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Section editor transclusions Note: there is significant overlap between regimens for gastric cancer and esophageal cancer, if you can't find the regimen you're looking for here, please try the esophageal cancer page. If you still can't find it, it is possible that we've moved it to the historical regimens page. For placebo or observational studies in this condition, please visit this page.

Note: this page contains regimens which were not tested in biomarker-specific populations. The following links will take you to biomarker-specific subpages:

Regimens for HER2 positive gastric cancer are here.

0 regimens on this page 0 variants on this page

Guidelines

ESMO

2019: Stjepanovic et al. Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up
2016: Smyth et al. Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

ESMO/ESSO/ESTRO

2013: Waddell et al. Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up PubMed

NCCN

NCCN Guidelines - Gastric Cancer

Perioperative therapy

This section contains protocols with a pre-planned neoadjuvant (preoperative) and adjuvant (postoperative) component.

Capecitabine & Cisplatin (CX)

CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (KEYNOTE-585)	2017-ongoing	Phase 3 (C)	1. Perioperative CX & Pembrolizumab 2. Perioperative CF & Pembrolizumab 3. FLOT & Pembrolizumab	To be determined

Chemotherapy, neoadjuvant CX portion

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

Surgery

Surgical resection

Chemotherapy, adjuvant CX portion

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

References

KEYNOTE-585: contains dosing details on CT.gov NCT03221426

Cisplatin & Fluorouracil (CF)

CF: Cisplatin & Fluorouracil
FP: Fluorouracil & Platinol (Cisplatin)

Protocol variant #1, 80/4000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (KEYNOTE-585)	2017-ongoing	Phase 3 (C)	1. Perioperative CX & Pembrolizumab 2. Perioperative CF & Pembrolizumab 3. FLOT & Pembrolizumab	To be determined

Chemotherapy, neoadjuvant CF portion

Cisplatin (Platinol) 80 mg/m² IV 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)

21-day cycle for 3 cycles

Surgery

Surgical resection

Chemotherapy, adjuvant CF portion

Cisplatin (Platinol) 80 mg/m² IV 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)

21-day cycle for 3 cycles

Protocol variant #2, 100/4000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ychou et al. 2011 (ACCORD 07)	1995-2003	Phase 3 (E-esc)	Surgery alone	Superior OS OS60: 38% vs 24% (HR 0.69, 95% CI 0.50-0.95)

ACCORD 07 included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).

Chemotherapy, neoadjuvant CF portion

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

Surgery

Surgical resection

Chemotherapy, adjuvant CF portion

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. link to original article contains dosing details in abstract PubMed NCT00002883
KEYNOTE-585: contains dosing details on CT.gov NCT03221426

ECF

ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2006 (MAGIC)	1994-2002	Phase 3 (E-esc)	Surgery alone	Superior OS OS60: 36% vs 23% (HR 0.75, 95% CI 0.60-0.93)
Cats et al. 2018 (CRITICS)	2007-2015	Phase 3 (C)	1. ECF/CX & RT 2. ECX/CX & RT 3. EOF/CX & RT 4. EOX/CX & RT	Did not meet primary endpoint of OS Median OS: 43 vs 37 mo (HR 1.01, 95% CI 0.84-1.22)

MAGIC included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction). CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction Note: In CRITICS, only patients with trouble swallowing pills were assigned to this treatment arm.

Chemotherapy, neoadjuvant ECF portion

Epirubicin (Ellence) 50 mg/m² IV 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: 4000 mg/m²)

Supportive therapy

MAGIC, suggested as thrombosis prophylaxis:
- Warfarin (Coumadin) 1 mg PO once per day

21-day cycle for 3 cycles

Surgery

MAGIC: Surgical resection is performed 3 to 6 weeks after the completion of cycle 3
CRITICS: Surgery with a D1+ lymph node resection

Followed in 6 to 12 weeks by:

Chemotherapy, adjuvant ECF portion

Epirubicin (Ellence) 50 mg/m² IV 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: 4000 mg/m²)

Supportive therapy

MAGIC, suggested as thrombosis prophylaxis:
- Warfarin (Coumadin) 1 mg PO once per day

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 contains dosing details in abstract PubMed NCT00002615
CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains dosing details in manuscript PubMed NCT00407186

ECX

ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cats et al. 2018 (CRITICS)	2007-2015	Phase 3 (C)	1. ECF/CX & RT 2. ECX/CX & RT 3. EOF/CX & RT 4. EOX/CX & RT	Did not meet primary endpoint of OS Median OS: 43 vs 37 mo (HR 1.01, 95% CI 0.84-1.22)

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction

Chemotherapy, neoadjuvant ECX portion

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

Surgery

Surgery with a D1+ lymph node resection

Chemotherapy, adjuvant ECX portion

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains dosing details in manuscript PubMed NCT00407186

EOF

EOF: Epirubicin, Oxaliplatin, Fluourouracil

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cats et al. 2018 (CRITICS)	2007-2015	Phase 3 (C)	1. ECF/CX & RT 2. ECX/CX & RT 3. EOF/CX & RT 4. EOX/CX & RT	Did not meet primary endpoint of OS Median OS: 43 vs 37 mo (HR 1.01, 95% CI 0.84-1.22)

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction Note: Only patients with trouble swallowing pills were assigned to this treatment arm.

Chemotherapy, neodjuvant EOF portion

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 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: 4000 mg/m²)

21-day cycle for 3 cycles

Surgery

Surgery with a D1+ lymph node resection

Chemotherapy, adjuvant EOF portion

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 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: 4000 mg/m²)

21-day cycle for 3 cycles

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains dosing details in manuscript PubMed NCT00407186

EOX

EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cats et al. 2018 (CRITICS)	2007-2015	Phase 3 (C)	1. ECF/CX & RT 2. ECX/CX & RT 3. EOF/CX & RT 4. EOX/CX & RT	Did not meet primary endpoint of OS Median OS: 43 vs 37 mo (HR 1.01, 95% CI 0.84-1.22)

CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction

Chemotherapy, neoadjuvant EOX portion

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Capecitabine (Xeloda) 625 mg/m² PO twice per day

21-day cycle for 3 cycles

Surgery

Surgery with a D1+ lymph node resection

Chemotherapy, adjuvant EOX portion

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Capecitabine (Xeloda) 625 mg/m² PO twice per day

21-day cycle for 3 cycles

References

CRITICS: Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. link to original article contains dosing details in manuscript PubMed NCT00407186

FLOT

FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)

Protocol variant #1, 3 + 3

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (KEYNOTE-585)	2017-ongoing	Phase 3 (C)	1. Perioperative CX & Pembrolizumab 2. Perioperative CF & Pembrolizumab 3. FLOT & Pembrolizumab	To be determined

Chemotherapy, neoadjuvant FLOT portion

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on day 1
Folinic acid (Leucovorin) as follows:
- Cycle 1: 200 mg/m² IV once per day on days 1 & 15
- Cycle 2: 200 mg/m² IV once on day 8
- Cycle 3: 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

21-day cycle for 3 cycles

Surgery

Surgery

Chemotherapy, adjuvant FLOT portion

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on day 1
Folinic acid (Leucovorin) as follows:
- Cycle 1: 200 mg/m² IV once per day on days 1 & 15
- Cycle 2: 200 mg/m² IV once on day 8
- Cycle 3: 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

21-day cycle for 3 cycles

Protocol variant #2, 4 + 4

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Al-Batran et al. 2016 (FLOT4-AIO)	2010-2015	Phase 2/3 (E-switch-ic)	1. Perioperative ECF 2. Perioperative ECX	Superior OS¹ Median OS: 50 vs 35 mo (HR 0.77, 95% CI 0.63-0.94)

¹Reported efficacy is based on the 2019 update.

Chemotherapy, neoadjuvant FLOT portion

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on day 1
Folinic acid (Leucovorin) 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

Surgery

Surgery

Chemotherapy, adjuvant FLOT portion

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on day 1
Folinic acid (Leucovorin) 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
1. 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
KEYNOTE-585: contains dosing details on CT.gov NCT03221426
MATTERHORN: NCT04592913
RAMSES: NCT02661971

SOX

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Yu et al. 2022 (FOCUS_gastric)	2011-2016	Phase 3 (E-switch-ic)	Perioperative mFOLFOX6	Non-inferior OS OS36: 75.2% vs 67.8%

Chemotherapy, neoadjuvant SOX portion

Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 14
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

21-day cycle for 2 to 4 cycles

Preceding treatment

Gastrectomy with at least D2 dissection

Chemotherapy, adjuvant SOX portion

Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 14
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

21-day cycle for 2 to 4 cycles

References

RESOLVE_gastric: Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. link to original article PubMed NCT01534546
FOCUS_gastric: Yu J, Gao Y, Chen L, Wu D, Shen Q, Zhao Z, Liu W, Yang H, Zhang Q, Wang X, Hu P, Zheng Z, Wang X, Liu H, Xu Z, Yan Z, Wu Y, Jin M, Zhang Q, Liu X, Zhu K, Shou C. Effect of S-1 Plus Oxaliplatin Compared With Fluorouracil, Leucovorin Plus Oxaliplatin as Perioperative Chemotherapy for Locally Advanced, Resectable Gastric Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e220426. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01364376

Neoadjuvant chemotherapy

DOS

DOS: Docetaxel, Oxaliplatin, S-1

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kang et al. 2021 (PRODIGY)	2012-2017	Phase 3 (E-esc)	No neoadjuvant therapy	Seems to have superior PFS PFS36: 66% vs 60% (aHR 0.70, 95% CI 0.52-0.95)

Chemotherapy

Docetaxel (Taxotere) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 100 mg/m² IV once on day 1
S-1 40 mg/m² PO twice per day on days 1 to 14

21-day cycle for 3 cycles

Subsequent treatment

Surgery, then adjuvant S-1

References

PRODIGY: Kang YK, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, Ryu MH, Rha SY, Chung IJ, Kim IH, Oh SC, Park YS, Son T, Jung MR, Heo MH, Kim HK, Park C, Yoo CH, Choi JH, Zang DY, Jang YJ, Sul JY, Kim JG, Kim BS, Beom SH, Cho SH, Ryu SW, Kook MC, Ryoo BY, Kim HK, Yoo MW, Lee NS, Lee SH, Kim G, Lee Y, Lee JH, Noh SH. PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. J Clin Oncol. 2021 Sep 10;39(26):2903-2913. Epub 2021 Jun 16. link to original article contains dosing details in manuscript link to PMC article PubMed NCT01515748

ECF

ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (TOPGEAR)	2009-ongoing	Phase 3 (C)	1. ECF/5-FU & RT 2. ECX/Capecitabine & RT 3. EOX/Capecitabine & RT 4. FLOT/Capecitabine & RT	Awaiting results

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV 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: 4000 mg/m²)

21-day cycle for 3 cycles

References

TOPGEAR: NCT01924819

Adjuvant therapy

CapeOx

CapeOX: Capecitabine & OXaliplatin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bang et al. 2012 (CLASSIC)	2006-2009	Phase 3 (E-esc)	Surgery alone	Superior OS¹ OS60: 78% vs 69% (HR 0.66, 95% CI 0.51-0.85)
Zhang et al. 2021 (RESOLVE_gastric)	2012-2017	Phase 3 (C)	1. Perioperative SOX	Seems to have inferior DFS36
Zhang et al. 2021 (RESOLVE_gastric)	2012-2017	Phase 3 (C)	2. Adjuvant SOX	Non-inferior DFS36

¹Reported efficacy for CLASSIC is based on the 2014 update.
Note: RESOLVE should not be confused for the trial by the same name in pancreatic cancer.

Preceding treatment

Gastrectomy with D2 dissection

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycle for 8 cycles

References

CLASSIC: Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012 Jan 28;379(9813):315-21. Epub 2012 Jan 7. link to original article contains dosing details in abstract PubMed NCT00411229
1. Update: Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. Epub 2014 Oct 15. link to original article PubMed
RESOLVE_gastric: Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. link to original article contains dosing details in abstract PubMed NCT01534546

Carboplatin & Docetaxel

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bamias et al. 2010	2002-2005	Phase 3 (C)	Carboplatin, Docetaxel, RT	Did not meet primary endpoint of OS

Note: the original protocol was for cisplatin & docetaxel but was changed due to excess CINV. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.

Preceding treatment

Surgery

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1
Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycle for 6 cycles

References

Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, Samantas E, Christodoulou Ch, Pentheroudakis G, Pectasides D, Dimopoulos MA, Fountzilas G. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010 May;65(6):1009-21. Epub 2010 Feb 4. link to original article contains dosing details in abstract PubMed

Capecitabine & Cisplatin (CX)

CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lee et al. 2011 (ARTIST_gastric)	2004-2008	Phase 3 (C)	XP, then RT, then XP	Might have inferior DFS

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. This trial should not be confused for the one by the same name in colorectal cancer.

Preceding treatment

R0 gastrectomy and at least D2 dissection

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for 6 cycles

References

ARTIST: Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. link to original article contains dosing details in manuscript PubMed NCT00323830
1. Update: Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. link to original article PubMed

Docetaxel & S-1

DS: Docetaxel & S-1

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lee et al. 2018 (POST)	2010-2013	Phase 3 (E-switch-ic)	SP	Did not meet primary endpoint of DFS36

Preceding treatment

Surgery

Chemotherapy

Docetaxel (Taxotere) 35 mg/m² IV once per day on days 1 & 8
S-1 35 mg/m² PO twice per day on days 1 to 14

21-day cycle for 8 cycles

Regimen variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Yoshida et al. 2019 (JACCRO GC-07)	2013-2017	Phase 3 (E-esc)	S-1	Superior OS¹ OS36: 77.7% vs 71.2% (HR 0.74, 95% CI 0.60-0.925)

¹Reported efficacy is based on the 2021 update; primary endpoint was RFS.

Preceding treatment

Surgery

Chemotherapy

Docetaxel (Taxotere) as follows:
- Cycles 1 to 7: 40 mg/m² IV once on day 1
S-1 as follows:
- Cycles 1 to 7: 80 to 120 mg/m² PO on days 1 to 14
- Cycles 8 to 11: 80 to 120 mg/m² PO on days 1 to 28

21-day cycle for 1 cycle, then 42-day cycle for 10 cycles

References

POST: Lee CK, Jung M, Kim HS, Jung I, Shin DB, Kang SY, Zang DY, Kim KH, Lee MH, Kim BS, Lee KH, Cheong JH, Hyung WJ, Noh SH, Chung HC, Rha SY. S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial. Cancer Res Treat. 2019 Jan;51(1):1-11. Epub 2018 Feb 5. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01283217
JACCRO GC-07: Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matsuyama J, Yamada M, Ito S, Takeuchi M, Fujii M. Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol. 2019 May 20;37(15):1296-1304. Epub 2019 Mar 29. link to original article link to PMC article PubMed UMIN000010337
1. Update: Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022 Jan;25(1):188-196. Epub 2021 Aug 5. link to original article PubMed

FP/Capecitabine & RT

FP/Capecitabine & RT: Fluorouracil & Platinol (Cisplatin) alternating with Capecitabine & Radiation Therapy

Protocol

Study	Years of enrollment	Evidence
Lee et al. 2006	NR	Phase 2

Note: In contrast to the primary reference, some guidelines list this regimen without FP cycles 1, 3, 4, 5. Dosage of Capecitabine (Xeloda) was listed as 625 to 825 mg/m² PO twice per day on days 1 to 5 or 1 to 7 while radiation is being given.

Preceding treatment

Surgery, 3 weeks prior

Chemotherapy, part 1

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose: 5000 mg/m²)

21-day cycle, followed immediately by:

Chemotherapy, part 2

Capecitabine (Xeloda) 825 mg/m² PO twice per day

Radiotherapy

Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions (total dose of 45 Gy)

5-week course, followed 4 weeks later by:

Chemotherapy, part 3

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m²)

21-day cycle for 3 cycles

References

Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. link to original article contains dosing details in manuscript link to PMC article PubMed

FULV

FULV: 5-FU & LeucoVorin (Folinic acid)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bajetta et al. 2014 (ITACA-S)	2005-2009	Phase 3 (C)	FOLFIRI, then Cisplatin & Docetaxel	Did not meet primary endpoint of DFS

Preceding treatment

Surgery

Chemotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1 & 2, then 600 mg/m² IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m²)
Folinic acid (Leucovorin) 100 mg/m² IV over 2 hours once per day on days 1 & 2

14-day cycle for 9 cycles

References

ITACA-S: Bajetta E, Floriani I, Di Bartolomeo M, Labianca R, Falcone A, Di Costanzo F, Comella G, Amadori D, Pinto C, Carlomagno C, Nitti D, Daniele B, Mini E, Poli D, Santoro A, Mosconi S, Casaretti R, Boni C, Pinotti G, Bidoli P, Landi L, Rosati G, Ravaioli A, Cantore M, Di Fabio F, Aitini E, Marchet A; ITACA-S (Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach Trial) Study Group. Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer. Ann Oncol. 2014 Jul;25(7):1373-1378. Epub 2014 Apr 12. link to original article contains dosing details in manuscript PubMed NCT01640782

FULV/FULV & RT

FULV/FULV & RT: FluoroUracil & LeucoVorin (Folinic acid) alternating with FluoroUracil, LeucoVorin (Folinic acid) & Radiation Therapy

Protocol

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Macdonald et al. 2001 (INT-0116)	1991-1998	Phase 3 (E-esc)	Surgery alone	Superior OS
Fuchs et al. 2017 (CALGB 80101)	2002-2009	Phase 3 (C)	ECF, then FULV & RT, then ECF	Did not meet primary endpoint of OS

Treatment is to start 20 to 40 days after surgery. Study included patients with GE junction malignancy as well (20% GE junction) and included patients with a performance status of 2.

Preceding treatment

INT-0116: Surgery with R0 resection (10% underwent D2 dissection, 36% underwent D1 dissection and 54% underwent D0 dissection)
CALGB 80101: Surgery

Chemotherapy, part 1

Fluorouracil (5-FU) 425 mg/m² IV bolus once per day on days 1 to 5
Folinic acid (Leucovorin) 20 mg/m² IV bolus once per day on days 1 to 5

28-day cycle for 1 cycle, followed by:

Chemotherapy, part 2

Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
Folinic acid (Leucovorin) 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 180 cGy x 25 fractions (total of 45 Gy)

35-day course, followed in 1 month by:

Chemotherapy, part 3

Fluorouracil (5-FU) 425 mg/m² IV bolus once per day on days 1 to 5
Folinic acid (Leucovorin) 20 mg/m² IV bolus once per day on days 1 to 5

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 contains dosing details in abstract PubMed
1. Update: Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. link to original article link to PMC article PubMed
CALGB 80101: Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, Mayer RJ. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10;35(32):3671-3677. Epub 2017 Oct 4. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00052910

S-1 monotherapy

Regimen variant #1, 21-day cycles

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Tsuburaya et al. 2014 (SAMIT)	2004-2009	Phase 3 (C)	1. Paclitaxel, then S-1 2. Paclitaxel, then UFT	Did not meet primary endpoint of DFS
Tsuburaya et al. 2014 (SAMIT)	2004-2009	Phase 3 (C)	3. UFT	Superior DFS DFS36: 58.2% vs 53% (HR 0.81, 95% CI 0.70-0.93)

Preceding treatment

R0 or R1 gastrectomy with at least D2 dissection, within 2 to 8 weeks

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) 80 mg/m² PO twice per day on days 1 to 14

21-day cycle for 16 cycles (1 year)

Regimen variant #2, 42-day cycles

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Sakuramoto et al. 2007 (ACTS-GC)	2001-2004	Phase 3 (E-esc)	Observation	Superior OS¹ OS60: 72% vs 61% (HR 0.67, 95% CI 0.54-0.83)
Yoshikawa et al. 2019 (OPAS-1)	2012-2017	Phase 3 (C)	S-1 x 6 mo	Inconclusive whether non-inferior RFS
Park et al. 2020 (ARTIST 2)	2013-2018	Phase 3 (C)	1. SOX	Seems to have inferior DFS
Park et al. 2020 (ARTIST 2)	2013-2018	Phase 3 (C)	2. SOXRT	Might have inferior DFS

¹Reported efficacy for ACTS-GC is based on the 2011 update.

Preceding treatment

R0 gastrectomy with at least D2 dissection, within 6 weeks

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) by the following criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 28
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 28

42-day cycle for 8 cycles (1 year)

References

ACTS-GC: Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. link to original article contains dosing details in manuscript PubMed NCT00152217
1. Update: Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. link to original article PubMed
SAMIT: Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. link to original article contains dosing details in manuscript PubMed UMIN C000000082
OPAS-1: Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, Yabusaki H, Yoshida K, Ito S, Takeno A, Yasuda T, Kawachi Y, Katayama H, Fukuda H, Boku N, Sano T, Sasako M. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104[OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019 Mar;4(3):208-216. Epub 2019 Jan 22. Erratum in: Lancet Gastroenterol Hepatol. 2019 Apr;4(4):e3. link to original article PubMed UMIN000007306
JACCRO GC-07: Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matsuyama J, Yamada M, Ito S, Takeuchi M, Fujii M. Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol. 2019 May 20;37(15):1296-1304. Epub 2019 Mar 29. link to original article link to PMC article PubMed UMIN000010337
1. Update: Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022 Jan;25(1):188-196. Epub 2021 Aug 5. link to original article PubMed
ARTIST 2: Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, Kang JH, Oh SY, Hwang IG, Ji JH, Shin DB, Yu JI, Kim KM, An JY, Choi MG, Lee JH, Kim S, Hong JY, Park JO, Park YS, Lim HY, Bae JM, Kang WK; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-374. Epub 2020 Dec 3. link to original article contains dosing details in abstract PubMed NCT0176146
HKIT-GC: NCT00216034

SOX

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Park et al. 2020 (ARTIST 2)	2013-2018	Phase 3 (E-esc)	1. S-1	Seems to have superior DFS DFS36: 74.3% vs 64.8% (HR 0.69, 95% CI 0.41-0.99)
Park et al. 2020 (ARTIST 2)	2013-2018	Phase 3 (E-esc)	2. SOXRT	Did not meet primary endpoint of DFS

Preceding treatment

R0 or R1 gastrectomy with at least D2 dissection

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) by the following criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 14
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1

21-day cycle for up to 8 cycles (6 months)

References

ARTIST 2: Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, Kang JH, Oh SY, Hwang IG, Ji JH, Shin DB, Yu JI, Kim KM, An JY, Choi MG, Lee JH, Kim S, Hong JY, Park JO, Park YS, Lim HY, Bae JM, Kang WK; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-374. Epub 2020 Dec 3. link to original article contains dosing details in manuscript PubMed NCT0176146
TOTTG030103: Zhao Q, Lian C, Huo Z, Li M, Liu Y, Fan L, Tan B, Zhao X, Zhang Z, Wang D, Liu Y, Guo H, Yang P, Tian Y, Li Y. The efficacy and safety of neoadjuvant chemotherapy on patients with advanced gastric cancer: A multicenter randomized clinical trial. Cancer Med. 2020 Aug;9(16):5731-5745. Epub 2020 Jun 24. link to original article link to PMC article PubMed NCT01516944

Metastatic or locally advanced disease, first-line

Capecitabine monotherapy

X: Xeloda (Capecitabine)

Regimen variant #1, 2000 mg/m²/day

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hwang et al. 2017 (SMC 2010-04-118)	2010-2014	Phase 3 (C)	XELOX	Did not meet primary endpoint of OS

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycles

Regimen variant #2, 2500 mg/m²/day

Study	Years of enrollment	Evidence
Hong et al. 2004	NR	Phase 2

Study only included patients with Karnofsky status of at least 70%

Chemotherapy

Capecitabine (Xeloda) 1250 mg/m² PO twice per day on days 1 to 14

21-day cycle for up to 6 cycles

References

Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. link to original article contains dosing details in manuscript PubMed
SMC 2010-04-118: Hwang IG, Ji JH, Kang JH, Lee HR, Lee HY, Chi KC, Park SW, Lee SJ, Kim ST, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol. 2017 May;8(3):170-175. Epub 2017 Jan 21. link to original article contains dosing details in abstract PubMed NCT01470742

Capecitabine & Cisplatin (CX)

CX: Cisplatin, Xeloda (Capecitabine)
XP: Xeloda (Capecitabine), Platinol (Cisplatin)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kang et al. 2009 (ML17032)	2003-2005	Phase 3 (E-switch-ic)	CF	Non-inferior PFS
Ohtsu et al. 2011 (AVAGAST)	2007-2008	Phase 3 (C)	CX & Bevacizumab	Did not meet primary endpoint of OS
Lordick et al. 2013 (EXPAND)	2008-2010	Phase 3 (C)	CX & Cetuximab	Did not meet primary endpoint of PFS
Shen et al. 2014 (AVATAR)	2009-2010	Phase 3 (C)	CX & Bevacizumab	Did not meet primary endpoint of OS
Kim et al. 2014 (SMC 2008-12-019)	2009-2012	Phase 3 (C)	CX & Simvastatin	Did not meet primary endpoint of PFS
Lu et al. 2018 (PAC-C)	2009-2014	Phase 3 (C)	Capecitabine & Paclitaxel	Did not meet primary endpoint of PFS
Fuchs et al. 2019 (RAINFALL)	2015-2016	Phase 3 (C)	CX & Ramucirumab	Did not meet primary endpoint of PFS¹

¹while the primary analysis of RAINFALL showed that this arm seemed to have inferior PFS, independent central review did not confirm this finding.
The following studies included patients with GE junction malignancy as well:

AVAGAST patients: 86% gastric and 14% GE junction. 5.4% of patients had an ECOG of 2.
EXPAND patients: 83% gastric, 5% GE junction and 16% unknown
SMC 2008-12-019 patients: 79% gastric, 16% GE junction and 5% unknown

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
- EXPAND: 1000 mg/m² PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)

Supportive therapy

Some protocols: "Hyperhydration" for cisplatin

21-day cycles, varied duration (see below)

Subsequent treatment

AVAGAST & AVATAR: after 6 cycles, capecitabine maintenance
SMC 2008-12-019: after 8 cycles, capecitabine maintenance

References

ML17032: Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org NCT02563054
AVAGAST: Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains dosing details in manuscript PubMed NCT00548548
EXPAND: Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains dosing details in manuscript PubMed NCT00678535
AVATAR: Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, Xu R, Chen L, Liu Y, Yu S, Bu L, Piao Y. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015 Jan;18(1):168-76. Epub 2014 Feb 21. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00887822
SMC 2008-12-019: Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains dosing details in manuscript PubMed NCT01099085
PAC-C: Lu Z, Zhang X, Liu W, Liu T, Hu B, Li W, Fan Q, Xu J, Xu N, Bai Y, Pan Y, Xu Q, Bai W, Xia L, Gao Y, Wang W, Shu Y, Shen L. A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer. Gastric Cancer. 2018 Sep;21(5):782-791. Epub 2018 Feb 27. link to original article link to PMC article contains dosing details in manuscript PubMed NCT01015339
RAINFALL: Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):420-435. Epub 2019 Feb 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. link to original article contains dosing details in abstract PubMed NCT02314117

Capecitabine & Cisplatin (CX) & Pembrolizumab

CX & Pembrolizumab: Cisplatin, Xeloda (Capecitabine), Pembrolizumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (E-esc)	1. CF 2. CX	Might have superior OS Median OS: 12.5 vs 11.1 mo (HR 0.85, 95% CI 0.70-1.03)
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (E-esc)	3. Pembrolizumab	Not reported

KEYNOTE-062 included patients with GEJ malignancy

Biomarker eligibility criteria

PD-L1 Combined Positive Score (CPS) of 1 or more as determined by an FDA-approved test

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Cisplatin (Platinol) 80 mg/m² IV once on day 1

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycles

References

KEYNOTE-062: Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02494583

CapeOx

CapeOX: Capecitabine & OXaliplatin

Regimen variant #1, 750/78

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hall et al. 2021 (GO2)	2014-2017	Phase 3 (E-de-esc)	CapeOx; 130/1250	Non-inferior PFS

Chemotherapy

Capecitabine (Xeloda) 375 mg/m² PO twice per day
Oxaliplatin (Eloxatin) 78 mg/m² IV once on day 1

21-day cycles

Regimen variant #2, 1000/104

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hall et al. 2021 (GO2)	2014-2017	Phase 3 (E-de-esc)	CapeOx; 130/1250	Non-inferior PFS

Chemotherapy

Capecitabine (Xeloda) 500 mg/m² PO twice per day
Oxaliplatin (Eloxatin) 104 mg/m² IV once on day 1

21-day cycles

Regimen variant #3, 1250/130

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hall et al. 2021 (GO2)	2014-2017	Phase 3 (C)	1. CapeOx; 750/78 2. CapeOx; 1000/104	Non-inferior PFS

Chemotherapy

Capecitabine (Xeloda) 625 mg/m² PO twice per day
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycles

Regimen variant #4, 1700/130

Study	Years of enrollment	Evidence
Jatoi et al. 2006	2002-2004	Phase 2

Chemotherapy

Capecitabine (Xeloda) 850 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1

21-day cycles

Regimen variant #5, 2000/130

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Moehler et al. 2020 (JAVELIN Gastric 100)	2015-2017	Phase 3 (C)	1. CapeOx x 4, then Avelumab 2. mFOLFOX4 x 4, then Avelumab 3. mFOLFOX6 x 4, then Avelumab	Did not meet primary endpoint of OS
Awaiting publication (ARMANI)	2016-2019	Phase 3 (C)	1. CapeOx x 3 mo, then Paclitaxel & Ramucirumab 2. FOLFOX4 x 3 mo, then Paclitaxel & Ramucirumab 3. mFOLFOX6 x 3 mo, then Paclitaxel & Ramucirumab	TBD
Kang et al. 2022 (ATTRACTION-4)	2017-2018	Phase 3 (C)	1. CapeOx & Nivolumab 2. SOX & Nivolumab	Inferior PFS
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (C)	1. CapeOx & Nivolumab 2. mFOLFOX6 & Nivolumab	Inferior OS
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (C)	3. Ipilimumab & Nivolumab	Not reported
Awaiting publication (BGB-A317-305)	2018-ongoing	Phase 3 (C)	1. CapeOx & Tislelizumab 2. CF & Tislelizumab	TBD
Awaiting publication (KEYNOTE-859)	2018-ongoing	Phase 3 (C)	1. CapeOx & Pembrolizumab 2. CF & Pembrolizumab	TBD

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

Regimen variant #6, 2000/130, limited oxaliplatin

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Zhu et al. 2022 (EXELOX)	2015-2020	Phase 3 (E-de-esc)	EOX	Non-inferior PFS Median PFS: 5 vs 5.5 mo (HR 0.989, 95% CI 0.81-1.20)

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14
Oxaliplatin (Eloxatin) as follows:
- Cycles 1 up to 8: 130 mg/m² IV once on day 1

21-day cycles

References

Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr; North Central Cancer Treatment Group. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006 Jan;17(1):29-34. Epub 2005 Nov 22. link to original article contains dosing details in abstract PubMed
JAVELIN Gastric 100: Moehler M, Dvorkin M, Boku N, Özgüroğlu M, Ryu MH, Muntean AS, Lonardi S, Nechaeva M, Bragagnoli AC, Coşkun HS, Cubillo Gracian A, Takano T, Wong R, Safran H, Vaccaro GM, Wainberg ZA, Silver MR, Xiong H, Hong J, Taieb J, Bang YJ. Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100. J Clin Oncol. 2021 Mar 20;39(9):966-977. Epub 2020 Nov 16. link to original article contains dosing details in manuscript 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 contains dosing details in manuscript PubMed NCT02872116
GO2: Hall PS, Swinson D, Cairns DA, Waters JS, Petty R, Allmark C, Ruddock S, Falk S, Wadsley J, Roy R, Tillett T, Nicoll J, Cummins S, Mano J, Grumett S, Stokes Z, Kamposioras KV, Chatterjee A, Garcia A, Waddell T, Guptal K, Maisey N, Khan M, Dent J, Lord S, Crossley A, Katona E, Marshall H, Grabsch HI, Velikova G, Ow PL, Handforth C, Howard H, Seymour MT; GO2 Trial Investigators. Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):869-877. Erratum in: JAMA Oncol. 2021 Aug 1;7(8):1249. link to original article link to PMC article contains dosing details in manuscript PubMed ISRCTN44687907
ATTRACTION-4: Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. Epub 2022 Jan 11. link to original article contains dosing details in abstract PubMed NCT02746796
EXELOX: Zhu XD, Huang MZ, Wang YS, Feng WJ, Chen ZY, He YF, Zhang XW, Liu X, Wang CC, Zhang W, Ying JE, Wu J, Yang L, Qin YR, Luo JF, Zhao XY, Li WH, Zhang Z, Qiu LX, Geng QR, Zou JL, Zhang JY, Zheng H, Song XF, Wu SS, Zhang CY, Gong Z, Liu QQ, Wang XF, Xu Q, Wang Q, Ji JM, Zhao J, Guo WJ. XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX). Cancer Commun (Lond). 2022 Apr;42(4):314-326. Epub 2022 Feb 25. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02395640
ARMANI: NCT02934464
BGB-A317-305: contains dosing details on CT.gov NCT03777657
KEYNOTE-859: contains dosing details on CT.gov NCT03675737
ORIENT-16: NCT03745170

CapeOx & Nivolumab

CapeOx & Nivolumab: Capecitabine, OXaliplatin, Nivolumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kang et al. 2022 (ATTRACTION-4)	2017-2018	Phase 3 (E-esc)	1. CapeOx 2. SOX	Superior PFS Median PFS: 10.45 vs 8.3 mo (HR 0.68, 98.51% 0.51-0.90)
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (E-RT-esc)	1. CapeOx 2. mFOLFOX6	Superior OS¹ Median OS: 14.4 vs 11.1 mo (HR 0.71, 98.4% CI 0.59-0.86)
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (E-RT-esc)	3. Ipilimumab & Nivolumab	Not reported

¹Reported efficacy is for the group with PD-L1 CPS of 5 or more.

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 (Opdivo) 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 contains dosing details in manuscript PubMed NCT02872116
ATTRACTION-4: Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. Epub 2022 Jan 11. link to original article contains dosing details in abstract PubMed NCT02746796

Carboplatin & Paclitaxel (CP)

Regimen

Study	Years of enrollment	Evidence
Philip et al. 1997	NR in abstract	Phase 2
Gadgeel et al. 2003	1996-2000	Phase 2

Note: In contrast to the original reference, some guidelines list the dosage of carboplatin as AUC 6. Philip et al. included patients with locally advanced metastatic or recurrent esophageal or gastric cancer Gadgeel et al. study showed an ORR of 35%

Chemotherapy

Carboplatin (Paraplatin) AUC 5 IV once on day 1, given second
Paclitaxel (Taxol) 200 mg/m² IV over 3 hours once on day 1, given first

21-day cycles

References

Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. contains dosing details in abstract PubMed
Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. link to original article contains dosing details in abstract PubMed

Cisplatin & Docetaxel (DC)

DC: Docetaxel, Cisplatin
TC: Taxotere (Docetaxel), Cisplatin

Regimen variant #1, 75/75

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Roth et al. 2007	1999-2003	Randomized Phase 2 (E-de-esc)	1. ECF	Not reported
Roth et al. 2007	1999-2003	Randomized Phase 2 (E-de-esc)	2. TCF	Might have inferior ORR

Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m² to 75 mg/m² based on high incidence of febrile neutropenia.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 4 hours once on day 1
Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1

Supportive therapy

3 liters per day "hyperhydration"
Dexamethasone (Decadron) 8 mg PO given 12 hours & 6 hours before Docetaxel (Taxotere), then 8 mg PO twice per day for 4 days after Docetaxel (Taxotere)
5-HT3 antagonist for emesis prophylaxis
Growth factor support allowed, such as with Filgrastim (Neupogen)

21-day cycle for up to 8 cycles

Regimen variant #2, 75/85

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ajani et al. 2005 (V-325)	1998-1999	Randomized Phase 2 (C)	DCF	Seems to have inferior ORR

Patients: 100% adenocarcinoma histology (32% esophagogastric junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Docetaxel (Taxotere) 85 mg/m² IV over 60 minutes once on day 1

Supportive therapy

Dexamethasone (Decadron) 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (total dose per cycle: 48 mg)
Dexamethasone (Decadron) 20 mg IV before Cisplatin (Platinol) and 8 hours after Cisplatin (Platinol)
Ondansetron (Zofran) 8 mg IV before Cisplatin (Platinol), 4 hours after Cisplatin (Platinol), and 8 hours after Cisplatin (Platinol)
"Hydration was administered in a standard manner"

21-day cycles

References

V-325: Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. link to original article contains dosing details in manuscript PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains dosing details in manuscript PubMed

Cisplatin & Fluorouracil (CF)

CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol (Cisplatin)

Regimen variant #1, 60/5000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lee et al. 2009a	2000-2004	Phase 3 (C)	Fluorouracil & Heptaplatin (FH)	Equivalent OS

Note: this is reported to be an equivalence study but the statistical analysis does not provide details on the definition of equivalence.

