | |[[Esophageal_adenocarcinoma_-_null_regimens#Placebo_3|Placebo]] |
− | | style="background-color:# | + | | style="background-color:#1a9850" |Superior OS (co-primary endpoint)<br>Median OS: 6.5 vs 4.7 mo<br>(HR 0.71, 95% CI 0.54-0.94) |
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Apatinib (Aitan)]] 850 mg PO once per day | *[[Apatinib (Aitan)]] 850 mg PO once per day | ||
− | |||
'''Continued indefinitely''' | '''Continued indefinitely''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | + | #'''HENGRUI 20101208:''' Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016 May 1;34(13):1448-54. Epub 2016 Feb 16. [https://doi.org/10.1200/jco.2015.63.5995 link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/26884585/ PubMed] [https://clinicaltrials.gov/study/NCT01512745 NCT01512745] | |
− | #Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016 May 1;34(13):1448-54. Epub 2016 Feb 16. [https://doi.org/10.1200/jco.2015.63.5995 link to original article] ''' | ||
==Cetuximab monotherapy {{#subobject:5aca6d|Regimen=1}}== | ==Cetuximab monotherapy {{#subobject:5aca6d|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:b11ea0|Variant=1}}=== | ===Regimen {{#subobject:b11ea0|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397 Gold et al. 2010 (SWOG S0415)] | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397 Gold et al. 2010 (SWOG S0415)] | ||
− | | style="background-color:#91cf61" |Phase | + | |2005-2007 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% metastatic esophageal adenocarcinoma who failed one prior chemotherapy regimen. 10% had ECOG PS of 2.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Targeted therapy==== | ====Targeted therapy==== | ||
− | |||
*[[Cetuximab (Erbitux)]] as follows: | *[[Cetuximab (Erbitux)]] as follows: | ||
− | **Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours on day 1 | + | **Cycle 1: 400 mg/m<sup>2</sup> IV over 2 hours once on day 1 |
− | **Cycle 2 onwards: 250 mg/m<sup>2</sup> IV once | + | **Cycle 2 onwards: 250 mg/m<sup>2</sup> IV over 60 minutes once on day 1 |
− | + | ====Supportive therapy==== | |
− | ====Supportive | + | *[[Diphenhydramine (Benadryl)]] 50 mg IV or PO once, given 30 to 60 minutes prior to cetuximab |
− | + | '''7-day cycles''' | |
− | *[[Diphenhydramine (Benadryl)]] 50 mg IV or PO once | + | </div></div> |
− | |||
− | ''' | ||
− | |||
===References=== | ===References=== | ||
− | + | #'''SWOG S0415:''' Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. [https://doi.org/10.1097/JTO.0b013e3181e77a92 link to original article] '''dosing details in manuscript have been reviewed by our editors''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/20631636/ PubMed] [https://clinicaltrials.gov/study/NCT00096031 NCT00096031] | |
− | #'''SWOG S0415:''' Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. [https:// | ||
− | |||
==Docetaxel monotherapy {{#subobject:421f5e|Regimen=1}}== | ==Docetaxel monotherapy {{#subobject:421f5e|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen variant #1, 75 mg/m<sup>2</sup> x 6 {{#subobject:044193|Variant=1}}=== | ===Regimen variant #1, 75 mg/m<sup>2</sup> x 6 {{#subobject:044193|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045(13)70549-7 Ford et al. 2013 (COUGAR-02)] |
|2008-2012 | |2008-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |[[ | + | |[[Esophageal_adenocarcinoma_-_null_regimens#Best_supportive_care|Active symptom control]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 5.2 vs 3.6 mo<br>(HR 0.67, 95% CI 0.49-0.92) |
|- | |- | ||
|} | |} | ||
− | ''COUGAR-02 patients | + | ''Note: COUGAR-02 patients had 100% adenocarcinoma histology (20% esophageal, 35% gastroesophageal junction, 45% stomach). 15% ECOG PS of 2. 12% locally advanced, 88% metastatic disease.'' |
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
+ | ====Prior treatment criteria==== | ||
+ | *Progression on or within 6 months of treatment with a platinum-fluoropyrimidine combination | ||
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
− | |||
'''21-day cycle for up to 6 cycles''' | '''21-day cycle for up to 6 cycles''' | ||
− | + | </div></div><br> | |
+ | <div class="toccolours" style="background-color:#eeeeee"> | ||
===Regimen variant #2, 75 mg/m<sup>2</sup>, indefinite {{#subobject:abe193|Variant=1}}=== | ===Regimen variant #2, 75 mg/m<sup>2</sup>, indefinite {{#subobject:abe193|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,553: | Line 1,381: | ||
|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)] | |[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)] | ||
|2008-2010 | |2008-2010 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
− | |1. [[#Irinotecan_monotherapy_2|Irinotecan]]<br> 2. [[#Irinotecan_liposomal_monotherapy|Irinotecan liposomal]] | + | |1. [[#Irinotecan_monotherapy_2|Irinotecan]]<br>2. [[#Irinotecan_liposomal_monotherapy|Irinotecan liposomal]] |
| style="background-color:#d3d3d3" |Not powered to draw conclusions | | style="background-color:#d3d3d3" |Not powered to draw conclusions | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | *[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23406728/ PubMed] [https://clinicaltrials.gov/study/NCT00813072 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:// | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24332238/ PubMed] [https://clinicaltrials.gov/study/NCT00978549 NCT00978549] |
− | |||
==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}== | ==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:9b9808|Variant=1}}=== | ===Regimen {{#subobject:9b9808|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,583: | Line 1,406: | ||
|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)] | |[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)] | ||
|2008-2010 | |2008-2010 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (C) |
− | |1. [[#Docetaxel_monotherapy|Docetaxel]]<br> 2. [[#Irinotecan_liposomal_monotherapy|Irinotecan liposomal]] | + | |1. [[#Docetaxel_monotherapy|Docetaxel]]<br>2. [[#Irinotecan_liposomal_monotherapy|Irinotecan liposomal]] |
| style="background-color:#d3d3d3" |Not powered to draw conclusions | | style="background-color:#d3d3d3" |Not powered to draw conclusions | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1 | *[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] ''' | + | #'''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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23406728/ PubMed] [https://clinicaltrials.gov/study/NCT00813072 NCT00813072] |
− | |||
==Irinotecan liposomal monotherapy {{#subobject:9a99c8|Regimen=1}}== | ==Irinotecan liposomal monotherapy {{#subobject:9a99c8|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:c50e15|Variant=1}}=== | ===Regimen {{#subobject:c50e15|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
Line 1,612: | Line 1,430: | ||
|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)] | |[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)] | ||
|2008-2010 | |2008-2010 | ||
− | | style="background-color:#1a9851" |Randomized Phase | + | | style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic) |
− | |1. [[#Docetaxel_monotherapy|Docetaxel]]<br> 2. [[#Irinotecan_monotherapy_2|Irinotecan]] | + | |1. [[#Docetaxel_monotherapy|Docetaxel]]<br>2. [[#Irinotecan_monotherapy_2|Irinotecan]] |
| style="background-color:#d3d3d3" |Not powered to draw conclusions | | style="background-color:#d3d3d3" |Not powered to draw conclusions | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan liposome (Onivyde)]] 120 mg/m<sup>2</sup> IV over 90 minutes once on day 1 | *[[Irinotecan liposome (Onivyde)]] 120 mg/m<sup>2</sup> IV over 90 minutes once on day 1 | ||
− | |||
'''21-day cycles''' | '''21-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/23406728/ PubMed] [https://clinicaltrials.gov/study/NCT00813072 NCT00813072] | |
− | #'''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] ''' | ||
− | |||
==Irinotecan & Mitomycin {{#subobject:dfc95f|Regimen=1}}== | ==Irinotecan & Mitomycin {{#subobject:dfc95f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:4a905|Variant=1}}=== | ===Regimen {{#subobject:4a905|Variant=1}}=== | ||
− | {| class="wikitable" style="width: | + | {| class="wikitable sortable" style="width: 60%; text-align:center;" |
− | ! style="width: | + | !style="width: 33%"|Study |
− | ! style="width: | + | !style="width: 33%"|Dates of enrollment |
+ | !style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
|- | |- | ||
− | |[ | + | |[https://doi.org/10.1097/01.coc.0000190398.52142.7f Giuliani et al. 2005 (GOIM 2106)] |
− | | style="background-color:#91cf61" |Phase | + | |2001-05 to 2003-04 |
+ | | style="background-color:#91cf61" |Phase 2 | ||
|- | |- | ||
|} | |} | ||
− | ''Patients | + | ''Note: Patients had 100% gastric adenocarcinoma. Treatment given as second-line chemotherapy for pretreated patients with advanced or metastatic disease.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 15 | *[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 15 | ||
*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once on day 1 | *[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once on day 1 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===References=== | ||
− | #Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale. Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. [ | + | #'''GOIM 2106:''' Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale. Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. [https://doi.org/10.1097/01.coc.0000190398.52142.7f link to original article] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/16317268/ PubMed] |
− | |||
==Nivolumab monotherapy {{#subobject:7011e1|Regimen=1}}== | ==Nivolumab monotherapy {{#subobject:7011e1|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:#f2fd8e|Variant=1}}=== | ===Regimen {{#subobject:#f2fd8e|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
! style="width: 20%" |Study | ! style="width: 20%" |Study | ||
− | ! style="width: 20%" | | + | ! style="width: 20%" |Dates of enrollment |
! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]] | ||
! style="width: 20%" |Comparator | ! style="width: 20%" |Comparator | ||
! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ Janjigian et al. 2018 (CheckMate | + | |[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ Janjigian et al. 2018 (CheckMate 032<sub>UGI</sub>)] |
|2013-2015 | |2013-2015 | ||
− | | style="background-color:#91cf61" |Phase | + | | style="background-color:#91cf61" |Phase 1/2 |
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
| style="background-color:#d3d3d3" | | | style="background-color:#d3d3d3" | | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(17)31827-5 Kang et al. 2017 (ATTRACTION-2)] |
|2014-2016 | |2014-2016 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |[[ | + | |[[Esophageal_adenocarcinoma_-_null_regimens#Placebo_3|Placebo]] |
− | | style="background-color:#1a9850" |Superior OS | + | | style="background-color:#1a9850" |Superior OS (primary endpoint)<br>Median OS: 5.26 vs 4.14 mo<br>(HR 0.63, 95% CI 0.51-0.78) |
|- | |- | ||
|} | |} | ||
− | ''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'' | + | ''Note: 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.'' |
− | + | <div class="toccolours" style="background-color:#b3e2cd"> | |
====Immunotherapy==== | ====Immunotherapy==== | ||
− | |||
*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | *[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/28993052/ PubMed] [https://clinicaltrials.gov/study/NCT02267343 NCT02267343] | |
− | #'''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:// | + | ##'''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] |
− | ##'''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:// | + | #'''CheckMate 032<sub>UGI</sub>:''' 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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/30110194/ PubMed] [https://clinicaltrials.gov/study/NCT01928394 NCT01928394] |
− | #'''CheckMate | ||
==Paclitaxel monotherapy {{#subobject:ec998a|Regimen=1}}== | ==Paclitaxel monotherapy {{#subobject:ec998a|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:cc40a4|Variant=1}}=== | ===Regimen {{#subobject:cc40a4|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2814%2970420-6 Wilke et al. 2014 (RAINBOW)] |
|2010-2012 | |2010-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (C) |
|[[#Paclitaxel_.26_Ramucirumab|Paclitaxel & Ramucirumab]] | |[[#Paclitaxel_.26_Ramucirumab|Paclitaxel & Ramucirumab]] | ||
| style="background-color:#fc8d59" |Seems to have inferior OS | | style="background-color:#fc8d59" |Seems to have inferior OS | ||
|- | |- | ||
|} | |} | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
− | |||
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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. [https:// | + | #'''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] '''dosing details in abstract have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25240821/ PubMed] [https://clinicaltrials.gov/study/NCT01170663 NCT01170663] |
− | + | ##'''PRO analysis:''' Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim TY, Cunningham D, Rougier P, Muro K, Liepa AM, Chandrawansa K, Emig M, Ohtsu A, Wilke H. Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma. Ann Oncol. 2016 Apr;27(4):673-9. Epub 2016 Jan 7. [https://doi.org/10.1093/annonc/mdv625 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4803452/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26747859/ PubMed] | |
==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}== | ==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:f66446|Variant=1}}=== | ===Regimen {{#subobject:f66446|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
− | |||