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV over 60 minutes once on day 1, given first
Fluorouracil (5-FU) 1000 mg/m² IV over 12 hours once per day on days 1 to 5, given second

28-day cycles

Regimen variant #2, 80/4000 x 8

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ajani et al. 2017 (DIGEST)	2011-2014	Phase 3 (C)	CS	Did not meet primary endpoint of OS

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m²)

Supportive therapy

Some protocols: "Hyperhydration" for cisplatin

21-day cycle for 8 cycles

Regimen variant #3, 80/4000, indefinite

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kang et al. 2009 (ML17032)	2003-2005	Phase 3 (C)	CX	Non-inferior PFS
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (C)	1. CF & Pembrolizumab 2. CX & Pembrolizumab	Might have inferior OS
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (C)	Pembrolizumab	Non-inferior OS
Awaiting publication (BGB-A317-305)	2018-ongoing	Phase 3 (C)	1. CapeOx & Tislelizumab 2. CF & Tislelizumab	TBD
Awaiting publication (KEYNOTE-859)	2018-ongoing	Phase 3 (C)	1. CapeOx & Pembrolizumab 2. CF & Pembrolizumab	TBD

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 1 to 3 hours once on day 1, given first
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 4000 mg/m²)

Supportive therapy

Some protocols: "Hyperhydration" for cisplatin

21-day cycles

Regimen variant #4, 100/4000

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Duffour et al. 2006 (FFCD 9404)	1995-1998	Phase 3 (C)	FLP	Inconclusive whether non-inferior ORR

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on either day 1 or 2
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 cycles

Regimen variant #5, 100/4000, split-dose cisplatin

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ohtsu et al. 2003 (JCOG 9205)	1992-1997	Phase 3 (E-esc)	1. Fluorouracil	Did not meet primary endpoint of OS
Ohtsu et al. 2003 (JCOG 9205)	1992-1997	Phase 3 (E-esc)	2. UFTM	Did not meet primary endpoint of OS

Study included patients with PFS of 2 (9.6%)

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1 to 5
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 up to 6 cycles

Regimen variant #6, 100/5000

Study	Years 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
Ajani et al. 2010 (FLAGS)	2005-2007	Phase 3 (C)	CS	Did not meet primary endpoint of OS

Van Cutsem et al Patients: 100% adenocarcinoma histology (22% Esophagogastric junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70. Dank et al Patients: 100% adenocarcinoma histology (20% Esophagogastric junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.

Chemotherapy

Cisplatin (Platinol) 100 mg/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/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
Atropine (Atropen) prn cholinergic symptoms
Loperamide (Imodium) prn delayed diarrhea

28-day cycles

References

JCOG 9205: Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; JCOG. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains dosing details in manuscript PubMed
FFCD 9404: Duffour J, Bouché O, Rougier P, Milan C, Bedenne L, Seitz JF, Buecher B, Legoux JL, Ducreux M, Vetter D, Raoul JL, François E, Ychou M. Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Anticancer Res. 2006 Sep-Oct;26(5B):3877-83. link to original article contains dosing details in manuscript PubMed
TAX 325: Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. link to original article contains dosing details in manuscript 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 contains dosing details in manuscript PubMed
ML17032: Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains dosing details in manuscript PubMed NCT02563054
Lee KH, Hyun MS, Kim HK, Jin HM, Yang J, Song HS, Do YR, Ryoo HM, Chung JS, Zang DY, Lim HY, Jin JY, Yim CY, Park HS, Kim JS, Sohn CH, Lee SN. Randomized, multicenter, phase III trial of heptaplatin 1-hour infusion and 5-fluorouracil combination chemotherapy comparing with cisplatin and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. Cancer Res Treat. 2009 Mar;41(1):12-8. Epub 2009 Mar 31. link to original article link to PMC article contains dosing details in manuscript PubMed
FLAGS: Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. link to original article contains dosing details in abstract PubMed NCT00400179
AVAGAST: Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains dosing details in manuscript PubMed NCT00548548
DIGEST: Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. link to original article contains dosing details in manuscript PubMed NCT01285557
KEYNOTE-062: Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. link to original article link to PMC article PubMed NCT02494583
BGB-A317-305: contains dosing details on CT.gov NCT03777657
KEYNOTE-859: contains dosing details on CT.gov NCT03675737

Cisplatin & Fluorouracil (CF) & Pembrolizumab

CF & Pembrolizumab: Cisplatin, Fluorouracil, Pembrolizumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (E-esc)	1. CF 2. CX	Might have superior OS Median OS: 12.5 vs 11.1 mo (HR 0.85, 95% CI 0.70-1.03)
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (E-esc)	3. Pembrolizumab	Not reported

KEYNOTE-062 included patients with GEJ malignancy

Biomarker eligibility criteria

PD-L1 Combined Positive Score (CPS) of 1 or more as determined by an FDA-approved test

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV 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)

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycles

References

KEYNOTE-062: Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. link to original article link to PMC article PubMed NCT02494583

Cisplatin & S-1

CS: Cisplatin & S-1
SP: S-1 & Platinol (Cisplatin)

Regimen variant #1, q3wk ("SP3")

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ryu et al. 2015 (SOS)	2009-2012	Phase 3 (E-switch-ic)	Cisplatin & S-1; SP5	Seems to have superior PFS Median PFS: 5.5 vs 4.9 mo (HR 0.82, 95% CI 0.68-0.99)
Lee et al. 2020 (SOPP)	2012-2014	Phase 3 (C)	SOX	Non-inferior PFS

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Tegafur, gimeracil, oteracil (S-1) 40 mg/m² PO twice per day on days 1 to 14

21-day cycles

Regimen variant #2, q4wk

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ajani et al. 2010 (FLAGS)	2005-2007	Phase 3 (E-switch-ic)	CF	Did not meet primary endpoint of OS
Ajani et al. 2017 (DIGEST)	2011-2014	Phase 3 (E-switch-ic)	CF	Did not meet primary endpoint of OS

Note: this is an experimental arm of a study where the primary endpoint was not met. Included because CS has been shown to be superior in comparison to other regimens (see above).

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Tegafur, gimeracil, oteracil (S-1) 25 mg/m² PO twice per day on days 1 to 21

28-day cycles

Regimen variant #3, q5wk ("SP5")

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Koizumi et al. 2008 (SPIRITS)	2002-2004	Phase 3 (E-esc)	S-1	Seems to have superior OS Median OS: 13 vs 11 mo (HR 0.77, 95% CI 0.61-0.98)
Fujitani et al. 2016 (REGATTA)	2008-2013	Non-randomized portion of phase 3 RCT
Ryu et al. 2015 (SOS)	2009-2012	Phase 3 (C)	Cisplatin & S-1; SP3	Seems to have inferior PFS
Yamada et al. 2014 (G-SOX)	2010-2011	Phase 3 (C)	SOX	Non-inferior PFS
Ishigami et al. 2018 (PHOENIX-GC)	2011-2013	Phase 3 (C)	IV/IP Paclitaxel & S-1	Might have inferior OS
Yamada et al. 2019 (JCOG1013)	2012-2016	Phase 3 (C)	Cisplatin, Docetaxel, S-1	Did not meet primary endpoint of OS
Kang et al. 2020 (SOLAR)	2015-2016	Phase 3 (C)	Oxaliplatin & TAS-118	Seems to have inferior PFS

Note: in REGATTA, there was no difference in outcome amongst patients who did or did not undergo surgery. Inclusion criteria for REGATTA included the presence of a single non-curable factor (ex: hepatic, peritoneal, and para-aortic mets), see link for further details SPIRITS trial included patients with ECOG of 2 (3% of patients) Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details

Preceding treatment

REGATTA: Non-laparoscopic gastrectomy with D1 lymphadenectomy versus no surgery; chemotherapy began within 8 weeks of surgery

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 8
Tegafur, gimeracil, oteracil (S-1) by the following criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 21
- BSA at least 1.25 m² and less than 1.5 m²: 50 mg PO twice per day on days 1 to 21
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 21

35-day cycles

References

SPIRITS: Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. link to original article contains dosing details in manuscript PubMed NCT00150670
FLAGS: Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. link to original article contains dosing details in abstract PubMed NCT00400179
G-SOX: Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015 Jan;26(1):141-8. Epub 2014 Oct 14. link to original article contains dosing details in abstract PubMed JapicCTI-101021
SOS: Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, Kang YK; SOS study investigators. Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol. 2015 Oct;26(10):2097-101. Epub 2015 Jul 27. link to original article contains dosing details in abstract PubMed NCT00915382
REGATTA: Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. link to original article contains dosing details in manuscript PubMed UMIN000001012
DIGEST: Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. link to original article contains dosing details in manuscript PubMed NCT01285557
PHOENIX-GC: Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. link to original article contains dosing details in manuscript PubMed UMIN000005930
JCOG1013: Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jul;4(7):501-510. Epub 2019 May 14. link to original article contains dosing details in abstract PubMed UMIN000007652
SOPP: Lee KW, Chung IJ, Ryu MH, Park YI, Nam BH, Oh HS, Lee KH, Han HS, Seo BG, Jo JC, Lee HR, Kim JW, Park SR, Cho SH, Kang YK; SOPP study investigators. Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial). Gastric Cancer. 2021 Jan;24(1):156-167. Epub 2020 Jun 28. link to original article contains dosing details in abstract PubMed NCT01671449
SOLAR: Kang YK, Chin K, Chung HC, Kadowaki S, Oh SC, Nakayama N, Lee KW, Hara H, Chung IJ, Tsuda M, Park SH, Hosaka H, Hironaka S, Miyata Y, Ryu MH, Baba H, Hyodo I, Bang YJ, Boku N. S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer (SOLAR): a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 Aug;21(8):1045-1056. Epub 2020 Jul 16. link to original article contains dosing details in abstract PubMed NCT02322593

CLF

CLF: Cisplatin, Leucovorin, Fluorouracil
FLP: Fluorouracil, Leucovorin, Platinol (Cisplatin)

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Al-Batran et al. 2008	2003-2006	Phase 3 (C)	FLO	Might have inferior PFS

Note: In contrast to the original reference, some guidelines list 5-FU as being given every 2 weeks rather than the schedule below. Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric).

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
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)

Supportive therapy

Up to 3 liters normal saline as hydration with cisplatin
per "local protocols"

8-week cycles

Regimen variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bouché et al. 2004 (FFCD 9803)	1999-2001	Randomized Phase 2 (E-esc)	1. LV5FU2 2. LV5FU2 & Irinotecan	Not powered to draw conclusions

Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 60 minutes once on either day 1 or 2
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m² IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m²)

Supportive therapy

1 liter hydration over 3 hours before and after Cisplatin (Platinol)
5-HT3 antagonist IV before Cisplatin (Platinol)
Methylprednisolone (Solumedrol) 120 mg IV 10 minutes before Cisplatin (Platinol)
Oral and from days 2 to 5

14-day cycle for at least 4 cycles

References

FFCD 9803: Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. link to original article contains dosing details in manuscript PubMed
Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. link to original article contains dosing details in manuscript PubMed

DCF

DCF: Docetaxel, Cisplatin, Fluorouracil
TCF: Taxotere (Docetaxel), Cisplatin, Fluorouracil

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ajani et al. 2005 (V-325)	1998-1999	Randomized Phase 2 (E-esc)	DC	Seems to have superior ORR
Van Cutsem et al. 2006 (TAX 325)	1999-2003	Phase 3 (E-RT-esc)	CF	Seems to have superior OS

Note: In contrast to the original references, some guidelines list each cycle as lasting 28 days. Anjani et al. Patients: 100% adenocarcinoma histology (32% gastroesophageal junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70. Van Cutsem et al Patients: 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS score of 70.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m²)

Supportive therapy

(varied depending on reference):
Dexamethasone (Decadron) 8 mg PO once the night before chemotherapy, then 8 mg PO once on day 1; 1 hour prior to chemotherapy, then 8 mg PO twice per day until day 2 (total dose per cycle: 48 mg)
Dexamethasone (Decadron) 20 mg IV before Cisplatin (Platinol) and 8 hours after Cisplatin (Platinol)
Ondansetron (Zofran) 8 mg IV before Cisplatin (Platinol), 4 hours after Cisplatin (Platinol), and 8 hours after Cisplatin (Platinol)
"Hydration (was) administered in a standard manner"

21-day cycles

Regimen variant #2

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Roth et al. 2007	1999-2003	Randomized Phase 2 (E-esc)	1. ECF	Not reported
Roth et al. 2007	1999-2003	Randomized Phase 2 (E-esc)	2. TC	Might have superior ORR

Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m² to 75 mg/m² based on high incidence of febrile neutropenia.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 4 hours once on day 1
Fluorouracil (5-FU) 300 mg/m²/day IV continuous infusion over 14 days, started on day 1 (total dose per cycle: 4200 mg/m²)

Supportive therapy

3 liters per day "hyperhydration"
Dexamethasone (Decadron) 8 mg PO given 12 hours & 6 hours before Docetaxel (Taxotere), then 8 mg PO twice per day for 4 days after Docetaxel (Taxotere)
5-HT3 antagonist for emesis prophylaxis
Growth factor support allowed, such as with Filgrastim (Neupogen)

21-day cycle for up to 8 cycles

References

V-325: Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. link to original article contains dosing details in manuscript PubMed
TAX 325: Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. link to original article contains dosing details in manuscript PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains dosing details in manuscript PubMed

mDCF

mDCF: modified Docetaxel, Cisplatin, Fluorouracil

Regimen variant #1, 40/40/2800

Study	Years of enrollment	Evidence
Shah et al. 2010 (MSK 06-096)	2006-2008	Phase 2

Note: In contrast to the primary reference, some guidelines list this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab. Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 40 mg/m² IV over 1 to 3 hours once on day 3
Folinic acid (Leucovorin) 400 mg/m² IV once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m²/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m²)

Supportive therapy

"Standard premedication and delayed emesis regimens"

14-day cycles

Regimen variant #2, 60/60/3000, 4-day 5-FU infusion

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Wang et al. 2015 (DOCET L 02195)	2008-2010	Phase 3 (E-esc)	CF	Seems to have superior OS Median OS: 10.2 vs 8.5 mo (HR 0.71, 95% CI 0.52-0.97)

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 3000 mg/m²)

21-day cycles

Regimen variant #3, 60/60/3000, 5-day 5-FU infusion

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Wang et al. 2015 (DOCET L 02195)	2008-2010	Phase 3 (E-esc)	CF	Seems to have superior OS Median OS: 10.2 vs 8.5 mo (HR 0.71, 95% CI 0.52-0.97)

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 600 mg/m²/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3000 mg/m²)

21-day cycles

References

MSK 06-096: Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00390416
DOCET L 02195: Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-44. Epub 2015 Jan 21. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00811447

mDCF & Bevacizumab

mDCF & Bevacizumab: modified Docetaxel, Cisplatin, Fluorouracil & Bevacizumab

Regimen

Study	Years of enrollment	Evidence
Shah et al. 2010 (MSK 06-096)	2006-2008	Phase 2

Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV over 60 minutes once on day 1
Cisplatin (Platinol) 40 mg/m² IV over 1 to 3 hours once on day 3
Folinic acid (Leucovorin) 400 mg/m² IV once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m²/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m²)

Targeted therapy

Bevacizumab (Avastin) 10 mg/kg IV once on day 1

Supportive therapy

"Standard premedication and delayed emesis regimens"

14-day cycles

References

MSK 06-096: Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00390416

Docetaxel & S-1

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Koizumi et al. 2013 (START_gastric)	2005-2008	Phase 3 (E-esc)	S-1	Seems to have superior OS Median OS: 12.5 vs 10.8 mo (HR 0.84, 95% CI 0.71-0.99)

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV once on day 1
Tegafur, gimeracil, oteracil (S-1) by the following criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 14
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 14

21-day cycles

References

START: Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO; KCSG. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00287768

ECF

ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Findlay et al. 1994	1988-1992	Phase 2
Webb et al. 1997	1992-1995	Randomized (E-switch-ic)	FAMTX	Superior OS
Ross et al. 2002	1995-1998	Phase 3 (C)	MCF	Seems to have non-inferior OS
Roth et al. 2007	1999-2003	Randomized Phase 2 (C)	1. TC 2. TCF	Not reported
Cunningham et al. 2008 (REAL-2)	2000-2005	Phase 3 (C)	1. ECX	Non-inferior OS
			2. EOF	Non-inferior OS
			3. EOX	Seems to have inferior OS

Findlay et al. Patients: all metastatic gastric cancer Ross et al. Patients: adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma histology, all advanced esophagogastric cancer. Roth et al. Patients: all metastatic gastric cancer REAL-2 Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1
Cisplatin (Platinol) 60 mg/m² IV over 4 hours 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

(varied depending on reference):
3 liters per day "hyperhydration"
5-HT3 antagonist for emesis prophylaxis
Growth factor support allowed, such as with Filgrastim (Neupogen)
Ross et al. 2002 & Cunningham et al. 2008 used Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis

21-day cycle for up to 8 cycles

References

Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. link to original article contains dosing details in manuscript PubMed
Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7. link to original article contains dosing details in manuscript PubMed
1. Update: Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer. 1999 Apr;80(1-2):269-72. link to original article link to PMC article PubMed
Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. link to original article contains dosing details in manuscript PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains dosing details in manuscript PubMed
REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains dosing details in manuscript PubMed ISRCTN51678883

ECX

ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
ECC: Epirubicin, Cisplatin, Capecitabine

Regimen variant #1, continuous capecitabine

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2008 (REAL-2)	2000-2005	Phase 3 (E-switch-ic)	1. ECF	Non-inferior OS
Cunningham et al. 2008 (REAL-2)	2000-2005	Phase 3 (E-switch-ic)	2. EOF 3. EOX	Non-inferior OS
Catenacci et al. 2017 (RILOMET-1)	2012-2014	Randomized Phase 2 (C)	ECX & Rilotumumab	Superior OS Median OS: 10.7 vs 8.8 mo (HR 0.75, 95% CI 0.61-0.91)

REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2. RILOMET-1 patients had unresectable or metastatic MET-positive gastric or gastro-esophageal junction cancer. RILOMET-1 patients: ~80% gastric, 20% GE junction and 10% distal esophageal

Chemotherapy

Epirubicin (Ellence) 50 mg/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 up to 10 cycles

Regimen variant #2, intermittent capecitabine

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Konings et al. 2010	2005-2009	Randomized Phase 2 (C)	ECC & Pravastatin	Did not meet primary endpoint of PFS6

Patients: 6.6% of patients had an ECOG of 2

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1, given first
Cisplatin (Platinol) 60 mg/m² IV over 3 hours once on day 1, given second
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycle for up to 6 cycles

References

REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains dosing details in manuscript PubMed ISRCTN51678883
Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. link to original article contains dosing details in manuscript PubMed
RILOMET-1: Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. link to original article contains dosing details in manuscript PubMed NCT01697072

EOF

EOF: Epirubicin, Oxaliplatin, Fluorouracil

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2008 (REAL-2)	2000-2005	Phase 3 (E-switch-ic)	1. ECF 2. ECX	Non-inferior OS
Cunningham et al. 2008 (REAL-2)	2000-2005	Phase 3 (E-switch-ic)	3. EOX	Non-inferior OS

Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m²)

Supportive therapy

Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis

21-day cycle for up to 8 cycles

References

REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains dosing details in manuscript PubMed ISRCTN51678883

EOX

EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)
EOC: Epirubicin, Oxaliplatin, Capecitabine

Regimen variant #1

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cunningham et al. 2008 (REAL-2)	2000-2005	Phase 3 (E-switch-ic)	1. ECF	Seems to have superior OS Median OS: 11.2 vs 9.9 mo (HR 0.80, 95% CI 0.66-0.97)
			2. ECX	Non-inferior OS
			3. EOF	Non-inferior OS
Waddell et al. 2013 (REAL3)	2008-2011	Phase 3 (C)	mEOC+P	Superior OS Median OS: 11.3 vs 8.3 mo (HR 0.73, 95% CI 0.57-0.93)

REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2. REAL3 patients: 99% adenocarcinoma, 1% undifferentiated histology. 39% esophagus, 31% gastroesophageal junction, 30% gastric. 6% ECOF PS of 2. 89% metastatic disease.

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 625 mg/m² PO twice per day on days 1 to 21

21-day cycle for up to 8 cycles

Regimen variant #2, with maintenance capecitabine

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Zhu et al. 2022 (EXELOX)	2015-2020	Phase 3 (C)	CapeOx	Non-inferior PFS

Chemotherapy

Epirubicin (Ellence) as follows:
- Cycles 1 up to 8: 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) as follows:
- Cycles 1 up to 8: 130 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycles

References

REAL-2: Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains dosing details in manuscript PubMed content property of HemOnc.org ISRCTN51678883
REAL3: Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. Epub 2013 Apr 15. link to original article contains dosing details in manuscript link to PMC article PubMed NCT00824785
EXELOX: Zhu XD, Huang MZ, Wang YS, Feng WJ, Chen ZY, He YF, Zhang XW, Liu X, Wang CC, Zhang W, Ying JE, Wu J, Yang L, Qin YR, Luo JF, Zhao XY, Li WH, Zhang Z, Qiu LX, Geng QR, Zou JL, Zhang JY, Zheng H, Song XF, Wu SS, Zhang CY, Gong Z, Liu QQ, Wang XF, Xu Q, Wang Q, Ji JM, Zhao J, Guo WJ. XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX). Cancer Commun (Lond). 2022 Apr;42(4):314-326. Epub 2022 Feb 25. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02395640

Fluorouracil monotherapy

Regimen variant #1, CI

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ohtsu et al. 2003 (JCOG 9205)	1992-1997	Phase 3 (C)	1. FP	Did not meet primary endpoint of OS
Ohtsu et al. 2003 (JCOG 9205)	1992-1997	Phase 3 (C)	2. UFTM	Did not meet primary endpoint of OS
Boku et al. 2009 (JCOG 9912)	2000-2006	Phase 3 (C)	1. Cisplatin & Irinotecan	Might have inferior OS
Boku et al. 2009 (JCOG 9912)	2000-2006	Phase 3 (C)	2. S-1	Non-inferior OS
Shirao et al. 2013 (JCOG 0106)	2002-2007	Phase 3 (C)	MF	Did not meet primary endpoint of OS50%

JCOG 9205 included patients with PFS of 2 (9.6%)

Chemotherapy

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 cycles

Regimen variant #2, intermittent, BSA-based

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Cullinan et al. 1985	NR	Phase 3 (E-de-esc)	1. FA 2. FAM	Did not meet primary endpoint of OS

Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.

Chemotherapy

Fluorouracil (5-FU) 500 mg/m² IV once per day on days 1 to 5

28-day cycle for 2 cycles, then 35-day cycles

Regimen variant #3, intermittent, weight-based

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kolarić et al. 1986	NR	Phase 3 (C)	Epirubicin & Fluorouracil	Seems to have inferior DOR

Chemotherapy

Fluorouracil (5-FU) 12 mg/kg IV once per day on days 1 to 5

21- to 28-day cycles

Regimen variant #4, PVI

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Tebbutt et al. 2002	1994-2001	Phase 3 (C)	5-FU & Mitomycin	Did not meet primary endpoint of ORR

Chemotherapy

Fluorouracil (5-FU) 300 mg/m²/day IV continuous infusion

Up to 24-week course

References

Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. link to original article PubMed
Kolarić K, Potrebica V, Stanovnik M. Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer. Oncology. 1986;43(2):73-7. link to original article contains dosing details in abstract PubMed
Tebbutt NC, Norman A, Cunningham D, Iveson T, Seymour M, Hickish T, Harper P, Maisey N, Mochlinski K, Prior Y, Hill M. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002 Oct;13(10):1568-75. link to original article contains dosing details in manuscript PubMed
JCOG 9205: Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; JCOG. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains dosing details in manuscript PubMed
JCOG 9912: Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. link to original article contains dosing details in abstract PubMed NCT00142350
JCOG 0106: Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Randomized Phase III study of 5-fluorouracil continuous infusion vs sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol. 2013 Oct;43(10):972-80. Epub 2013 Sep 7. link to original article contains dosing details in manuscript PubMed NCT00149201

Fluorouracil, Folinic acid, Mitomycin

Regimen

Study	Years of enrollment	Evidence
Hofheinz et al. 2002	1998-2000	Phase 2, <20 pts in this subgroup

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 15,600 mg/m²)
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
Mitomycin (Mutamycin) 10 mg/m² IV once per day on days 1 & 22

56-day cycle for 2 cycles

References

Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. link to original article contains dosing details in abstract PubMed

FOLFIRI

FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
IF: Irinotecan & 5-Fluorouracil

Regimen variant #1, 6 out of 7 weeks ("AIO regimen")

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Dank et al. 2008	2000-2002	Phase 3 (E-switch-ic)	CF	Might have superior TTP

Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric origin). 96% with metastatic disease.

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)
Folinic acid (Leucovorin) 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/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
Atropine (Atropen) prn cholinergic symptoms
Loperamide (Imodium) prn delayed diarrhea

7-week cycles

Regimen variant #2, LV5FU2 & Irinotecan (200/1600/180)

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bouché et al. 2004 (FFCD 9803)	1999-2001	Randomized Phase 2 (E-esc)	1. LV5FU2 2. LV5FU2 & Cisplatin	Not powered to draw conclusions

Patients: 100% adenocarcinoma (70% gastric origin, 30% cardia). Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.

Chemotherapy

Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m² IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m²)
Irinotecan (Camptosar) 180 mg/m² IV over 90 minutes once on day 1

14-day cycle for at least 4 cycles

Regimen variant #3, 400/2800/180

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Guimbaud et al. 2014 (FFCD 03-07)	2005-2008	Phase 3 (E-switch-ic)	ECX	Superior TTF

Chemotherapy

Folinic acid (Leucovorin) 400 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 2400 mg/m² IV continuous infusion over 46 hours, given third (total dose per cycle: 2800 mg/m²)
Irinotecan (Camptosar) 180 mg/m² IV over 90 minutes once on day 1

14-day cycles

References

FFCD 9803: Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. link to original article contains dosing details in manuscript 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 contains dosing details in manuscript PubMed
FFCD 03-07: Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. link to original article contains dosing details in manuscript PubMed NCT00374036

mFOLFOX6

mFOLFOX6: modified FOLinic acid, Fluorouracil, OXaliplatin

Regimen variant #1, limited duration

Study	Years 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)
Folinic acid (Leucovorin) 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

Regimen variant #2, indefinite

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (C)	1. CapeOx & Nivolumab 2. mFOLFOX6 & Nivolumab	Inferior OS
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (C)	3. Ipilimumab & Nivolumab	Not reported

Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.

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)
Folinic acid (Leucovorin) 400 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV once on day 1

14-day cycles

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 contains dosing details in manuscript 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 contains dosing details in manuscript PubMed NCT02872116

mFOLFOX6 (L-Leucovorin)

mFOLFOX6: modified L-FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Study	Years 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 contains dosing details in manuscript PubMed NCT02545504
ARMANI: NCT02934464

mFOLFOX6 & Nivolumab

mFOLFOX6 & Nivolumab: modified FOLinic acid, Fluorouracil, OXaliplatin, Nivolumab

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (E-RT-esc)	1. CapeOx 2. mFOLFOX6	Superior OS¹ Median OS: 14.4 vs 11.1 mo (HR 0.71, 98.4% CI 0.59-0.86)
Janjigian et al. 2021 (CheckMate 649)	2017-2019	Phase 3 (E-RT-esc)	3. Ipilimumab & Nivolumab	Not reported

¹Reported efficacy is for the group with PD-L1 CPS of 5 or more.

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)
Folinic acid (Leucovorin) 400 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV once on day 1

Immunotherapy

Nivolumab (Opdivo) 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 contains dosing details in manuscript PubMed NCT02872116

FULV

FULV: 5-FU & LeucoVorin (Folinic acid)

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Bouché et al. 2004 (FFCD 9803)	1999-2001	Randomized Phase 2 (E-de-esc)	1. LV5FU2 & Cisplatin 2. LV5FU2 & Irinotecan	Not powered to draw conclusions

Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used. Patients: 100% adenocarcinoma (70% gastric origin, 30% cardia)

Chemotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus once on day 1, then 1200 mg/m² IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m²)
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1

14-day cycle for at least 4 cycles

References

FFCD 9803: Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. link to original article contains dosing details in manuscript PubMed

FULV (L-leucovorin)

FULV: 5-FU & Levo-LeucoVorin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Nakajima et al. 2020 (JCOG1108)	2013-2017	Phase 2/3 (C)	FLTAX	Did not meet primary endpoint of OS

Chemotherapy

Fluorouracil (5-FU) 600 mg/m² IV bolus once per day on days 1, 8, 15, 22, 29, 36, given second, 60 minutes after levoleucovorin
Levoleucovorin (Fusilev) 250 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, given first

8-week cycles

References

JCOG1108: Nakajima TE, Yamaguchi K, Boku N, Hyodo I, Mizusawa J, Hara H, Nishina T, Sakamoto T, Shitara K, Shinozaki K, Katayama H, Nakamura S, Muro K, Terashima M. Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G). Gastric Cancer. 2020 Jul;23(4):677-688. Epub 2020 Feb 8. link to original article contains dosing details in manuscript PubMed UMIN000010949

Irinotecan monotherapy

Regimen

Study	Years of enrollment	Evidence
Enzinger et al. 2005	NR in abstract	Phase 2

Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m² IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable." Study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GEJ and 33% distal esophagus) Regimen showed a 14% response rate and 53% disease control rate.

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

OLF

OLF: Oxaliplatin, Leucovorin, Fluorouracil
FLO: Fluorouracil, Leucovorin, Oxaliplatin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Al-Batran et al. 2008	2003-2006	Phase 3 (E-switch-ic)	FLP	Might have superior PFS Median PFS: 5.8 vs 3.9 mo

Patients: 100% adenocarcinoma histology (20% esophagogastric junction, 80% gastric).

Chemotherapy

Oxaliplatin (Eloxatin) 85 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on days 1, 15, 29, 43 (total dose per cycle: 10,400 mg/m²)

Supportive therapy

per "local protocols"

8-week cycles

References

Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. link to original article contains dosing details in manuscript PubMed

Paclitaxel & S-1

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ishigami et al. 2018 (PHOENIX-GC)	2011-2013	Phase 3 (C)	Cisplatin & S-1	Might have superior OS Median OS: 17.7 vs 15.2 mo (HR 0.72, 95% CI 0.49-1.04)

Note: Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details

Chemotherapy

Paclitaxel (Taxol) 50 mg/m² IV once per day on days 1 and 8
Tegafur, gimeracil, oteracil (S-1) by the following criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 14
- BSA 1.25 to less than 1.5 m²: 50 mg PO twice per day on days 1 to 14
- BSA more than 1.5 m²: 60 mg PO twice per day on days 1 to 14
Paclitaxel (Taxol) 20 mg/m² IP once per day over 1 hour on days 1 and 8

Supportive therapy

500 mL of normal saline was given prior to intraperitoneal Paclitaxel (Taxol)

35-day cycles

References

PHOENIX-GC: Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. link to original article contains dosing details in manuscript PubMed UMIN000005930

Pembrolizumab monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (E-switch-ooc)	1. CF 2. CX	Non-inferior OS¹
Shitara et al. 2020 (KEYNOTE-062)	2015-2017	Phase 3 (E-switch-ooc)	3. CF & Pembrolizumab 4. CX & Pembrolizumab	Not reported

¹Reported efficacy is for patients with PD-L1 CPS score of 1 or more. Improved OS was seen in patients with PD-L1 CPS score of 10 or more (HR: 0.62) but was not tested per analysis plan.
KEYNOTE-062 included patients with GEJ malignancy.

Biomarker eligibility criteria

PD-L1 CPS score of 1 or more

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycles

References

KEYNOTE-062: Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. link to original article link to PMC article contains dosing details in abstract PubMed NCT02494583

S-1 monotherapy

Regimen variant #1, BSA-based

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Boku et al. 2009 (JCOG 9912)	2000-2006	Phase 3 (E-switch-ic)	1. Cisplatin & Irinotecan	Not reported
Boku et al. 2009 (JCOG 9912)	2000-2006	Phase 3 (E-switch-ic)	2. 5-FU	Non-inferior OS

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) 40 mg/m² PO twice per day on days 1 to 28

42-day cycles

Regimen variant #2, weight-based

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Koizumi et al. 2008 (SPIRITS)	2002-2004	Phase 3 (C)	Cisplatin & S-1	Seems to have inferior OS
Narahara et al. 2011 (TOP-002)	2004-2005	Phase 3 (C)	IRIS	Did not meet primary endpoint of OS
Koizumi et al. 2013 (START_gastric)	2005-2008	Phase 3 (C)	Docetaxel & S-1	Seems to have inferior OS
Yoshino et al. 2016 (JFMC36-0701)	2007-2010	Phase 3 (C)	Lentinan & S-1	Did not meet primary endpoint of OS

Note: there is another trial named START in NSCLC.

Chemotherapy

Tegafur, gimeracil, oteracil (S-1) by the following criteria:
- BSA less than 1.25 m²: 40 mg PO twice per day on days 1 to 28
- BSA between 1.25 and 1.5 m²: 50 mg PO twice per day on days 1 to 28
- BSA 1.5 m² or more: 60 mg PO twice per day on days 1 to 28

42-day cycles

References

SPIRITS: Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. link to original article contains dosing details in manuscript PubMed NCT00150670
JCOG 9912: Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. link to original article contains dosing details in abstract PubMed NCT00142350
TOP-002: Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011 Mar;14(1):72-80. Epub 2011 Feb 23. link to original article link to PMC article contains dosing details in manuscript PubMed JapicCTI-050083
START: Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO; KCSG. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. link to original article link to PMC article contains dosing details in manuscript PubMed NCT00287768
JFMC36-0701: Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, Shimizu R, Yoshikawa T, Osanai H, Imano M, Naitoh H, Tanaka A, Tajiri T, Gochi A, Suzuki M, Sakamoto J, Saji S, Oka M. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016 Sep;65:164-71. Epub 2016 Aug 5. link to original article PubMed UMIN000000574
RESCUE-GC: NCT02867839

UFTM

UFTM: UFT (Tegafur and uracil) & Mitomycin

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ohtsu et al. 2003 (JCOG 9205)	1992-1995	Phase 3 (E-esc)	1. Fluorouracil	Did not meet primary endpoint of OS
Ohtsu et al. 2003 (JCOG 9205)	1992-1995	Phase 3 (E-esc)	2. FP	Did not meet primary endpoint of OS

Note: this arm of the study was terminated early. Study included patients with PFS of 2 (9.6%). Mitomycin was interrupted for 1 month after patients received a total cumulative dose of 60 mg.

Chemotherapy

Tegafur and uracil (UFT) 187.5 mg/m² PO twice per day
Mitomycin (Mutamycin) 5 mg/m² IV once per day on days 1, 8, 15, 22

28-day cycles (see note)

References

JCOG 9205: Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; JCOG. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains dosing details in manuscript PubMed

Maintenance after first-line therapy

Capecitabine monotherapy

Regimen

Study	Years of enrollment	Evidence
Ohtsu et al. 2011 (AVAGAST)	2007-2008	Non-randomized portion of RCT
Kim et al. 2014 (SMC 2008-12-019)	2009-2012	Non-randomized portion of RCT

AVAGAST patients: 86% gastric and 14% GEJ. 5.4% of patients had an ECOG of 2. SMC 2008-12-019 patients: 79% gastric, 5% GEJ, and 16% unknown. 2% of patients had an ECOG of 2.

Preceding treatment

AVAGAST: CX x 6
SMC 2008-12-019: CX x 8

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO twice per day on days 1 to 14

21-day cycles

References

AVAGAST: Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. link to original article contains dosing details in manuscript PubMed NCT00548548
SMC 2008-12-019: Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. link to original article contains dosing details in manuscript PubMed NCT01099085

Metastatic or locally advanced disease, subsequent lines of therapy

Apatinib monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Awaiting publication (ANGEL)	2017-2018	Phase 3 (E-esc)	Placebo	Superior PFS

ANGEL included patients with GEJ malignancy

Targeted therapy

Apatinib (Aitan) 700 mg once per day

28-day cycles

References

ANGEL: NCT03042611
1. Abstract: Kang Y, Kang WK, Di Bartolomeo M, Chau I, Yoon HH, Cascinu S, Ryu M, Kim JG, Lee K, Oh SC, Takashima A, Kryzhanivska A, Chao Y, Vladimirov V, Evesque L, Schenker M, McGinn A, Sankar N, Wyrwicz L, Boku N. Randomized Phase 3 ANGEL study of rivoceranib (apatinib) + best supportive care (BSC) vs placebo + BSC in patients with advanced/metastatic gastric cancer. 2019 European Society of Medical Oncology annual meeting. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394 link to abstract

Docetaxel monotherapy

Regimen variant #1, 60 mg/m²

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kang et al. 2012 (SMC 2008-08-055)	2008-2010	Phase 3 (E-esc)	Best supportive care	Superior OS Median OS: 5.3 vs 3.8 mo (HR 0.66, 95% CI 0.485-0.89)

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1

21-day cycles

Regimen variant #2, 75 mg/m² x 6

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Ford et al. 2014 (COUGAR-02)	2008-2012	Phase 3 (E-esc)	Best supportive care	Superior OS Median OS: 5.2 vs 3.6 mo (HR 0.67, 95% CI 0.49-0.92)

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1

21-day cycle for up to 6 cycles

References

SMC 2008-08-055: Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article contains dosing details in abstract PubMed NCT00821990
PEP0206: Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article 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 contains dosing details in abstract PubMed NCT00978549
INTEGRATEIIb: NCT04879368

Fluorouracil, Folinic acid, Mitomycin

Regimen

Study	Years of enrollment	Evidence
Hofheinz et al. 2002	1998-2000	Phase 2, <20 pts in this subgroup

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 15,600 mg/m²)
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
Mitomycin (Mutamycin) 10 mg/m² IV once per day on days 1 & 22

56-day cycle for 2 cycles

References

Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. link to original article contains dosing details in abstract PubMed

Irinotecan monotherapy

Regimen variant #1, 125 mg/m², 4 weeks out of 6

Study	Years of enrollment	Evidence
Enzinger et al. 2005	NR in abstract	Phase 2

Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m² IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable." Study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GE junction and 33% distal esophagus) Regimen showed a 14% response rate and 53% disease control rate.