− | |||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S1470-2045%2814%2970420-6 Wilke et al. 2014 (RAINBOW)] |
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-31-1 <span style="color:white;">ESMO-MCBS (2)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2010-2012 | |2010-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
|[[#Paclitaxel_monotherapy_2|Paclitaxel]] | |[[#Paclitaxel_monotherapy_2|Paclitaxel]] | ||
− | | style="background-color:#91cf60" |Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>Median OS: 9.6 vs 7.4 mo<br>(HR 0.81, 95% CI 0.68-0.96) |
− | |||
− | |||
|- | |- | ||
|} | |} | ||
− | '' | + | ''Note: Patients had 100% adenocarcinoma histology, 20% gastroesophageal junction, 80% gastric origin.'' |
− | + | <div class="toccolours" style="background-color:#fdcdac"> | |
− | + | ====Prior treatment criteria==== | |
− | + | *RAINBOW: 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 | |
+ | </div> | ||
+ | <div class="toccolours" style="background-color:#b3e2cd"> | ||
====Targeted therapy==== | ====Targeted therapy==== | ||
*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once per day on days 1 & 15 | *[[Ramucirumab (Cyramza)]] 8 mg/kg IV once per day on days 1 & 15 | ||
====Chemotherapy==== | ====Chemotherapy==== | ||
*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | *[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15 | ||
− | |||
'''28-day cycles''' | '''28-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/25240821/ PubMed] [https://clinicaltrials.gov/study/NCT01170663 NCT01170663] | |
− | #'''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. [https:// | + | ##'''PRO analysis:''' Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim TY, Cunningham D, Rougier P, Muro K, Liepa AM, Chandrawansa K, Emig M, Ohtsu A, Wilke H. Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma. Ann Oncol. 2016 Apr;27(4):673-9. Epub 2016 Jan 7. [https://doi.org/10.1093/annonc/mdv625 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc4803452/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/26747859/ PubMed] |
− | |||
==Ramucirumab monotherapy {{#subobject:425b15|Regimen=1}}== | ==Ramucirumab monotherapy {{#subobject:425b15|Regimen=1}}== | ||
− | + | <div class="toccolours" style="background-color:#eeeeee"> | |
− | |||
− | |||
− | |||
===Regimen {{#subobject:813cff|Variant=1}}=== | ===Regimen {{#subobject:813cff|Variant=1}}=== | ||
{| class="wikitable sortable" style="width: 100%; text-align:center;" | {| class="wikitable sortable" style="width: 100%; text-align:center;" | ||
!style="width: 20%"|Study | !style="width: 20%"|Study | ||
− | !style="width: 20%"| | + | !style="width: 20%"|Dates of enrollment |
!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]] | ||
!style="width: 20%"|Comparator | !style="width: 20%"|Comparator | ||
!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]] | ||
|- | |- | ||
− | |[https:// | + | |[https://doi.org/10.1016/S0140-6736(13)61719-5 Fuchs et al. 2013 (REGARD)] |
+ | <!-- {| class="wikitable" style="margin:auto; color:white; background-color:#1B4F26" | ||
+ | |'''[https://www.esmo.org/guidelines/esmo-mcbs/esmo-mcbs-scorecards/scorecard-32-1 <span style="color:white;">ESMO-MCBS (1)</span>]''' | ||
+ | |- | ||
+ | |} --> | ||
|2009-2012 | |2009-2012 | ||
− | | style="background-color:#1a9851" |Phase | + | | style="background-color:#1a9851" |Phase 3 (E-esc) |
− | |[[ | + | |[[Esophageal_adenocarcinoma_-_null_regimens#Placebo_3|Placebo]] |
− | | style="background-color:#91cf60" |Seems to have superior OS | + | | style="background-color:#91cf60" |Seems to have superior OS (primary endpoint)<br>Median OS: 5.2 vs 3.8 mo<br>(HR 0.78, 95% CI 0.60-0.998) |
|- | |- | ||
|} | |} | ||
− | ''Patients in REGARD | + | ''Note: Patients in REGARD had 100% adenocarcinoma histology (25% gastroesophageal junction, 75% gastric origin).'' |
− | + | <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==== | ====Targeted therapy==== | ||
− | |||
*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once on day 1 | *[[Ramucirumab (Cyramza)]] 8 mg/kg IV once on day 1 | ||
− | |||
'''14-day cycles''' | '''14-day cycles''' | ||
− | + | </div></div> | |
===References=== | ===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] '''dosing details in manuscript have been reviewed by our editors''' [https://pubmed.ncbi.nlm.nih.gov/24094768/ PubMed] [https://clinicaltrials.gov/study/NCT00917384 NCT00917384] | |
− | #'''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:// | ||
− | |||
[[Category:Esophageal cancer regimens]] | [[Category:Esophageal cancer regimens]] | ||
− | [[Category: | + | [[Category:Histology-specific pages]] |
− | [[Category: | + | [[Category:Esophageal cancers]] |
Latest revision as of 23:38, 15 July 2024
Section editor | |
---|---|
Travis Zack, MD, PhD University of California San Francisco San Francisco, CA, USA |
Are you looking for a regimen but can't find it here? For placebo or observational studies in this condition, please visit this page. If you still can't find it, please let us know so we can add it!.
Note: these are regimens tested in histology-specific populations, please see the main esophageal cancer page for other regimens.
42 regimens on this page
47 variants on this page
|
Guidelines
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
NCCN
- NCCN does not currently have guidelines at this granular level; please see NCCN Guidelines - Esophageal and Esophagogastric Junction Cancers.
Perioperative therapy
This section contains protocols with a pre-planned neoadjuvant (preoperative) and adjuvant (postoperative) component.
Cisplatin & Fluorouracil (CF)
CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol (Cisplatin)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ychou et al. 2011 (ACCORD 07) | 1995-2003 | Phase 3 (E-esc) | Surgery alone | Superior OS (primary endpoint) OS60: 38% vs 24% (HR 0.69, 95% CI 0.50-0.95) |
Note: Study included patients with gastric malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).
Neoadjuvant
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
28-day cycle for 2 to 3 cycles, followed by:
Definitive
Local therapy
Adjuvant
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 28
- Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
28-day cycle for 3 to 4 cycles, for a total of 6 cycles
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. Epub 2011 Mar 28. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00002883
ECF
ECF: Epirubicin, Cisplatin, Fluorouracil
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2006 (MAGIC) | 1994-2002 | Phase 3 (E-esc) | Surgery alone | Superior OS (primary endpoint) OS60: 36% vs 23% (HR 0.75, 95% CI 0.60-0.93) |
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase 2/3 (C) | Perioperative FLOT | Inferior OS |
Note: MAGIC patients had 100% adenocarcinoma histology. 75% gastric adenocarcinoma, 15% lower esophagus, 11% gastroesophageal junction.
Neoadjuvant
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
21-day cycle for 3 cycles, followed by:
Definitive
Local therapy
- Surgery occurs 3 to 6 weeks after completing cycle 3
Adjuvant chemotherapy is started 6 to 12 weeks after surgery:
Adjuvant
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
Supportive therapy
- MAGIC: Warfarin (Coumadin) 1 mg PO once per day recommended for thrombosis prophylaxis
21-day cycle for 3 cycles
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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00002615
- 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. link to original article 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, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter 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. link to original article PubMed
ECX
ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2017 (UK MRC ST03) | 2007-2014 | Phase 3 (C) | Perioperative ECX & Bevacizumab | Did not meet primary endpoint of OS |
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase 2/3 (C) | Perioperative FLOT | Inferior OS |
Note: UK MRC ST03 patients had 100% adenocarcinoma histology (36% gastric, 14% lower esophageal, 50% gastroesophageal junction). FLOT4-AIO patients had 100% adenocarcinoma histology including gastroesophageal junction (AEG I-III) or the stomach.
Neoadjuvant
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day
21-day cycle for 3 cycles, followed by:
Definitive
Local therapy
Adjuvant
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day
21-day cycle for 3 cycles
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. link to original article 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, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter 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. link to original article PubMed
- UK MRC ST03: Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. link to original article dosing details in abstract have been reviewed by our editors link to PMC article PubMed NCT00450203
FLOT
FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase 2/3 (E-switch-ic) | 1a. Perioperative ECF 1b. Perioperative ECX |
Superior OS1 (primary endpoint) Median OS: 50 vs 35 mo (HR 0.77, 95% CI 0.63-0.94) |
1Reported efficacy is based on the 2019 update.
Note: FLOT4-AIO patients had 100% adenocarcinoma histology of the gastroesophageal junction (AEG I-III) or the stomach.
Neoadjuvant
Chemotherapy
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 50 mg/m2 IV once on day 1
14-day cycle for 4 cycles, followed by:
Definitive
Local therapy
Adjuvant
Chemotherapy
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous infusion over 24 hours, started on day 1
- Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
- Docetaxel (Taxotere) 50 mg/m2 IV once on day 1
14-day cycle for 4 cycles
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. link to original article 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. link to original article PubMed
Neoadjuvant induction therapy
Cisplatin & Fluorouracil (CF)
CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol (Cisplatin)
Regimen variant #1, 40/4200
Study | Dates of enrollment | Evidence |
---|---|---|
Ajani et al. 2006 (RTOG 9904) | 1999-2004 | Phase 2 |
Note: Patients had 100% adenocarcinoma histology. The majority of patients had gastric adenocarcinoma. Although gastroesophageal junction was involved, percentages were not included.
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 & 5
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
28-day cycle for 2 cycles
Subsequent treatment
- Neoadjuvant fluorouracil, paclitaxel, RT, then surgery
Regimen variant #2, 80/4000, 4 day 5-FU infusion
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alderson et al. 2017 (UK MRC OE05) | 2005-2011 | Phase 3 (C) | ECX | Might have inferior OS |
Note: UK MRC OE05 patients had 100% adenocarcinoma of the esophagus (including Siewert types 1 and 2 gastroesophageal junction tumors)
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycle for 2 cycles
Subsequent treatment
References
- RTOG 9904: Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- UK MRC OE05: Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, Grabsch HI, Langer R, Pritchard S, Okines A, Krysztopik R, Coxon F, Thompson J, Falk S, Robb C, Stenning S, Langley RE. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1249-1260. Epub 2017 Aug 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00041262
Cisplatin & Irinotecan (IC)
IC: Irinotecan & Cisplatin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Rivera et al. 2009 | 2003-12 to 2004-10 | Phase 2 |
Note: Rivera et al. patients had 100% adenocarcinoma histology (43% gastroesophageal junction, 57% gastric adenocarcinoma)
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
- Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
Supportive therapy
- Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1 & 8, prior to chemotherapy
- One of the following:
- Granisetron 2 mg PO once per day on days 1 & 8, prior to chemotherapy
- Ondansetron (Zofran) 32 mg IV once per day on days 1 & 8, prior to chemotherapy
- At least 500 mL D5NS or NS as supportive hydration
- Atropine (Atropen) 0.5 to 1 mg IV prn cholinergic symptoms
21-day cycle for 2 cycles
Subsequent treatment
- Neoadjuvant cisplatin, irinotecan, RT, then surgery
References
- Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed
CLF
CLF: Cisplatin, Leucovorin, Fluorouracil
PLF: Platinol (Cisplatin), Leucovorin, Fluorouracil
Regimen variant #1, 12 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stahl et al. 2009 (POET) | 2000-2005 | Phase 3 (E-de-esc) | See link | See link |
Note: Patients had 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1, 15, 29
- Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m2)
42-day cycle for 2 cycles
Subsequent treatment
- Neoadjuvant Cisplatin, Etoposide, RT, then surgery
Regimen variant #2, 15 weeks
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stahl et al. 2009 (POET) | 2000-2005 | Phase 3 (C) | PLF x 12 wk, then EP & RT | Might have inferior OS |
Note: this regimen is given for 2.5 cycles, which is a highly unusual instruction; total duration of treatment is 15 weeks. Patients had 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1, 15, 29
- Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m2)
42-day cycle for 2.5 cycles
Subsequent treatment
- Surgery, in 3 to 4 weeks
References
- POET: Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. link to original article PubMed
ECX
ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alderson et al. 2017 (UK MRC OE05) | 2005-2011 | Phase 3 (E-esc) | CF | Might have superior OS (primary endpoint) Median OS: 26.1 vs 23.4 mo (HR 0.90, 95% CI 0.77-1.05) |
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Capecitabine (Xeloda) 1250 mg/m2/day PO on days 1 to 21
21-day cycle for 4 cycles
Subsequent treatment
References
- UK MRC OE05: Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, Grabsch HI, Langer R, Pritchard S, Okines A, Krysztopik R, Coxon F, Thompson J, Falk S, Robb C, Stenning S, Langley RE. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1249-1260. Epub 2017 Aug 4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT00041262
Neoadjuvant chemoradiotherapy
Note: while these regimens are listed as neoadjuvant (pre-operative), in some cases they are also used as definitive therapy in patients that are not surgical candidates.