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV over 90 minutes once per day on days 1, 8, 15, 22

42-day cycles

Regimen variant #2, 150 mg/m² q2wk

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hironaka et al. 2013 (WJOG 4007)	2007-2010	Phase 3 (E-switch-ic)	Paclitaxel	Did not meet primary endpoint of OS
Nishikawa et al. 2015 (TRICS)	2007-2011	Phase 3 (C)	Cisplatin & Irinotecan	Did not meet primary endpoint of OS
Kang et al. 2012 (SMC 2008-08-055)	2008-2010	Phase 3 (E-esc)	Best supportive care	Superior OS Median OS: 5.3 vs 3.8 mo (HR 0.66, 95% CI 0.485-0.89)
Higuchi et al. 2014 (BIRIP)	2008-2011	Phase 3 (C)	Cisplatin & Irinotecan	Seems to have inferior PFS
Tanabe et al. 2015 (JACCRO GC-05)	2008-2011	Phase 3 (C)	Irinotecan & S-1	Did not meet primary endpoint of OS
Bang et al. 2018 (JAVELIN Gastric 300)	2015-2017	Phase 3 (C)	Avelumab	Did not meet primary endpoint of OS

Hironaka et al patients: 3.7% patients with an ECOG PS of 2

Chemotherapy

Irinotecan (Camptosar) 150 mg/m² IV once on day 1

14-day cycles

Regimen variant #3, 300 mg/m² q3wk

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Roy et al. 2013 (PEP0206)	2008-2010	Randomized Phase 2 (C)	1. Docetaxel 2. Irinotecan liposomal	Did not meet primary endpoint of ORR

Study included patients with GE junction malignancy (77% gastric, 23% GE junction) and included patients with ECOG of 2

Chemotherapy

Irinotecan (Camptosar) 300 mg/m² IV over 90 minutes once on day 1

21-day cycles

Regimen variant #4, 350 mg/m² q3wk

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Thuss-Patience et al. 2011	2002-2006	Phase 3 (E-esc)	Best supportive care	Seems to have superior OS Median OS: 4 vs 2.4 mo (HR 0.48, 95% CI 0.25-0.92)

Thuss-Patience et al. 2011 included patients with GE junction malignancy (~58% gastric, 43% GE junction) and included patients with ECOG of 2

Chemotherapy

Irinotecan (Camptosar) as follows:
- Cycle 1: 250 mg/m² (maximum dose of 500 mg) IV over 30 minutes once on day 1
- Cycles 2 to 10 (depending on toxicity): 350 mg/m² IV over 30 minutes once on day 1

Supportive therapy

Atropine (Atropen) 0.25 mg SC once on day 1, given prior to Irinotecan (Camptosar)
5-HT3 antagonist
Dexamethasone (Decadron)

21-day cycle for up to 10 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
Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains dosing details in manuscript PubMed NCT00144378
SMC 2008-08-055: Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed NCT00821990
PEP0206: Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article PubMed NCT00813072
WJOG 4007: Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. link to original artile contains dosing details in abstract PubMed UMIN000001252
BIRIP: Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W; Tokyo Cooperative Oncology Group. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014 May;50(8):1437-45. Epub 2014 Feb 20. link to original article contains dosing details in abstract PubMed UMIN000001028
TRICS: Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M, Tamura S, Sugimoto N, Shigematsu T, Yoshikawa T, Ishiguro T, Nakamura M, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J, Tsujinaka T. Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer. 2015 May;51(7):808-16. Epub 2015 Mar 18. link to original article contains dosing details in abstract PubMed UMIN000002571
JACCRO GC-05: Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. Epub 2015 Jun 24. link to original article PubMed NCT00639327
JAVELIN Gastric 300: Bang YJ, Yanez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. link to original article link to PMC article contains dosing details in abstract PubMed NCT02625623
INTEGRATEIIb: NCT04879368

Irinotecan liposomal monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Roy et al. 2013 (PEP0206)	2008-2010	Randomized Phase 2 (E-switch-ic)	1. Docetaxel 2. Irinotecan	Did not meet primary endpoint of ORR

Chemotherapy

Irinotecan liposome (Onivyde) 120 mg/m² IV over 90 minutes once on day 1

21-day cycles

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 contains dosing details in manuscript PubMed NCT00813072

Nivolumab monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Janjigian et al. 2018 (CheckMate 032)	2013-2015	Phase 2
Kang et al. 2017 (ATTRACTION-2)	2014-2016	Phase 3 (E-esc)	Placebo	Superior OS¹ Median OS: 5.3 vs 4.1 mo (HR 0.62, 95% CI 0.50-0.75)

¹Reported efficacy is based on the 2021 update.
ATTRACTION-2 included patients with GE junction malignancy (82.6% gastric, 8.5% GE junction) and 12.3% of patients had a PD-L1 CPS score of at least 1

Immunotherapy

Nivolumab (Opdivo) 3 mg/kg IV once on day 1

14-day cycles

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 contains dosing details in manuscript PubMed NCT02267343
1. 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
2. Update: Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Sameshima H, Kang YK, Boku N. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020 May;23(3):510-519. Epub 2019 Dec 20. link to original article link to PMC article PubMed
3. Update: Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Nishiyama T, Chen LT, Kang YK. Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab. Gastric Cancer. 2021 Jul;24(4):946-958. Epub 2021 Mar 20. link to original article link to PMC article PubMed
CheckMate 032: Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate 032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. Epub 2018 Aug 15. link to original article link to PMC article PubMed NCT01928394

Paclitaxel monotherapy

Regimen variant #1, 70 mg/m², 3 out of 4 weeks

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Lee et al. 2018 (KCSG ST10-01)	2011-2015	Phase 3 (C)	Irinotecan	Inconclusive whether non-inferior PFS

Chemotherapy

Paclitaxel (Taxol) 70 mg/m² IV once per day on days 1, 8, 15

28-day cycles

Regimen variant #2, 80 mg/m² weekly

Study	Years of enrollment	Evidence
Kodera et al. 2007 (CCOG0302)	2003-2006	Phase 2

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15

21-day cycles

Regimen variant #3, 80 mg/m², 3 out of 4 weeks

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Hironaka et al. 2006	2002-2004	Non-randomized
Hironaka et al. 2013 (WJOG 4007)	2007-2010	Phase 3 (E-switch-ic)	Irinotecan	Did not meet primary endpoint of OS (HR 0.88, 95% CI 0.67-1.16)
Wilke et al. 2014 (RAINBOW)	2010-2012	Phase 3 (C)	Paclitaxel & Ramucirumab	Seems to have inferior OS
Lorenzen et al. 2020 (RADPAC)	2011-2015	Phase 3 (C)	Everolimus & Paclitaxel	Did not meet primary endpoint of OS
Shitara et al. 2017 (ABSOLUTE)	2013-2015	Phase 3 (C)	1. nab-Paclitaxel weekly	Non-inferior OS
Shitara et al. 2017 (ABSOLUTE)	2013-2015	Phase 3 (C)	2. nab-Paclitaxel q3wk	Might have superior OS
Bang et al. 2017 (GOLD)	2013-2016	Phase 3 (C)	Olaparib & Paclitaxel	Might have inferior OS
Shitara et al. 2018 (KEYNOTE-061)	2015-2016	Phase 3 (C)	Pembrolizumab	Seems to have inferior OS¹
Bang et al. 2018 (JAVELIN Gastric 300)	2015-2017	Phase 3 (C)	Avelumab	Did not meet primary endpoint of OS
Chung et al. 2021 (KEYNOTE-063)	2017-2018	Phase 3 (C)	Pembrolizumab	Seems to have superior PFS Median PFS: 4 vs 2 mo (HR 0.62, 95% CI 0.40-0.96)
Xu et al. 2021 (RAINBOW-Asia)	2017-2020	Phase 3 (C)	Paclitaxel & Ramucirumab	Seems to have inferior PFS

¹Reported efficacy is based on the 2021 update, for the CPS ≥ 1 group.
Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline." RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction) Satoh et al. patients: 98.5% gastric. 1.5 other Hironaka et al patients: 3.7% patients with a PFS of 2

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV over 60 minutes once per day on days 1, 8, 15

28-day cycles

Regimen variant #4, 175 mg/m² q3wk

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Kang et al. 2018 (DREAM)	2013-2015	Phase 3 (C)	DHP107	Non-inferior PFS

Chemotherapy

Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycles

References

Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2006;9(1):14-8. link to original article contains dosing details in manuscript PubMed
CCOG0302: Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, Matsui T, Kojima H, Takase T, Ohashi N, Fujiwara M, Sakamoto J, Akimasa N; Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007 Jul-Aug;27(4C):2667-71. link to original article contains dosing details in abstract PubMed
WJOG 4007: Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. link to original artile contains dosing details in abstract PubMed UMIN000001252
RAINBOW: Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. Epub 2014 Sep 17. link to original article contains dosing details in manuscript PubMed NCT01170663
ABSOLUTE: Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. link to original article contains dosing details in abstract PubMed JapicCTI-132059
GOLD: Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. link to original article PubMed NCT01924533
DREAM: Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Park YI, Park SR, Rha SY, Kang MJ, Cho JY, Kang SY, Roh SY, Ryoo BY, Nam BH, Jo YW, Yoon KE, Oh SC. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol. 2018 May 1;29(5):1220-1226. link to original article contains dosing details in abstract PubMed NCT01839773
KEYNOTE-061: Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. link to original article contains dosing details in manuscript PubMed NCT02370498
1. Update: Fuchs CS, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. Epub 2021 Sep 1. link to original article link to PMC article PubMed
KCSG ST10-01: Lee KW, Maeng CH, Kim TY, Zang DY, Kim YH, Hwang IG, Oh SC, Chung JS, Song HS, Kim JW, Jeong SJ, Cho JY. A phase III study to compare the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer who failed in first-line therapy (KCSG ST10-01). Oncologist. 2019 Jan;24(1):18-e24. Epub 2018 Aug 20. link to original article contains dosing details in abstract link to PMC article PubMed NCT01224652
JAVELIN Gastric 300: Bang YJ, Yanez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. link to original article link to PMC article contains dosing details in abstract PubMed NCT02625623
RADPAC: Lorenzen S, Knorrenschild JR, Pauligk C, Hegewisch-Becker S, Seraphin J, Thuss-Patience P, Kopp HG, Dechow T, Vogel A, Luley KB, Pink D, Stahl M, Kullmann F, Hebart H, Siveke J, Egger M, Homann N, Probst S, Goetze TO, Al-Batran SE. Phase III randomized, double-blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC). Int J Cancer. 2020 Nov 1;147(9):2493-2502. Epub 2020 May 7. link to original article contains dosing details in abstract PubMed NCT01248403
RAINBOW-Asia: Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. Epub 2021 Oct 6. Epub ahead of print. link to original article contains dosing details in abstract PubMed NCT02898077
KEYNOTE-063: Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, Park YL, Koo DH, Lu J, Xu J, Chon HJ, Bai LY, Zeng S, Yuan Y, Chen YY, Gu K, Zhong WY, Kuang S, Shih CS, Qin SK. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer. 2022 Mar 1;128(5):995-1003. Epub 2021 Dec 8. link to original article contains dosing details in manuscript PubMed NCT03019588
INTEGRATEIIb: NCT04879368

nab-Paclitaxel monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2017 (ABSOLUTE)	2013-2015	Phase 3 (E-switch-ic)	1. Paclitaxel; weekly	Non-inferior OS
Shitara et al. 2017 (ABSOLUTE)	2013-2015	Phase 3 (E-switch-ic)	2. nab-Paclitaxel; q3wk	Not reported

Chemotherapy

Paclitaxel, nanoparticle albumin-bound (Abraxane) 100 mg/m² IV once per day on days 1, 8, 15

28-day cycles

References

ABSOLUTE: Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. link to original article contains dosing details in abstract PubMed JapicCTI-132059

Paclitaxel & Ramucirumab

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Wilke et al. 2014 (RAINBOW)	2010-2012	Phase 3 (E-RT-esc)	Paclitaxel	Seems to have superior OS Median OS: 9.6 vs 7.4 mo (HR 0.81, 95% CI 0.68-0.96)
Xu et al. 2021 (RAINBOW-Asia)	2017-2020	Phase 3 (E-esc)	Paclitaxel	Seems to have superior PFS Median PFS: 4.1 vs 3.15 mo (HR 0.77, 95% CI 0.61-0.955)

Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline." RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction).

Targeted therapy

Ramucirumab (Cyramza) 8 mg/kg IV over 60 minutes once per day on days 1 & 15, given first

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV once per day on days 1, 8, 15, given second

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 contains dosing details in manuscript PubMed NCT01170663
RAINBOW-Asia: Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. Epub 2021 Oct 6. link to original article contains dosing details in abstract PubMed NCT02898077
RAMIRIS: NCT03081143

Pembrolizumab monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fuchs et al. 2018 (KEYNOTE-059)	2015-2016	Phase 2 (RT)		ORR: 12% (95% CI 8-16)
Shitara et al. 2018 (KEYNOTE-061)	2015-2016	Phase 3 (E-switch-ooc)	Paclitaxel	Seems to have superior OS¹ Median OS: 9.1 vs 8.3 mo (HR 0.81, 95% CI 0.66-1.00)

¹Reported efficacy is based on the 2021 update, for the CPS ≥ 1 group.
Both studies included patients with GE junction malignancy:

KEYNOTE-059: 48.3% gastric, 51.4% GE junction and 57.1% of patients had a PD-L1 CPS score of at least 1
KEYNOTE-061: 68.8% gastric, 31.2% GE junction and 66% of all patients receiving pembrolizumab had a PD-L1 CPS score of at least 1

Biomarker eligibility criteria

PD-L1 (combined positive score > 1%) as determined by an FDA-approved test.

Immunotherapy

Pembrolizumab (Keytruda) 200 mg IV once on day 1

21-day cycle for up to 35 cycles (2 years)

References

KEYNOTE-059: Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013. Epub 2018 May 10. link to original article link to PMC article contains dosing details in manuscript PubMed NCT02335411
KEYNOTE-061: Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. link to original article contains dosing details in manuscript PubMed NCT02370498
1. Update: Fuchs CS, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. Epub 2021 Sep 1. link to original article link to PMC article PubMed

Ramucirumab monotherapy

Regimen

FDA-recommended dose

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Fuchs et al. 2013 (REGARD)	2009-2012	Phase 3 (E-RT-esc)	Placebo	Seems to have superior OS Median OS: 5.2 vs 3.8 mo (HR 0.78, 95% CI 0.60-0.998)

Patients in REGARD previously had "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." Study includes patients with GE junction malignancy (75% gastric, 25% GE junction).

Targeted therapy

Ramucirumab (Cyramza) 8 mg/kg IV over 60 minutes once on day 1

14-day cycles

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 contains dosing details in manuscript PubMed NCT00917384

Regorafenib monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Pavlakis et al. 2016 (INTEGRATE)	2012-2014	Randomized Phase 2 (E-esc)	Placebo	Superior PFS Median PFS: 2.6 vs 0.9 mo (HR 0.40, 95% CI 0.28-0.59)

INTEGRATE included patients with GEJ malignancy: 62% stomach or other, 38% GEJ

Targeted therapy

Regorafenib (Stivarga) 160 mg PO once per day on days 1 to 21

28-day cycles

References

INTEGRATE: Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. link to original article contains dosing details in manuscript link to PMC article PubMed ANZCTR12612000239864

Trifluridine and tipiracil monotherapy

Regimen

Study	Years of enrollment	Evidence	Comparator	Comparative Efficacy
Shitara et al. 2018 (TAGS)	2016-2018	Phase 3 (E-RT-esc)	Placebo	Superior OS Median OS: 5.7 vs 3.6 mo (HR 0.69, 95% CI 0.56-0.85)

Chemotherapy

Trifluridine and tipiracil (Lonsurf) 35 mg/m² PO twice per day on days 1 to 5, 8 to 12

28-day cycles

References

TAGS: Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. link to original article contains dosing details in abstract PubMed NCT02500043
INTEGRATEIIb: NCT04879368