Cisplatin, Etoposide, RT
EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stahl et al. 2009 (POET) | 2000-2005 | Phase 3 (E-esc) | See link | See link |
Note: Patients had 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III. Chemoradiation is to start 2 weeks after the last day of PLF.
Preceding treatment
- PLF induction x 12 wk
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1 & 8
- Etoposide (Vepesid) 80 mg/m2 IV over 60 minutes once per day on days 3 to 5
Radiotherapy
- Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19 (15 fractions; target dose of 3000 cGy)
3-week course
Subsequent treatment
- Surgery, in 3 to 4 weeks
References
- POET: Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- Update: Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. link to original article PubMed
Cisplatin & Fluorouracil (CF) & RT
CF & RT: Cisplatin, Fluourouracil, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Walsh et al. 1996 | 1990-1995 | Randomized Phase 2 (E-esc) | Surgery alone | Superior OS (primary endpoint) |
Note: of historic interest only.
Chemotherapy
- Cisplatin (Platinol) 15 mg/kg IV over 16 hours once per day on days 1 to 5
- Fluorouracil (5-FU) 75 mg/m2 IV over 8 hours once on day 7
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 1: 267 cGy per fraction on days 1 to 5, 8 to 12, 15 to 19
5-week cycle for 2 cycles
Subsequent treatment
References
- Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Cisplatin, Irinotecan, RT
Cisplatin, Irinotecan, RT: Cisplatin, Irinotecan, Radiation Therapy
Regimen variant #1, 60/130 x 2 + 4500 cGy
Study | Dates of enrollment | Evidence |
---|---|---|
Yoon et al. 2011 (ECOG E1201) | 2002-2004 | Phase 2 |
Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 22, 29
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1, 8, 22, 29
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy)
5-week course
Regimen variant #2
Study | Dates of enrollment | Evidence |
---|---|---|
Rivera et al. 2009 | 2003-12 to 2004-10 | Phase 2 |
Note: Patients had 100% adenocarcinoma histology (43% gastroesophageal junction, 57% gastric adenocarcinoma)
Preceding treatment
- IC induction x 2
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1, 8, 15, 22
Radiotherapy
- Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy)
5-week course
Subsequent treatment
- Surgery, 5 to 8 weeks after finishing chemoradiation
References
- Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. link to original article dosing details in manuscript have been reviewed by our editors PubMed
- ECOG E1201: Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Cisplatin, Paclitaxel, RT
Cisplatin, Paclitaxel, RT: Cisplatin, Paclitaxel, Radiation Therapy
Regimen variant #1, weekly cisplatin
Study | Dates of enrollment | Evidence |
---|---|---|
Yoon et al. 2011 (ECOG E1201) | 2002-2004 | Phase 2 |
Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy)
5-week course
Subsequent treatment
- Surgery no earlier than 28 days after finishing chemoradiation, then adjuvant cisplatin & paclitaxel no earlier than 28 days after surgical resection
References
- ECOG E1201: Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Fluorouracil, Paclitaxel, RT
Fluorouracil, Paclitaxel, RT: Fluorouracil, Paclitaxel, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Ajani et al. 2006 (RTOG 9904) | 1999-2004 | Phase 2 |
Note: Patients had 100% adenocarcinoma histology. The majority of patients had gastric adenocarcinoma. Although gastroesophageal junction was involved, percentages were not included.
Preceding treatment
- CF induction x 2
Chemotherapy
- Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 7500 mg/m2)
- Paclitaxel (Taxol) 45 mg/m2 IV once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 4500 cGy)
5-week course
Subsequent treatment
References
- RTOG 9904: Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Adjuvant therapy
Cisplatin & Irinotecan (IC)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Yoon et al. 2011 (ECOG E1201) | 2002-2004 | Phase 2 |
Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Preceding treatment
- Neoadjuvant cisplatin, irinotecan, RT, then surgery
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycle for 3 cycles
References
- ECOG E1201: Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
Cisplatin & Paclitaxel
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Yoon et al. 2011 (ECOG E1201) | 2002-2004 | Phase 2 |
Note: Patients had 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Preceding treatment
- Neoadjuvant cisplatin, paclitaxel, RT, then surgery
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
References
- ECOG E1201: Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
ECF/5-FU & RT
ECF/5-FU & RT: Epirubicin, Cisplatin, Fluorouracil alternating with 5-FluoroUracil & Radiation Therapy sandwich
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Leong et al. 2010 | 2003-07 to 2006-10 | Phase 2 |
Note: In contrast to the primary reference, some guidelines list this regimen without ECF cycles 1, 3, 4. Patients had 100% adenocarcinoma (6% gastroesophageal junction, 94% gastric origin).
Preceding treatment
- Surgery, within 10 weeks
Chemotherapy
- Epirubicin (Ellence) as follows:
- Cycle 1: 50 mg/m2 IV bolus once on day 1
- Cycles 3 & 4: 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) as follows:
- Cycle 1: 60 mg/m2 IV once on day 1
- Cycles 3 & 4: 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) as follows:
- Cycle 1: 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
- Cycle 2 (chemoradiation): 225 mg/m2/day IV continuous infusion over 35 days, started on day 1 (total dose: 7875 mg/m2)
- Cycles 3 & 4: 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 2 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
4- to 6-week course, then 9-week course, then 21-day cycle for 2 cycles
References
- Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M; Trans-Tasman Radiation Oncology Group. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):690-5. Epub 2010 May 14. link to original article dosing details in manuscript have been reviewed by our editors PubMed
FULV & RT
FULV & RT: FluoroUracil, LeucoVorin, Radiation Therapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Macdonald et al. 2001 (INT-0116) | 1991-1998 | Phase 3 (E-esc) | Observation | Superior OS (primary endpoint) Median OS: 36 vs 27 mo (HR 0.74, 95% CI 0.60-0.92) |
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) as follows:
- Cycles 1, 3, 4: 425 mg/m2 IV bolus once per day on days 1 to 5 (total dose per cycle: 2125 mg/m2)
- Cycle 2 (chemoradiation): 400 mg/m2 IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy (total dose: 2800 mg/m2)
- Leucovorin (Folinic acid) as follows:
- Cycles 1, 3, 4: 20 mg/m2 IV bolus once per day on days 1 to 5
- Cycle 2 (chemoradiation): 20 mg/m2 IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
Radiotherapy
- Concurrent radiation therapy as follows:
- Cycle 2 (chemoradiation): 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
28-day course, then 9-week course, then 28-day cycle for 2 cycles
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. link to original article dosing details in manuscript have been reviewed by our editors PubMed
Metastatic or locally advanced disease, first-line
Capecitabine & Cisplatin (CX)
CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2009 | 2003-2006 | Randomized Phase 2 (E-switch-ic) | XI | Did not meet primary endpoint of ORR |
Lordick et al. 2013 (EXPAND) | 2008-2010 | Phase 3 (C) | CX & Cetuximab | Did not meet primary endpoint of PFS |
Note: EXPAND patients had 100% adenocarcinoma (stomach or gastroesophageal junction) locally advanced unresectable (M0) or metastatic (M1).