@@ Line 3: / Line 3: @@
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-{{#lst:Section editor transclusions|thoracic}}
+{{#lst:Section editor transclusions|gi}}
-''Are you looking for a regimen but can't find it here? It is possible that we've moved it to the [[Small cell lung cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Small cell lung cancer - null regimens|this page]]. If you still can't find it, please let us know so we can add it!''.
+<big>Note: there is significant overlap between regimens for gastric cancer and '''[[esophageal cancer]]''', if you can't find the regimen you're looking for here, please try the esophageal cancer page. If you still can't find it, it is possible that we've moved it to the [[Gastric_cancer_-_historical|historical regimens page]]. For placebo or observational studies in this condition, please visit [[Gastric cancer - null regimens|this page]].
+*'''Note: this page contains regimens which were not tested in biomarker-specific populations. The following links will take you to biomarker-specific subpages:'''
+*Regimens for [[Gastric_cancer,_HER2-positive|'''HER2 positive gastric cancer are here''']]</big>.
 {| class="wikitable" style="float:right; margin-right: 5px;"
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@@ Line 12: / Line 14: @@
 {{TOC limit|limit=3}}
 =Guidelines=
-==[http://www.asco.org/ ASCO]==
-*'''2021:''' Daly et al. [https://doi.org/10.1200/jco.20.03364 Radiation Therapy for Small-Cell Lung Cancer: ASCO Guideline Endorsement of an ASTRO Guideline]
-*'''2020:''' Schneider et al. [https://doi.org/10.1200/jco.19.02748 Lung Cancer Surveillance After Definitive Curative-Intent Therapy: ASCO Guideline]
-*'''2015:''' Rudin et al. [https://doi.org/10.1200/JCO.2015.63.7918 Treatment of small-cell lung cancer: American Society of Clinical Oncology endorsement of the American College of Chest Physicians guideline] [https://pubmed.ncbi.nlm.nih.gov/26351333 PubMed]
 ==[http://www.esmo.org/ ESMO]==
-*'''2021:''' Dingemans et al. [https://doi.org/10.1016/j.annonc.2021.03.207 Small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
+*'''2019:''' Stjepanovic et al. [https://academic.oup.com/annonc/article/30/10/1558/5543095 Hereditary gastrointestinal cancers: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up]
-===Older===
+*'''2016:''' Smyth et al. [https://www.esmo.org/Guidelines/Gastrointestinal-Cancers/Gastric-Cancer Gastric cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/27664260 PubMed]
-*'''2013:''' Früh et al. [https://doi.org/10.1093/annonc/mdt178 Small-cell lung cancer (SCLC): ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up.] [https://pubmed.ncbi.nlm.nih.gov/23813929 PubMed]
+==ESMO/ESSO/ESTRO==
+*'''2013:''' Waddell et al. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdt344 Gastric cancer: ESMO-ESSO-ESTRO Clinical Practice Guidelines for diagnosis, treatment and follow-up] [https://pubmed.ncbi.nlm.nih.gov/24078663 PubMed]
 ==[https://www.nccn.org/ NCCN]==
-*[https://www.nccn.org/professionals/physician_gls/pdf/sclc.pdf NCCN Guidelines - Small Cell Lung Cancer]
+*[https://www.nccn.org/professionals/physician_gls/pdf/gastric.pdf NCCN Guidelines - Gastric Cancer]
-=Limited stage, induction=
+=Perioperative therapy=
-==Carboplatin & Etoposide (CE) {{#subobject:f0013f|Regimen=1}}==
+''This section contains protocols with a pre-planned neoadjuvant (preoperative) and adjuvant (postoperative) component.''
-EP: '''<u>E</u>'''toposide, '''<u>P</u>'''araplatin (Carboplatin)
+==Capecitabine & Cisplatin (CX) {{#subobject:tr26bc|Regimen=1}}==
+CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 2 days of oral etoposide per cycle {{#subobject:89f0ef|Variant=1}}===
+===Protocol {{#subobject:cz7085|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)]
+|Awaiting publication (KEYNOTE-585)
-|2003-2006
+|2017-ongoing
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]], then RT
+|1. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab_66|Perioperative CX & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab_66|Perioperative CF & Pembrolizumab]]<br>3. [[#FLOT_.26_Pembrolizumab_66|FLOT & Pembrolizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d3d3d3" |To be determined
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, neoadjuvant CX portion====
-*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-'''21-day cycle for up to 6 cycles'''
+'''21-day cycle for 3 cycles'''
-</div>
+====Surgery====
-<div class="toccolours" style="background-color:#cbd5e7">
+*[[Surgery#Gastrectomy|Surgical resection]]
-====Subsequent treatment====
+====Chemotherapy, adjuvant CX portion====
-*Patients with complete or partial responses: [[#Radiation_therapy|Thoracic radiotherapy]] and [[#Whole_brain_irradiation|prophylactic cranial irradiation]], approximately 3 weeks after the last cycle, "according to local practice".
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-</div></div><br>
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+'''21-day cycle for 3 cycles'''
+</div></div>
+===References===
+#'''KEYNOTE-585:''' '''contains dosing details on CT.gov''' NCT03221426
+==Cisplatin & Fluorouracil (CF) {{#subobject:7b88be|Regimen=1}}==
+CF: '''<u>C</u>'''isplatin & '''<u>F</u>'''luorouracil
+<br>FP: '''<u>F</u>'''luorouracil & '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 1 day of oral etoposide per cycle {{#subobject:3cbc9f|Variant=1}}===
+===Protocol variant #1, 80/4000 {{#subobject:c2yy1e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)]
+|Awaiting publication (KEYNOTE-585)
-|2003-2006
+|2017-ongoing
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]], then RT
+|1. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab_66|Perioperative CX & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab_66|Perioperative CF & Pembrolizumab]]<br>3. [[#FLOT_.26_Pembrolizumab_66|FLOT & Pembrolizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d3d3d3" |To be determined
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, neoadjuvant CF portion====
-*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''21-day cycle for up to 6 cycles'''
+'''21-day cycle for 3 cycles'''
-</div>
+====Surgery====
-<div class="toccolours" style="background-color:#cbd5e7">
+*[[Surgery#Gastrectomy|Surgical resection]]
-====Subsequent treatment====
+====Chemotherapy, adjuvant CF portion====
-*Patients with complete or partial responses: [[#Radiation_therapy|Thoracic radiotherapy]] and [[#Whole_brain_irradiation|prophylactic cranial irradiation]], approximately 3 weeks after the last cycle, "according to local practice".
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-</div></div>
+*[[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>)
-===References===
+'''21-day cycle for 3 cycles'''
-# '''LLCG-STUDY-12:''' Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. [https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19608997 PubMed] NCT00061919
+</div></div><br>
-==Cisplatin & Etoposide (EP) {{#subobject:189bcc|Regimen=1}}==
-EP: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:dd9b40|Variant=1}}===
+===Protocol variant #2, 100/4000 {{#subobject:c2dc1e|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985]
+|[https://doi.org/10.1200/jco.2010.33.0597 Ychou et al. 2011 (ACCORD 07)]
-|1981-1984
+|1995-2003
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Surgery#Gastrectomy|Surgery alone]]
+| style="background-color:#1a9850" |Superior OS<br>OS60: 38% vs 24%<br>(HR 0.69, 95% CI 0.50-0.95)
 |-
 |}
-''Patients with limited stage disease responding to therapy received [[#Whole_brain_irradiation|prophylactic cranial irradiation]], 4 Gy fractions once per day x 5 fractions (total dose: 20 Gy) over 5 days between cycles 3 and 4.''
+''ACCORD 07 included patients with lower esophageal malignancy as well (25% gastric, 11% lower esophagus, and 64% GE junction).''
-====Chemotherapy====
+====Chemotherapy, neoadjuvant CF portion====
-*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV slow push once per day on days 1 to 3, '''given second'''
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over at least 30 minutes once per day on days 1 to 3, '''given first'''
+*[[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>)
-====Supportive therapy====
+'''28-day cycle for 2 to 3 cycles'''
-*[[Dexamethasone (Decadron)]] 10 mg IV once per day on days 1 to 3, prior to chemotherapy
+====Surgery====
-*[[Metoclopramide (Reglan)]] 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
+*[[Surgery#Gastrectomy|Surgical resection]]
-*[[Prochlorperazine (Compazine)]] 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy
+====Chemotherapy, adjuvant CF portion====
-*"No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 28
-'''21- to 28-day cycle for 6 cycles'''
+*[[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>)
-</div>
+'''28-day cycle for 3 to 4 cycles, for a total of 6 cycles'''
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Radiation_therapy|Thoracic radiation]]
 </div></div>
 ===References===
-# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2997406 PubMed]
+#'''ACCORD 07:''' Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P; FNCLCC; FFCD. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. [https://doi.org/10.1200/jco.2010.33.0597 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/21444866 PubMed] NCT00002883
-=Limited stage, definitive chemoradiotherapy=
+#'''KEYNOTE-585:''' '''contains dosing details on CT.gov''' NCT03221426
-==Carboplatin, Etoposide, RT {{#subobject:6c0ece|Regimen=1}}==
+==ECF {{#subobject:f0281c|Regimen=1}}==
-EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''araplatin (Carboplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1 {{#subobject:9e4385|Variant=1}}===
+===Regimen {{#subobject:66f602|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1023/a:1012295131640 Skarlos et al. 2001]
+|[https://doi.org/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)]
-|1993-1999
+|1994-2002
-| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Carboplatin.2C_Etoposide.2C_RT|Carboplatin, Etoposide, RT]]; early HTRT
+|[[Surgery#Gastrectomy|Surgery alone]]
-| style="background-color:#d9ef8b" |Might have superior ORR
+| style="background-color:#1a9850" |Superior OS<br>OS60: 36% vs 23%<br>(HR 0.75, 95% CI 0.60-0.93)
+|-
+|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
+|2007-2015
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 |-
 |}
+''MAGIC included patients with lower esophageal malignancy as well (74% gastric, 14.8% lower esophagus, and 11.2% GE junction).''
+''CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction''
+''Note: In CRITICS, only patients with trouble swallowing pills were assigned to this treatment arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, neoadjuvant ECF portion====
-*[[Carboplatin (Paraplatin)]] AUC 6 IV over 60 minutes once on day 1, '''given first, before etoposide'''
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 to 3, '''given second, after carboplatin'''
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-*Concurrent [[External beam radiotherapy|hyperfractionated thoracic radiation therapy (HTRT)]], 1.5 Gy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks. Skarlos et al. 2001 examined two different timings for radiation therapy. There was no significant difference between early vs. late HTRT, though there was a trend toward higher response rate for late HTRT. Early HTRT is given during cycle 1 of chemotherapy; late HTRT is given during cycle 4 of chemotherapy.
+====Supportive therapy====
-'''21-day cycle for up to 6 cycles'''
+*MAGIC, suggested as thrombosis prophylaxis:
-</div>
+**[[Warfarin (Coumadin)]] 1 mg PO once per day
-<div class="toccolours" style="background-color:#cbd5e7">
+'''21-day cycle for 3 cycles'''
-====Subsequent treatment====
+====Surgery====
-*Patients with CR: [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
+*MAGIC: [[Surgery#Gastrectomy|Surgical resection]] is performed 3 to 6 weeks after the completion of cycle 3
-</div></div><br>
+*CRITICS: [[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
+'''Followed in 6 to 12 weeks by:'''
+====Chemotherapy, adjuvant ECF portion====
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+====Supportive therapy====
+*MAGIC, suggested as thrombosis prophylaxis:
+**[[Warfarin (Coumadin)]] 1 mg PO once per day
+'''21-day cycle for 3 cycles'''
+</div></div>
+===References===
+#'''MAGIC:''' Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [https://doi.org/10.1056/NEJMoa055531 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16822992 PubMed] NCT00002615
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
+==ECX {{#subobject:c8ab0e|Regimen=1}}==
+ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2 {{#subobject:bb6fc|Variant=1}}===
+===Protocol {{#subobject:27f848|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.1999.17.11.3540 Okamoto et al. 1999]
+|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
-| style="background-color:#91cf61" |Phase 2
+|2007-2015
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 |-
 |}
-''Patients in Okamoto et al. 1999 were greater than or equal to 70 years old.''
+''CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction''
-====Chemotherapy====
+====Chemotherapy, neoadjuvant ECX portion====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given first'''
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3, '''given second'''
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[External beam radiotherapy|Thoracic radiation]], '''given third'''
+'''21-day cycle for 3 cycles'''
-*Palliative radiation therapy was allowed to control persistent pain from bony metastases
+====Surgery====
-====Supportive therapy====
+*[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
-*[[Dexamethasone (Decadron)]] 8 mg IV once per day on days 1 to 3, prior to chemotherapy
+====Chemotherapy, adjuvant ECX portion====
-*[[Granisetron]] 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-'''28-day cycle for up to 4 cycles'''
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+'''21-day cycle for 3 cycles'''
 </div></div>
 ===References===
-<!-- Presented in part at the Thirty-Fourth Annual Meeting of the American Society of Clinical Oncology, Los Angeles, CA, May 16-19, 1998. -->
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
-# Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. [https://doi.org/10.1200/jco.1999.17.11.3540 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10550152 PubMed]
+==EOF {{#subobject:139705|Regimen=1}}==
-# Skarlos DV, Samantas E, Briassoulis E, Panoussaki E, Pavlidis N, Kalofonos HP, Kardamakis D, Tsiakopoulos E, Kosmidis P, Tsavdaridis D, Tzitzikas J, Tsekeris P, Kouvatseas G, Zamboglou N, Fountzilas G; Hellenic Cooperative Oncology Group. Randomized comparison of early versus late hyperfractionated thoracic irradiation concurrently with chemotherapy in limited disease small-cell lung cancer: a randomized phase II study of the Hellenic Cooperative Oncology Group (HeCOG). Ann Oncol. 2001 Sep;12(9):1231-8. [https://doi.org/10.1023/a:1012295131640 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11697833 PubMed]
+EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luourouracil
-==Cisplatin, Etoposide, RT {{#subobject:fb5cd7|Regimen=1}}==
-EP & RT: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin), '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<br>PE + RT: '''<u>P</u>'''latinol (Cisplatin), '''<u>E</u>'''toposide, '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 60/360/45 {{#subobject:63584c|Variant=1}}===
+===Protocol {{#subobject:bf7464|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1056/NEJM199901283400403 Turrisi et al. 1999 (Intergroup 0096)]
+|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
-|1989-1992
+|2007-2015
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; once per day RT
+|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
-| style="background-color:#91cf60" |Seems to have superior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
 |-
 |}
+''CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction''
+''Note: Only patients with trouble swallowing pills were assigned to this treatment arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, neodjuvant EOF portion====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.5 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
+'''21-day cycle for 3 cycles'''
-'''21-day cycle for 4 cycles'''
+====Surgery====
-</div>
+*[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
-<div class="toccolours" style="background-color:#cbd5e7">
+====Chemotherapy, adjuvant EOF portion====
-====Subsequent treatment====
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*After completing 4 cycles of chemotherapy, patients were restaged. Because of the high rate of brain metastases (50%), patients with CR were offered [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-</div></div><br>
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
+'''21-day cycle for 3 cycles'''
+</div></div>
+===References===
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
+==EOX {{#subobject:86ee8e|Regimen=1}}==
+EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 70/300/52.5, early RT {{#subobject:97533b|Variant=1}}===
+===Protocol {{#subobject:edae45|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
+! style="width: 20%" |Study
-!style="width: 15%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[https://doi.org/10.1093/annonc/mdt140 Sun et al. 2013 (SMC 2003-02-016)]
+|[https://doi.org/10.1016/S1470-2045(18)30132-3 Cats et al. 2018 (CRITICS)]
-|2003-2010
+|2007-2015
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; late RT
+|1. [[#ECF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECF/CX & RT]]<br>2. [[#ECX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|ECX/CX & RT]]<br>3. [[#EOF.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOF/CX & RT]]<br>4. [[#EOX.2FCapecitabine_.26_Cisplatin_.28CX.29_.26_RT_99|EOX/CX & RT]]
-| style="background-color:#eeee01" |Non-inferior CR rate
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 43 vs 37 mo<br>(HR 1.01, 95% CI 0.84-1.22)
-| style="background-color:#fc8d59" |Seems to have higher rates of neutropenic fever
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''CRITICS trial included few patients with GE junction malignancy: 83% gastric, 17% GE junction''
-====Chemotherapy====
+====Chemotherapy, neoadjuvant EOX portion====
-*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
-*Concurrent [[External_beam_radiotherapy|radiation therapy]], 2.1 Gy fractions x 25 fractions over 5 weeks, given during cycle 1 of chemotherapy (total dose: 52.5 Gy)
+'''21-day cycle for 3 cycles'''
-'''21-day cycle for 4 cycles'''
+====Surgery====
-</div></div><br>
+*[[Surgery#Gastrectomy|Surgery]] with a D1+ lymph node resection
+====Chemotherapy, adjuvant EOX portion====
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
+'''21-day cycle for 3 cycles'''
+</div></div>
+===References===
+#'''CRITICS:''' Cats A, Jansen EPM, van Grieken NCT, Sikorska K, Lind P, Nordsmark M, Meershoek-Klein Kranenbarg E, Boot H, Trip AK, Swellengrebel HAM, van Laarhoven HWM, Putter H, van Sandick JW, van Berge Henegouwen MI, Hartgrink HH, van Tinteren H, van de Velde CJH, Verheij M; CRITICS investigators. Chemotherapy versus chemoradiotherapy after surgery and preoperative chemotherapy for resectable gastric cancer (CRITICS): an international, open-label, randomised phase 3 trial. Lancet Oncol. 2018 May;19(5):616-628. Epub 2018 Apr 9. [https://doi.org/10.1016/S1470-2045(18)30132-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29650363 PubMed] NCT00407186
+==FLOT {{#subobject:aa7f4f|Regimen=1}}==
+FLOT: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin, '''<u>T</u>'''axotere (Docetaxel)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 70/300/52.5, late RT {{#subobject:2140dc|Variant=1}}===
+===Protocol variant #1, 3 + 3 {{#subobject:16408e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
+! style="width: 20%" |Study
-!style="width: 15%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[https://doi.org/10.1093/annonc/mdt140 Sun et al. 2013 (SMC 2003-02-016)]
+|Awaiting publication (KEYNOTE-585)
-|2003-2010
+|2017-ongoing
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; early RT
+|1. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab_66|Perioperative CX & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab_66|Perioperative CF & Pembrolizumab]]<br>3. [[#FLOT_.26_Pembrolizumab_66|FLOT & Pembrolizumab]]
-| style="background-color:#eeee01" |Non-inferior CR rate
+| style="background-color:#d3d3d3" |To be determined
-| style="background-color:#91cf60" |Seems to have lower rates of neutropenic fever
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, neoadjuvant FLOT portion====
-*[[Cisplatin (Platinol)]] 70 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
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Folinic acid (Leucovorin)]] as follows:
-====Radiotherapy====
+**Cycle 1: 200 mg/m<sup>2</sup> IV once per day on days 1 & 15
-*Concurrent [[External_beam_radiotherapy|radiation therapy]], 2.1 Gy fractions x 25 fractions over 5 weeks, given during cycle 3 of chemotherapy (total dose: 52.5 Gy)
+**Cycle 2: 200 mg/m<sup>2</sup> IV once on day 8
-'''21-day cycle for 4 cycles'''
+**Cycle 3: 200 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 3 cycles'''
+====Surgery====
+*[[Surgery#Gastrectomy|Surgery]]
+====Chemotherapy, adjuvant FLOT portion====
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
+*[[Folinic acid (Leucovorin)]] as follows:
+**Cycle 1: 200 mg/m<sup>2</sup> IV once per day on days 1 & 15
+**Cycle 2: 200 mg/m<sup>2</sup> IV once on day 8
+**Cycle 3: 200 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycle for 3 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 75/180/45, pre-planned dose reduction {{#subobject:2b9803|Variant=1}}===
+===Protocol variant #2, 4 + 4 {{#subobject:16408e|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
+! style="width: 20%" |Study
-!style="width: 15%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-|[https://doi.org/10.1200/JCO.1995.13.7.1632 Bunn et al. 1995]
+|[https://doi.org/10.1016/S1470-2045(16)30531-9 Al-Batran et al. 2016 (FLOT4-AIO)]
-|1989-1991
+|2010-2015
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 2/3 (E-switch-ic)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; with GM-CSF support
+|1. [[#ECF|Perioperative ECF]]<br>2. [[#ECX|Perioperative ECX]]
-| style="background-color:#ffffbf" |Did not meet secondary endpoints
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 50 vs 35 mo<br>(HR 0.77, 95% CI 0.63-0.94)
-| style="background-color:#1a9850" |Less toxic
 |-
 |}
-''Note: toxicity was the primary endpoint in this study.''
+''<sup>1</sup>Reported efficacy is based on the 2019 update.''
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, neoadjuvant FLOT portion====
-*[[Cisplatin (Platinol)]] as follows:
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
-**Cycles 1 to 3: 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
-**Cycles 4 to 6: 40 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] as follows:
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
-**Cycles 1 to 3: 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''14-day cycle for 4 cycles'''
-**Cycles 4 to 6: 50 mg/m<sup>2</sup> IV once per day on days 1 to 3
+====Surgery====
-====Radiotherapy====
+*[[Surgery#Gastrectomy|Surgery]]
-*Concurrent [[External_beam_radiotherapy|radiation therapy]] during cycles 1 & 2, 1.8 Gy fractions x 25 fractions (total dose: 45 Gy)
+====Chemotherapy, adjuvant FLOT portion====
-'''21-day cycle for 6 cycles'''
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on day 1
-</div></div><br>
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
+'''14-day cycle for 4 cycles'''
+</div></div>
+===References===
+#'''FLOT4-AIO:''' Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. [https://doi.org/10.1016/S1470-2045(16)30531-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27776843 PubMed] NCT01216644
+##'''Update:''' Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, von Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Weniger J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Jäger E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. [https://doi.org/10.1016/s0140-6736(18)32557-1 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30982686 PubMed]
+#'''KEYNOTE-585:''' '''contains dosing details on CT.gov''' NCT03221426
+#'''MATTERHORN:''' NCT04592913
+#'''RAMSES:''' NCT02661971
+==SOX {{#subobject:ecig8a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, 75/300/45 {{#subobject:7ed43e|Variant=1}}===
+===Protocol {{#subobject:5guz13|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/pmc8886520/ Yu et al. 2022 (FOCUS<sub>gastric</sub>)]
+|2011-2016
+|style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#mFOLFOX6_88|Perioperative mFOLFOX6]]
+| style="background-color:#eeee01" |Non-inferior OS<br>OS36: 75.2% vs 67.8%
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, neoadjuvant SOX portion====
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
+**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+'''21-day cycle for 2 to 4 cycles'''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Gastrectomy|Gastrectomy]] with at least D2 dissection
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, adjuvant SOX portion====
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following BSA-based criteria:
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
+**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+'''21-day cycle for 2 to 4 cycles'''
+</div></div>
+===References===
+#'''RESOLVE<sub>gastric</sub>:''' Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. [https://doi.org/10.1016/s1470-2045(21)00297-7 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34252374/ PubMed] NCT01534546
+#'''FOCUS<sub>gastric</sub>:''' Yu J, Gao Y, Chen L, Wu D, Shen Q, Zhao Z, Liu W, Yang H, Zhang Q, Wang X, Hu P, Zheng Z, Wang X, Liu H, Xu Z, Yan Z, Wu Y, Jin M, Zhang Q, Liu X, Zhu K, Shou C. Effect of S-1 Plus Oxaliplatin Compared With Fluorouracil, Leucovorin Plus Oxaliplatin as Perioperative Chemotherapy for Locally Advanced, Resectable Gastric Cancer: A Randomized Clinical Trial. JAMA Netw Open. 2022 Feb 1;5(2):e220426. [https://doi.org/10.1001/jamanetworkopen.2022.0426 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8886520/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35226081/ PubMed] NCT01364376
+=Neoadjuvant chemotherapy=
+==DOS {{#subobject:a2ug18|Regimen=1}}==
+DOS: '''<u>D</u>'''ocetaxel, '''<u>O</u>'''xaliplatin, '''<u>S</u>'''-1
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:gu1503|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555437/ Faivre-Finn et al. 2017 (CONVERT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425847/ Kang et al. 2021 (PRODIGY)]
-|2008-2013
+|2012-2017
 | style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; once per day RT
+|[[Gastric_cancer_-_null_regimens#No_neoadjuvant_therapy|No neoadjuvant therapy]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#91cf60" |Seems to have superior PFS<br>PFS36: 66% vs 60%<br>(aHR 0.70, 95% CI 0.52-0.95)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 100 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Tegafur, gimeracil, oteracil (S-1)|S-1]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.5 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
+'''21-day cycle for 3 cycles'''
-'''21-day cycle for 4 or 6 cycles'''
+</div>
-</div></div><br>
+<div class="toccolours" style="background-color:#cbd5e7">
-<div class="toccolours" style="background-color:#eeeeee">
+====Subsequent treatment====
-===Regimen variant #6, 75/300/45, split doses of cisplatin {{#subobject:c54e7b|Variant=1}}===
+*[[Surgery#Gastrectomy|Surgery]], then adjuvant [[#S-1_monotherapy|S-1]]
+</div></div>
+===References===
+#'''PRODIGY:''' Kang YK, Yook JH, Park YK, Lee JS, Kim YW, Kim JY, Ryu MH, Rha SY, Chung IJ, Kim IH, Oh SC, Park YS, Son T, Jung MR, Heo MH, Kim HK, Park C, Yoo CH, Choi JH, Zang DY, Jang YJ, Sul JY, Kim JG, Kim BS, Beom SH, Cho SH, Ryu SW, Kook MC, Ryoo BY, Kim HK, Yoo MW, Lee NS, Lee SH, Kim G, Lee Y, Lee JH, Noh SH. PRODIGY: A Phase III Study of Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Versus Surgery and Adjuvant S-1 for Resectable Advanced Gastric Cancer. J Clin Oncol. 2021 Sep 10;39(26):2903-2913. Epub 2021 Jun 16. [https://doi.org/10.1200/jco.20.02914 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8425847/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34133211/ PubMed] NCT01515748
+==ECF {{#subobject:f0281c|Regimen=1}}==
+ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:66f602|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/PMC5555437/ Faivre-Finn et al. 2017 (CONVERT)]
+|Awaiting publication (TOPGEAR)
-|2008-2013
+|2009-ongoing
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; once per day RT
+|1. [[#ECF.2FFluorouracil_.26_RT_66|ECF/5-FU & RT]]<br>2. [[#ECX.2FCapecitabine_.26_RT|ECX/Capecitabine & RT]]<br>3. [[#EOX.2FCapecitabine_.26_RT|EOX/Capecitabine & RT]]<br>4. [[#FLOT.2FCapecitabine_.26_RT|FLOT/Capecitabine & RT]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|Awaiting results
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.5 Gy fractions given twice per day x 30 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 45 Gy)
+'''21-day cycle for 3 cycles'''
-'''21-day cycle for 4 or 6 cycles'''
+</div></div>
-</div></div><br>
+===References===
+#'''TOPGEAR:''' NCT01924819
+=Adjuvant therapy=
+==CapeOx {{#subobject:cf9acc|Regimen=1}}==
+CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #7, 75/700/42, partially oral etoposide {{#subobject:b5305|Variant=1}}===
+===Regimen {{#subobject:1ef938|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2002.12.111 Sundstrøm et al. 2002]
+|[https://doi.org/10.1016/S0140-6736(11)61873-4 Bang et al. 2012 (CLASSIC)]
-|1989-1994
+|2006-2009
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Small_cell_lung_cancer_-_historical#CEV_.26_RT|CEV & RT]]
+|[[Gastric_cancer_-_null_regimens#Observation|Surgery alone]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 78% vs 69%<br>(HR 0.66, 95% CI 0.51-0.85)
+|-
+|rowspan=2|[https://doi.org/10.1016/s1470-2045(21)00297-7 Zhang et al. 2021 (RESOLVE<sub>gastric</sub>)]
+|rowspan=2|2012-2017
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#SOX|Perioperative SOX]]
+| style="background-color:#fc8d59" |Seems to have inferior DFS36
+|-
+|2. [[#SOX_2|Adjuvant SOX]]
+| style="background-color:#eeee01" |Non-inferior DFS36
 |-
 |}
-''Note: Oral etoposide to be taken on an empty stomach.''
+''<sup>1</sup>Reported efficacy for CLASSIC is based on the 2014 update.''<br>
+''Note: RESOLVE should not be confused for the trial by the same name in pancreatic cancer.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Gastrectomy|Gastrectomy]] with D2 dissection
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> PO once per day on days 2 to 4
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+'''21-day cycle for 8 cycles'''
-*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 2.8 Gy fractions once per day x 15 fractions (total dose: 42 Gy) over 3 weeks, given "between the third and fourth chemotherapy courses"
+</div></div>
-====Supportive therapy====
+===References===
-*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
+#'''CLASSIC:''' Bang YJ, Kim YW, Yang HK, Chung HC, Park YK, Lee KH, Lee KW, Kim YH, Noh SI, Cho JY, Mok YJ, Kim YH, Ji J, Yeh TS, Button P, Sirzén F, Noh SH; CLASSIC trial investigators. Adjuvant capecitabine and oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): a phase 3 open-label, randomised controlled trial. Lancet. 2012 Jan 28;379(9813):315-21. Epub 2012 Jan 7. [https://doi.org/10.1016/S0140-6736(11)61873-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22226517 PubMed] NCT00411229
-'''21-day cycle for up to 5 cycles'''
+##'''Update:''' Noh SH, Park SR, Yang HK, Chung HC, Chung IJ, Kim SW, Kim HH, Choi JH, Kim HK, Yu W, Lee JI, Shin DB, Ji J, Chen JS, Lim Y, Ha S, Bang YJ; CLASSIC trial investigators. Adjuvant capecitabine plus oxaliplatin for gastric cancer after D2 gastrectomy (CLASSIC): 5-year follow-up of an open-label, randomised phase 3 trial. Lancet Oncol. 2014 Nov;15(12):1389-96. Epub 2014 Oct 15. [https://doi.org/10.1016/S1470-2045(14)70473-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25439693 PubMed]
-</div>
+#'''RESOLVE<sub>gastric</sub>:''' Zhang X, Liang H, Li Z, Xue Y, Wang Y, Zhou Z, Yu J, Bu Z, Chen L, Du Y, Wang X, Wu A, Li G, Su X, Xiao G, Cui M, Wu D, Chen L, Wu X, Zhou Y, Zhang L, Dang C, He Y, Zhang Z, Sun Y, Li Y, Chen H, Bai Y, Qi C, Yu P, Zhu G, Suo J, Jia B, Li L, Huang C, Li F, Ye Y, Xu H, Wang X, Yuan Y, E JY, Ying X, Yao C, Shen L, Ji J; RESOLVE study group. Perioperative or postoperative adjuvant oxaliplatin with S-1 versus adjuvant oxaliplatin with capecitabine in patients with locally advanced gastric or gastro-oesophageal junction adenocarcinoma undergoing D2 gastrectomy (RESOLVE): an open-label, superiority and non-inferiority, phase 3 randomised controlled trial. Lancet Oncol. 2021 Aug;22(8):1081-1092. Epub 2021 Jul 9. Erratum in: Lancet Oncol. 2021 Aug;22(8):e347. [https://doi.org/10.1016/s1470-2045(21)00297-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34252374/ PubMed] NCT01534546
-<div class="toccolours" style="background-color:#cbd5e7">
+==Carboplatin & Docetaxel {{#subobject:7263b8|Regimen=1}}==
-====Subsequent treatment====
-*Patients with CR: [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
-</div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #8, 80/240/50 {{#subobject:d203ec|Variant=1}}===
+===Regimen {{#subobject:cd8hbq|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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://insights.ovid.com/pubmed?pmid=15685040 McClay et al. 2005 (CALGB 9235)]
+|[https://doi.org/10.1007/s00280-010-1256-6 Bamias et al. 2010]
-|1993-1999
+|2002-2005
-| style="background-color:#1a9851" |Phase 3 (E-de-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#EP.2C_Tamoxifen.2C_RT|EP, Tamoxifen, RT]]
+|[[#Carboplatin.2C_Docetaxel.2C_RT_99|Carboplatin, Docetaxel, RT]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+''Note: the original protocol was for cisplatin & docetaxel but was changed due to excess CINV. To our knowledge, this regimen was not tested as an experimental arm in an RCT prior to becoming a standard comparator arm.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Gastrectomy|Surgery]]
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
-*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+'''21-day cycle for 6 cycles'''
-*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 200 cGy fractions once per day x 25 fractions (total dose: 50 Gy) over 5 weeks, started on cycle 4 day 1 of chemotherapy
+</div></div>
-'''21-day cycle for 5 cycles'''
+===References===
-</div></div><br>
+#Bamias A, Karina M, Papakostas P, Kostopoulos I, Bobos M, Vourli G, Samantas E, Christodoulou Ch, Pentheroudakis G, Pectasides D, Dimopoulos MA, Fountzilas G. A randomized phase III study of adjuvant platinum/docetaxel chemotherapy with or without radiation therapy in patients with gastric cancer. Cancer Chemother Pharmacol. 2010 May;65(6):1009-21. Epub 2010 Feb 4. [https://doi.org/10.1007/s00280-010-1256-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20130877 PubMed]
+==Capecitabine & Cisplatin (CX) {{#subobject:4896bc|Regimen=1}}==
+CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #9, 80/300/45, 1 cycle of chemo {{#subobject:6426d9|Variant=1}}===
+===Regimen {{#subobject:877085|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)]
+|[https://doi.org/10.1200/jco.2011.39.1953 Lee et al. 2011 (ARTIST<sub>gastric</sub>)]
-|2000-2002
+|2004-2008
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#1a9851" |Phase 3 (C)
-|-
+|[[#Capecitabine_.26_Cisplatin_.28CX.29_2|XP]], then [[#Radiation_therapy_88|RT]], then [[#Capecitabine_.26_Cisplatin_.28CX.29_2|XP]]
-|[https://doi.org/10.1016/S1470204513705114 Kubota et al. 2013 (JCOG0202)]
+| style="background-color:#fee08b" |Might have inferior DFS
-|2002-2006
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
 |-
 |}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. This trial should not be confused for the one by the same name in colorectal cancer.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*R0 [[Surgery#Gastrectomy|gastrectomy]] and at least D2 dissection
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-====Radiotherapy====
+'''21-day cycle for 6 cycles'''
-*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 1.5 Gy fractions given twice per day (at least 4, but preferably 6 hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
+</div></div>
-'''28-day cycle for 1 cycle'''
+===References===
-</div>
+#'''ARTIST:''' Lee J, Lim DH, Kim S, Park SH, Park JO, Park YS, Lim HY, Choi MG, Sohn TS, Noh JH, Bae JM, Ahn YC, Sohn I, Jung SH, Park CK, Kim KM, Kang WK. Phase III trial comparing capecitabine plus cisplatin versus capecitabine plus cisplatin with concurrent capecitabine radiotherapy in completely resected gastric cancer with D2 lymph node dissection: the ARTIST trial. J Clin Oncol. 2012 Jan 20;30(3):268-73. Epub 2011 Dec 19. [https://doi.org/10.1200/jco.2011.39.1953 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22184384 PubMed] NCT00323830
-<div class="toccolours" style="background-color:#cbd5e7">
+##'''Update:''' Park SH, Sohn TS, Lee J, Lim DH, Hong ME, Kim KM, Sohn I, Jung SH, Choi MG, Lee JH, Bae JM, Kim S, Kim ST, Park JO, Park YS, Lim HY, Kang WK. Phase III trial to compare adjuvant chemotherapy with capecitabine and cisplatin versus concurrent chemoradiotherapy in gastric cancer: Final report of the adjuvant chemoradiotherapy in stomach tumors trial, including survival and subset analyses. J Clin Oncol. 2015 Oct 1;33(28):3130-6. Epub 2015 Jan 5. [https://doi.org/10.1200/jco.2014.58.3930 link to original article] [https://pubmed.ncbi.nlm.nih.gov/25559811 PubMed]
-====Subsequent treatment====
+==Docetaxel & S-1 {{#subobject:a22c2a|Regimen=1}}==
-*WJTOG 9902: [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] consolidation
+DS: '''<u>D</u>'''ocetaxel & '''<u>S</u>'''-1
-*JCOG0202: EP x 3 versus [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] consolidation
-</div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #10, 80/300/45, 4 cycles of chemo {{#subobject:77843f|Variant=1}}===
+===Regimen variant #1 {{#subobject:82ca03|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2002.12.071 Takada et al. 2002 (JCOG 9104)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6333977/ Lee et al. 2018 (POST)]
-|1991-1995
+|2010-2013
 | style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Etoposide_.28EP.29|EP]], then [[#Radiation_therapy|RT]]
+|[[#Cisplatin_.26_S-1_88|SP]]
-| style="background-color:#d9ef8b" |Might have superior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS36
-|-
 |}
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Gastrectomy|Surgery]]
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Tegafur, gimeracil, oteracil (S-1)|S-1]] 35 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-====Radiotherapy====
+'''21-day cycle for 8 cycles'''
-*Concurrent [[External_beam_radiotherapy|thoracic radiation therapy]], 1.5 Gy fractions given twice per day (4 or more hours between fractions) x 30 fractions (total dose: 45 Gy) over 3 weeks, started on cycle 1 day 2 of chemotherapy
-'''28-day cycle for 4 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*JCOG 9104 patients with CR or near-CR ("a scar-like shadow on chest films but no positive cytology and/or bronchoscopic biopsy"): [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #11, 90/300/39.9 {{#subobject:71c93e|Variant=1}}===
+===Regimen variant #2 {{#subobject:82ca03|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1093/annonc/mdn354 Sculier et al. 2008]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524985/ Yoshida et al. 2019 (JACCRO GC-07)]
-|1993-2006
+|2013-2017
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]; daily cisplatin
+|[[#S-1 monotherapy_2|S-1]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS36: 77.7% vs 71.2%<br>(HR 0.74, 95% CI 0.60-0.925)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2021 update; primary endpoint was RFS.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*[[Surgery#Gastrectomy|Surgery]]
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 90 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] as follows:
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+**Cycles 1 to 7: 40 mg/m<sup>2</sup> IV once on day 1
-====Radiotherapy====
+*[[Tegafur, gimeracil, oteracil (S-1)|S-1]] as follows:
-*Concurrent [[External_beam_radiotherapy|radiation therapy]], 2.66 Gy fractions once per day x 15 fractions over 3 weeks, given during cycle 1 of chemotherapy (total dose: 39.9 Gy)
+**Cycles 1 to 7: 80 to 120 mg/m<sup>2</sup> PO on days 1 to 14
-'''21-day cycle for up to 6 cycles'''
+**Cycles 8 to 11: 80 to 120 mg/m<sup>2</sup> PO on days 1 to 28
+'''21-day cycle for 1 cycle, then 42-day cycle for 10 cycles'''
 </div></div>
 ===References===
-# Bunn PA Jr, Crowley J, Kelly K, Hazuka MB, Beasley K, Upchurch C, Livingston R; [[Study_Groups#SWOG|SWOG]]. Chemoradiotherapy with or without granulocyte-macrophage colony-stimulating factor in the treatment of limited-stage small-cell lung cancer: a prospective phase III randomized study of the Southwest Oncology Group. J Clin Oncol. 1995 Jul;13(7):1632-41. Erratum in: J Clin Oncol 1995 Nov;13(11):2860. [https://doi.org/10.1200/JCO.1995.13.7.1632 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7602352 PubMed]
+#'''POST:''' Lee CK, Jung M, Kim HS, Jung I, Shin DB, Kang SY, Zang DY, Kim KH, Lee MH, Kim BS, Lee KH, Cheong JH, Hyung WJ, Noh SH, Chung HC, Rha SY. S-1 Based Doublet as an Adjuvant Chemotherapy for Curatively Resected Stage III Gastric Cancer: Results from the Randomized Phase III POST Trial. Cancer Res Treat. 2019 Jan;51(1):1-11. Epub 2018 Feb 5. [https://doi.org/10.4143/crt.2018.028 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6333977/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29397659/ PubMed] NCT01283217
-# '''Intergroup 0096:''' Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. [https://doi.org/10.1056/NEJM199901283400403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9920950 PubMed]
+<!-- #'''Abstract:''' Kodera Y, Yoshida K, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Nakamura M, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matssuyama J, Yamada M, Ito Y, Takeuchi M, Fujii M; JACCRO. A randomized phase III study comparing S-1 plus docetaxel with S-1 alone as a postoperative adjuvant chemotherapy for curatively resected stage III gastric cancer (JACCRO GC-07 trial). 2019 American Society of Clinical Oncology annual meeting. DOI: 10.1200/JCO.2018.36.15_suppl.4007  36, no. 15_suppl (May 20, 2018) 4007-4007. [https://doi.org/10.1200/JCO.2018.36.15_suppl.4007 link to abstract] -->
-# '''JCOG 9104:''' Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. [https://doi.org/10.1200/jco.2002.12.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12118018 PubMed] content property of [http://hemonc.org HemOnc.org]
+#'''JACCRO GC-07:''' Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matsuyama J, Yamada M, Ito S, Takeuchi M, Fujii M. Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol. 2019 May 20;37(15):1296-1304. Epub 2019 Mar 29. [https://doi.org/10.1200/jco.18.01138 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524985/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30925125/ PubMed] UMIN000010337
-# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed]
+##'''Update:''' Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022 Jan;25(1):188-196. Epub 2021 Aug 5. [https://doi.org/10.1007/s10120-021-01224-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34351555/ PubMed]
-#Schild SE, Bonner JA, Shanahan TG, Brooks BJ, Marks RS, Geyer SM, Hillman SL, Farr GH Jr, Tazelaar HD, Krook JE, Geoffroy FJ, Salim M, Arusell RM, Mailliard JA, Schaefer PL, Jett JR. Long-term results of a phase III trial comparing once-daily radiotherapy with twice-daily radiotherapy in limited-stage small-cell lung cancer. Int J Radiat Oncol Biol Phys. 2004 Jul 15;59(4):943-51. [https://doi.org/10.1016/j.ijrobp.2004.01.055 link to original article] [https://pubmed.ncbi.nlm.nih.gov/15234027/ PubMed]
+==FP/Capecitabine & RT {{#subobject:778727|Regimen=1}}==
-# '''CALGB 9235:''' McClay EF, Bogart J, Herndon JE 2nd, Watson D, Evans L, Seagren SL, Green MR; [[Study_Groups#CALGB|CALGB]]. A phase III trial evaluating the combination of cisplatin, etoposide, and radiation therapy with or without tamoxifen in patients with limited-stage small cell lung cancer: Cancer and Leukemia Group B Study (9235). Am J Clin Oncol. 2005 Feb;28(1):81-90. [https://insights.ovid.com/pubmed?pmid=15685040 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15685040 PubMed]
+FP/Capecitabine & RT: '''<u>F</u>'''luorouracil & '''<u>P</u>'''latinol (Cisplatin) alternating with Capecitabine & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-# '''WJTOG 9902:''' Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. [https://doi.org/10.1200/jco.2006.07.1605 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17114657 PubMed]
-# Sculier JP, Lafitte JJ, Efremidis A, Florin MC, Lecomte J, Berchier MC, Richez M, Berghmans T, Scherpereel A, Meert AP, Koumakis G, Leclercq N, Paesmans M, Van Houtte P; European Lung Cancer Working Party. A phase III randomised study of concomitant induction radiochemotherapy testing two modalities of radiosensitisation by cisplatin (standard versus daily) for limited small-cell lung cancer. Ann Oncol. 2008 Oct;19(10):1691-7. Epub 2008 May 25. [https://doi.org/10.1093/annonc/mdn354 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18504252 PubMed]
-# '''SMC 2003-02-016:''' Sun JM, Ahn YC, Choi EK, Ahn MJ, Ahn JS, Lee SH, Lee DH, Pyo H, Song SY, Jung SH, Jo JS, Jo J, Sohn HJ, Suh C, Lee JS, Kim SW, Park K. Phase III trial of concurrent thoracic radiotherapy with either first- or third-cycle chemotherapy for limited-disease small-cell lung cancer. Ann Oncol. 2013 Aug;24(8):2088-92. Epub 2013 Apr 16. Erratum in: Ann Oncol. 2014 Aug;25(8):1672. [https://doi.org/10.1093/annonc/mdt140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23592701 PubMed] NCT01125995
-# '''JCOG0202:''' Kubota K, Hida T, Ishikura S, Mizusawa J, Nishio M, Kawahara M, Yokoyama A, Imamura F, Takeda K, Negoro S, Harada M, Okamoto H, Yamamoto N, Shinkai T, Sakai H, Matsui K, Nakagawa K, Shibata T, Saijo N, Tamura T; [[Study_Groups#JCOG|JCOG]]. Etoposide and cisplatin versus irinotecan and cisplatin in patients with limited-stage small-cell lung cancer treated with etoposide and cisplatin plus concurrent accelerated hyperfractionated thoracic radiotherapy (JCOG0202): a randomised phase 3 study. Lancet Oncol. 2014 Jan;15(1):106-13. Epub 2013 Dec 3. [https://doi.org/10.1016/S1470204513705114 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24309370 PubMed] NCT00144989
-# '''CONVERT:''' Faivre-Finn C, Snee M, Ashcroft L, Appel W, Barlesi F, Bhatnagar A, Bezjak A, Cardenal F, Fournel P, Harden S, Le Pechoux C, McMenemin R, Mohammed N, O'Brien M, Pantarotto J, Surmont V, Van Meerbeeck JP, Woll PJ, Lorigan P, Blackhall F; CONVERT Study Team. Concurrent once-daily versus twice-daily chemoradiotherapy in patients with limited-stage small-cell lung cancer (CONVERT): an open-label, phase 3, randomised, superiority trial. Lancet Oncol. 2017 Aug;18(8):1116-1125. Epub 2017 Jun 20. [https://doi.org/10.1016/S1470204517303182 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555437/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28642008 PubMed] NCT00433563
-#'''CALGB 30610:''' NCT00632853
-=Limited stage, adjuvant therapy=
-==Cisplatin & Etoposide (EP) {{#subobject:ughacc|Regimen=1}}==
-EP: '''<u>E</u>'''toposide & '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:18ytia|Variant=1}}===
+===Protocol {{#subobject:20ea7f|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.20.01806 Kenmotsu et al. 2020 (JCOG1205/1206)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066094/ Lee et al. 2006]
-|2013-2018
+|NR
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#91cf61" |Phase 2
-|[[#Cisplatin_.26_Irinotecan_.28IC.29_99|Cisplatin & Irinotecan]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of RFS
 |-
 |}
+''Note: In contrast to the primary reference, some guidelines list this regimen without FP cycles 1, 3, 4, 5. Dosage of [[Capecitabine (Xeloda)]] was listed as 625 to 825 mg/m<sup>2</sup> PO twice per day on days 1 to 5 or 1 to 7 while radiation is being given.''
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[Surgery#Lung_cancer_surgery|Complete surgical resection]]
+*[[Surgery#Gastrectomy|Surgery]], 3 weeks prior
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Chemotherapy, part 1====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose: 5000 mg/m<sup>2</sup>)
-'''21-day cycle for up to 4 cycles'''
+'''21-day cycle, followed immediately by:'''
+====Chemotherapy, part 2====
+*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> PO twice per day
+====Radiotherapy====
+*Concurrent [[External_beam_radiotherapy|radiation therapy]], 1.8 Gy fractions x 25 fractions (total dose of 45 Gy)
+'''5-week course, followed 4 weeks later by:'''
+====Chemotherapy, part 3====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m<sup>2</sup>)
+'''21-day cycle for 3 cycles'''
 </div></div>
 ===References===
-#'''JCOG1205/1206:''' Kenmotsu H, Niho S, Tsuboi M, Wakabayashi M, Ishii G, Nakagawa K, Daga H, Tanaka H, Saito H, Aokage K, Takahashi T, Menju T, Kasai T, Yoshino I, Minato K, Okada M, Eba J, Asamura H, Ohe Y, Watanabe SI. Randomized Phase III Study of Irinotecan Plus Cisplatin Versus Etoposide Plus Cisplatin for Completely Resected High-Grade Neuroendocrine Carcinoma of the Lung: JCOG1205/1206. J Clin Oncol. 2020 Dec 20;38(36):4292-4301. Epub 2020 Nov 2. [https://doi.org/10.1200/jco.20.01806 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33136471 PubMed] UMIN000010298
+#Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. [http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4066094/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/16489675 PubMed]
-=Limited stage, consolidation after upfront therapy=
+==FULV {{#subobject:5bbh1e|Regimen=1}}==
-==Cisplatin & Irinotecan (IC) {{#subobject:fe9413|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
-IP: '''<u>I</u>'''rinotecan, '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:540b9f|Variant=1}}===
+===Regimen {{#subobject:1tzi01|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)]
+|[https://doi.org/10.1093/annonc/mdu146 Bajetta et al. 2014 (ITACA-S)]
-| style="background-color:#91cf61" |Phase 2
+|2005-2009
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#FOLFIRI_99|FOLFIRI]], then [[#Cisplatin_.26_Docetaxel_.28DC.29_99|Cisplatin & Docetaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
 |-
 |}
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Cisplatin.2C_Etoposide.2C_RT|Cisplatin, Etoposide, RT]] induction
+*[[Surgery#Gastrectomy|Surgery]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 & 2, then 600 mg/m<sup>2</sup> IV continuous infusion over 22 hours after each bolus (total dose per cycle: 2000 mg/m<sup>2</sup>)
-*[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Folinic acid (Leucovorin)]] 100 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2
-====Supportive therapy====
+'''14-day cycle for 9 cycles'''
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] (no additional details given) starting after day 4
+</div></div>
-'''28-day cycle for 3 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Patients with complete or good partial responses: [[#Whole_brain_irradiation|Prophylactic cranial irradiation]]
-</div></div>
 ===References===
-# '''WJTOG 9902:''' Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. [https://doi.org/10.1200/jco.2006.07.1605 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17114657 PubMed]
+#'''ITACA-S:''' Bajetta E, Floriani I, Di Bartolomeo M, Labianca R, Falcone A, Di Costanzo F, Comella G, Amadori D, Pinto C, Carlomagno C, Nitti D, Daniele B, Mini E, Poli D, Santoro A, Mosconi S, Casaretti R, Boni C, Pinotti G, Bidoli P, Landi L, Rosati G, Ravaioli A, Cantore M, Di Fabio F, Aitini E, Marchet A; ITACA-S (Intergroup Trial of Adjuvant Chemotherapy in Adenocarcinoma of the Stomach Trial) Study Group. Randomized trial on adjuvant treatment with FOLFIRI followed by docetaxel and cisplatin versus 5-fluorouracil and folinic acid for radically resected gastric cancer. Ann Oncol. 2014 Jul;25(7):1373-1378. Epub 2014 Apr 12. [https://doi.org/10.1093/annonc/mdu146 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24728035/ PubMed] NCT01640782
-==Radiation therapy {{#subobject:508a85|Regimen=1}}==
+==FULV/FULV & RT {{#subobject:2cd29|Regimen=1}}==
+FULV/FULV & RT: '''<u>F</u>'''luoro'''<u>U</u>'''racil & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid) alternating with '''<u>F</u>'''luoro'''<u>U</u>'''racil, '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid) & '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:c48aca|Variant=1}}===
+===Protocol {{#subobject:dfd3ec|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa010187 Macdonald et al. 2001 (INT-0116)]
+|1991-1998
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Observation|Surgery alone]]
+| style="background-color:#1a9850" |Superior OS
 |-
-|[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678342/ Fuchs et al. 2017 (CALGB 80101)]
-|1981-1984
+|2002-2009
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#ECF_2|ECF]], then [[#FULV_.26_RT_99|FULV & RT]], then [[#ECF_2|ECF]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+''Treatment is to start 20 to 40 days after surgery.''
+''Study included patients with GE junction malignancy as well (20% GE junction) and included patients with a performance status of 2.''
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 6
+*INT-0116: [[Surgery#Gastrectomy|Surgery]] with R0 resection (10% underwent D2 dissection, 36% underwent D1 dissection and 54% underwent D0 dissection)
+*CALGB 80101: [[Surgery#Gastrectomy|Surgery]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy, part 1====
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+'''28-day cycle for 1 cycle, followed by:'''
+====Chemotherapy, part 2====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
+*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
 ====Radiotherapy====
-*"Patients who did not have evidence of tumor spread beyond the mediastinum and/or ipsilateral supraclavicular notes" received [[External beam radiotherapy|thoracic radiation]] in 250 cGy fractions x 10 fractions (total dose: 25 Gy)
+*Concurrent [[External_beam_radiotherapy|radiation therapy]] 180 cGy x 25 fractions (total of 45 Gy)
+'''35-day course, followed in 1 month by:'''
+====Chemotherapy, part 3====
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+'''28-day cycle for 2 cycles'''
 </div></div>
 ===References===
-# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2997406 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://doi.org/10.1056/NEJMoa010187 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11547741 PubMed]
-# '''LLCG-STUDY-12:''' Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. [https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 link to original article] '''does not contain dosing details''' [https://pubmed.ncbi.nlm.nih.gov/19608997 PubMed] NCT00061919
+##'''Update:''' Smalley SR, Benedetti JK, Haller DG, Hundahl SA, Estes NC, Ajani JA, Gunderson LL, Goldman B, Martenson JA, Jessup JM, Stemmermann GN, Blanke CD, Macdonald JS. Updated analysis of SWOG-directed intergroup study 0116: a phase III trial of adjuvant radiochemotherapy versus observation after curative gastric cancer resection. J Clin Oncol. 2012 Jul 1;30(19):2327-33. Epub 2012 May 14. [https://doi.org/10.1200/JCO.2011.36.7136 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4517071/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/22585691 PubMed]
-==Whole brain irradiation {{#subobject:49c1e3|Regimen=1}}==
+#'''CALGB 80101:''' Fuchs CS, Niedzwiecki D, Mamon HJ, Tepper JE, Ye X, Swanson RS, Enzinger PC, Haller DG, Dragovich T, Alberts SR, Bjarnason GA, Willett CG, Gunderson LL, Goldberg RM, Venook AP, Ilson D, O'Reilly E, Ciombor K, Berg DJ, Meyerhardt J, Mayer RJ. Adjuvant chemoradiotherapy with epirubicin, cisplatin, and fluorouracil compared with adjuvant chemoradiotherapy with fluorouracil and leucovorin after curative resection of gastric cancer: results from CALGB 80101 (Alliance). J Clin Oncol. 2017 Nov 10;35(32):3671-3677. Epub 2017 Oct 4. [https://doi.org/10.1200/JCO.2017.74.2130 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5678342/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28976791 PubMed] NCT00052910
-PCI: '''<u>P</u>'''rophylactic '''<u>C</u>'''ranial '''<u>I</u>'''rradiation
+==S-1 monotherapy {{#subobject:ec10ef|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 20 Gy {{#subobject:900486|Variant=1}}===
+===Regimen variant #1, 21-day cycles {{#subobject:5dbc53|Variant=1}}===
-{| class="wikitable sortable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://jamanetwork.com/journals/jama/fullarticle/373562 Cox et al. 1981]
+| rowspan="2" |[https://doi.org/10.1016/S1470-2045(14)70025-7 Tsuburaya et al. 2014 (SAMIT)]
-|1975-1978
+| rowspan="2" |2004-2009
-| style="background-color:#91cf61" |Non-randomized
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
-|-
+|1. [[#Paclitaxel_monotherapy_99|Paclitaxel]], then [[#S-1_monotherapy|S-1]]<br> 2. [[#Paclitaxel_monotherapy_99|Paclitaxel]], then [[#UFT_monotherapy_99|UFT]]
-|[https://doi.org/10.1200/jco.1985.3.11.1471 Evans et al. 1985]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-|1981-1984
-| style="background-color:#91cf61" |Phase 2
 |-
-|[https://doi.org/10.1023/a:1012295131640 Skarlos et al. 2001]
+|3. [[#UFT_monotherapy_99|UFT]]
-|1993-1999
+| style="background-color:#1a9850" |Superior DFS<br>DFS36: 58.2% vs 53%<br>(HR 0.81, 95% CI 0.70-0.93)
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 |-
 |}
-''Note: in Evans et al. 1985, the WB-XRT is given in-between cycles 3 & 4.''
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*Evans et al. 1985: [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 3
+*R0 or R1 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 2 to 8 weeks
-*Skarlos et al. 2001: [[#Carboplatin.2C_Etoposide.2C_RT|EP & early HTRT]] versus [[#Carboplatin.2C_Etoposide.2C_RT|EP & late HTRT]]
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
+====Chemotherapy====
-*[[External beam radiotherapy|Whole brain irradiation]], 4 Gy fractions once per day x 5 fractions (total dose: 20 Gy)
+*[[Tegafur, gimeracil, oteracil (S-1)]] 80 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-'''1-week course'''
+'''21-day cycle for 16 cycles (1 year)'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Evans et al. 1985: [[#Cisplatin_.26_Etoposide_.28EP.29|EP]] x 3
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 24 Gy {{#subobject:5b88f0|Variant=1}}===
+===Regimen variant #2, 42-day cycles {{#subobject:0ee98c|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1056/NEJMoa072252 Sakuramoto et al. 2007 (ACTS-GC)]
+|2001-2004
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Observation|Observation]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>OS60: 72% vs 61%<br>(HR 0.67, 95% CI 0.54-0.83)
+|-
+|[https://doi.org/10.1016/S2468-1253(18)30383-2 Yoshikawa et al. 2019 (OPAS-1)]
+|2012-2017
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#S-1_monotherapy|S-1]] x 6 mo
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior RFS
+|-
+|rowspan=2|[https://doi.org/10.1016/j.annonc.2020.11.017 Park et al. 2020 (ARTIST 2)]
+|rowspan=2|2013-2018
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#SOX|SOX]]
+| style="background-color:#fc8d59" |Seems to have inferior DFS
 |-
-|[https://doi.org/10.1200/jco.2002.12.071 Takada et al. 2002 (JCOG 9104)]
+|2. [[#SOX_.26_RT_88|SOXRT]]
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
+| style="background-color:#fee08b" |Might have inferior DFS
 |-
 |}
+''<sup>1</sup>Reported efficacy for ACTS-GC is based on the 2011 update.''
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*[[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]] versus [[#Cisplatin_.26_Etoposide_.28EP.29|EP]], then [[#Radiation_therapy|RT]]
+*R0 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection, within 6 weeks
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
+====Chemotherapy====
-*[[External beam radiotherapy|Whole brain irradiation]], 1.5 Gy fractions given twice per day x 16 fractions (total dose: 24 Gy)
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
-'''2-week course'''
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
-</div></div><br>
+**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
+'''42-day cycle for 8 cycles (1 year)'''
+</div></div>
+===References===
+#'''ACTS-GC:''' Sakuramoto S, Sasako M, Yamaguchi T, Kinoshita T, Fujii M, Nashimoto A, Furukawa H, Nakajima T, Ohashi Y, Imamura H, Higashino M, Yamamura Y, Kurita A, Arai K; ACTS-GC Group. Adjuvant chemotherapy for gastric cancer with S-1, an oral fluoropyrimidine. N Engl J Med. 2007 Nov 1;357(18):1810-20. Erratum in: N Engl J Med. 2008 May 1;358(18):1977. [https://doi.org/10.1056/NEJMoa072252 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17978289 PubMed] NCT00152217
+##'''Update:''' Sasako M, Sakuramoto S, Katai H, Kinoshita T, Furukawa H, Yamaguchi T, Nashimoto A, Fujii M, Nakajima T, Ohashi Y. Five-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 versus surgery alone in stage II or III gastric cancer. J Clin Oncol. 2011 Nov 20;29(33):4387-93. Epub 2011 Oct 17. [https://doi.org/10.1200/JCO.2011.36.5908 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22010012 PubMed]
+#'''SAMIT:''' Tsuburaya A, Yoshida K, Kobayashi M, Yoshino S, Takahashi M, Takiguchi N, Tanabe K, Takahashi N, Imamura H, Tatsumoto N, Hara A, Nishikawa K, Fukushima R, Nozaki I, Kojima H, Miyashita Y, Oba K, Buyse M, Morita S, Sakamoto J. Sequential paclitaxel followed by tegafur and uracil (UFT) or S-1 versus UFT or S-1 monotherapy as adjuvant chemotherapy for T4a/b gastric cancer (SAMIT): a phase 3 factorial randomised controlled trial. Lancet Oncol. 2014 Jul;15(8):886-93. Epub 2014 Jun 18. [https://doi.org/10.1016/S1470-2045(14)70025-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24954805 PubMed] UMIN C000000082
+#'''OPAS-1:''' Yoshikawa T, Terashima M, Mizusawa J, Nunobe S, Nishida Y, Yamada T, Kaji M, Fukushima N, Hato S, Choda Y, Yabusaki H, Yoshida K, Ito S, Takeno A, Yasuda T, Kawachi Y, Katayama H, Fukuda H, Boku N, Sano T, Sasako M. Four courses versus eight courses of adjuvant S-1 for patients with stage II gastric cancer (JCOG1104[OPAS-1]): an open-label, phase 3, non-inferiority, randomised trial. Lancet Gastroenterol Hepatol. 2019 Mar;4(3):208-216. Epub 2019 Jan 22. Erratum in: Lancet Gastroenterol Hepatol. 2019 Apr;4(4):e3. [https://doi.org/10.1016/S2468-1253(18)30383-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/30679107 PubMed] UMIN000007306
+#'''JACCRO GC-07:''' Yoshida K, Kodera Y, Kochi M, Ichikawa W, Kakeji Y, Sano T, Nagao N, Takahashi M, Takagane A, Watanabe T, Kaji M, Okitsu H, Nomura T, Matsui T, Yoshikawa T, Matsuyama J, Yamada M, Ito S, Takeuchi M, Fujii M. Addition of Docetaxel to Oral Fluoropyrimidine Improves Efficacy in Patients With Stage III Gastric Cancer: Interim Analysis of JACCRO GC-07, a Randomized Controlled Trial. J Clin Oncol. 2019 May 20;37(15):1296-1304. Epub 2019 Mar 29. [https://doi.org/10.1200/jco.18.01138 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc6524985/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30925125/ PubMed] UMIN000010337
+##'''Update:''' Kakeji Y, Yoshida K, Kodera Y, Kochi M, Sano T, Ichikawa W, Lee SW, Shibahara K, Shikano T, Kataoka M, Ishiguro A, Ojima H, Sakai Y, Musha N, Takase T, Kimura T, Takeuchi M, Fujii M. Three-year outcomes of a randomized phase III trial comparing adjuvant chemotherapy with S-1 plus docetaxel versus S-1 alone in stage III gastric cancer: JACCRO GC-07. Gastric Cancer. 2022 Jan;25(1):188-196. Epub 2021 Aug 5. [https://doi.org/10.1007/s10120-021-01224-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/34351555/ PubMed]
+#'''ARTIST 2:''' Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, Kang JH, Oh SY, Hwang IG, Ji JH, Shin DB, Yu JI, Kim KM, An JY, Choi MG, Lee JH, Kim S, Hong JY, Park JO, Park YS, Lim HY, Bae JM, Kang WK; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-374. Epub 2020 Dec 3. [https://doi.org/10.1016/j.annonc.2020.11.017 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33278599/ PubMed] NCT0176146
+#'''HKIT-GC:''' NCT00216034
+==SOX {{#subobject:ecig8a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 25 Gy {{#subobject:1475db|Variant=1}}===
+===Regimen {{#subobject:5guz13|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1056/NEJM199901283400403 Turrisi et al. 1999 (Intergroup 0096)]
+|rowspan=2|[https://doi.org/10.1016/j.annonc.2020.11.017 Park et al. 2020 (ARTIST 2)]
-|1989-1992
+|rowspan=2|2013-2018
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
-| style="background-color:#d3d3d3" |
+|1. [[#S-1_monotherapy|S-1]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#91cf60" |Seems to have superior DFS<br>DFS36: 74.3% vs 64.8%<br>(HR 0.69, 95% CI 0.41-0.99)
 |-
-|[https://doi.org/10.1016/S1470-2045(09)70101-9 Le Péchoux et al. 2009 (PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01)]
+|2. [[#SOX_.26_RT_88|SOXRT]]
-|1999-2005
+| style="background-color:#ffffbf" |Did not meet primary endpoint of DFS
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Whole_brain_irradiation|PCI]] x 36 Gy
-| style="background-color:#ffffbf" |Did not meet primary endpoint of incidence of brain metastases at 2 years
 |-
-|[https://doi.org/10.1200/jco.2006.07.1605 Saito et al. 2006 (WJTOG 9902)]
+|}
-|2000-2002
-| style="background-color:#91cf61" |Phase 2
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
-|-
-|}
 <div class="toccolours" style="background-color:#cbd5e8">
 ====Preceding treatment====
-*Intergroup 0096: [[#Cisplatin.2C_Etoposide.2C_RT|EP & once-daily RT]] versus [[#Cisplatin.2C_Etoposide.2C_RT|EP & twice-daily RT]]
+*R0 or R1 [[Surgery#Gastrectomy|gastrectomy]] with at least D2 dissection
-*WJTOG 9902: [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]], then [[#Cisplatin_.26_Irinotecan_.28IC.29|IP]] x 3
 </div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
+====Chemotherapy====
-*[[External beam radiotherapy|Whole brain irradiation]], 2.5 Gy fractions x 10 fractions (total dose: 25 Gy)
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
-'''2-week course'''
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
-</div></div><br>
+**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
-<div class="toccolours" style="background-color:#eeeeee">
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
-===Regimen variant #4, 30 Gy {{#subobject:63970e|Variant=1}}===
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-{| class="wikitable" style="width: 40%; text-align:center;"
+'''21-day cycle for up to 8 cycles (6 months)'''
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
-|-
-|}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[Small_cell_lung_cancer_-_historical#CEV_.26_RT|CEV & RT]] versus [[#Cisplatin.2C_Etoposide.2C_RT|EP & RT]]
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
-====Radiotherapy====
-*[[External beam radiotherapy|Whole brain irradiation]], 2 Gy fractions once per day x 15 fractions (total dose: 30 Gy)
-'''3-week course'''
 </div></div>
 ===References===
-# Cox JD, Stanley K, Petrovich Z, Paig C, Yesner R. Cranial irradiation in cancer of the lung of all cell types. JAMA. 1981 Feb 6;245(5):469-72. [https://jamanetwork.com/journals/jama/fullarticle/373562 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7452872 PubMed]
+#'''ARTIST 2:''' Park SH, Lim DH, Sohn TS, Lee J, Zang DY, Kim ST, Kang JH, Oh SY, Hwang IG, Ji JH, Shin DB, Yu JI, Kim KM, An JY, Choi MG, Lee JH, Kim S, Hong JY, Park JO, Park YS, Lim HY, Bae JM, Kang WK; ARTIST 2 investigators. A randomized phase III trial comparing adjuvant single-agent S1, S-1 with oxaliplatin, and postoperative chemoradiation with S-1 and oxaliplatin in patients with node-positive gastric cancer after D2 resection: the ARTIST 2 trial. Ann Oncol. 2021 Mar;32(3):368-374. Epub 2020 Dec 3. [https://doi.org/10.1016/j.annonc.2020.11.017 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33278599/ PubMed] NCT0176146
-# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2997406 PubMed]
+#'''TOTTG030103:''' Zhao Q, Lian C, Huo Z, Li M, Liu Y, Fan L, Tan B, Zhao X, Zhang Z, Wang D, Liu Y, Guo H, Yang P, Tian Y, Li Y. The efficacy and safety of neoadjuvant chemotherapy on patients with advanced gastric cancer: A multicenter randomized clinical trial. Cancer Med. 2020 Aug;9(16):5731-5745. Epub 2020 Jun 24. [https://doi.org/10.1002/cam4.3224 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7433829/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32583567/ PubMed] NCT01516944
-# '''Intergroup 0096:''' Turrisi AT 3rd, Kim K, Blum R, Sause WT, Livingston RB, Komaki R, Wagner H, Aisner S, Johnson DH. Twice-daily compared with once-daily thoracic radiotherapy in limited small-cell lung cancer treated concurrently with cisplatin and etoposide. N Engl J Med. 1999 Jan 28;340(4):265-71. [https://doi.org/10.1056/NEJM199901283400403 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/9920950 PubMed]
+=Metastatic or locally advanced disease, first-line=
-# '''Meta-analysis:''' Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. [https://doi.org/10.1056/NEJM199908123410703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10441603 PubMed]
+==Capecitabine monotherapy {{#subobject:a9eb0b|Regimen=1}}==
-# '''JCOG 9104:''' Takada M, Fukuoka M, Kawahara M, Sugiura T, Yokoyama A, Yokota S, Nishiwaki Y, Watanabe K, Noda K, Tamura T, Fukuda H, Saijo N. Phase III study of concurrent versus sequential thoracic radiotherapy in combination with cisplatin and etoposide for limited-stage small-cell lung cancer: results of the Japan Clinical Oncology Group Study 9104. J Clin Oncol. 2002 Jul 15;20(14):3054-60. [https://doi.org/10.1200/jco.2002.12.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12118018 PubMed] content property of [http://hemonc.org HemOnc.org]
+X: '''<u>X</u>'''eloda (Capecitabine)
-# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed]
-# '''WJTOG 9902:''' Saito H, Takada Y, Ichinose Y, Eguchi K, Kudoh S, Matsui K, Nakagawa K, Takada M, Negoro S, Tamura K, Ando M, Tada T, Fukuoka M; West Japan Thoracic Oncology Group. Phase II study of etoposide and cisplatin with concurrent twice-daily thoracic radiotherapy followed by irinotecan and cisplatin in patients with limited-disease small-cell lung cancer: West Japan Thoracic Oncology Group 9902. J Clin Oncol. 2006 Nov 20;24(33):5247-52. [https://doi.org/10.1200/jco.2006.07.1605 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17114657 PubMed]
-# '''PCI 99-01/EORTC 22003-08004/RTOG 0212/IFCT 99-01:''' Le Péchoux C, Dunant A, Senan S, Wolfson A, Quoix E, Faivre-Finn C, Ciuleanu T, Arriagada R, Jones R, Wanders R, Lerouge D, Laplanche A; Prophylactic Cranial Irradiation (PCI) Collaborative Group. Standard-dose versus higher-dose prophylactic cranial irradiation (PCI) in patients with limited-stage small-cell lung cancer in complete remission after chemotherapy and thoracic radiotherapy (PCI 99-01, EORTC 22003-08004, RTOG 0212, and IFCT 99-01): a randomised clinical trial. Lancet Oncol. 2009 May;10(5):467-74. Epub 2009 Apr 20. [https://doi.org/10.1016/S1470-2045(09)70101-9 link to original article] [https://pubmed.ncbi.nlm.nih.gov/19386548 PubMed] NCT00005062
-=Extensive stage, induction=
-==Belotecan & Cisplatin {{#subobject:9fbf31|Regimen=1}}==
-BP: '''<u>B</u>'''elotecan and '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:949381|Variant=1}}===
+===Regimen variant #1, 2000 mg/m<sup>2</sup>/day {{#subobject:b6ba4c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/PMC5002146/ Oh et al. 2016 (COMBAT)]
+|[https://www.geriatriconcology.net/article/S1879-4068(17)30022-X Hwang et al. 2017 (SMC 2010-04-118)]
-|2009-2013
+|2010-2014
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; 60/100
+|[[#CapeOx_2|XELOX]]
-| style="background-color:#eeee01" |Non-inferior RR
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Belotecan (Camptobell)]] 0.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 4
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+'''21-day cycles'''
-'''21-day cycle for 4 to 8 cycles'''
+</div></div><br>
-</div></div>
-===References===
-# '''COMBAT:''' Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. [https://doi.org/10.1186/s12885-016-2741-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27566413 PubMed] NCT00826644
-==Carboplatin & Etoposide (CE) {{#subobject:de3ba6|Regimen=1}}==
-CE: '''<u>C</u>'''arboplatin & '''<u>E</u>'''toposide
-<br>EP: '''<u>E</u>'''toposide & '''<u>P</u>'''araplatin (Carboplatin)
-<br>EC: '''<u>E</u>'''toposide & '''<u>C</u>'''arboplatin
-<br>Ca/E: '''<u>Ca</u>'''rboplatin & '''<u>E</u>'''toposide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, AUC 4/600, PO etoposide {{#subobject:8ac097|Variant=1}}===
+===Regimen variant #2, 2500 mg/m<sup>2</sup>/day {{#subobject:b6ba4c|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2007.15.7545 Hermes et al. 2008]
+|[https://doi.org/10.1093/annonc/mdh343 Hong et al. 2004]
-|2001-2005
+|NR
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#91cf61" |Phase 2
-|[[#Carboplatin_.26_Irinotecan|Carboplatin & Irinotecan]]
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Study only included patients with Karnofsky status of at least 70%''
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 4 (Chatelut formula) IV once on day 1
+*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> PO once per day on days 1 to 5
+'''21-day cycle for up to 6 cycles'''
-'''21-day cycle for 4 cycles'''
+</div></div>
-</div></div><br>
+===References===
+#Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. [https://doi.org/10.1093/annonc/mdh343 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15319239 PubMed]
+#'''SMC 2010-04-118:''' Hwang IG, Ji JH, Kang JH, Lee HR, Lee HY, Chi KC, Park SW, Lee SJ, Kim ST, Lee J, Park SH, Park JO, Park YS, Lim HY, Kang WK. A multi-center, open-label, randomized phase III trial of first-line chemotherapy with capecitabine monotherapy versus capecitabine plus oxaliplatin in elderly patients with advanced gastric cancer. J Geriatr Oncol. 2017 May;8(3):170-175. Epub 2017 Jan 21. [https://www.geriatriconcology.net/article/S1879-4068(17)30022-X link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28119041 PubMed] NCT01470742
+==Capecitabine & Cisplatin (CX) {{#subobject:2bd34d|Regimen=1}}==
+CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, AUC 5/240 {{#subobject:471848|Variant=1}}===
+===Regimen {{#subobject:82b184|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1093/annonc/mdn717 Kang et al. 2009 (ML17032)]
+|2003-2005
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
+| style="background-color:#eeee01" |Non-inferior PFS
+|-
+|[https://doi.org/10.1200/JCO.2011.36.2236 Ohtsu et al. 2011 (AVAGAST)]
+|2007-2008
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Stub#Capecitabine_.26_Cisplatin_.28CX.29_.26_Bevacizumab|CX & Bevacizumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/S1470-2045(13)70102-5 Lordick et al. 2013 (EXPAND)]
+|2008-2010
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Cetuximab_99|CX & Cetuximab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ Okamoto et al. 2007 (JCOG 9702)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544634/ Shen et al. 2014 (AVATAR)]
-|1998-2004
+|2009-2010
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; split-dose
+|[[Stub#Capecitabine_.26_Cisplatin_.28CX.29_.26_Bevacizumab|CX & Bevacizumab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.clinical-lung-cancer.com/article/S1525-7304(13)00232-5 Sekine et al. 2013 (D0702002)]
+|[https://www.ejcancer.com/article/S0959-8049(14)00884-3 Kim et al. 2014 (SMC 2008-12-019)]
-|2006-2007
+|2009-2012
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Amrubicin_monotherapy_99|Amrubicin]]
+|[[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Simvastatin_99|CX & Simvastatin]]
-| style="background-color:#ffffbf" |Inconclusive whether non-inferior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097104/ Lu et al. 2018 (PAC-C)]
+|2009-2014
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Capecitabine_.26_Paclitaxel_99|Capecitabine & Paclitaxel]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS
+|-
+|[https://doi.org/10.1016/S1470-2045(18)30791-5 Fuchs et al. 2019 (RAINFALL)]
+|2015-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[Stub#Capecitabine_.26_Cisplatin_.28CX.29_.26_Ramucirumab|CX & Ramucirumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS<sup>1</sup>
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''<sup>1</sup>while the primary analysis of RAINFALL showed that this arm seemed to have inferior PFS, independent central review did not confirm this finding.''<br>
+The following studies included patients with GE junction malignancy as well:
+*''AVAGAST patients: 86% gastric and 14% GE junction. 5.4% of patients had an ECOG of 2.''
+*''EXPAND patients: 83% gastric, 5% GE junction and 16% unknown''
+*''SMC 2008-12-019 patients: 79% gastric, 16% GE junction and 5% unknown''
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+**EXPAND: 1000 mg/m<sup>2</sup> PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)
 ====Supportive therapy====
-*JCOG 9702: [[:Category:Granulocyte colony-stimulating factors|G-CSF]]
+*Some protocols: [[:Category:Hydration|"Hyperhydration"]] for cisplatin
-'''21-day cycle for 4 to 6 cycles'''
+'''21-day cycles, varied duration (see below)'''
-</div></div><br>
+</div>
+<div class="toccolours" style="background-color:#cbd5e7">
+====Subsequent treatment====
+*AVAGAST & AVATAR: after 6 cycles, [[#Capecitabine_monotherapy_2|capecitabine]] maintenance
+*SMC 2008-12-019: after 8 cycles, [[#Capecitabine_monotherapy_2|capecitabine]] maintenance
+</div></div>
+===References===
+#'''ML17032:''' Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [https://doi.org/10.1093/annonc/mdn717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19153121 PubMed] content property of [http://hemonc.org HemOnc.org] NCT02563054
+#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://doi.org/10.1200/JCO.2011.36.2236 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21844504 PubMed] NCT00548548
+#'''EXPAND:''' Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [https://doi.org/10.1016/S1470-2045(13)70102-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23594786 PubMed] NCT00678535
+#'''AVATAR:''' Shen L, Li J, Xu J, Pan H, Dai G, Qin S, Wang L, Wang J, Yang Z, Shu Y, Xu R, Chen L, Liu Y, Yu S, Bu L, Piao Y. Bevacizumab plus capecitabine and cisplatin in Chinese patients with inoperable locally advanced or metastatic gastric or gastroesophageal junction cancer: randomized, double-blind, phase III study (AVATAR study). Gastric Cancer. 2015 Jan;18(1):168-76. Epub 2014 Feb 21. [https://doi.org/10.1007/s10120-014-0351-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4544634/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24557418 PubMed] NCT00887822
+#'''SMC 2008-12-019:''' Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25218337 PubMed] NCT01099085
+#'''PAC-C:''' Lu Z, Zhang X, Liu W, Liu T, Hu B, Li W, Fan Q, Xu J, Xu N, Bai Y, Pan Y, Xu Q, Bai W, Xia L, Gao Y, Wang W, Shu Y, Shen L. A multicenter, randomized trial comparing efficacy and safety of paclitaxel/capecitabine and cisplatin/capecitabine in advanced gastric cancer. Gastric Cancer. 2018 Sep;21(5):782-791. Epub 2018 Feb 27. [https://doi.org/10.1007/s10120-018-0809-y link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6097104/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29488121 PubMed] NCT01015339
+#'''RAINFALL:''' Fuchs CS, Shitara K, Di Bartolomeo M, Lonardi S, Al-Batran SE, Van Cutsem E, Ilson DH, Alsina M, Chau I, Lacy J, Ducreux M, Mendez GA, Alavez AM, Takahari D, Mansoor W, Enzinger PC, Gorbounova V, Wainberg ZA, Hegewisch-Becker S, Ferry D, Lin J, Carlesi R, Das M, Shah MA; RAINFALL Study Group. Ramucirumab with cisplatin and fluoropyrimidine as first-line therapy in patients with metastatic gastric or junctional adenocarcinoma (RAINFALL): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2019 Mar;20(3):420-435. Epub 2019 Feb 1. Erratum in: Lancet Oncol. 2019 May;20(5):e242. [https://doi.org/10.1016/S1470-2045(18)30791-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30718072 PubMed] NCT02314117
+==Capecitabine & Cisplatin (CX) & Pembrolizumab {{#subobject:ahg7ab|Regimen=1}}==
+CX & Pembrolizumab: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), Pembrolizumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, AUC 5/300 {{#subobject:1eba05|Variant=1}}===
+===Regimen {{#subobject:1yt34c|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
+|rowspan=2|2015-2017
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]<br> 2. [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
+| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 12.5 vs 11.1 mo<br>(HR 0.85, 95% CI 0.70-1.03)
+|-
+|3. [[#Pembrolizumab_monotherapy|Pembrolizumab]]
+| style="background-color:#d3d3d3" |Not reported
+|}
+''KEYNOTE-062 included patients with GEJ malignancy''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+PD-L1 Combined Positive Score (CPS) of 1 or more as determined by an FDA-approved test
+</div>
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+====Immunotherapy====
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
+#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
+==CapeOx {{#subobject:4e3bb4|Regimen=1}}==
+CapeOX: '''<u>Cape</u>'''citabine & '''<u>OX</u>'''aliplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #1, 750/78 {{#subobject:4faj81|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+!style="width: 20%"|Study
 !style="width: 20%"|Years of enrollment
 !style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
@@ Line 781: / Line 1,029: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2009.23.1548 Socinski et al. 2009 (JMHO)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ Hall et al. 2021 (GO2)]
-|2006-2007
+|2014-2017
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#Carboplatin_.26_Pemetrexed_99|Carboplatin & Pemetrexed]]
+|[[#CapeOx_2|CapeOx]]; 130/1250
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#eeee01" |Non-inferior PFS
 |-
-|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
+|}
-|2007-2008
+<div class="toccolours" style="background-color:#b3e2cd">
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
+====Chemotherapy====
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab|EP & Bevacizumab]]
+*[[Capecitabine (Xeloda)]] 375 mg/m<sup>2</sup> PO twice per day
-| style="background-color:#fc8d59" |Seems to have inferior PFS
+*[[Oxaliplatin (Eloxatin)]] 78 mg/m<sup>2</sup> IV once on day 1
-|-
+'''21-day cycles'''
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ Ready et al. 2015 (CALGB 30504)]
+</div></div><br>
-|2007-2011
+<div class="toccolours" style="background-color:#eeeeee">
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
+===Regimen variant #2, 1000/104 {{#subobject:4faj65|Variant=1}}===
-| style="background-color:#d3d3d3" |
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-| style="background-color:#d3d3d3" |
+!style="width: 20%"|Study
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2016.67.6601 Reck et al. 2016 (CA184-156)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ Hall et al. 2021 (GO2)]
-|2012-2014
+|2014-2017
-|style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Ipilimumab|CE & Ipilimumab]]
+|[[#CapeOx_2|CapeOx]]; 130/1250
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#eeee01" |Non-inferior PFS
-|-
-|[https://doi.org/10.1200/JCO.2016.71.7454 Jalal et al. 2017 (MATISSE)]
-|2012-2013
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#PaCE_99|PaCE]]
-| style="background-color:#d9ef8b" |Might have superior OS
-|-
-|[https://doi.org/10.1056/NEJMoa1809064 Horn et al. 2018 (IMpower133)]
-|2016-2017
-|style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_.26_Atezolizumab|CE & Atezolizumab]]
-| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
-|-
-|[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)]
-|2017-2018
-|style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Durvalumab|CE & Durvalumab]]<br> 2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Durvalumab|EP & Durvalumab]]
-| style="background-color:#d73027" |Inferior OS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
-|2017-2018
-|style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Small_cell_lung_cancer_-_historical#Carboplatin_.26_Etoposide_.28CE.29_.26_Pembrolizumab|CE & Pembrolizumab]]<br> 2. [[Small_cell_lung_cancer_-_historical#Cisplatin_.26_Etoposide_.28EP.29_.26_Pembrolizumab|EP & Pembrolizumab]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
-|-
-|[https://doi.org/10.1016/s1470-2045(22)00224-8 Wang et al. 2022 (CAPSTONE-1)]
-|2018-2020
-|style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_.26_Adebrelimab_77|CE & Adebrelimab]]
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-''<sup>1</sup>Reported efficacy for IMpower133 is based on the 2020 update.''<br>
-''Note: CASPIAN gave a range of dosing; see paper for details.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Capecitabine (Xeloda)]] 500 mg/m<sup>2</sup> PO twice per day
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 104 mg/m<sup>2</sup> IV once on day 1
-====Supportive therapy====
+'''21-day cycles'''
-*Socinksi et al. 2009: "supportive therapies, such as erythropoietic agents or granulocyte colony-stimulating factors, were administered according to the American Society of Clinical Oncology guidelines"
-'''21-day cycle for 4 to 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*CALGB 30504, SD or better: [[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]] versus [[#Sunitinib_monotherapy|sunitinib]] maintenance
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, AUC 5 or 6/360 {{#subobject:927150|Variant=1}}===
+===Regimen variant #3, 1250/130 {{#subobject:guzj65|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 859: / Line 1,073: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ Hall et al. 2021 (GO2)]
-|2007-2012
+|2014-2017
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
+|1. [[#CapeOx_2|CapeOx]]; 750/78<br>2. [[#CapeOx_2|CapeOx]]; 1000/104
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#eeee01" |Non-inferior PFS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
-**AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = 130 mL/min/1.73m<sup>2</sup>
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''21-day cycles'''
-'''21-day cycle for 6 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, AUC 5/420 {{#subobject:69fffb|Variant=1}}===
+===Regimen variant #4, 1700/130 {{#subobject:4faee3|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://journals.lww.com/amjclinicaloncology/Abstract/2009/02000/Multicenter_Randomized_Open_Label_Phase_III_Study.13.aspx Heigener et al. 2009]