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Alternative dosing in Lordick et al. 2013: 1000 mg/m2 PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)
21-day cycles
References
- Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. link to original article PubMed
- 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00678535
Capecitabine & Cisplatin (CX) & Cetuximab
CX-C: Cisplatin, Xeloda (Capecitabine), Cetuximab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lordick et al. 2013 (EXPAND) | 2008-2010 | Phase 3 (E-esc) | CX | Did not meet primary endpoint of PFS |
Note: Patients had 100% adenocarcinoma (stomach or gastroesophageal junction) locally advanced unresectable (M0) or metastatic (M1).
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV once on day 1
- Cycle 2 onwards: 250 mg/m2 IV once per day on days 1, 8, 15
21-day cycles
References
- 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00678535
CapeOx
CapeOX: Capecitabine & OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2020 (JAVELIN Gastric 100) | 2015-2017 | Phase 3 (C) | 1a. CapeOx-Avelumab 1b. FOLFOX6-Avelumab 1c. mFOLFOX6-Avelumab |
Did not meet primary endpoint of OS |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycles
References
- 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02872116
- Update: Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. link to original article link to PMC article PubMed
- HRQoL analysis: Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. link to original article link to PMC article PubMed
- Update: Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. link to original article link to PMC article PubMed
CapeOx & Nivolumab
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2021 (CheckMate 649) | 2017-03 to 2019-04 | Phase 3 (E-RT-esc) | 1a. CapeOx 1b. mFOLFOX6 |
Superior OS1 (co-primary endpoint) Median OS: 14.4 vs 11.1 mo (HR 0.70, 95% CI 0.61-0.81) Superior PFS (co-primary endpoint) Median PFS: 7.7 vs 6.05 mo (HR 0.68, 98% CI 0.56-0.81) |
2. Ipilimumab & Nivolumab | Not reported |
1Reported efficacy and MCBS score are for the group with PD-L1 CPS of 5 or more; reported efficacy is based on the 2022 update.
Note: CheckMate 649 included patients on both 21-day (Nivo/CapeOx) and 14-day (Nivo/FOLFOX) regimens in the immunotherapy + chemo arm. 60% PD-L1 CPS >5, 82% PD-L1 CPS >1.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
Immunotherapy
- Nivolumab 360 mg IV once on day 1
21-day cycles
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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02872116
- Update: Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. link to original article link to PMC article PubMed
- HRQoL analysis: Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. link to original article link to PMC article PubMed
- Update: Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. link to original article link to PMC article PubMed
CAPIRI
CapeIRI: Capecitabine and IRInotecan
CAPIRI: CAPecitabine and IRInotecan
XELIRI: XELox (Capecitabine) and IRInotecan
XI: Xeloda (Capecitabine) and Irinotecan
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2009 | 2003-2006 | Randomized Phase 2 (E-switch-ic) | XP | Did not meet primary endpoint of ORR |
Note: Patients had 45% esophageal, 38% gastroesophageal junction, 17% gastric origin. 93% adenocarcinoma, 7% squamous cell histology. 86% metastatic disease. 14% ECOG PS of 2.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Irinotecan (Camptosar) 250 mg/m2 IV over 30 to 90 minutes once on day 1
Supportive therapy
- Atropine (Atropen) 0.25 mg SC once on day 1, given prior to irinotecan
- Loperamide (Imodium) 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool
- Ciprofloxacin (Cipro) 250 mg PO twice per day prn diarrhea lasting longer than 24 hours despite loperamide
21-day cycles
References
- Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. link to original article PubMed
Cisplatin & Fluorouracil (CF)
CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Van Cutsem et al. 2006 (TAX 325) | 1999-2003 | Phase 3 (C) | DCF | Seems to have inferior OS |
Dank et al. 2008 | 2000-2002 | Phase 3 (C) | IF | Might have inferior TTP |
Note: TAX 325 patients had 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70. Dank et al. patients had 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 1 to 3 hours once on day 1, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 5000 mg/m2)
Supportive therapy
- As described in Dank et al. 2008:
- "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/μL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
- Atropine (Atropen) prn cholinergic symptoms
- Loperamide (Imodium) prn delayed diarrhea
28-day cycles
References
- 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. link to original article dosing details in manuscript have been reviewed by our editors 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed
ECX
ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen variant #1, 50/60/1250
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Iveson et al. 2014 (Amgen 20060317) | 2009 | Randomized Phase 2 (C) | ECX & Rilotumumab | Seems to have inferior PFS |
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV over 4 hours once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 21
21-day cycles
Regimen variant #2, 50/60/2000
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Guimbaud et al. 2014 (FFCD 03-07) | 2005-2008 | Phase 3 (C) | FOLFIRI | Inferior TTF |
Chemotherapy
- Epirubicin (Ellence) as follows:
- Cycles 1 up to 18: 50 mg/m2 IV over 15 minutes once on day 1 (maximum cumulative dose of 900 mg/m2)
- Cisplatin (Platinol) 60 mg/m2 IV over 60 minutes once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 2 to 15
21-day cycles
References
- Amgen 20060317: Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. Epub 2014 Jun 22. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT00719550
- 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00374036
Erlotinib monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Dragovich et al. 2006 (SWOG 0127) | 2002-2003 | Phase 2 |
Note: Patients had 100% adenocarcinoma (63% gastroesophageal junction, 37% gastric origin). All with ECOG PS of 0 or 1.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28, taken at least 1 hour before a meal or 2 hours after a meal
28-day cycles
References
- SWOG 0127: Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00032123
FLOT
FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Al-Batran et al. 2008a | 2006 | Phase 2 |
Note: Patients had 100% adenocarcinoma histology (44% gastroesophageal junction, 56% gastric origin). 93% metastatic disease. 15% with ECOG 2-3.