+|[https://doi.org/10.1093/annonc/mdj063 Jatoi et al. 2006]
-|2000-2003
+|2002-2004
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#91cf61" |Phase 2
-|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]; dose-intense
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1093/annonc/mdj137 Schmittel et al. 2006]
-|2002-2008
-| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
-|[[#Carboplatin_.26_Irinotecan|IP]]
-| style="background-color:#fee08b" |Might have inferior OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1
+*[[Capecitabine (Xeloda)]] 850 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-*[[Etoposide (Vepesid)]] 140 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-====Supportive therapy====
+'''21-day cycles'''
-*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV once per day on days 1 to 3, prior to chemotherapy
-*[[Loperamide (Imodium)]] 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
-'''21- to 28-day cycle for up to 6 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #6, AUC 5 or 6/440, 1 day of oral etoposide per cycle {{#subobject:47c27e|Variant=1}}===
+===Regimen variant #5, 2000/130 {{#subobject:4fagg3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 913: / Line 1,113: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)]
+|[https://doi.org/10.1200/jco.20.00892 Moehler et al. 2020 (JAVELIN Gastric 100)]
-|2003-2006
+|2015-2017
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]]
+|1. [[#CapeOx_2|CapeOx]] x 4, then [[#Avelumab_monotherapy_99|Avelumab]]<br> 2. [[#mFOLFOX4_88|mFOLFOX4]] x 4, then [[#Avelumab_monotherapy_99|Avelumab]]<br> 3. [[#mFOLFOX6|mFOLFOX6]] x 4, then [[#Avelumab_monotherapy_99|Avelumab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
+|Awaiting publication (ARMANI)
-|2007-2012
+|2016-2019
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
+|1. [[#CapeOx_2|CapeOx]] x 3 mo, then [[#Paclitaxel_.26_Ramucirumab_88|Paclitaxel & Ramucirumab]]<br> 2. [[#FOLFOX4_88|FOLFOX4]] x 3 mo, then [[#Paclitaxel_.26_Ramucirumab_88|Paclitaxel & Ramucirumab]]<br> 3. [[#mFOLFOX6|mFOLFOX6]] x 3 mo, then [[#Paclitaxel_.26_Ramucirumab_88|Paclitaxel & Ramucirumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d3d3d3" |TBD
+|-
+|[https://doi.org/10.1016/s1470-2045(21)00692-6 Kang et al. 2022 (ATTRACTION-4)]
+|2017-2018
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#CapeOx_.26_Nivolumab|CapeOx & Nivolumab]]<br>2. [[#SOX_.26_Nivolumab_77|SOX & Nivolumab]]
+| style="background-color:#d73027" |Inferior PFS
+|-
+|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
+|rowspan=2|2017-2019
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#CapeOx_.26_Nivolumab|CapeOx & Nivolumab]]<br> 2. [[#mFOLFOX6_.26_Nivolumab|mFOLFOX6 & Nivolumab]]
+| style="background-color:#d73027" |Inferior OS
+|-
+|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+|Awaiting publication (BGB-A317-305)
+|2018-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#CapeOx_.26_Tislelizumab_77|CapeOx & Tislelizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Tislelizumab_77|CF & Tislelizumab]]
+| style="background-color:#d3d3d3" |TBD
+|-
+|Awaiting publication (KEYNOTE-859)
+|2018-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#CapeOx_.26_Pembrolizumab_66|CapeOx & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]
+| style="background-color:#d3d3d3" |TBD
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-**'''LLCG-STUDY-12''': AUC 5 is used
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-**'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup>
+'''21-day cycles'''
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
-'''21-day cycle for up to 6 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #7, AUC 5 or 6/520, 2 days of oral etoposide per cycle {{#subobject:ae04e8|Variant=1}}===
+===Regimen variant #6, 2000/130, limited oxaliplatin {{#subobject:4hazb3|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 943: / Line 1,168: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 Lee et al. 2009 (LLCG-STUDY-12)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ Zhu et al. 2022 (EXELOX)]
-|2003-2006
+|2015-2020
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[Stub#Carboplatin_.26_Etoposide_.28CE.29_.26_Thalidomide|CE & Thalidomide]]
+|[[#EOX_2|EOX]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#eeee01" |Non-inferior PFS<br>Median PFS: 5 vs 5.5 mo<br>(HR 0.989, 95% CI 0.81-1.20)
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
-|2007-2012
-| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 or 6 (maximum dose of 1000 mg) IV once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-**'''LLCG-STUDY-12''': AUC 5 is used
+*[[Oxaliplatin (Eloxatin)]] as follows:
-**'''LUNGSTAR''': AUC 5 is used if eGFR calculated by EDTA; AUC 6 is used if eGFR calculated by Cockcroft Gault. If eGFR greater than 130 mL/min/1.73m<sup>2</sup>, dose calculation to be capped at GFR = mL/min/1.73m<sup>2</sup>
+**Cycles 1 up to 8: 130 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3
+'''21-day cycles'''
-'''21-day cycle for up to 6 cycles'''
+</div></div>
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #8, AUC 5/300, 28-day cycles {{#subobject:d904aa|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
-!style="width: 33%"|Study
-!style="width: 33%"|Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.1999.17.11.3540 Okamoto et al. 1999]
-|1995-1996
-| style="background-color:#91cf61" |Phase 2
-|-
-|[https://doi.org/10.1023/a:1011171722175 Quoix et al. 2001]
-|1997-1999
-| style="background-color:#91cf61" |Phase 2
-|-
-|}
-''Patients in Okamoto et al. 1999 and Quoix et al. 2001 were greater than or equal to 70 years old.''
-====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1, '''given first'''
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1 to 3, '''given second'''
-====Supportive therapy====
-*[[Dexamethasone (Decadron)]] 8 mg IV once per day on days 1 to 3, prior to chemotherapy
-*[[Granisetron]] 40 mcg/kg IV once per day on days 1 to 3, prior to chemotherapy
-*Okamoto et al. 1999: [[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 2 mcg/kg SC given for grade 3 or greater leukopenia/neutropenia
-*Quiox et al. 2001: "Haematopoietic growth factors were allowed as prophylactic or curative treatment only if grade 4 neutropenia greater than 7 days occurred"
-'''28-day cycle for 4 to 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Palliative radiation therapy was allowed to control persistent pain from bony metastases
-</div></div>
 ===References===
-# Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, Masutani M, Nakata K, Tsuchiya S, Isobe H, Saijo N. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standard-dose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999 Nov;17(11):3540-5. [https://doi.org/10.1200/jco.1999.17.11.3540 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10550152 PubMed]
+#Jatoi A, Murphy BR, Foster NR, Nikcevich DA, Alberts SR, Knost JA, Fitch TR, Rowland KM Jr; North Central Cancer Treatment Group. Oxaliplatin and capecitabine in patients with metastatic adenocarcinoma of the esophagus, gastroesophageal junction and gastric cardia: a phase II study from the North Central Cancer Treatment Group. Ann Oncol. 2006 Jan;17(1):29-34. Epub 2005 Nov 22. [https://doi.org/10.1093/annonc/mdj063 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16303863 PubMed]
-# Quoix E, Breton JL, Daniel C, Jacoulet P, Debieuvre D, Paillot N, Kessler R, Moreau L, Coëtmeur D, Lemarié E, Milleron B. Etoposide phosphate with carboplatin in the treatment of elderly patients with small-cell lung cancer: a phase II study. Ann Oncol. 2001 Jul;12(7):957-62. [https://doi.org/10.1023/a:1011171722175 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11521802 PubMed]
+#'''JAVELIN Gastric 100:''' Moehler M, Dvorkin M, Boku N, Özgüroğlu M, Ryu MH, Muntean AS, Lonardi S, Nechaeva M, Bragagnoli AC, Coşkun HS, Cubillo Gracian A, Takano T, Wong R, Safran H, Vaccaro GM, Wainberg ZA, Silver MR, Xiong H, Hong J, Taieb J, Bang YJ. Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100. J Clin Oncol. 2021 Mar 20;39(9):966-977. Epub 2020 Nov 16. [https://doi.org/10.1200/jco.20.00892 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33197226/ PubMed] NCT02625610
-# Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. [https://doi.org/10.1093/annonc/mdj137 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16423848 PubMed]
+#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
-## '''Update:''' Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. [https://doi.org/10.1093/annonc/mdq652 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21266516 PubMed]
+#'''GO2:''' Hall PS, Swinson D, Cairns DA, Waters JS, Petty R, Allmark C, Ruddock S, Falk S, Wadsley J, Roy R, Tillett T, Nicoll J, Cummins S, Mano J, Grumett S, Stokes Z, Kamposioras KV, Chatterjee A, Garcia A, Waddell T, Guptal K, Maisey N, Khan M, Dent J, Lord S, Crossley A, Katona E, Marshall H, Grabsch HI, Velikova G, Ow PL, Handforth C, Howard H, Seymour MT; GO2 Trial Investigators. Efficacy of Reduced-Intensity Chemotherapy With Oxaliplatin and Capecitabine on Quality of Life and Cancer Control Among Older and Frail Patients With Advanced Gastroesophageal Cancer: The GO2 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2021 Jun 1;7(6):869-877. Erratum in: JAMA Oncol. 2021 Aug 1;7(8):1249. [https://doi.org/10.1001/jamaoncol.2021.0848 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8120440/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33983395/ PubMed] ISRCTN44687907
-# '''JCOG 9702:''' Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. [https://www.nature.com/articles/6603810 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17579629 PubMed]
+#'''ATTRACTION-4:''' Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. Epub 2022 Jan 11. [https://doi.org/10.1016/s1470-2045(21)00692-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35030335/ PubMed] NCT02746796
-# Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. [https://doi.org/10.1200/JCO.2007.15.7545 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18779613 PubMed]
+#'''EXELOX:''' Zhu XD, Huang MZ, Wang YS, Feng WJ, Chen ZY, He YF, Zhang XW, Liu X, Wang CC, Zhang W, Ying JE, Wu J, Yang L, Qin YR, Luo JF, Zhao XY, Li WH, Zhang Z, Qiu LX, Geng QR, Zou JL, Zhang JY, Zheng H, Song XF, Wu SS, Zhang CY, Gong Z, Liu QQ, Wang XF, Xu Q, Wang Q, Ji JM, Zhao J, Guo WJ. XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX). Cancer Commun (Lond). 2022 Apr;42(4):314-326. Epub 2022 Feb 25. [https://doi.org/10.1002/cac2.12278 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35212487/ PubMed] NCT02395640
-# Heigener DF, Manegold C, Jäger E, Saal JG, Zuna I, Gatzemeier U. Multicenter randomized open-label phase III study comparing efficacy, safety, and tolerability of conventional carboplatin plus etoposide versus dose-intensified carboplatin plus etoposide plus lenograstim in small-cell lung cancer in "extensive disease" stage. Am J Clin Oncol. 2009 Feb;32(1):61-4. [https://journals.lww.com/amjclinicaloncology/Abstract/2009/02000/Multicenter_Randomized_Open_Label_Phase_III_Study.13.aspx link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19194127 PubMed]
+#'''ARMANI:''' NCT02934464
-# '''LLCG-STUDY-12:''' Lee SM, Woll PJ, Rudd R, Ferry D, O'Brien M, Middleton G, Spiro S, James L, Ali K, Jitlal M, Hackshaw A. Anti-angiogenic therapy using thalidomide combined with chemotherapy in small cell lung cancer: a randomized, double-blind, placebo-controlled trial. J Natl Cancer Inst. 2009 Aug 5;101(15):1049-57. Epub 2009 Jul 16. [https://academic.oup.com/jnci/article-lookup/doi/10.1093/jnci/djp200 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19608997 PubMed] NCT00061919
+#'''BGB-A317-305:''' '''contains dosing details on CT.gov''' NCT03777657
-<!-- Presented in part as an oral presentation at the 44th Annual Meeting of the American Society of Clinical Oncology, May 30-June 3, 2008, Chicago, IL, and the 8th Annual Targeted Therapies for the Treatment of Lung Cancer Meeting, February 20-23, 2008, Santa Monica, CA. -->
+#'''KEYNOTE-859:''' '''contains dosing details on CT.gov''' NCT03675737
-# '''JMHO:''' Socinski MA, Smit EF, Lorigan P, Konduri K, Reck M, Szczesna A, Blakely J, Serwatowski P, Karaseva NA, Ciuleanu T, Jassem J, Dediu M, Hong S, Visseren-Grul C, Hanauske AR, Obasaju CK, Guba SC, Thatcher N. Phase III study of pemetrexed plus carboplatin compared with etoposide plus carboplatin in chemotherapy-naive patients with extensive-stage small-cell lung cancer. J Clin Oncol. 2009 Oct 1;27(28):4787-92. Epub 2009 Aug 31. [https://doi.org/10.1200/jco.2009.23.1548 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19720897 PubMed] NCT00363415
+#'''ORIENT-16:''' NCT03745170
-# '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] NCT00403403
+==CapeOx & Nivolumab {{#subobject:1ybz18|Regimen=1}}==
-# '''D0702002:''' Sekine I, Okamoto H, Horai T, Nakagawa K, Ohmatsu H, Yokoyama A, Katakami N, Shibuya M, Saijo N, Fukuoka M. A randomized phase III study of single-agent amrubicin vs carboplatin/etoposide in elderly patients with extensive-disease small-cell lung cancer. Clin Lung Cancer. 2014 Mar;15(2):96-102. Epub 2013 Nov 14. [https://www.clinical-lung-cancer.com/article/S1525-7304(13)00232-5 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24361248 PubMed] NCT00286169
+CapeOx & Nivolumab: '''<u>Cape</u>'''citabine, '''<u>OX</u>'''aliplatin, Nivolumab
-# '''CALGB 30504:''' Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.57.3105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732163 PubMed] NCT00453154
-# '''CA184-156:''' Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. [https://doi.org/10.1200/JCO.2016.67.6601 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27458307 PubMed] NCT01450761
-# '''LUNGSTAR:''' Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. [https://doi.org/10.1200/JCO.2016.69.7391 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28240967 PubMed] NCT00433498
-# '''MATISSE:''' Jalal SI, Lavin P, Lo G, Lebel F, Einhorn L. Carboplatin and etoposide with or without palifosfamide in untreated extensive-stage small-cell lung cancer: A multicenter, adaptive, randomized phase III study (MATISSE). J Clin Oncol. 2017 Aug 10;35(23):2619-2623. Epub 2017 Jun 12. [https://doi.org/10.1200/JCO.2016.71.7454 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28605291 PubMed] NCT01555710
-# '''IMpower133:''' Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. [https://doi.org/10.1056/NEJMoa1809064 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30280641 PubMed] NCT02763579
-## '''Update:''' Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. [https://doi.org/10.1200/jco.20.01055 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33439693/ PubMed]
-# '''CASPIAN:''' Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. [https://doi.org/10.1016/S0140-6736(19)32222-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31590988 PubMed] NCT03043872
-##'''Update:''' Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. [https://doi.org/10.1016/s1470-2045(20)30539-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33285097 PubMed]
-# '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778
-# '''CAPSTONE-1:''' Wang J, Zhou C, Yao W, Wang Q, Min X, Chen G, Xu X, Li X, Xu F, Fang Y, Yang R, Yu G, Gong Y, Zhao J, Fan Y, Liu Q, Cao L, Yao Y, Liu Y, Li X, Wu J, He Z, Lu K, Jiang L, Hu C, Zhao W, Zhang B, Shi W, Zhang X, Cheng Y; CAPSTONE-1 Study Group. Adebrelimab or placebo plus carboplatin and etoposide as first-line treatment for extensive-stage small-cell lung cancer (CAPSTONE-1): a multicentre, randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Jun;23(6):739-747. Epub 2022 May 13. [https://doi.org/10.1016/s1470-2045(22)00224-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35576956/ PubMed] NCT03711305
-==Carboplatin & Etoposide (CE) & Atezolizumab {{#subobject:760b97|Regimen=1}}==
-CE & Atezolizumab: '''<u>C</u>'''arboplatin, '''<u>E</u>'''toposide, Atezolizumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:6a356b|Variant=1}}===
+===Regimen {{#subobject:1bja1f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 1,029: / Line 1,204: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1056/NEJMoa1809064 Horn et al. 2018 (IMpower133)]
+|[https://doi.org/10.1016/s1470-2045(21)00692-6 Kang et al. 2022 (ATTRACTION-4)]
-|2016-2017
+|2017-2018
-|style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
+|1. [[#CapeOx_2|CapeOx]]<br>2. [[#SOX_88|SOX]]
-| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 12.3 vs 10.3 mo<br>(HR 0.76, 95% CI 0.60-0.95)
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 10.45 vs 8.3 mo<br>(HR 0.68, 98.51% 0.51-0.90)
+|-
+|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
+|rowspan=2|2017-2019
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|1. [[#CapeOx_2|CapeOx]]<br> 2. [[#mFOLFOX6|mFOLFOX6]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 14.4 vs 11.1 mo<br>(HR 0.71, 98.4% CI 0.59-0.86)
+|-
+|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
+| style="background-color:#d3d3d3" |Not reported
 |-
 |}
-''<sup>1</sup>Reported efficacy for IMpower133 is based on the 2020 update.''
+''<sup>1</sup>Reported efficacy is for the group with PD-L1 CPS of 5 or more.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] as follows:
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-**Cycles 1 to 4: AUC 5 IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] as follows:
-**Cycles 1 to 4: 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
 ====Immunotherapy====
-*[[Atezolizumab (Tecentriq)]] 1200 mg IV once on day 1
+*[[Nivolumab (Opdivo)]] 360 mg IV once on day 1
 '''21-day cycles'''
 </div></div>
 ===References===
-# '''IMpower133:''' Horn L, Mansfield AS, Szczęsna A, Havel L, Krzakowski M, Hochmair MJ, Huemer F, Losonczy G, Johnson ML, Nishio M, Reck M, Mok T, Lam S, Shames DS, Liu J, Ding B, Lopez-Chavez A, Kabbinavar F, Lin W, Sandler A, Liu SV; IMpower133 Study Group. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N Engl J Med. 2018 Dec 6;379(23):2220-2229. Epub 2018 Sep 25. [https://doi.org/10.1056/NEJMoa1809064 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/30280641 PubMed] NCT02763579
+#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
-## '''Update:''' Liu SV, Reck M, Mansfield AS, Mok T, Scherpereel A, Reinmuth N, Garassino MC, De Castro Carpeno J, Califano R, Nishio M, Orlandi F, Alatorre-Alexander J, Leal T, Cheng Y, Lee JS, Lam S, McCleland M, Deng Y, Phan S, Horn L. Updated Overall Survival and PD-L1 Subgroup Analysis of Patients With Extensive-Stage Small-Cell Lung Cancer Treated With Atezolizumab, Carboplatin, and Etoposide (IMpower133). J Clin Oncol. 2021 Feb 20;39(6):619-630. Epub 2021 Jan 13. [https://doi.org/10.1200/jco.20.01055 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33439693/ PubMed]
+#'''ATTRACTION-4:''' Kang YK, Chen LT, Ryu MH, Oh DY, Oh SC, Chung HC, Lee KW, Omori T, Shitara K, Sakuramoto S, Chung IJ, Yamaguchi K, Kato K, Sym SJ, Kadowaki S, Tsuji K, Chen JS, Bai LY, Oh SY, Choda Y, Yasui H, Takeuchi K, Hirashima Y, Hagihara S, Boku N. Nivolumab plus chemotherapy versus placebo plus chemotherapy in patients with HER2-negative, untreated, unresectable advanced or recurrent gastric or gastro-oesophageal junction cancer (ATTRACTION-4): a randomised, multicentre, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):234-247. Epub 2022 Jan 11. [https://doi.org/10.1016/s1470-2045(21)00692-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35030335/ PubMed] NCT02746796
-#'''IMforte:''' NCT05091567
+==Carboplatin & Paclitaxel (CP) {{#subobject:4df570|Regimen=1}}==
-==Carboplatin & Etoposide (CE) & Bevacizumab {{#subobject:d61f26|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3eed0d|Variant=1}}===
+===Regimen {{#subobject:9725d8|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+|-
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|[https://pubmed.ncbi.nlm.nih.gov/9427274 Philip et al. 1997]
+|NR in abstract
+| style="background-color:#91cf61" |Phase 2
 |-
-|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
+|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract Gadgeel et al. 2003]
-|2007-2008
+|1996-2000
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+| style="background-color:#91cf61" |Phase 2
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-| style="background-color:#91cf60" |Seems to have superior PFS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Note: In contrast to the original reference, some guidelines list the dosage of carboplatin as AUC 6.''
+''Philip et al. included patients with locally advanced metastatic or recurrent esophageal or gastric cancer''
+''Gadgeel et al. study showed an ORR of 35%''
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1, '''given second'''
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-====Targeted therapy====
+'''21-day cycles'''
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
-'''21-day cycle for 4 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Bevacizumab_monotherapy|Bevacizumab]] maintenance
 </div></div>
 ===References===
-# '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] NCT00403403
+#Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/9427274 PubMed]
-==Carboplatin & Etoposide (CE) & Durvalumab {{#subobject:ddgb26|Regimen=1}}==
+#Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12576922 PubMed]
+==Cisplatin & Docetaxel (DC) {{#subobject:724868|Regimen=1}}==
+DC: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin
+<br>TC: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3cbz3d|Variant=1}}===
+===Regimen variant #1, 75/75 {{#subobject:cd0910|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1200/jco.2006.08.0135 Roth et al. 2007]
+| rowspan="2" |1999-2003
+| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
+|1. [[#ECF_3|ECF]]
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)]
+|2. [[#DCF|TCF]]
-|2017-2018
+| style="background-color:#fee08b" |Might have inferior ORR
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br> 2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 12.9 vs 10.5 mo<br>(HR 0.75, 95% CI 0.62-0.91)
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2021 update.''
+''Note: the protocol was amended to change the original dose of docetaxel from 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] as follows:
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
-**Cycles 1 to 4: AUC 5 to 6 IV once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Etoposide (Vepesid)]] as follows:
+====Supportive therapy====
-**Cycles 1 to 4: 80 to 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*3 liters per day [[:Category:Hydration|"hyperhydration"]]
-====Immunotherapy====
+*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO twice per day for 4 days after [[Docetaxel (Taxotere)]]
-*[[Durvalumab (Imfinzi)]] 1500 mg IV once on day 1
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
-'''21-day cycle for 4 cycles, then 28-day cycles'''
+*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-</div></div>
+'''21-day cycle for up to 8 cycles'''
-===References===
+</div></div><br>
-# '''CASPIAN:''' Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. [https://doi.org/10.1016/S0140-6736(19)32222-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/31590988 PubMed] NCT03043872
-##'''Update:''' Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. [https://doi.org/10.1016/s1470-2045(20)30539-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33285097 PubMed]
-==Carboplatin & Etoposide (CE) & Serplulimab {{#subobject:ijg126|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:kcla3d|Variant=1}}===
+===Regimen variant #2, 75/85 {{#subobject:f1913d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1001/jama.2022.16464 Cheng et al. 2022 (ASTRUM-005)]
+|[https://doi.org/10.1200/jco.2005.17.376 Ajani et al. 2005 (V-325)]
-|2019-2021
+|1998-1999
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
+|[[#DCF|DCF]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 15.4 vs 10.9 mo<br>(HR 0.63, 95% CI 0.49-0.82)
+| style="background-color:#fc8d59" |Seems to have inferior ORR
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Patients: 100% adenocarcinoma histology (32% esophagogastric junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.''
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]]
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
-*[[Etoposide (Vepesid)]]
+*[[Docetaxel (Taxotere)]] 85 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-====Immunotherapy====
+====Supportive therapy====
-*[[Serplulimab (Hansizhuang)]] 4.5 mg/kg IV once on day 1
+*[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (total dose per cycle: 48 mg)
+*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
+*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
+*"[[:Category:Hydration|Hydration]] was administered in a standard manner"
 '''21-day cycles'''
 </div></div>
 ===References===
-#'''ASTRUM-005:''' Cheng Y, Han L, Wu L, Chen J, Sun H, Wen G, Ji Y, Dvorkin M, Shi J, Pan Z, Shi J, Wang X, Bai Y, Melkadze T, Pan Y, Min X, Viguro M, Li X, Zhao Y, Yang J, Makharadze T, Arkania E, Kang W, Wang Q, Zhu J; ASTRUM-005 Study Group. Effect of First-Line Serplulimab vs Placebo Added to Chemotherapy on Survival in Patients With Extensive-Stage Small Cell Lung Cancer: The ASTRUM-005 Randomized Clinical Trial. JAMA. 2022 Sep 27;328(12):1223-1232. [https://doi.org/10.1001/jama.2022.16464 link to original article] '''contains partial dosing information in abstract''' [https://pubmed.ncbi.nlm.nih.gov/36166026/ PubMed] NCT04063163
+#'''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [https://doi.org/10.1200/jco.2005.17.376 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16110025 PubMed]
-==Carboplatin & Irinotecan {{#subobject:b2ac71|Regimen=1}}==
+#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [https://doi.org/10.1200/jco.2006.08.0135 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17664469 PubMed]
-IC: '''<u>I</u>'''rinotecan & '''<u>C</u>'''arboplatin
+==Cisplatin & Fluorouracil (CF) {{#subobject:4d9936|Regimen=1}}==
-<br>IP: '''<u>I</u>'''rinotecan & '''<u>P</u>'''araplatin (Carboplatin)
+CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, AUC 4/175 {{#subobject:3de550|Variant=1}}===
+===Regimen variant #1, 60/5000 {{#subobject:9yt155|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2007.15.7545 Hermes et al. 2008]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2699097/ Lee et al. 2009a]
-|2001-2005
+|2000-2004
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
+|[[#Fluorouracil_.26_Heptaplatin_.28FH.29_77|Fluorouracil & Heptaplatin (FH)]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 8.5 vs 7.1 mo<br>(HR 0.71, 95% CI 0.53-0.94)
+| style="background-color:#eeee01" |Equivalent OS
 |-
 |}
+''Note: this is reported to be an equivalence study but the statistical analysis does not provide details on the definition of equivalence.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 4 (Chatelut formula) IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given first'''
-*[[Irinotecan (Camptosar)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup> IV over 12 hours once per day on days 1 to 5, '''given second'''
-'''21-day cycle for 4 cycles'''
+'''28-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, AUC 5/150 {{#subobject:38a7ba|Variant=1}}===
+===Regimen variant #2, 80/4000 x 8 {{#subobject:9abe95|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1093/annonc/mdj137 Schmittel et al. 2006]
+|[https://doi.org/10.1093/annonc/mdx275 Ajani et al. 2017 (DIGEST)]
-|2002-2008
+|2011-2014
-| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
+|[[#Cisplatin_.26_S-1|CS]]
-| style="background-color:#d9ef8b" |Might have superior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV over 60 minutes once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
-*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
 ====Supportive therapy====
-*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV once per day on days 1, 8, 15, prior to chemotherapy
+*Some protocols: [[:Category:Hydration|"Hyperhydration"]] for cisplatin
-*[[Loperamide (Imodium)]] 4 mg PO prn first episode of diarrhea, then 2 mg PO Q2H until diarrhea stops
+'''21-day cycle for 8 cycles'''
-'''28-day cycle for up to 6 cycles'''
+</div></div><br>
-</div></div>
-===References===
-# Schmittel A, Fischer von Weikersthal L, Sebastian M, Martus P, Schulze K, Hortig P, Reeb M, Thiel E, Keilholz U. A randomized phase II trial of irinotecan plus carboplatin versus etoposide plus carboplatin treatment in patients with extended disease small-cell lung cancer. Ann Oncol. 2006 Apr;17(4):663-7. Epub 2006 Jan 19. [https://doi.org/10.1093/annonc/mdj137 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16423848 PubMed]
-## '''Update:''' Schmittel A, Sebastian M, Fischer von Weikersthal L, Martus P, Gauler TC, Kaufmann C, Hortig P, Fischer JR, Link H, Binder D, Fischer B, Caca K, Eberhardt WE, Keilholz U; Arbeitsgemeinschaft Internistische Onkologie Thoracic Oncology Study Group. A German multicenter, randomized phase III trial comparing irinotecan-carboplatin with etoposide-carboplatin as first-line therapy for extensive-disease small-cell lung cancer. Ann Oncol. 2011 Aug;22(8):1798-804. Epub 2011 Jan 25. [https://doi.org/10.1093/annonc/mdq652 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21266516 PubMed]
-# Hermes A, Bergman B, Bremnes R, Ek L, Fluge S, Sederholm C, Sundstrøm S, Thaning L, Vilsvik J, Aasebø U, Sörenson S. Irinotecan plus carboplatin versus oral etoposide plus carboplatin in extensive small-cell lung cancer: a randomized phase III trial. J Clin Oncol. 2008 Sep 10;26(26):4261-7. [https://doi.org/10.1200/JCO.2007.15.7545 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18779613 PubMed]
-==Carboplatin & Paclitaxel (CP) & Ipilimumab {{#subobject:9695b3|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, phased ipilimumab {{#subobject:7dbd39|Variant=1}}===
+===Regimen variant #3, 80/4000, indefinite {{#subobject:69c795|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1093/annonc/mdn717 Kang et al. 2009 (ML17032)]
+|2003-2005
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
+| style="background-color:#eeee01" |Non-inferior PFS
 |-
-| rowspan="2" |[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041)]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
-|rowspan=2|2008-2009
+|rowspan=2|2015-2017
-| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_88|CP]]
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Pembrolizumab|CX & Pembrolizumab]]
-| style="background-color:#91cf60" |Seems to have superior irPFS
+| style="background-color:#fee08b" |Might have inferior OS
 |-
-|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|CP & Ipilimumab]]; concurrent Ipilimumab
+|[[#Pembrolizumab_monotherapy|Pembrolizumab]]
-| style="background-color:#d3d3d3" |Not reported
+| style="background-color:#eeee01" |Non-inferior OS
 |-
-|}
+|Awaiting publication (BGB-A317-305)
-<div class="toccolours" style="background-color:#b3e2cd">
+|2018-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#CapeOx_.26_Tislelizumab_77|CapeOx & Tislelizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Tislelizumab_77|CF & Tislelizumab]]
+| style="background-color:#d3d3d3" |TBD
+|-
+|Awaiting publication (KEYNOTE-859)
+|2018-ongoing
+| style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#CapeOx_.26_Pembrolizumab_66|CapeOx & Pembrolizumab]]<br>2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]
+| style="background-color:#d3d3d3" |TBD
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1, '''given second''' (total dose per cycle: 4000 mg/m<sup>2</sup>)
-====Immunotherapy====
+====Supportive therapy====
-*[[Ipilimumab (Yervoy)]] as follows:
+*Some protocols: [[:Category:Hydration|"Hyperhydration"]] for cisplatin
-**Cycles 3 to 6: 10 mg/kg IV once on day 1
+'''21-day cycles'''
-'''21-day cycle for up to 6 cycles'''
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Ipilimumab_monotherapy|Ipilimumab]] maintenance
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, concurrent ipilimumab {{#subobject:069d62|Variant=1}}===
+===Regimen variant #4, 100/4000 {{#subobject:16f88f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041)]
+|[http://ar.iiarjournals.org/content/26/5B/3877.long Duffour et al. 2006 (FFCD 9404)]
-|rowspan=2|2008-2009
+|1995-1998
-| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Paclitaxel_.28CP.29_88|CP]]
+|[[#CLF|FLP]]
-| style="background-color:#ffffbf" |Did not meet secondary endpoints
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior ORR
-|-
-|2. [[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|CP & Ipilimumab]]; phased Ipilimumab
-| style="background-color:#d3d3d3" |Not reported
 |-
 |}
-''Note: all efficacy endpoints in the ED-SCLC cohort were secondary.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on either day 1 or 2
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-====Immunotherapy====
+'''28-day cycles'''
-*[[Ipilimumab (Yervoy)]] as follows:
+</div></div><br>
-**Cycles 1 to 4: 10 mg/kg IV once on day 1
+<div class="toccolours" style="background-color:#eeeeee">
-'''21-day cycle for up to 6 cycles'''
+===Regimen variant #5, 100/4000, split-dose cisplatin {{#subobject:16f18e|Variant=1}}===
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*[[#Ipilimumab_monotherapy|Ipilimumab]] maintenance
-</div></div>
-===References===
-# '''CA184-041:''' Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. [https://doi.org/10.1093/annonc/mds213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22858559 PubMed] NCT00527735
-==Cisplatin & Etoposide (EP) {{#subobject:ec90cd|Regimen=1}}==
-EP: '''<u>E</u>'''toposide and '''<u>P</u>'''latinol (Cisplatin)
-<br>PE: '''<u>P</u>'''latinol (Cisplatin) and '''<u>E</u>'''toposide
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 60/300 {{#subobject:dd1718|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1200/jco.2003.04.130 Ohtsu et al. 2003 (JCOG 9205)]
+| rowspan="2" |1992-1997
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#Fluorouracil_monotherapy|Fluorouracil]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ Oh et al. 2016 (COMBAT)]
+|2. [[#UFTM|UFTM]]
-|2009-2013
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Belotecan_.26_Cisplatin|BP]]
-| style="background-color:#eeee01" |Non-inferior RR
 |-
 |}
-''Note: the total number of planned cycles is not described in the manuscript; total duration information here was provided by the authors.''
+''Study included patients with PFS of 2 (9.6%)''
-<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''21-day cycle for 4 to 8 cycles'''
+'''28-day cycle for up to 6 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 60/360 {{#subobject:5c4b41|Variant=1}}===
+===Regimen variant #6, 100/5000 {{#subobject:10f0c6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2005.04.8595 Hanna et al. 2006]
+|[https://doi.org/10.1200/jco.2006.06.8429 Van Cutsem et al. 2006 (TAX 325)]
-|2000-2003
+|1999-2003
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Irinotecan_.28IC.29_2|Cisplatin & Irinotecan]]
+|[[#DCF|DCF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
+|[https://doi.org/10.1093/annonc/mdn166 Dank et al. 2008]
-|2007-2012
+|2000-2002
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
+|[[#FOLFIRI|IF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#fee08b" |Might have inferior TTP
+|-
+|[https://doi.org/10.1200/JCO.2009.25.4706 Ajani et al. 2010 (FLAGS)]
+|2005-2007
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_S-1|CS]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Van Cutsem et al Patients: 100% adenocarcinoma histology (22% Esophagogastric junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70.''
+''Dank et al Patients: 100% adenocarcinoma histology (20% Esophagogastric junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given first'''
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[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====
-*Per Hanna et al. 2006:
+*As described in Dank et al. 2008:
-**[[:Category:Granulocyte colony-stimulating factors|G-CSF]] used according to 1999 American Society of Clinical Oncology guidelines
+*[[:Category:Hydration|"Hyperhydration"]] for 2 to 3 days with each infusion
-**"Erythropoietin was allowed at the discretion of the treating physician."
+*[[Ondansetron (Zofran)]] IV for antiemetic prophylaxis
-'''21-day cycle for 4 to 6 cycles'''
+*[[Dexamethasone (Decadron)]] IV for antiemetic prophylaxis, then PO for 2 to 3 days
-</div></div><br>
+*[[Metoclopramide (Reglan)]] for antiemetic prophylaxis
+*[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
+*[[Atropine (Atropen)]] prn cholinergic symptoms
+*[[Loperamide (Imodium)]] prn delayed diarrhea
+'''28-day cycles'''
+</div></div>
+===References===
+#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; [[Study_Groups#JCOG|JCOG]]. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [https://doi.org/10.1200/jco.2003.04.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506170 PubMed]
+#'''FFCD 9404:''' Duffour J, Bouché O, Rougier P, Milan C, Bedenne L, Seitz JF, Buecher B, Legoux JL, Ducreux M, Vetter D, Raoul JL, François E, Ychou M. Safety of cisplatin combined with continuous 5-FU versus bolus 5-FU and leucovorin, in metastatic gastrointestinal cancer (FFCD 9404 randomised trial). Anticancer Res. 2006 Sep-Oct;26(5B):3877-83. [http://ar.iiarjournals.org/content/26/5B/3877.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17094417 PubMed]
+#'''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [https://doi.org/10.1200/jco.2006.06.8429 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17075117 PubMed]
+#Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [https://doi.org/10.1093/annonc/mdn166 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18558665 PubMed]
+#'''ML17032:''' Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [https://doi.org/10.1093/annonc/mdn717 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19153121 PubMed] NCT02563054
+#Lee KH, Hyun MS, Kim HK, Jin HM, Yang J, Song HS, Do YR, Ryoo HM, Chung JS, Zang DY, Lim HY, Jin JY, Yim CY, Park HS, Kim JS, Sohn CH, Lee SN. Randomized, multicenter, phase III trial of heptaplatin 1-hour infusion and 5-fluorouracil combination chemotherapy comparing with cisplatin and 5-fluorouracil combination chemotherapy in patients with advanced gastric cancer. Cancer Res Treat. 2009 Mar;41(1):12-8. Epub 2009 Mar 31. [https://doi.org/10.4143/crt.2009.41.1.12 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc2699097/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19688066/ PubMed]
+#'''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://doi.org/10.1200/JCO.2009.25.4706 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20159816 PubMed] NCT00400179
+#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://doi.org/10.1200/JCO.2011.36.2236 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21844504 PubMed] NCT00548548
+#'''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://doi.org/10.1093/annonc/mdx275 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911091 PubMed] NCT01285557
+<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
+#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
+#'''BGB-A317-305:''' '''contains dosing details on CT.gov''' NCT03777657
+#'''KEYNOTE-859:''' '''contains dosing details on CT.gov''' NCT03675737
+==Cisplatin & Fluorouracil (CF) & Pembrolizumab==
+CF & Pembrolizumab: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, Pembrolizumab
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 60/440, 1 day of oral etoposide per cycle {{#subobject:47c27e|Variant=1}}===
+===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
-|2007-2012
+|rowspan=2|2015-2017
-| style="background-color:#1a9851" |Phase 3 (C)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]<br> 2. [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 12.5 vs 11.1 mo<br>(HR 0.85, 95% CI 0.70-1.03)
 |-
+|3. [[#Pembrolizumab_monotherapy|Pembrolizumab]]
+| style="background-color:#d3d3d3" |Not reported
 |}
+''KEYNOTE-062 included patients with GEJ malignancy''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+PD-L1 Combined Positive Score (CPS) of 1 or more as determined by an FDA-approved test
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2, then 100 mg PO twice per day on day 3
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''21-day cycle for up to 6 cycles'''
+====Immunotherapy====
-</div></div><br>
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
+'''21-day cycles'''
+</div></div>
+===References===
+<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
+#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
+==Cisplatin & S-1 {{#subobject:252c51|Regimen=1}}==
+CS: '''<u>C</u>'''isplatin & '''<u>S</u>'''-1
+<br>SP: '''<u>S</u>'''-1 & '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #4, 60/520, 2 days of oral etoposide per cycle {{#subobject:ae04e8|Variant=1}}===
+===Regimen variant #1, q3wk ("SP3") {{#subobject:4ff7cf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1093/annonc/mdv316 Ryu et al. 2015 (SOS)]
+|2009-2012
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]; SP5
+| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 5.5 vs 4.9 mo<br>(HR 0.82, 95% CI 0.68-0.99)
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ Seckl et al. 2017 (LUNGSTAR)]
+|[https://doi.org/10.1007/s10120-020-01101-4 Lee et al. 2020 (SOPP)]
-|2007-2012
+|2012-2014
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Pravastatin_99|CE & Pravastatin]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Pravastatin_99|EP & Pravastatin]]
+|[[#SOX_88|SOX]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#eeee01" |Non-inferior PFS
 |-
 |}
@@ Line 1,361: / Line 1,588: @@
 ====Chemotherapy====
 *[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 100 mg PO twice per day on days 2 & 3
+*[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-'''21-day cycle for up to 6 cycles'''
+'''21-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #5, 70/300 {{#subobject:5b9a41|Variant=1}}===
+===Regimen variant #2, q4wk {{#subobject:03b3c4|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.liebertpub.com/doi/abs/10.1089/107999099314180 Ruotsalainen et al. 1999]
+|[https://doi.org/10.1200/JCO.2009.25.4706 Ajani et al. 2010 (FLAGS)]
-|NR in abstract
+|2005-2007
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Interferon_alfa_99|EP & IFN-alpha]]
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
-| style="background-color:#ffffbf" |Did not meet endpoint of OS50%
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334001/ Kim et al. 2018 (CRCST-L-0001)]
+|[https://doi.org/10.1093/annonc/mdx275 Ajani et al. 2017 (DIGEST)]
-|2006-2011
+|2011-2014
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Irinotecan_.28IC.29_2|Cisplatin & Irinotecan]]
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+''Note: this is an experimental arm of a study where the primary endpoint was not met. Included because CS has been shown to be superior in comparison to other regimens (see above).''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Tegafur, gimeracil, oteracil (S-1)]] 25 mg/m<sup>2</sup> PO twice per day on days 1 to 21
-'''21-day cycle for up to 6 cycles'''
+'''28-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #6, 75/240, split cisplatin {{#subobject:8907be|Variant=1}}===
+===Regimen variant #3, q5wk ("SP5") {{#subobject:cdcc15|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1016/S1470-2045(08)70035-4 Koizumi et al. 2008 (SPIRITS)]
+|2002-2004
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#S-1_monotherapy_2|S-1]]