Chemotherapy
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous infusion over 24 hours, started on day 1, given fourth
- Leucovorin (Folinic acid) 200 mg/m2 IV over 1 to 2 hours once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 1 to 2 hours once on day 1
- Docetaxel (Taxotere) 50 mg/m2 IV over 1 to 2 hours once on day 1
Supportive therapy
- Dexamethasone (Decadron) 8 mg PO once per day on days 0 to 3
14-day cycle for up to 8 (or more) cycles
References
- Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. link to original article dosing details in manuscript have been reviewed by our editors PubMed
FOLFIRI
FOLFIRI: FOLinic acid (Leucovorin), Fluorouracil, IRInotecan
IF: Irinotecan & 5-Fluorouracil
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Wolff et al. 2009 | 2002-2006 | Phase 2 |
Chemotherapy
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 22 hours, started on days 1, 8, 15, 22, 29, 36, given third (total dose per cycle: 12,000 mg/m2)
- Leucovorin (Folinic acid) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given second
- Irinotecan (Camptosar) 80 mg/m2 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/μL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
- Atropine (Atropen) prn cholinergic symptoms
- Loperamide (Imodium) prn delayed diarrhea
7-week cycles
References
- Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. link to original article dosing details in abstract have been reviewed by our editors PubMed
Irinotecan monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Enzinger et al. 2005 | 1997-12 to 2000-08 | Phase 2 |
Note: In contrast to the primary reference, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles. Patients had 100% adenocarcinoma histology, both gastric and esophageal.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22
42-day cycles
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. link to original article PubMed
Irinotecan & Mitomycin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lustberg et al. 2010 | 2002-2006 | Randomized Phase 2 (E-switch-ic) | Irinotecan & Mitomycin; alternate schedule | No statistical comparison |
Note: Patients had 56% lower esophageal, 44% gastroesophageal junction. 100% adenocarcinoma histology. 100% previously untreated 6% with ECOG PS = 2. 77% stage four disease.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV once per day on days 2 & 9
- Mitomycin (Mutamycin) 6 mg/m2 IV once on day 1
Supportive therapy
- Ondansetron (Zofran) or Granisetron and Dexamethasone (Decadron) premedication
- Loperamide (Imodium) started with first episode of diarrhea
- Erythropoietin for hemoglobin less than 10 g/dL permitted
28-day cycle for up to 6 cycles
References
- Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed
FOLFOX6
FOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2020 (JAVELIN Gastric 100) | 2015-2017 | Phase 3 (C) | 1a. CapeOx-Avelumab 1b. FOLFOX6-Avelumab 1c. mFOLFOX6-Avelumab |
Did not meet primary endpoint of OS |
Chemotherapy
- Leucovorin (Folinic acid) 200 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous infusion over 24 hours, started on day 1, given last
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycles
References
- 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02625610
mFOLFOX6
mFOLFOX6: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shah et al. 2021 (GAMMA-1) | 2015-2019 | Phase 3 (C) | mFOLFOX6 & Andecaliximab | 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.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 12 cycles
Subsequent treatment
- FULV maintenance
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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article 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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02872116
- Update: Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. link to original article link to PMC article PubMed
- HRQoL analysis: Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. link to original article link to PMC article PubMed
- Update: Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. link to original article link to PMC article PubMed
mFOLFOX6 (L-Leucovorin)
mFOLFOX6: modified L-FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shah et al. 2021 (GAMMA-1) | 2015-2019 | Phase 3 (C) | mFOLFOX6 & Andecaliximab | 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.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Levoleucovorin (Fusilev) 200 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
14-day cycle for 12 cycles
Subsequent treatment
- FULV maintenance
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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02545504
mFOLFOX6 & Nivolumab
mFOLFOX6 & Nivolumab: modified L-FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Nivolumab
Regimen
FDA-recommended dose |
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2021 (CheckMate 649) | 2017-03 to 2019-04 | Phase 3 (E-RT-esc) | 1a. CapeOx 1b. mFOLFOX6 |
Superior OS1 (co-primary endpoint) Median OS: 14.4 vs 11.1 mo (HR 0.70, 95% CI 0.61-0.81) Superior PFS (co-primary endpoint) Median PFS: 7.7 vs 6.05 mo (HR 0.68, 98% CI 0.56-0.81) |
2. Ipilimumab & Nivolumab | Not reported |
1Reported efficacy and MCBS score are for the group with PD-L1 CPS of 5 or more; reported efficacy is based on the 2022 update.
Note: CheckMate 649 included patients on both 21-day (Nivo/CapeOx) and 14-day (Nivo/FOLFOX) regimens in the immunotherapy + chemo arm. 60% PD-L1 CPS >5, 82% PD-L1 CPS >1.
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m2)
- Leucovorin (Folinic acid) 400 mg/m2 IV once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV once on day 1
Immunotherapy
- Nivolumab 240 mg IV once on day 1
14-day cycles
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. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT02872116
- Update: Shitara K, Ajani JA, Moehler M, Garrido M, Gallardo C, Shen L, Yamaguchi K, Wyrwicz L, Skoczylas T, Bragagnoli AC, Liu T, Tehfe M, Elimova E, Bruges R, Zander T, de Azevedo S, Kowalyszyn R, Pazo-Cid R, Schenker M, Cleary JM, Yanez P, Feeney K, Karamouzis MV, Poulart V, Lei M, Xiao H, Kondo K, Li M, Janjigian YY. Nivolumab plus chemotherapy or ipilimumab in gastro-oesophageal cancer. Nature. 2022 Mar;603(7903):942-948. Epub 2022 Mar 23. link to original article link to PMC article PubMed
- HRQoL analysis: Moehler M, Xiao H, Blum SI, Elimova E, Cella D, Shitara K, Ajani JA, Janjigian YY, Garrido M, Shen L, Yamaguchi K, Liu T, Schenker M, Kowalyszyn R, Bragagnoli AC, Bruges R, Montesarchio V, Pazo-Cid R, Hunter S, Davenport E, Wang J, Kondo K, Li M, Wyrwicz L. Health-Related Quality of Life With Nivolumab Plus Chemotherapy Versus Chemotherapy in Patients With Advanced Gastric/Gastroesophageal Junction Cancer or Esophageal Adenocarcinoma From CheckMate 649. J Clin Oncol. 2023 Dec 10;41(35):5388-5399. Epub 2023 Sep 15. link to original article link to PMC article PubMed
- Update: Janjigian YY, Ajani JA, Moehler M, Shen L, Garrido M, Gallardo C, Wyrwicz L, Yamaguchi K, Cleary JM, Elimova E, Karamouzis M, Bruges R, Skoczylas T, Bragagnoli A, Liu T, Tehfe M, Zander T, Kowalyszyn R, Pazo-Cid R, Schenker M, Feeny K, Wang R, Lei M, Chen C, Nathani R, Shitara K. First-Line Nivolumab Plus Chemotherapy for Advanced Gastric, Gastroesophageal Junction, and Esophageal Adenocarcinoma: 3-Year Follow-Up of the Phase III CheckMate 649 Trial. J Clin Oncol. 2024 Jun 10;42(17):2012-2020. Epub 2024 Feb 21. link to original article link to PMC article PubMed
Metastatic or locally advanced disease, subsequent lines of therapy
Apatinib monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2016 (HENGRUI 20101208) | 2011-01 to 2012-11 | Phase 3 (E-esc) | Placebo | Superior OS (co-primary endpoint) Median OS: 6.5 vs 4.7 mo (HR 0.71, 95% CI 0.54-0.94) |
References
- HENGRUI 20101208: Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016 May 1;34(13):1448-54. Epub 2016 Feb 16. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01512745
Cetuximab monotherapy
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Gold et al. 2010 (SWOG S0415) | 2005-2007 | Phase 2 |
Note: Patients had 100% metastatic esophageal adenocarcinoma who failed one prior chemotherapy regimen. 10% had ECOG PS of 2.
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV over 2 hours once on day 1
- Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once on day 1
Supportive therapy
- Diphenhydramine (Benadryl) 50 mg IV or PO once, given 30 to 60 minutes prior to cetuximab
7-day cycles
References
- SWOG S0415: Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article PubMed NCT00096031
Docetaxel monotherapy
Regimen variant #1, 75 mg/m2 x 6
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ford et al. 2013 (COUGAR-02) | 2008-2012 | Phase 3 (E-esc) | Active symptom control | Superior OS (primary endpoint) Median OS: 5.2 vs 3.6 mo (HR 0.67, 95% CI 0.49-0.92) |
Note: COUGAR-02 patients had 100% adenocarcinoma histology (20% esophageal, 35% gastroesophageal junction, 45% stomach). 15% ECOG PS of 2. 12% locally advanced, 88% metastatic disease.
Prior treatment criteria
- Progression on or within 6 months of treatment with a platinum-fluoropyrimidine combination
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycle for up to 6 cycles
Regimen variant #2, 75 mg/m2, indefinite
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roy et al. 2013 (PEP0206) | 2008-2010 | Randomized Phase 2 (C) | 1. Irinotecan 2. Irinotecan liposomal |
Not powered to draw conclusions |
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. link to original article dosing details in manuscript have been reviewed by our editors 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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00978549
Irinotecan monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roy et al. 2013 (PEP0206) | 2008-2010 | Randomized Phase 2 (C) | 1. Docetaxel 2. Irinotecan liposomal |
Not powered to draw conclusions |
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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00813072
Irinotecan liposomal monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roy et al. 2013 (PEP0206) | 2008-2010 | Randomized Phase 2 (E-switch-ic) | 1. Docetaxel 2. Irinotecan |
Not powered to draw conclusions |
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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00813072
Irinotecan & Mitomycin
Regimen
Study | Dates of enrollment | Evidence |
---|---|---|
Giuliani et al. 2005 (GOIM 2106) | 2001-05 to 2003-04 | Phase 2 |
Note: Patients had 100% gastric adenocarcinoma. Treatment given as second-line chemotherapy for pretreated patients with advanced or metastatic disease.
Chemotherapy
- Irinotecan (Camptosar) 150 mg/m2 IV once per day on days 1 & 15
- Mitomycin (Mutamycin) 8 mg/m2 IV once on day 1
28-day cycles
References
- GOIM 2106: Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale. Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. link to original article dosing details in abstract have been reviewed by our editors PubMed
Nivolumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2018 (CheckMate 032UGI) | 2013-2015 | Phase 1/2 | ||
Kang et al. 2017 (ATTRACTION-2) | 2014-2016 | Phase 3 (E-esc) | Placebo | Superior OS (primary endpoint) Median OS: 5.26 vs 4.14 mo (HR 0.63, 95% CI 0.51-0.78) |
Note: 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.
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. link to original article dosing details in manuscript have been reviewed by our editors 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. link to original article link to original article PubMed
- CheckMate 032UGI: 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. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors PubMed NCT01928394
Paclitaxel monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wilke et al. 2014 (RAINBOW) | 2010-2012 | Phase 3 (C) | Paclitaxel & Ramucirumab | Seems to have inferior OS |
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. link to original article dosing details in abstract have been reviewed by our editors PubMed NCT01170663
- PRO analysis: Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim TY, Cunningham D, Rougier P, Muro K, Liepa AM, Chandrawansa K, Emig M, Ohtsu A, Wilke H. Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma. Ann Oncol. 2016 Apr;27(4):673-9. Epub 2016 Jan 7. link to original article link to PMC article PubMed
Paclitaxel & Ramucirumab
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wilke et al. 2014 (RAINBOW) | 2010-2012 | Phase 3 (E-esc) | Paclitaxel | Seems to have superior OS (primary endpoint) Median OS: 9.6 vs 7.4 mo (HR 0.81, 95% CI 0.68-0.96) |
Note: Patients had 100% adenocarcinoma histology, 20% gastroesophageal junction, 80% gastric origin.
Prior treatment criteria
- RAINBOW: 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
Targeted therapy
- Ramucirumab (Cyramza) 8 mg/kg IV once per day on days 1 & 15
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT01170663
- PRO analysis: Al-Batran SE, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov ON, Kim TY, Cunningham D, Rougier P, Muro K, Liepa AM, Chandrawansa K, Emig M, Ohtsu A, Wilke H. Quality-of-life and performance status results from the phase III RAINBOW study of ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated gastric or gastroesophageal junction adenocarcinoma. Ann Oncol. 2016 Apr;27(4):673-9. Epub 2016 Jan 7. link to original article link to PMC article PubMed
Ramucirumab monotherapy
Regimen
Study | Dates of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fuchs et al. 2013 (REGARD) | 2009-2012 | Phase 3 (E-esc) | Placebo | Seems to have superior OS (primary endpoint) Median OS: 5.2 vs 3.8 mo (HR 0.78, 95% CI 0.60-0.998) |
Note: Patients in REGARD had 100% adenocarcinoma histology (25% gastroesophageal junction, 75% gastric origin).
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
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. link to original article dosing details in manuscript have been reviewed by our editors PubMed NCT00917384