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 13 vs 11 mo<br>(HR 0.77, 95% CI 0.61-0.98)
+|-
+|[https://doi.org/10.1016/S1470-2045(15)00553-7 Fujitani et al. 2016 (REGATTA)]
+|2008-2013
+| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
+|-
+|[https://doi.org/10.1093/annonc/mdv316 Ryu et al. 2015 (SOS)]
+|2009-2012
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]; SP3
+| style="background-color:#fc8d59" |Seems to have inferior PFS
+|-
+|[https://doi.org/10.1093/annonc/mdu472 Yamada et al. 2014 (G-SOX)]
+|2010-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#SOX_88|SOX]]
+| style="background-color:#eeee01" |Non-inferior PFS
+|-
+|[https://doi.org/10.1200/JCO.2018.77.8613 Ishigami et al. 2018 (PHOENIX-GC)]
+|2011-2013
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Paclitaxel_.26_S-1|IV/IP Paclitaxel & S-1]]
+| style="background-color:#fee08b" |Might have inferior OS
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ Okamoto et al. 2007 (JCOG 9702)]
+|[https://doi.org/10.1016/s2468-1253(19)30083-4 Yamada et al. 2019 (JCOG1013)]
-|1998-2004
+|2012-2016
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]
+|[[#Cisplatin_.26_Docetaxel_.28DC.29_.26_S-1_99|Cisplatin, Docetaxel, S-1]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://doi.org/10.1016/s1470-2045(20)30315-6 Kang et al. 2020 (SOLAR)]
+|2015-2016
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Oxaliplatin_.26_TAS-118_77|Oxaliplatin & TAS-118]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |}
+''Note: in REGATTA, there was no difference in outcome amongst patients who did or did not undergo surgery.''
+''Inclusion criteria for REGATTA included the presence of a single non-curable factor (ex: hepatic, peritoneal, and para-aortic mets), see link for further details''
+''SPIRITS trial included patients with ECOG of 2 (3% of patients)''
+''Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*REGATTA: Non-laparoscopic [[Surgery#Gastrectomy|gastrectomy]] with D1 [[Surgery#Lymphadenectomy|lymphadenectomy]] versus [[Surgery#No_surgery|no surgery]]; chemotherapy began within 8 weeks of surgery
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 8
-*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
-'''21- to 28-day cycle for 4 cycles'''
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 21
-</div></div><br>
+**BSA at least 1.25 m<sup>2</sup> and less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 21
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 21
+'''35-day cycles'''
+</div></div>
+===References===
+#'''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://doi.org/10.1016/S1470-2045(08)70035-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18282805 PubMed] NCT00150670
+#'''FLAGS:''' Ajani JA, Rodriguez W, Bodoky G, Moiseyenko V, Lichinitser M, Gorbunova V, Vynnychenko I, Garin A, Lang I, Falcon S. Multicenter phase III comparison of cisplatin/S-1 with cisplatin/infusional fluorouracil in advanced gastric or gastroesophageal adenocarcinoma study: the FLAGS trial. J Clin Oncol. 2010 Mar 20;28(9):1547-53. Epub 2010 Feb 16. [https://doi.org/10.1200/JCO.2009.25.4706 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20159816 PubMed] NCT00400179
+#'''G-SOX:''' Yamada Y, Higuchi K, Nishikawa K, Gotoh M, Fuse N, Sugimoto N, Nishina T, Amagai K, Chin K, Niwa Y, Tsuji A, Imamura H, Tsuda M, Yasui H, Fujii H, Yamaguchi K, Yasui H, Hironaka S, Shimada K, Miwa H, Hamada C, Hyodo I. Phase III study comparing oxaliplatin plus S-1 with cisplatin plus S-1 in chemotherapy-naïve patients with advanced gastric cancer. Ann Oncol. 2015 Jan;26(1):141-8. Epub 2014 Oct 14. [https://doi.org/10.1093/annonc/mdu472 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25316259 PubMed] JapicCTI-101021
+#'''SOS:''' Ryu MH, Baba E, Lee KH, Park YI, Boku N, Hyodo I, Nam BH, Esaki T, Yoo C, Ryoo BY, Song EK, Cho SH, Kang WK, Yang SH, Zang DY, Shin DB, Park SR, Shinozaki K, Takano T, Kang YK; SOS study investigators. Comparison of two different S-1 plus cisplatin dosing schedules as first-line chemotherapy for metastatic and/or recurrent gastric cancer: a multicenter, randomized phase III trial (SOS). Ann Oncol. 2015 Oct;26(10):2097-101. Epub 2015 Jul 27. [https://doi.org/10.1093/annonc/mdv316 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/26216386 PubMed] NCT00915382
+#'''REGATTA:''' Fujitani K, Yang HK, Mizusawa J, Kim YW, Terashima M, Han SU, Iwasaki Y, Hyung WJ, Takagane A, Park DJ, Yoshikawa T, Hahn S, Nakamura K, Park CH, Kurokawa Y, Bang YJ, Park BJ, Sasako M, Tsujinaka T; REGATTA study investigators. Gastrectomy plus chemotherapy versus chemotherapy alone for advanced gastric cancer with a single non-curable factor (REGATTA): a phase 3, randomised controlled trial. Lancet Oncol. 2016 Mar;17(3):309-18. Epub 2016 Jan 26. [https://doi.org/10.1016/S1470-2045(15)00553-7 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/26822397 PubMed] UMIN000001012
+#'''DIGEST:''' Ajani JA, Abramov M, Bondarenko I, Shparyk Y, Gorbunova V, Hontsa A, Otchenash N, Alsina M, Lazarev S, Feliu J, Elme A, Esko V, Abdalla K, Verma U, Benedetti F, Aoyama T, Mizuguchi H, Makris L, Rosati G; DIGEST Study Group. A phase III trial comparing oral S-1/cisplatin and intravenous 5-fluorouracil/cisplatin in patients with untreated diffuse gastric cancer. Ann Oncol. 2017 Sep 1;28(9):2142-2148. [https://doi.org/10.1093/annonc/mdx275 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28911091 PubMed] NCT01285557
+#'''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.77.8613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29746229 PubMed] UMIN000005930
+#'''JCOG1013:''' Yamada Y, Boku N, Mizusawa J, Iwasa S, Kadowaki S, Nakayama N, Azuma M, Sakamoto T, Shitara K, Tamura T, Chin K, Hata H, Nakamori M, Hara H, Yasui H, Katayama H, Fukuda H, Yoshikawa T, Sasako M, Terashima M. Docetaxel plus cisplatin and S-1 versus cisplatin and S-1 in patients with advanced gastric cancer (JCOG1013): an open-label, phase 3, randomised controlled trial. Lancet Gastroenterol Hepatol. 2019 Jul;4(7):501-510. Epub 2019 May 14. [https://doi.org/10.1016/s2468-1253(19)30083-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/31101534 PubMed] UMIN000007652
+#'''SOPP:''' Lee KW, Chung IJ, Ryu MH, Park YI, Nam BH, Oh HS, Lee KH, Han HS, Seo BG, Jo JC, Lee HR, Kim JW, Park SR, Cho SH, Kang YK; SOPP study investigators. Multicenter phase III trial of S-1 and cisplatin versus S-1 and oxaliplatin combination chemotherapy for first-line treatment of advanced gastric cancer (SOPP trial). Gastric Cancer. 2021 Jan;24(1):156-167. Epub 2020 Jun 28. [https://doi.org/10.1007/s10120-020-01101-4 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32596783/ PubMed] NCT01671449
+#'''SOLAR:''' Kang YK, Chin K, Chung HC, Kadowaki S, Oh SC, Nakayama N, Lee KW, Hara H, Chung IJ, Tsuda M, Park SH, Hosaka H, Hironaka S, Miyata Y, Ryu MH, Baba H, Hyodo I, Bang YJ, Boku N. S-1 plus leucovorin and oxaliplatin versus S-1 plus cisplatin as first-line therapy in patients with advanced gastric cancer (SOLAR): a randomised, open-label, phase 3 trial. Lancet Oncol. 2020 Aug;21(8):1045-1056. Epub 2020 Jul 16. [https://doi.org/10.1016/s1470-2045(20)30315-6 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32682457 PubMed] NCT02322593
+==CLF {{#subobject:b913d6|Regimen=1}}==
+CLF: '''<u>C</u>'''isplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
+<br>FLP: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #7, 75/300 {{#subobject:da2da4|Variant=1}}===
+===Regimen variant #1 {{#subobject:beef19|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.clinical-lung-cancer.com/article/S1525-7304(11)70409-0/pdf Ignatiadis et al. 2005]
+|[https://doi.org/10.1200/jco.2007.13.9378 Al-Batran et al. 2008]
-|2000-2003
+|2003-2006
-|style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Etoposide_.28EP.29.2FTopotecan_monotherapy_99|EP/Topotecan]]
+|[[#OLF|FLO]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#fee08b" |Might have inferior PFS
-|-
-|rowspan=2|[https://www.jto.org/article/S1556-0864(15)32944-0 Fink et al. 2012 (GSK 104864-A/479)]
-|rowspan=2|2002-2006
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Cisplatin_.26_Topotecan_88|Cisplatin & Topotecan]]
-| style="background-color:#eeee01" |Non-inferior OS
-|-
-|2. [[#Etoposide_.26_Topotecan_99|Etoposide & Topotecan]]
-| style="background-color:#d3d3d3" |Not reported
-|-
-|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
-|2007-2008
-| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab|EP & Bevacizumab]]
-| style="background-color:#fc8d59" |Seems to have inferior PFS
-|-
-|[https://doi.org/10.1200/JCO.2016.67.6601 Reck et al. 2016 (CA184-156)]
-|2012-2014
-|style="background-color:#1a9851" |Phase 3 (C)
-|[[Stub#EP_.26_Ipilimumab|EP & Ipilimumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ Rudin et al. 2020 (KEYNOTE-604)]
-|2017-2018
-|style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Small_cell_lung_cancer_-_historical#Carboplatin_.26_Etoposide_.28CE.29_.26_Pembrolizumab|CE & Pembrolizumab]]<br> 2. [[Small_cell_lung_cancer_-_historical#Cisplatin_.26_Etoposide_.28EP.29_.26_Pembrolizumab|EP & Pembrolizumab]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Note: In contrast to the original reference, some guidelines list 5-FU as being given every 2 weeks rather than the schedule below.''
+''Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric'').
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
-'''21-day cycle for 4 (SALUTE & KEYNOTE-604) or 6 (GSK 104864-A/479 & CA184-156) cycles'''
+*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m<sup>2</sup>)
+====Supportive therapy====
+*Up to 3 liters [[normal saline]] as hydration with cisplatin
+*[[Category:Emesis prevention|Antiemetic medications]] per "local protocols"
+'''8-week cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #8, 75/300, split cisplatin {{#subobject:a51a22|Variant=1}}===
+===Regimen variant #2 {{#subobject:34890|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.1985.3.11.1471 Evans et al. 1985]
+|[https://doi.org/10.1200/jco.2004.01.140 Bouché et al. 2004 (FFCD 9803)]
-|1981-1984
+|1999-2001
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
-| style="background-color:#d3d3d3" |
+|1. [[#FULV_2|LV5FU2]]<br> 2. [[#FOLFIRI|LV5FU2 & Irinotecan]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |Not powered to draw conclusions
-|-
-|[https://doi.org/10.1200/JCO.2016.69.4844 Tiseo et al. 2017 (GOIRC-AIFA FARM6PMFJM)]
-|2009-2015
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab_99|EP & Bevacizumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''Note: in Evans et al. 1985, patients with disease responding to therapy received prophylactic cranial irradiation, 4 Gy fractions given daily x 5 fractions (total dose: 20 Gy) over 5 days between cycles 3 and 4; Locoregional radiation therapy was only used if symptoms persisted after 6 cycles of treatment: Radiation therapy, 250 cGy/rad fractions x 10 fractions (total dose: 2500 cGy/rad), given after cycle 6 of chemotherapy.''
+''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV slow push once per day on days 1 to 3, '''given second'''
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on either day 1 or 2
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV over at least 30 minutes once per day on days 1 to 3, '''given first'''
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup> IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m<sup>2</sup>)
 ====Supportive therapy====
-*[[Dexamethasone (Decadron)]] 10 mg IV once per day on days 1 to 3, prior to chemotherapy
+*1 liter [[:Category:Hydration|hydration]] over 3 hours before and after [[Cisplatin (Platinol)]]
-*[[Metoclopramide (Reglan)]] 10 mg IV or PO once per day on days 1 to 3, prior to chemotherapy
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] IV before [[Cisplatin (Platinol)]]
-*[[Prochlorperazine (Compazine)]] 10 mg IM or PO once per day on days 1 to 3, prior to chemotherapy
+*[[Methylprednisolone (Solumedrol)]] 120 mg IV 10 minutes before [[Cisplatin (Platinol)]]
-*"No special efforts were made to hydrate the patients," though PO fluid intake was encouraged, and 500 mL normal saline was given with etoposide infusion.
+*Oral [[Category:Emesis prevention|antiemetics]] and [[Category:Steroids|corticosteroids]] from days 2 to 5
-'''21- to 28-day cycle for up to 6 cycles'''
+'''14-day cycle for at least 4 cycles'''
-</div></div><br>
+</div></div>
+===References===
+#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [https://doi.org/10.1200/jco.2004.01.140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15514373 PubMed]
+#Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [https://doi.org/10.1200/jco.2007.13.9378 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18349393 PubMed]
+==DCF {{#subobject:efbdc5|Regimen=1}}==
+DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>TCF: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #9, 75/390, split cisplatin {{#subobject:3ed519|Variant=1}}===
+===Regimen variant #1 {{#subobject:5aba07|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2005.17.376 Ajani et al. 2005 (V-325)]
+|1998-1999
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|[[#Cisplatin_.26_Docetaxel_.28DC.29|DC]]
+| style="background-color:#91cf60" |Seems to have superior ORR
 |-
-|[https://doi.org/10.1200/JCO.1995.13.8.1871 Miller et al. 1995]
+|[https://doi.org/10.1200/jco.2006.06.8429 Van Cutsem et al. 2006 (TAX 325)]
-|1990-1993
+|1999-2003
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; oral etoposide
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#91cf60" |Seems to have superior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Note: In contrast to the original references, some guidelines list each cycle as lasting 28 days.''
+''Anjani et al. Patients: 100% adenocarcinoma histology (32% gastroesophageal junction/fundus and 68% gastric antrum/body). 95% were metastatic. 1% with Karnofsky PS score of 70.''
+''Van Cutsem et al Patients: 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS score of 70.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Etoposide (Vepesid)]] 130 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
-'''21-day cycle for 8 cycles'''
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3750 mg/m<sup>2</sup>)
+====Supportive therapy====
+*(varied depending on reference):
+*[[Dexamethasone (Decadron)]] 8 mg PO once the night before chemotherapy, then 8 mg PO once on day 1; 1 hour prior to chemotherapy, then 8 mg PO twice per day until day 2 (total dose per cycle: 48 mg)
+*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
+*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
+*"[[:Category:Hydration|Hydration]] (was) administered in a standard manner"
+'''21-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #10, 75/700, 3 days of oral etoposide per cycle {{#subobject:807314|Variant=1}}===
+===Regimen variant #2 {{#subobject:baa015|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1200/jco.2006.08.0135 Roth et al. 2007]
+| rowspan="2" |1999-2003
+| rowspan="2" style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|1. [[#ECF_3|ECF]]
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[https://doi.org/10.1200/jco.2002.12.111 Sundstrøm et al. 2002]
+|2. [[#Cisplatin_.26_Docetaxel_.28DC.29|TC]]
-|1989-1994
+| style="background-color:#d9ef8b" |Might have superior ORR
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[Small_cell_lung_cancer_-_historical#CEV_.28Cyclophosphamide.2FEpirubicin.29|CEV]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''Note: Patients in Sundstrøm et al. 2002 with extensive stage disease did not routinely receive radiation therapy. "However, chest or cranial irradiation was optional if severe symptoms could not be palliated by chemotherapy." Oral etoposide to be taken on an empty stomach.''
+''Note: the protocol was amended to change the original dose of ''docetaxel from'' 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once on day 1, then 200 mg/m<sup>2</sup> PO once per day on days 2 to 4
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
+*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion over 14 days, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>)
 ====Supportive therapy====
-*"Standard prehydration and posthydration procedures were followed in conjunction with cisplatin administration."
+*3 liters per day [[:Category:Hydration|"hyperhydration"]]
-'''21-day cycle for up to 5 cycles'''
+*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO twice per day for 4 days after [[Docetaxel (Taxotere)]]
-</div></div><br>
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
+*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
+'''21-day cycle for up to 8 cycles'''
+</div></div>
+===References===
+#'''V-325:''' Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [https://doi.org/10.1200/jco.2005.17.376 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16110025 PubMed]
+#'''TAX 325:''' Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [https://doi.org/10.1200/jco.2006.06.8429 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17075117 PubMed]
+#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [https://doi.org/10.1200/jco.2006.08.0135 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17664469 PubMed]
+==mDCF {{#subobject:70e20f|Regimen=1}}==
+mDCF: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #11, 80/240 {{#subobject:7b3c2e|Variant=1}}===
+===Regimen variant #1, 40/40/2800 {{#subobject:372f9c|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[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/PMC3646322/ Shah et al. 2010 (MSK 06-096)]
+|2006-2008
+| style="background-color:#91cf61" |Phase 2
 |-
-|[https://doi.org/10.1200/jco.1994.12.10.2022 Ihde et al. 1994]
+|}
-|1983-1991
+''Note: In contrast to the primary reference, some guidelines list this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab.''
-| style="background-color:#1a9851" |Phase 3 (C)
+''Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.''
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]; high-dose
+====Chemotherapy====
-| style="background-color:#ffffbf" |Did not meet primary endpoint of CR rate
+*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 3
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+====Supportive therapy====
+*"Standard premedication and delayed emesis regimens"
+'''14-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, 60/60/3000, 4-day 5-FU infusion {{#subobject:323b13|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2005.09.071 Niell et al. 2005 (CALGB 9732)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ Wang et al. 2015 (DOCET L 02195)]
-|1998-2001
+|2008-2010
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_.26_Paclitaxel_99|PET]]
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
-| style="background-color:#ffffbf" |Did not meet endpoints of FFS50%/OS50%
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 10.2 vs 8.5 mo<br>(HR 0.71, 95% CI 0.52-0.97)
 |-
 |}
-''Note: Concurrent radiation therapy with the start of chemotherapy was given to patients with brain metastases, epidural metastases, and impending pathologic bone fractures.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-====Supportive therapy====
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 3000 mg/m<sup>2</sup>)
-*"Half-normal saline was infused for 2 to 6 hours with [[Cisplatin (Platinol)]], usually in conjunction with a diuretic."
+'''21-day cycles'''
-*Corticosteroids were usually given for patients receiving radiation therapy for brain and epidural metastases.
-'''21-day cycle for 4 to 8 cycles'''
-====CNS therapy====
-*Patients with carcinomatous meningitis received [[Methotrexate (MTX)]] IT (dose/schedule not specified) and radiation to functionally compromised areas of the CNS
-</div>
-<div class="toccolours" style="background-color:#cbd5e7">
-====Subsequent treatment====
-*Ihde et al. 1994, CR after 4 cycles: an additional 4 cycles. Some patients were randomized to receive prophylactic cranial irradiation. Radiation could also be given at the patient's request. No details about dose/schedule given.
-*Ihde et al. 1994, PR, no response, or progressive disease: Salvage [[Small_cell_lung_cancer_-_historical#CAV_3|CAV]] or "an individualized 3-drug in vitro-selected regimen (IVSR) during cycles 5 to 8 if drug-sensitivity testing data were available."
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #12, 80/300 {{#subobject:26b7f1|Variant=1}}===
+===Regimen variant #3, 60/60/3000, 5-day 5-FU infusion {{#subobject:323bug|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-| rowspan="2" |[https://academic.oup.com/jnci/article-abstract/83/12/855/956642 Fukuoka et al. 1991 (JCOG8502)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ Wang et al. 2015 (DOCET L 02195)]
-|rowspan=2|1985-1988
+|2008-2010
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]
-| style="background-color:#d3d3d3" |Not reported
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 10.2 vs 8.5 mo<br>(HR 0.71, 95% CI 0.52-0.97)
 |-
-|2. [[Small_cell_lung_cancer_-_historical#CAV.2FPE|CAV/PE]]
+|}
-| style="background-color:#fee08b" |Might have inferior OS
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup>/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3000 mg/m<sup>2</sup>)
+'''21-day cycles'''
+</div></div>
+===References===
+#'''MSK 06-096:''' Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [https://doi.org/10.1200/jco.2010.32.0770 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21189380 PubMed] NCT00390416
+#'''DOCET L 02195:''' Wang J, Xu R, Li J, Bai Y, Liu T, Jiao S, Dai G, Xu J, Liu Y, Fan N, Shu Y, Ba Y, Ma D, Qin S, Zheng L, Chen W, Shen L. Randomized multicenter phase III study of a modified docetaxel and cisplatin plus fluorouracil regimen compared with cisplatin and fluorouracil as first-line therapy for advanced or locally recurrent gastric cancer. Gastric Cancer. 2016 Jan;19(1):234-44. Epub 2015 Jan 21. [https://doi.org/10.1007/s10120-015-0457-4 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4688303/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25604851 PubMed] NCT00811447
+==mDCF & Bevacizumab {{#subobject:30ea9e|Regimen=1}}==
+mDCF & Bevacizumab: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil & Bevacizumab
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:5485f9|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.karger.com/Article/Abstract/227087 Miyamoto et al. 1992]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ Shah et al. 2010 (MSK 06-096)]
-|NR in abstract
+|2006-2008
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#91cf61" |Phase 2
-|[[Stub#PEI|PEI]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://doi.org/10.1056/NEJMoa003034 Noda et al. 2002 (JCOG 9511)]
+|}
-|1995-1998
+''Patients: 100% adenocarcinoma (50% gastric, 45% gastroesophageal junction, 5% esophagus). 93% received no prior therapy.''
-| style="background-color:#1a9851" |Phase 3 (C)
+====Chemotherapy====
-|[[#Cisplatin_.26_Irinotecan_.28IC.29_2|IP]]
+*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 60 minutes once on day 1
-| style="background-color:#d73027" |Inferior OS
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 3
-|-
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
-|[https://doi.org/10.1200/JCO.2005.03.3332 Eckardt et al. 2006 (GSK 104864-A/389)]
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 48 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
-|2001-2003
+====Targeted therapy====
-| style="background-color:#1a9851" |Phase 3 (C)
+*[[Bevacizumab (Avastin)]] 10 mg/kg IV once on day 1
-|[[#Cisplatin_.26_Topotecan_88|Cisplatin & Topotecan]]
+====Supportive therapy====
-| style="background-color:#eeee01" |Non-inferior OS
+*"Standard premedication and delayed emesis regimens"
+'''14-day cycles'''
+</div></div>
+===References===
+#'''MSK 06-096:''' Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [https://doi.org/10.1200/jco.2010.32.0770 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3646322/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/21189380 PubMed] NCT00390416
+==Docetaxel & S-1 {{#subobject:a22c2a|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:82ca03|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ Lara et al. 2009 (SWOG S0124)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ Koizumi et al. 2013 (START<sub>gastric</sub>)]
-|2002-2007
+|2005-2008
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[#Cisplatin_.26_Irinotecan_.28IC.29_2|IP]]
+|[[#S-1_monotherapy_2|S-1]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 12.5 vs 10.8 mo<br>(HR 0.84, 95% CI 0.71-0.99)
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV once on day 1
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
+**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 14
+'''21-day cycles'''
+</div></div>
+===References===
+#'''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO; KCSG. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://doi.org/10.1007/s00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24366758 PubMed] NCT00287768
+==ECF {{#subobject:6325cb|Regimen=1}}==
+ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:e5ede0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://ar.iiarjournals.org/content/30/7/3031.long Baka et al. 2010]
+|[https://doi.org/10.1093/oxfordjournals.annonc.a058932 Findlay et al. 1994]
-|2002-2006
+|1988-1992
-| style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#91cf61" |Phase 2
-|[[#Cisplatin_.26_Etoposide_.28EP.29.2FTopotecan_monotherapy_99|EP/T]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1093/annonc/mdq036 Zatloukal et al. 2010]
-|2003-2007
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Irinotecan_.28IC.29_2|IP]]
-| style="background-color:#eeee01" |Non-inferior OS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ Ready et al. 2015 (CALGB 30504)]
-|2007-2011
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
 | style="background-color:#d3d3d3" |
 | style="background-color:#d3d3d3" |
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826513/ Sun et al. 2016 (D0750018)]
+|[https://doi.org/10.1200/JCO.1997.15.1.261 Webb et al. 1997]
-|2008-2010
+|1992-1995
+| style="background-color:#1a9851" |Randomized (E-switch-ic)
+|[[Gastric_cancer_-_historical#FAMTX|FAMTX]]
+| style="background-color:#1a9850" |Superior OS
+|-
+|[https://doi.org/10.1200/jco.2002.08.105 Ross et al. 2002]
+|1995-1998
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Amrubicin_.26_Cisplatin_88|Amrubicin & Cisplatin]]
+|[[#MCF|MCF]]
-| style="background-color:#fee08b" |Might have inferior OS
+| style="background-color:#eeee01" |Seems to have non-inferior OS
+|-
+|[https://doi.org/10.1200/jco.2006.08.0135 Roth et al. 2007]
+|1999-2003
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
+|1. [[#Cisplatin_.26_Docetaxel_.28DC.29|TC]]<br> 2. [[#DCF|TCF]]
+| style="background-color:#d3d3d3" |Not reported
+|-
+| rowspan="3" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+| rowspan="3" |2000-2005
+| rowspan="3" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#ECX_2|ECX]]
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|2. [[#EOF_2|EOF]]
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|3. [[#EOX_2|EOX]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Findlay et al. Patients: all metastatic gastric cancer''
+''Ross et al. Patients: adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma histology, all advanced esophagogastric cancer.''
+''Roth et al.  Patients: all metastatic gastric cancer''
+''REAL-2 Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
-**JCOG8502 & Miyamoto et al. 1992 gave etoposide on days 1, 3, 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>)
 ====Supportive therapy====
-*"Hydration and administration of antiemetic drugs."
+*(varied depending on reference):
-'''21-day cycle for 4 to 6 cycles'''
+*3 liters per day [[:Category:Hydration|"hyperhydration"]]
-</div>
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
-<div class="toccolours" style="background-color:#cbd5e7">
+*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-====Subsequent treatment====
+*Ross et al. 2002 & Cunningham et al. 2008 used [[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-*Baka et al. 2010: [[#Topotecan_monotherapy_88|Topotecan]] x 4
+'''21-day cycle for up to 8 cycles'''
-*CALGB 30504, SD or better: [[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]] versus [[#Sunitinib_monotherapy|sunitinib]] maintenance
+</div></div>
-</div></div><br>
+===References===
+#Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, Carter R, Hill A. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. [https://doi.org/10.1093/oxfordjournals.annonc.a058932 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7993836 PubMed]
+#Webb A, Cunningham D, Scarffe JH, Harper P, Norman A, Joffe JK, Hughes M, Mansi J, Findlay M, Hill A, Oates J, Nicolson M, Hickish T, O'Brien M, Iveson T, Watson M, Underhill C, Wardley A, Meehan M. Randomized trial comparing epirubicin, cisplatin, and fluorouracil versus fluorouracil, doxorubicin, and methotrexate in advanced esophagogastric cancer. J Clin Oncol. 1997 Jan;15(1):261-7. [https://doi.org/10.1200/JCO.1997.15.1.261 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/8996151 PubMed]
+##'''Update:''' Waters JS, Norman A, Cunningham D, Scarffe JH, Webb A, Harper P, Joffe JK, Mackean M, Mansi J, Leahy M, Hill A, Oates J, Rao S, Nicolson M, Hickish T. Long-term survival after epirubicin, cisplatin and fluorouracil for gastric cancer: results of a randomized trial. Br J Cancer. 1999 Apr;80(1-2):269-72. [https://www.nature.com/articles/6690350 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2363002/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/10390007 PubMed]
+#Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. [https://doi.org/10.1200/jco.2002.08.105 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11956258 PubMed]
+#Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [https://doi.org/10.1200/jco.2006.08.0135 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17664469 PubMed]
+#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] ISRCTN51678883
+==ECX {{#subobject:36cac7|Regimen=1}}==
+ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+<br>ECC: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>C</u>'''apecitabine
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #13, 80/400, split cisplatin {{#subobject:d389d3|Variant=1}}===
+===Regimen variant #1, continuous capecitabine {{#subobject:f0efc0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.1995.13.10.2594 Loehrer et al. 1995]
+| rowspan="2" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
-|1989-1993
+|rowspan=2|2000-2005
-| style="background-color:#1a9851" |Phase 3 (C)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[Small_cell_lung_cancer_-_historical#VIP|VIP]]
+|1. [[#ECF_2|ECF]]
-| style="background-color:#fc8d59" |Seems to have inferior OS
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|2. [[#EOF_2|EOF]]<br> 3. [[#EOX_2|EOX]]
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|[https://doi.org/10.1016/S1470-2045(17)30566-1 Catenacci et al. 2017 (RILOMET-1)]
+|2012-2014
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
+|[[#ECX_.26_Rilotumumab_77|ECX & Rilotumumab]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 10.7 vs 8.8 mo<br>(HR 0.75, 95% CI 0.61-0.91)
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
+''RILOMET-1 patients had unresectable or metastatic MET-positive gastric or gastro-esophageal junction cancer.''
+''RILOMET-1 patients: ~80% gastric, 20% GE junction and 10% distal esophageal''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 4
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 4
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for 4 cycles'''
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day
+'''21-day cycle for up to 10 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #14, 80/600, 2 days of oral etoposide per cycle {{#subobject:998892|Variant=1}}===
+===Regimen variant #2, intermittent capecitabine {{#subobject:f0efc0|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/PMC2527803/ Baka et al. 2008]
+|[https://www.ejcancer.com/article/S0959-8049(10)00731-8 Konings et al. 2010]
-|1999-2005
+|2005-2009
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|[[Small_cell_lung_cancer_-_historical#ACE|ACE]]
+|[[#ECX_.26_Pravastatin_99|ECC & Pravastatin]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS12
+| style="background-color:#ffffbf" |Did not meet primary endpoint of PFS6
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Patients: 6.6% of  patients had an ECOG of 2''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1, '''given first'''
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once on day 1, then 240 mg/m<sup>2</sup>/day PO on days 2 & 3
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given second'''
-'''21-day cycle for 6 cycles'''
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-</div></div><br>
+'''21-day cycle for up to 6 cycles'''
+</div></div>
+===References===
+#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] ISRCTN51678883
+#Konings IR, van der Gaast A, van der Wijk LJ, de Jongh FE, Eskens FA, Sleijfer S. The addition of pravastatin to chemotherapy in advanced gastric carcinoma: a randomised phase II trial. Eur J Cancer. 2010 Dec;46(18):3200-4. Epub 2010 Aug 18. [https://www.ejcancer.com/article/S0959-8049(10)00731-8 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20727735 PubMed]
+#'''RILOMET-1:''' Catenacci DVT, Tebbutt NC, Davidenko I, Murad AM, Al-Batran SE, Ilson DH, Tjulandin S, Gotovkin E, Karaszewska B, Bondarenko I, Tejani MA, Udrea AA, Tehfe M, De Vita F, Turkington C, Tang R, Ang A, Zhang Y, Hoang T, Sidhu R, Cunningham D. Rilotumumab plus epirubicin, cisplatin, and capecitabine as first-line therapy in advanced MET-positive gastric or gastro-oesophageal junction cancer (RILOMET-1): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Nov;18(11):1467-1482. Epub 2017 Sep 25. [https://doi.org/10.1016/S1470-2045(17)30566-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28958504 PubMed] NCT01697072
+==EOF {{#subobject:a6390c|Regimen=1}}==
+EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #15, 100/300 {{#subobject:5b54c7|Variant=1}}===
+===Regimen {{#subobject:abf19f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 1,717: / Line 2,113: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.clinical-lung-cancer.com/article/S1525-7304(11)70217-0/pdf Artal-Cortés et al. 2004]
+| rowspan="2" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
-|1994-1998
+|rowspan=2|2000-2005
-| style="background-color:#1a9851" |Phase 3 (C)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Epirubicin_99|Cisplatin & Epirubicin]]
+|1. [[#ECF_2|ECF]]<br> 2. [[#ECX_2|ECX]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#eeee01" |Non-inferior OS
 |-
-|[https://academic.oup.com/jnci/article/93/4/300/2906465 Pujol et al. 2001 (FNCLCC 95012)]
+|3. [[#EOX_2|EOX]]
-|1996-1999
+| style="background-color:#eeee01" |Non-inferior OS
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer_-_historical#PCDE|PCDE]]
-| style="background-color:#d73027" |Inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 2
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''21-day cycle for 6 cycles'''
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m<sup>2</sup>)
-</div></div><br>
+====Supportive therapy====
+*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
+'''21-day cycle for up to 8 cycles'''
+</div></div>
+===References===
+#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] ISRCTN51678883
+==EOX {{#subobject:438182|Regimen=1}}==
+EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
+<br>EOC: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>C</u>'''apecitabine
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #16, 100/400, split cisplatin {{#subobject:f8e87a|Variant=1}}===
+===Regimen variant #1 {{#subobject:339609|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 1,745: / Line 2,146: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.1992.10.2.282 Roth et al. 1992]
+| rowspan="3" |[https://doi.org/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
-|1985-1989
+|rowspan=3|2000-2005
+| rowspan="3" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|1. [[#ECF_2|ECF]]
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 11.2 vs 9.9 mo<br>(HR 0.80, 95% CI 0.66-0.97)
+|-
+|2. [[#ECX_2|ECX]]
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|3. [[#EOF_2|EOF]]
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ Waddell et al. 2013 (REAL3)]
+|2008-2011
 | style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]<br> 2. [[Small_cell_lung_cancer_-_historical#CAV.2FPE|CAV/PE]]
+|[[#mEOC.2BP_99|mEOC+P]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 11.3 vs 8.3 mo<br>(HR 0.73, 95% CI 0.57-0.93)
-|-
-|[https://doi.org/10.1200/jco.1995.13.6.1436 Hainsworth et al. 1995]
-|1992-1993
-| style="background-color:#1a9851" |Randomized Phase 2 (E-RT-switch-ic)
-|[[#Cisplatin_.26_Etoposide_phosphate_88|Cisplatin & Etoposide phosphate]]
-| style="background-color:#d3d3d3" |Not compared
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''REAL-2 patients: 35% esophageal, 25% gastroesophageal junction, 40% gastric. 11% ECOG PS of 2.''
+''REAL3 patients: 99% adenocarcinoma, 1% undifferentiated histology. 39% esophagus, 31% ''gastroesophageal'' junction, 30% gastric. 6% ECOF PS of 2. 89% metastatic disease.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''21-day cycle for 4 cycles'''
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO twice per day on days 1 to 21
-</div></div>
+'''21-day cycle for up to 8 cycles'''
-===References===
+</div></div><br>
-# Evans WK, Shepherd FA, Feld R, Osoba D, Dang P, Deboer G. VP-16 and cisplatin as first-line therapy for small-cell lung cancer. J Clin Oncol. 1985 Nov;3(11):1471-7. [https://doi.org/10.1200/jco.1985.3.11.1471 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2997406 PubMed]
-# '''JCOG8502:''' Fukuoka M, Furuse K, Saijo N, Nishiwaki Y, Ikegami H, Tamura T, Shimoyama M, Suemasu K. Randomized trial of cyclophosphamide, doxorubicin, and vincristine versus cisplatin and etoposide versus alternation of these regimens in small-cell lung cancer. J Natl Cancer Inst. 1991 Jun 19;83(12):855-61. [https://academic.oup.com/jnci/article-abstract/83/12/855/956642 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1648142 PubMed]
-# Miyamoto H, Nakabayashi T, Isobe H, Akita H, Kawakami Y, Arimoto T, Asakawa M, Suzuki A, Fujikane T, Shimizu T, Sakai E. A phase III comparison of etoposide/cisplatin with or without added ifosfamide in small-cell lung cancer. Oncology. 1992;49(6):431-5. [https://www.karger.com/Article/Abstract/227087 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/1334539 PubMed]
-# Roth BJ, Johnson DH, Einhorn LH, Schacter LP, Cherng NC, Cohen HJ, Crawford J, Randolph JA, Goodlow JL, Broun GO, Omura GA, Greco FA; Southeastern Cancer Study Group. Randomized study of cyclophosphamide, doxorubicin, and vincristine versus etoposide and cisplatin versus alternation of these two regimens in extensive small-cell lung cancer: a phase III trial of the Southeastern Cancer Study Group. J Clin Oncol. 1992 Feb;10(2):282-91. [https://doi.org/10.1200/JCO.1992.10.2.282 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1310103 PubMed]
-# Ihde DC, Mulshine JL, Kramer BS, Steinberg SM, Linnoila RI, Gazdar AF, Edison M, Phelps RM, Lesar M, Phares JC, Grayson J, Minna JD, Johnson BE. Prospective randomized comparison of high-dose and standard-dose etoposide and cisplatin chemotherapy in patients with extensive-stage small-cell lung cancer. J Clin Oncol. 1994 Oct;12(10):2022-34. [https://doi.org/10.1200/jco.1994.12.10.2022 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7931470 PubMed]
-# Hainsworth JD, Levitan N, Wampler GL, Belani CP, Seyedsadr MS, Randolph J, Schacter LP, Greco FA. Phase II randomized study of cisplatin plus etoposide phosphate or etoposide in the treatment of small-cell lung cancer. J Clin Oncol. 1995 Jun;13(6):1436-42. [https://doi.org/10.1200/jco.1995.13.6.1436 link to original article] [https://pubmed.ncbi.nlm.nih.gov/7751890 PubMed]
-# Miller AA, Herndon JE 2nd, Hollis DR, Ellerton J, Langleben A, Richards F 2nd, Green MR; [[Study_Groups#CALGB|CALGB]]. Schedule dependency of 21-day oral versus 3-day intravenous etoposide in combination with intravenous cisplatin in extensive-stage small-cell lung cancer: a randomized phase III study of the Cancer and Leukemia Group B. J Clin Oncol. 1995 Aug;13(8):1871-9. [https://doi.org/10.1200/JCO.1995.13.8.1871 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7636529 PubMed]
-# Loehrer PJ Sr, Ansari R, Gonin R, Monaco F, Fisher W, Sandler A, Einhorn LH; Hoosier Oncology Group. Cisplatin plus etoposide with and without ifosfamide in extensive small-cell lung cancer: a Hoosier Oncology Group study. J Clin Oncol. 1995 Oct;13(10):2594-9. [https://doi.org/10.1200/JCO.1995.13.10.2594 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/7595712 PubMed]
-# Ruotsalainen TM, Halme M, Tamminen K, Szopinski J, Niiranen A, Pyrhönen S, Riska H, Maasilta P, Jekunen A, Mäntylä M, Kajanti M, Joensuu H, Sarna S, Cantell K, Mattson K. Concomitant chemotherapy and IFN-alpha for small cell lung cancer: a randomized multicenter phase III study. J Interferon Cytokine Res. 1999 Mar;19(3):253-9. [https://www.liebertpub.com/doi/abs/10.1089/107999099314180 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10213464 PubMed]
-# '''FNCLCC 95012:''' Pujol JL, Daurès JP, Rivière A, Quoix E, Westeel V, Quantin X, Breton JL, Lemarié E, Poudenx M, Milleron B, Moro D, Debieuvre D, Le Chevalier T. Etoposide plus cisplatin with or without the combination of 4'-epidoxorubicin plus cyclophosphamide in treatment of extensive small-cell lung cancer: a French Federation of Cancer Institutes multicenter phase III randomized study. J Natl Cancer Inst. 2001 Feb 21;93(4):300-8. [https://academic.oup.com/jnci/article/93/4/300/2906465 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/11181777 PubMed] NCT00003606
-# '''JCOG 9511:''' Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; [[Study_Groups#JCOG|JCOG]]. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. [https://doi.org/10.1056/NEJMoa003034 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11784874 PubMed]
-# Sundstrøm S, Bremnes RM, Kaasa S, Aasebø U, Hatlevoll R, Dahle R, Boye N, Wang M, Vigander T, Vilsvik J, Skovlund E, Hannisdal E, Aamdal S; Norwegian Lung Cancer Study Group. Cisplatin and etoposide regimen is superior to cyclophosphamide, epirubicin, and vincristine regimen in small-cell lung cancer: results from a randomized phase III trial with 5 years' follow-up. J Clin Oncol. 2002 Dec 15;20(24):4665-72. [https://doi.org/10.1200/jco.2002.12.111 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12488411 PubMed]
-# Artal-Cortés A, Gomez-Codina J, Gonzalez-Larriba JL, Barneto I, Carrato A, Isla D, Camps C, Garcia-Giron C, Font A, Meana A, Lomas M, Vadell C, Arrivi A, Alonso C, Maestu I, Campbell J, Rosell R. Prospective randomized phase III trial of etoposide/cisplatin versus high-dose epirubicin/cisplatin in small-cell lung cancer. Clin Lung Cancer. 2004 Nov;6(3):175-83. [https://www.clinical-lung-cancer.com/article/S1525-7304(11)70217-0/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/15555219 PubMed]
-# '''CALGB 9732:''' Niell HB, Herndon JE 2nd, Miller AA, Watson DM, Sandler AB, Kelly K, Marks RS, Perry MC, Ansari RH, Otterson G, Ellerton J, Vokes EE, Green MR; [[Study_Groups#CALGB|CALGB]]. Randomized phase III intergroup trial of etoposide and cisplatin with or without paclitaxel and granulocyte colony-stimulating factor in patients with extensive-stage small-cell lung cancer: Cancer and Leukemia Group B Trial 9732. J Clin Oncol. 2005 Jun 1;23(16):3752-9. [https://doi.org/10.1200/JCO.2005.09.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15923572 PubMed] NCT00003299
-# Ignatiadis M, Mavroudis D, Veslemes M, Boukovinas J, Syrigos K, Agelidou M, Agelidou A, Gerogianni A, Pavlakou G, Tselepatiotis E, Nikolakopoulos J, Georgoulias V; Hellenic Oncology Research Group. Sequential versus alternating administration of cisplatin/etoposide and topotecan as first-line treatment in extensive-stage small-cell lung cancer: preliminary results of a Phase III Trial of the Hellenic Oncology Research Group. Clin Lung Cancer. 2005 Nov;7(3):183-9. [https://www.clinical-lung-cancer.com/article/S1525-7304(11)70409-0/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16354313 PubMed]
-<!-- Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. -->
-# Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. [https://doi.org/10.1200/jco.2005.04.8595 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648503 PubMed]
-# '''GSK 104864-A/389:''' Eckardt JR, von Pawel J, Papai Z, Tomova A, Tzekova V, Crofts TE, Brannon S, Wissel P, Ross G. Open-label, multicenter, randomized, phase III study comparing oral topotecan/cisplatin versus etoposide/cisplatin as treatment for chemotherapy-naive patients with extensive-disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2044-51. [https://doi.org/10.1200/JCO.2005.03.3332 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/16648504 PubMed] NCT00043927
-# '''JCOG 9702:''' Okamoto H, Watanabe K, Kunikane H, Yokoyama A, Kudoh S, Asakawa T, Shibata T, Kunitoh H, Tamura T, Saijo N. Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702. Br J Cancer. 2007 Jul 16;97(2):162-9. Epub 2007 Jun 19. [https://www.nature.com/articles/6603810 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2360311/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17579629 PubMed]
-# Baka S, Califano R, Ferraldeschi R, Aschroft L, Thatcher N, Taylor P, Faivre-Finn C, Blackhall F, Lorigan P. Phase III randomised trial of doxorubicin-based chemotherapy compared with platinum-based chemotherapy in small-cell lung cancer. Br J Cancer. 2008 Aug 5;99(3):442-7. [https://www.nature.com/articles/6604480 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2527803/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/18665190 PubMed]
-# '''SWOG S0124:''' Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. [https://doi.org/10.1200/JCO.2008.20.1061 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19349543 PubMed] NCT00045162
-# Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. [https://doi.org/10.1093/annonc/mdq036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20231298 PubMed] NCT00143455
-# Baka S, Agelaki S, Kotsakis A, Veslemes M, Papakotoulas P, Agelidou M, Agelidou A, Tsaroucha E, Pavlakou G, Gerogianni A, Androulakis N, Vamvakas L, Kalbakis K, Mavroudis D, Georgoulias V. Phase III study comparing sequential versus alternate administration of cisplatin-etoposide and topotecan as first-line treatment in small cell lung cancer. Anticancer Res. 2010 Jul;30(7):3031-8. [http://ar.iiarjournals.org/content/30/7/3031.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/20683051 PubMed]
-# '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] NCT00403403
-# '''GSK 104864-A/479:''' Fink TH, Huber RM, Heigener DF, Eschbach C, Waller C, Steinhauer EU, Virchow JC, Eberhardt F, Schweisfurth H, Schroeder M, Ittel T, Hummler S, Banik N, Bogenrieder T, Acker T, Wolf M; “Aktion Bronchialkarzinom” (ABC Study Group). Topotecan/cisplatin compared with cisplatin/etoposide as first-line treatment for patients with extensive disease small-cell lung cancer: final results of a randomized phase III trial. J Thorac Oncol. 2012 Sep;7(9):1432-9. [https://www.jto.org/article/S1556-0864(15)32944-0 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22895140 PubMed] NCT00320359
-# '''CALGB 30504:''' Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.57.3105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732163 PubMed] NCT00453154
-# '''D0750018:''' Sun Y, Cheng Y, Hao X, Wang J, Hu C, Han B, Liu X, Zhang L, Wan H, Xia Z, Liu Y, Li W, Hou M, Zhang H, Xiu Q, Zhu Y, Feng J, Qin S, Luo X. Randomized phase III trial of amrubicin/cisplatin versus etoposide/cisplatin as first-line treatment for extensive small-cell lung cancer. BMC Cancer. 2016 Apr 9;16:265. [https://doi.org/10.1186/s12885-016-2301-6 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826513/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27061082 PubMed] NCT00660504
-# '''COMBAT:''' Oh IJ, Kim KS, Park CK, Kim YC, Lee KH, Jeong JH, Kim SY, Lee JE, Shin KC, Jang TW, Lee HK, Lee KY, Lee SY. Belotecan/cisplatin versus etoposide/cisplatin in previously untreated patients with extensive-stage small cell lung carcinoma: a multi-center randomized phase III trial. BMC Cancer. 2016 Aug 26;16:690. [https://doi.org/10.1186/s12885-016-2741-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5002146/ link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27566413 PubMed] NCT00826644
-# '''CA184-156:''' Reck M, Luft A, Szczesna A, Havel L, Kim SW, Akerley W, Pietanza MC, Wu YL, Zielinski C, Thomas M, Felip E, Gold K, Horn L, Aerts J, Nakagawa K, Lorigan P, Pieters A, Kong Sanchez T, Fairchild J, Spigel D. Phase III randomized trial of ipilimumab plus etoposide and platinum versus placebo plus etoposide and platinum in extensive-stage small-cell lung cancer. J Clin Oncol. 2016 Nov 1;34(31):3740-3748. [https://doi.org/10.1200/JCO.2016.67.6601 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/27458307 PubMed] NCT01450761
-# '''GOIRC-AIFA FARM6PMFJM:''' Tiseo M, Boni L, Ambrosio F, Camerini A, Baldini E, Cinieri S, Brighenti M, Zanelli F, Defraia E, Chiari R, Dazzi C, Tibaldi C, Turolla GM, D'Alessandro V, Zilembo N, Trolese AR, Grossi F, Riccardi F, Ardizzoni A. Italian, multicenter, phase III, randomized study of cisplatin plus etoposide with or without bevacizumab as first-line treatment in extensive-disease small-cell lung cancer: the GOIRC-AIFA FARM6PMFJM trial. J Clin Oncol. 2017 Apr 20;35(12):1281-1287. Epub 2017 Jan 30. [https://doi.org/10.1200/JCO.2016.69.4844 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28135143 PubMed] EudraCT 2007-007949-13
-# '''LUNGSTAR:''' Seckl MJ, Ottensmeier CH, Cullen M, Schmid P, Ngai Y, Muthukumar D, Thompson J, Harden S, Middleton G, Fife KM, Crosse B, Taylor P, Nash S, Hackshaw A. Multicenter, phase III, randomized, double-blind, placebo-controlled trial of pravastatin added to first-line standard chemotherapy in small-cell lung cancer (LUNGSTAR). J Clin Oncol. 2017 May 10;35(14):1506-1514. Epub 2017 Feb 27. [https://doi.org/10.1200/JCO.2016.69.7391 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5455702/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/28240967 PubMed] NCT00433498
-# '''CRCST-L-0001:''' Kim DW, Kim HG, Kim JH, Park K, Kim HK, Jang JS, Kim BS, Kang JH, Lee KH, Kim SW, Ryoo HM, Kim JS, Lee KH, Kwon JH, Choi JH, Shin SW, Hahn S, Heo DS. Randomized phase III trial of irinotecan plus cisplatin versus etoposide plus cisplatin in chemotherapy-naïve Korean patients with extensive-disease small cell lung cancer. Cancer Res Treat. 2019 Jan;51(1):119-127. Epub 2018 Mar 12. [https://doi.org/10.4143/crt.2018.019 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6334001/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29529858 PubMed] NCT00349492
-# '''KEYNOTE-604:''' Rudin CM, Awad MM, Navarro A, Gottfried M, Peters S, Csőszi T, Cheema PK, Rodriguez-Abreu D, Wollner M, Yang JC, Mazieres J, Orlandi FJ, Luft A, Gümüş M, Kato T, Kalemkerian GP, Luo Y, Ebiana V, Pietanza MC, Kim HR; KEYNOTE-604 Investigators. Pembrolizumab or Placebo Plus Etoposide and Platinum as First-Line Therapy for Extensive-Stage Small-Cell Lung Cancer: Randomized, Double-Blind, Phase III KEYNOTE-604 Study. J Clin Oncol. 2020 Jul 20;38(21):2369-2379. Epub 2020 May 29. [https://doi.org/10.1200/jco.20.00793 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7474472/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32468956/ PubMed] NCT03066778
-==Cisplatin & Etoposide (EP) & Bevacizumab {{#subobject:f451bd|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3f85eb|Variant=1}}===
+===Regimen variant #2, with maintenance capecitabine {{#subobject:3gacn9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 1,808: / Line 2,182: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ Zhu et al. 2022 (EXELOX)]
-|2007-2008
+|2015-2020
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br>2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+|[[#CapeOx_2|CapeOx]]
-| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 5.5 vs 4.4 mo<br>(HR 0.53, 95% CI 0.32-0.86)
+| style="background-color:#eeee01" |Non-inferior PFS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Epirubicin (Ellence)]] as follows:
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+**Cycles 1 up to 8: 50 mg/m<sup>2</sup> IV once on day 1
-====Targeted therapy====
+*[[Oxaliplatin (Eloxatin)]] as follows:
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+**Cycles 1 up to 8: 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''21-day cycle for 4 cycles'''
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
-</div>
+'''21-day cycles'''
-<div class="toccolours" style="background-color:#cbd5e7">
+</div></div>
-====Subsequent treatment====
-*[[#Bevacizumab_monotherapy|Bevacizumab]] maintenance
-</div></div>
 ===References===
-# '''SALUTE:''' Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] NCT00403403
+#'''REAL-2:''' Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. [https://doi.org/10.1056/NEJMoa073149 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18172173 PubMed] content property of [http://hemonc.org HemOnc.org] ISRCTN51678883
-==Cisplatin & Etoposide (EP) & Durvalumab {{#subobject:ddba26|Regimen=1}}==
+#'''REAL3:''' Waddell T, Chau I, Cunningham D, Gonzalez D, Okines AF, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. Epub 2013 Apr 15. [https://doi.org/10.1016/s1470-2045(13)70096-2 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/23594787 PubMed] NCT00824785
+#'''EXELOX:''' Zhu XD, Huang MZ, Wang YS, Feng WJ, Chen ZY, He YF, Zhang XW, Liu X, Wang CC, Zhang W, Ying JE, Wu J, Yang L, Qin YR, Luo JF, Zhao XY, Li WH, Zhang Z, Qiu LX, Geng QR, Zou JL, Zhang JY, Zheng H, Song XF, Wu SS, Zhang CY, Gong Z, Liu QQ, Wang XF, Xu Q, Wang Q, Ji JM, Zhao J, Guo WJ. XELOX doublet regimen versus EOX triplet regimen as first-line treatment for advanced gastric cancer: An open-labeled, multicenter, randomized, prospective phase III trial (EXELOX). Cancer Commun (Lond). 2022 Apr;42(4):314-326. Epub 2022 Feb 25. [https://doi.org/10.1002/cac2.12278 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc9017757/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/35212487/ PubMed] NCT02395640
+==Fluorouracil monotherapy {{#subobject:588907|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3cbczd|Variant=1}}===
+===Regimen variant #1, CI {{#subobject:3289d8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1200/jco.2003.04.130 Ohtsu et al. 2003 (JCOG 9205)]
+| rowspan="2" |1992-1997
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|FP]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|2. [[#UFTM|UFTM]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+| rowspan="2" |[https://doi.org/10.1016/S1470-2045(09)70259-1 Boku et al. 2009 (JCOG 9912)]
+| rowspan="2" |2000-2006
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#Cisplatin_.26_Irinotecan_88|Cisplatin & Irinotecan]]
+| style="background-color:#fee08b" |Might have inferior OS
+|-
+|2. [[#S-1_monotherapy_2|S-1]]
+| style="background-color:#eeee01" |Non-inferior OS
 |-
-|[https://doi.org/10.1016/S0140-6736(19)32222-6 Paz-Ares et al. 2019 (CASPIAN)]
+|[https://academic.oup.com/jjco/article/43/10/972/851849 Shirao et al. 2013 (JCOG 0106)]
-|2017-2018
+|2002-2007
-| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Carboplatin_.26_Etoposide_.28CE.29_2|CE]]<br> 2. [[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+|[[#Fluorouracil_.26_Methotrexate_.28MF.29_99|MF]]
-| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 12.9 vs 10.5 mo<br>(HR 0.75, 95% CI 0.62-0.91)
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS50%
 |-
 |}
-''<sup>1</sup>Reported efficacy is based on the 2021 update.''
+''JCOG 9205 included patients with PFS of 2 (9.6%)''
-<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] as follows:
+*[[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>)
-**Cycles 1 to 4: 75 to 80 mg/m<sup>2</sup> IV once on day 1
+'''28-day cycles'''
-*[[Etoposide (Vepesid)]] as follows:
+</div></div><br>
-**Cycles 1 to 4: 80 to 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
-====Immunotherapy====
-*[[Durvalumab (Imfinzi)]] 1500 mg IV once on day 1
-'''21-day cycle for 4 cycles, then 28-day cycles'''
-</div></div>
-===References===
-# '''CASPIAN:''' Paz-Ares L, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Kazarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Shire N, Jiang H, Goldman JW; CASPIAN investigators. Durvalumab plus platinum-etoposide versus platinum-etoposide in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): a randomised, controlled, open-label, phase 3 trial. Lancet. 2019 Nov 23;394(10212):1929-1939. Epub 2019 Oct 4. [https://doi.org/10.1016/S0140-6736(19)32222-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/31590988 PubMed] NCT03043872
-##'''Update:''' Goldman JW, Dvorkin M, Chen Y, Reinmuth N, Hotta K, Trukhin D, Statsenko G, Hochmair MJ, Özgüroğlu M, Ji JH, Garassino MC, Voitko O, Poltoratskiy A, Ponce S, Verderame F, Havel L, Bondarenko I, Każarnowicz A, Losonczy G, Conev NV, Armstrong J, Byrne N, Thiyagarajah P, Jiang H, Paz-Ares L; CASPIAN investigators. Durvalumab, with or without tremelimumab, plus platinum-etoposide versus platinum-etoposide alone in first-line treatment of extensive-stage small-cell lung cancer (CASPIAN): updated results from a randomised, controlled, open-label, phase 3 trial. Lancet Oncol. 2021 Jan;22(1):51-65. Epub 2020 Dec 4. [https://doi.org/10.1016/s1470-2045(20)30539-8 link to original article] [https://pubmed.ncbi.nlm.nih.gov/33285097 PubMed]
-==Cisplatin & Irinotecan (IC) {{#subobject:277dbd|Regimen=1}}==
-IP: '''<u>I</u>'''rinotecan, '''<u>P</u>'''latinol (Cisplatin)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 30/65 {{#subobject:dc3fe1|Variant=1}}===
+===Regimen variant #2, intermittent, BSA-based {{#subobject:27a992|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2005.04.8595 Hanna et al. 2006]
+|[https://jamanetwork.com/journals/jama/fullarticle/397816 Cullinan et al. 1985]
-|2000-2003
+|NR
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-de-esc)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]]
+|1. [[#Doxorubicin_.26_Fluorouracil_.28FA.29_88|FA]]<br> 2. [[Gastric_cancer_-_historical#FAM|FAM]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+''Note: this is an experimental arm that did not meet its primary endpoint; included here because it represents a de-escalation strategy.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Fluorouracil (5-FU)]] 500 mg/m<sup>2</sup> IV once per day on days 1 to 5
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''28-day cycle for 2 cycles, then 35-day cycles'''
-====Supportive therapy====
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] used according to 1999 American Society of Clinical Oncology guidelines
-*"Erythropoietin was allowed at the discretion of the treating physician."
-'''21-day cycle for 4 cycles; additional cycles could be given at physician discretion'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 60/60 {{#subobject:c0be38|Variant=1}}===
+===Regimen variant #3, intermittent, weight-based {{#subobject:27jb82|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1056/NEJMoa003034 Noda et al. 2002 (JCOG 9511)]
+|[https://www.karger.com/Article/Abstract/226337 Kolarić et al. 1986]
-|1995-1998
+|NR
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-| style="background-color:#1a9850" |Superior OS
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ Lara et al. 2009 (SWOG S0124)]
-|2002-2007
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1200/JCO.2013.53.5153 Satouchi et al. 2014 (JCOG 0509)]
-|2007-2010
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Amrubicin_.26_Cisplatin_99|Amrubicin & Cisplatin]]
+|[[#Epirubicin_.26_Fluorouracil_88|Epirubicin & Fluorouracil]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#fc8d59" |Seems to have inferior DOR
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 12 mg/kg IV once per day on days 1 to 5
-*[[Irinotecan (Camptosar)]] 60 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+'''21- to 28-day cycles'''
-====Supportive therapy====
-*"Hydration and administration of antiemetic drugs."
-'''28-day cycle for 4 cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, 80/65 {{#subobject:dcf04b|Variant=1}}===
+===Regimen variant #4, PVI {{#subobject:d98c9f|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1093/annonc/mdq036 Zatloukal et al. 2010]
+|[https://doi.org/10.1093/annonc/mdf273 Tebbutt et al. 2002]
-|2003-2007
+|1994-2001
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+|[[#Fluorouracil_.26_Mitomycin_99|5-FU & Mitomycin]]
-| style="background-color:#eeee01" |Non-inferior OS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-''Note: this dosing was the result of a mid-protocol amendment.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
+'''Up to 24-week course'''
-'''21-day cycle for 6 cycles'''
 </div></div>
 ===References===
-# '''JCOG 9511:''' Noda K, Nishiwaki Y, Kawahara M, Negoro S, Sugiura T, Yokoyama A, Fukuoka M, Mori K, Watanabe K, Tamura T, Yamamoto S, Saijo N; [[Study_Groups#JCOG|JCOG]]. Irinotecan plus cisplatin compared with etoposide plus cisplatin for extensive small-cell lung cancer. N Engl J Med. 2002 Jan 10;346(2):85-91. [https://doi.org/10.1056/NEJMoa003034 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11784874 PubMed]
+#Cullinan SA, Moertel CG, Fleming TR, Rubin JR, Krook JE, Everson LK, Windschitl HE, Twito DI, Marschke RF, Foley JF, Pfeifle DM, Barlow JF. A comparison of three chemotherapeutic regimens in the treatment of advanced pancreatic and gastric carcinoma: fluorouracil vs fluorouracil and doxorubicin vs fluorouracil, doxorubicin, and mitomycin. JAMA. 1985 Apr 12;253(14):2061-7. [https://jamanetwork.com/journals/jama/fullarticle/397816 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2579257 PubMed]
-<!-- Presented in part (abstract and oral presentation) at the 41st Annual Meeting of the American Society of Clinical Oncology, Orlando, FL, May 13-17, 2005, and at the 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. -->
+#Kolarić K, Potrebica V, Stanovnik M. Controlled phase III clinical study of 4-epi-doxorubicin + 5-fluorouracil versus 5-fluorouracil alone in metastatic gastric and rectosigmoid cancer. Oncology. 1986;43(2):73-7. [https://www.karger.com/Article/Abstract/226337 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/3513075 PubMed]
-# Hanna N, Bunn PA Jr, Langer C, Einhorn L, Guthrie T Jr, Beck T, Ansari R, Ellis P, Byrne M, Morrison M, Hariharan S, Wang B, Sandler A. Randomized phase III trial comparing irinotecan/cisplatin with etoposide/cisplatin in patients with previously untreated extensive-stage disease small-cell lung cancer. J Clin Oncol. 2006 May 1;24(13):2038-43. [https://doi.org/10.1200/jco.2005.04.8595 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16648503 PubMed]
+#Tebbutt NC, Norman A, Cunningham D, Iveson T, Seymour M, Hickish T, Harper P, Maisey N, Mochlinski K, Prior Y, Hill M. A multicentre, randomised phase III trial comparing protracted venous infusion (PVI) 5-fluorouracil (5-FU) with PVI 5-FU plus mitomycin C in patients with inoperable oesophago-gastric cancer. Ann Oncol. 2002 Oct;13(10):1568-75. [https://doi.org/10.1093/annonc/mdf273 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12377644 PubMed]
-# '''SWOG S0124:''' Lara PN Jr, Natale R, Crowley J, Lenz HJ, Redman MW, Carleton JE, Jett J, Langer CJ, Kuebler JP, Dakhil SR, Chansky K, Gandara DR. Phase III trial of irinotecan/cisplatin compared with etoposide/cisplatin in extensive-stage small-cell lung cancer: clinical and pharmacogenomic results from SWOG S0124. J Clin Oncol. 2009 May 20;27(15):2530-5. Epub 2009 Apr 6. [https://doi.org/10.1200/JCO.2008.20.1061 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2684855/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/19349543 PubMed] NCT00045162
+#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; [[Study_Groups#JCOG|JCOG]]. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [https://doi.org/10.1200/jco.2003.04.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506170 PubMed]
-# Zatloukal P, Cardenal F, Szczesna A, Gorbunova V, Moiseyenko V, Zhang X, Cisar L, Soria JC, Domine M, Thomas M. A multicenter international randomized phase III study comparing cisplatin in combination with irinotecan or etoposide in previously untreated small-cell lung cancer patients with extensive disease. Ann Oncol. 2010 Sep;21(9):1810-6. Epub 2010 Mar 15. [https://doi.org/10.1093/annonc/mdq036 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/20231298 PubMed] NCT00143455
+#'''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://doi.org/10.1016/S1470-2045(09)70259-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19818685 PubMed] NCT00142350
-<!-- Presented in part at the 49th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31-June 4, 2013. -->
+#'''JCOG 0106:''' Shirao K, Boku N, Yamada Y, Yamaguchi K, Doi T, Goto M, Nasu J, Denda T, Hamamoto Y, Takashima A, Fukuda H, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Randomized Phase III study of 5-fluorouracil continuous infusion vs sequential methotrexate and 5-fluorouracil therapy in far advanced gastric cancer with peritoneal metastasis (JCOG0106). Jpn J Clin Oncol. 2013 Oct;43(10):972-80. Epub 2013 Sep 7. [https://academic.oup.com/jjco/article/43/10/972/851849 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24014884 PubMed] NCT00149201
-# '''JCOG 0509:''' Satouchi M, Kotani Y, Shibata T, Ando M, Nakagawa K, Yamamoto N, Ichinose Y, Ohe Y, Nishio M, Hida T, Takeda K, Kimura T, Minato K, Yokoyama A, Atagi S, Fukuda H, Tamura T, Saijo N. Phase III study comparing amrubicin plus cisplatin with irinotecan plus cisplatin in the treatment of extensive-disease small-cell lung cancer: JCOG 0509. J Clin Oncol. 2014 Apr 20;32(12):1262-8. Epub 2014 Mar 17. [https://doi.org/10.1200/JCO.2013.53.5153 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24638015 PubMed] UMIN000000720
+==Fluorouracil, Folinic acid, Mitomycin {{#subobject:a4ca9d|Regimen=1}}==
-==Docetaxel monotherapy {{#subobject:46f6bb|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:57c4cc|Variant=1}}===
+===Regimen {{#subobject:672a28|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://pubmed.ncbi.nlm.nih.gov/10439170 Hesketh et al. 1999]
+|[http://www.karger.com/Article/Abstract/64319 Hofheinz et al. 2002]
-| style="background-color:#91cf61" |Phase 2
+|1998-2000
+| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 15,600 mg/m<sup>2</sup>)
-'''21-day cycles'''
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
+*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 22
+'''56-day cycle for 2 cycles'''
 </div></div>
 ===References===
-# Hesketh PJ, Crowley JJ, Burris HA 3rd, Williamson SK, Balcerzak SP, Peereboom D, Goodwin JW, Gross HM, Moore DF Jr, Livingston RB, Gandara DR; [[Study_Groups#SWOG|SWOG]]. Evaluation of docetaxel in previously untreated extensive-stage small cell lung cancer: a Southwest Oncology Group phase II trial. Cancer J Sci Am. 1999 Jul-Aug;5(4):237-41. '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/10439170 PubMed]
+#Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12119460 PubMed]
-==Ifosfamide monotherapy {{#subobject:d04316|Regimen=1}}==
+==FOLFIRI {{#subobject:ba35aa|Regimen=1}}==
+FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
+<br>IF: '''<u>I</u>'''rinotecan & 5-'''<u>F</u>'''luorouracil
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:3276f5|Variant=1}}===
+===Regimen variant #1, 6 out of 7 weeks ("AIO regimen") {{#subobject:cec083|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
+! style="width: 20%" |Study
-!style="width: 15%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-| rowspan="2" |[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
+|[https://doi.org/10.1093/annonc/mdn166 Dank et al. 2008]
-|rowspan=2|1988-1990
+|2000-2002
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]
+|[[#Cisplatin_.26_Fluorouracil_.28CF.29_4|CF]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d9ef8b" |Might have superior TTP
-| style="background-color:#1a9851" |Less toxic
-|-
-|2. [[#Teniposide_monotherapy|Teniposide]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-| style="background-color:#d3d3d3" |Not reported
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric origin). 96% with metastatic disease.''
 ====Chemotherapy====
-*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous infusion over 22 hours, started on days 1, 8, 15, 22, 29, 36, '''given third''' (total dose per cycle: 12,000 mg/m<sup>2</sup>)
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given second'''
+*[[Irinotecan (Camptosar)]] 80 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
 ====Supportive therapy====
-*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV three times per day on days 1 to 5, '''given 0, 4, and 8 hours after each dose of [[Ifosfamide (Ifex)]]''' (total dose per cycle: 4500 mg/m<sup>2</sup>)
+*[[Ondansetron (Zofran)]] for antiemetic prophylaxis
-'''21-day cycle for 4 to 6 cycles'''
+*[[Dexamethasone (Decadron)]] for antiemetic prophylaxis
-</div>
+*[[Filgrastim (Neupogen)]] (dose not specified) SC once per day, starting on day 4, to be continued until ANC greater than 1000/uL for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
-<div class="toccolours" style="background-color:#cbd5e7">
+*[[Atropine (Atropen)]] prn cholinergic symptoms
-====Subsequent treatment====
+*[[Loperamide (Imodium)]] prn delayed diarrhea
-*Patients with CR: another 2 cycles of ifosfamide, then [[#Whole_brain_irradiation_2|prophylactic whole-brain irradiation]] if still in CR
+'''7-week cycles'''
-*Patients with PR: ifosfamide until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_4|EP]]
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #2, LV5FU2 & Irinotecan (200/1600/180) {{#subobject:56018a|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/jco.2004.01.140 Bouché et al. 2004 (FFCD 9803)]
+|1999-2001
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|1. [[#FULV_2|LV5FU2]]<br> 2. [[#CLF|LV5FU2 & Cisplatin]]
+| style="background-color:#d3d3d3" |Not powered to draw conclusions
+|-
+|}
+''Patients: 100% adenocarcinoma (70% gastric origin, 30% cardia).''
+''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.''
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup> IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m<sup>2</sup>)
+*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+'''14-day cycle for at least 4 cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 400/2800/180 {{#subobject:6526d0|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1200/JCO.2013.54.1011 Guimbaud et al. 2014 (FFCD 03-07)]
+|2005-2008
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|[[#ECX_2|ECX]]
+| style="background-color:#1a9850" |Superior TTF
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours, '''given third''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+'''14-day cycles'''
 </div></div>
 ===References===
-# '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
+#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [https://doi.org/10.1200/jco.2004.01.140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15514373 PubMed]
-==IVE {{#subobject:d04tr2|Regimen=1}}==
+#Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [https://doi.org/10.1093/annonc/mdn166 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18558665 PubMed]
-IVE: '''<u>I</u>'''fosfamide, '''<u>V</u>'''P-16 (Etoposide), '''<u>E</u>'''pirubicin
+#'''FFCD 03-07:''' Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. [https://doi.org/10.1200/JCO.2013.54.1011 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25287828 PubMed] NCT00374036
+==mFOLFOX6 {{#subobject:328g5a|Regimen=1}}==
+mFOLFOX6: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:32qeb5|Variant=1}}===
+===Regimen variant #1, limited duration {{#subobject:2057uf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 2,020: / Line 2,430: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5610723/ Berghmans et al. 2017 (ELCWP 01994)]
+|[https://doi.org/10.1200/jco.20.02755 Shah et al. 2021 (GAMMA-1)]
-|2000-2013
+|2015-2019
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin_.26_Etoposide_.28EP.29_3|EP]]
+|[[#mFOLFOX6_.26_Andecaliximab_77|mFOLFOX6 & Andecaliximab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-''Note: This combination is based on a commonly used backbone in Europe. 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====
-*[[Ifosfamide (Ifex)]] 1500 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[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>)
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
-*[[Epirubicin (Ellence)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
-====Supportive therapy====
+'''14-day cycle for 12 cycles'''
-*[[Mesna (Mesnex)]] 300 mg/m<sup>2</sup> IV once on day 1, '''given just before ifosfamide''', then 300 mg/m<sup>2</sup> IV once every 4 hours for 72 hours (total dose per cycle: 5700 mg/m<sup>2</sup>)
+</div>
-'''21-day cycles'''
+<div class="toccolours" style="background-color:#cbd5e7">
-</div></div>
+====Subsequent treatment====
-===References===
+*[[#FULV_2|FULV]] maintenance
-#'''ELCWP 01994:''' Berghmans T, Scherpereel A, Meert AP, Giner V, Lecomte J, Lafitte JJ, Leclercq N, Paesmans M, Sculier JP; European Lung Cancer Working Party (ELCWP). A Phase III Randomized Study Comparing a Chemotherapy with Cisplatin and Etoposide to a Etoposide Regimen without Cisplatin for Patients with Extensive Small-Cell Lung Cancer. Front Oncol. 2017 Sep 19;7:217. [https://doi.org/10.3389/fonc.2017.00217 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc5610723/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28975084/ PubMed] NCT00658580
+</div></div><br>
-==Teniposide monotherapy {{#subobject:60479c|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:964e45|Variant=1}}===
+===Regimen variant #2, indefinite {{#subobject:2057uf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 17%"|Study
+!style="width: 20%"|Study
-!style="width: 15%"|Years of enrollment
+!style="width: 20%"|Years of enrollment
-!style="width: 17%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 17%"|Comparator
+!style="width: 20%"|Comparator
-!style="width: 17%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-!style="width: 17%"|[[Levels_of_Evidence#Toxicity|Comparative Toxicity]]
 |-
-| rowspan="2" |[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
+|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
-|rowspan=2|1988-1990
+|rowspan=2|2017-2019
-| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
-|1. [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]]
+|1. [[#CapeOx_.26_Nivolumab|CapeOx & Nivolumab]]<br> 2. [[#mFOLFOX6_.26_Nivolumab|mFOLFOX6 & Nivolumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+| style="background-color:#d73027" |Inferior OS
-| style="background-color:#1a9851" |Less toxic
 |-
-|2. [[#Ifosfamide_monotherapy|Ifosfamide]]
+|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 | style="background-color:#d3d3d3" |Not reported
 |-
 |}
+''Note: to our knowledge, this regimen was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Teniposide (Vumon)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 5
+*[[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>)
-'''21-day cycle for 4 to 6 cycles'''
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
-</div>
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
-<div class="toccolours" style="background-color:#cbd5e7">
+'''14-day cycles'''
-====Subsequent treatment====
-*Patients with CR after 4 to 6 cycles: another 2 cycles of teniposide
-*Patients with CR after 6 to 8 cycles: [[#Whole_brain_irradiation_2|prophylactic whole-brain irradiation]]
-*Patients with PR: teniposide until progression of disease, then salvage [[#Cisplatin_.26_Etoposide_.28EP.29_4|EP]]
 </div></div>
 ===References===
-# '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
+#'''GAMMA-1:''' Shah MA, Bodoky G, Starodub A, Cunningham D, Yip D, Wainberg ZA, Bendell J, Thai D, He J, Bhargava P, Ajani JA. Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1). J Clin Oncol. 2021 Mar 20;39(9):990-1000. Epub 2021 Feb 12. [https://doi.org/10.1200/jco.20.02755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33577358/ PubMed] NCT02545504
-=Extensive stage, consolidation after first-line therapy=
+#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
-==Whole brain irradiation {{#subobject:37efe7|Regimen=1}}==
+==mFOLFOX6 (L-Leucovorin) {{#subobject:32hyaa|Regimen=1}}==
-PCI: '''<u>P</u>'''rophylactic '''<u>C</u>'''ranial '''<u>I</u>'''rradiation
+mFOLFOX6: '''<u>m</u>'''odified L-'''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:b0bc9a|Variant=1}}===
+===Regimen {{#subobject:21jxuf|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
 !style="width: 20%"|Study
@@ Line 2,087: / Line 2,490: @@
 !style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
+|[https://doi.org/10.1200/jco.20.02755 Shah et al. 2021 (GAMMA-1)]
-|1988-1990
+|2015-2019
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
+| style="background-color:#1a9851" |Phase 3 (C)
-| style="background-color:#d3d3d3" |
+|[[#mFOLFOX6_.26_Andecaliximab_77|mFOLFOX6 & Andecaliximab]]
-| style="background-color:#d3d3d3" |
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
-|-
-|[https://doi.org/10.1056/NEJMoa071780 Slotman et al. 2007 (EORTC 22993)]
-|2001-2006
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 6.7 vs 5.4 mo<br>(HR 0.68, 95% CI 0.52-0.88)
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+''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.''
-====Preceding treatment====
+<div class="toccolours" style="background-color:#b3e2cd">
-*ECOG E1588: [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] versus [[#Ifosfamide_monotherapy|Ifosfamide]] versus [[#Teniposide_monotherapy|Teniposide]]
+====Chemotherapy====
-*EORTC 22993: [[Regimen_classes#Chemotherapy|Chemotherapy]] x 4 to 6 cycles (regimen not specified)
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Levoleucovorin (Fusilev)]] 200 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+'''14-day cycle for 12 cycles'''
 </div>
-<div class="toccolours" style="background-color:#b3e2cd">
+<div class="toccolours" style="background-color:#cbd5e7">
-====Radiotherapy====
+====Subsequent treatment====
-*[[External beam radiotherapy|Whole brain irradiation]] by one of the following: 20 Gy in 5 or 8 fractions, 24 Gy in 12 fractions, 25 Gy in 10 fractions, or 30 Gy in 10 or 12 fractions
+*[[#FULV_2|FULV]] maintenance
-'''1- to 3-week course'''
 </div></div>
 ===References===
-# '''Meta-analysis:''' Aupérin A, Arriagada R, Pignon JP, Le Péchoux C, Gregor A, Stephens RJ, Kristjansen PE, Johnson BE, Ueoka H, Wagner H, Aisner J; Prophylactic Cranial Irradiation Overview Collaborative Group. Prophylactic cranial irradiation for patients with small-cell lung cancer in complete remission. N Engl J Med. 1999 Aug 12;341(7):476-84. [https://doi.org/10.1056/NEJM199908123410703 link to original article] [https://pubmed.ncbi.nlm.nih.gov/10441603 PubMed]
+#'''GAMMA-1:''' Shah MA, Bodoky G, Starodub A, Cunningham D, Yip D, Wainberg ZA, Bendell J, Thai D, He J, Bhargava P, Ajani JA. Phase III Study to Evaluate Efficacy and Safety of Andecaliximab With mFOLFOX6 as First-Line Treatment in Patients With Advanced Gastric or GEJ Adenocarcinoma (GAMMA-1). J Clin Oncol. 2021 Mar 20;39(9):990-1000. Epub 2021 Feb 12. [https://doi.org/10.1200/jco.20.02755 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33577358/ PubMed] NCT02545504
-# '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
+#'''ARMANI:''' NCT02934464
-# '''EORTC 22993:''' Slotman B, Faivre-Finn C, Kramer G, Rankin E, Snee M, Hatton M, Postmus P, Collette L, Musat E, Senan S; [[Study_Groups#EORTC|EORTC]] Radiation Oncology Group; [[Study_Groups#EORTC|EORTC]] Lung Cancer Group. Prophylactic cranial irradiation in extensive small-cell lung cancer. N Engl J Med. 2007 Aug 16;357(7):664-72. [https://doi.org/10.1056/NEJMoa071780 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17699816 PubMed] NCT00016211
+==mFOLFOX6 & Nivolumab {{#subobject:32ug18|Regimen=1}}==
-=Extensive stage, maintenance after first-line therapy=
+mFOLFOX6 & Nivolumab: '''<u>m</u>'''odified '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, Nivolumab
-==Bevacizumab monotherapy {{#subobject:e2a180|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:60322b|Variant=1}}===
+===Regimen {{#subobject:1gh7uf|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 20%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Years of enrollment
+!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 20%"|Comparator
+!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/JCO.2010.29.3423 Spigel et al. 2011 (SALUTE)]
+|rowspan=2|[https://doi.org/10.1016/s0140-6736(21)00797-2 Janjigian et al. 2021 (CheckMate 649)]
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
+|rowspan=2|2017-2019
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|1. [[#CapeOx_2|CapeOx]]<br> 2. [[#mFOLFOX6|mFOLFOX6]]
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 14.4 vs 11.1 mo<br>(HR 0.71, 98.4% CI 0.59-0.86)
+|-
+|3. [[#Ipilimumab_.26_Nivolumab_99|Ipilimumab & Nivolumab]]
+| style="background-color:#d3d3d3" |Not reported
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+''<sup>1</sup>Reported efficacy is for the group with PD-L1 CPS of 5 or more.''
-====Preceding treatment====
-*[[#Carboplatin_.26_Etoposide_.28CE.29_.26_Bevacizumab|CE & Bevacizumab]] induction x 4 or [[#Cisplatin_.26_Etoposide_.28EP.29_.26_Bevacizumab|EP & Bevacizumab]] induction x 4
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Chemotherapy====
-*[[Bevacizumab (Avastin)]] 15 mg/kg IV once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 hours (total dose per cycle: 2800 mg/m<sup>2</sup>)
-'''21-day cycles'''
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+====Immunotherapy====
+*[[Nivolumab (Opdivo)]] 240 mg IV once on day 1
+'''14-day cycles'''
 </div></div>
 ===References===
-# Spigel DR, Townley PM, Waterhouse DM, Fang L, Adiguzel I, Huang JE, Karlin DA, Faoro L, Scappaticci FA, Socinski MA. Randomized phase II study of bevacizumab in combination with chemotherapy in previously untreated extensive-stage small-cell lung cancer: results from the SALUTE trial. J Clin Oncol. 2011 Jun 1;29(16):2215-22. Epub 2011 Apr 18. [https://doi.org/10.1200/JCO.2010.29.3423 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21502556 PubMed] NCT00403403
+#'''CheckMate 649:''' Janjigian YY, Shitara K, Moehler M, Garrido M, Salman P, Shen L, Wyrwicz L, Yamaguchi K, Skoczylas T, Campos Bragagnoli A, Liu T, Schenker M, Yanez P, Tehfe M, Kowalyszyn R, Karamouzis MV, Bruges R, Zander T, Pazo-Cid R, Hitre E, Feeney K, Cleary JM, Poulart V, Cullen D, Lei M, Xiao H, Kondo K, Li M, Ajani JA. First-line nivolumab plus chemotherapy versus chemotherapy alone for advanced gastric, gastro-oesophageal junction, and oesophageal adenocarcinoma (CheckMate 649): a randomised, open-label, phase 3 trial. Lancet. 2021 Jul 3;398(10294):27-40. Epub 2021 Jun 5. [https://doi.org/10.1016/s0140-6736(21)00797-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34102137/ PubMed] NCT02872116
-==Ipilimumab monotherapy {{#subobject:492277|Regimen=1}}==
+==FULV {{#subobject:5aad1e|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & '''<u>L</u>'''euco'''<u>V</u>'''orin (Folinic acid)
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:be9690|Variant=1}}===
+===Regimen {{#subobject:2d601|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1093/annonc/mds213 Reck et al. 2012 (CA184-041)]
+|[https://doi.org/10.1200/jco.2004.01.140 Bouché et al. 2004 (FFCD 9803)]
-|2008-2009
+|1999-2001
-| style="background-color:#91cf61" |Non-randomized portion of phase 2 RCT
+| style="background-color:#1a9851" |Randomized Phase 2 (E-de-esc)
+|1. [[#CLF_2|LV5FU2 & Cisplatin]]<br> 2. [[#FOLFIRI|LV5FU2 & Irinotecan]]
+| style="background-color:#d3d3d3" |Not powered to draw conclusions
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.''
-====Preceding treatment====
+''Patients: 100% adenocarcinoma (70% gastric origin, 30% cardia)''
-*[[#Carboplatin_.26_Paclitaxel_.28CP.29_.26_Ipilimumab|Carboplatin, Paclitaxel, Ipilimumab]] induction
+====Chemotherapy====
-</div>
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once on day 1, then 1200 mg/m<sup>2</sup> IV continuous infusion over 22 hours (total dose per cycle: 1600 mg/m<sup>2</sup>)
-<div class="toccolours" style="background-color:#b3e2cd">
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
-====Immunotherapy====
+'''14-day cycle for at least 4 cycles'''
-*[[Ipilimumab (Yervoy)]] 10 mg/kg IV once on day 1
-'''12-week cycles'''
 </div></div>
 ===References===
-# '''CA184-041:''' Reck M, Bondarenko I, Luft A, Serwatowski P, Barlesi F, Chacko R, Sebastian M, Lu H, Cuillerot JM, Lynch TJ. Ipilimumab in combination with paclitaxel and carboplatin as first-line therapy in extensive-disease-small-cell lung cancer: results from a randomized, double-blind, multicenter phase 2 trial. Ann Oncol. 2013 Jan;24(1):75-83. Epub 2012 Aug 2. [https://doi.org/10.1093/annonc/mds213 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22858559 PubMed] NCT00527735
+#'''FFCD 9803:''' Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [https://doi.org/10.1200/jco.2004.01.140 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/15514373 PubMed]
-==Sunitinib monotherapy {{#subobject:fa7428|Regimen=1}}==
+==FULV (L-leucovorin) {{#subobject:5ga11e|Regimen=1}}==
+FULV: 5-'''<u>FU</u>''' & Levo-'''<u>L</u>'''euco'''<u>V</u>'''orin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:957c3e|Variant=1}}===
+===Regimen {{#subobject:2gahc1|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/PMC4429175/ Ready et al. 2015 (CALGB 30504)]
+|[https://doi.org/10.1007/s10120-020-01043-x Nakajima et al. 2020 (JCOG1108)]
-|2007-2011
+|2013-2017
-| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+| style="background-color:#1a9851" |Phase 2/3 (C)
-|[[Small_cell_lung_cancer_-_null_regimens#Observation_2|Observation]]
+|[[#CLF|FLTAX]]
-| style="background-color:#91cf60" |Seems to have superior PFS
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
-====Preceding treatment====
-*[[#Carboplatin_.26_Etoposide_.28CE.29_2|Carboplatin & Etoposide]] or [[#Cisplatin_.26_Etoposide_.28EP.29_3|Cisplatin & Etoposide]] for 4 to 6 cycles
-</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Targeted therapy====
+====Chemotherapy====
-*[[Sunitinib (Sutent)]] 150 mg PO once on day 1, then 37.5 mg PO once per day
+*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22, 29, 36, '''given second, 60 minutes after levoleucovorin'''
-'''Continued indefinitely'''
+*[[Levoleucovorin (Fusilev)]] 250 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36, '''given first'''
+'''8-week cycles'''
 </div></div>
 ===References===
-# '''CALGB 30504:''' Ready NE, Pang HH, Gu L, Otterson GA, Thomas SP, Miller AA, Baggstrom M, Masters GA, Graziano SL, Crawford J, Bogart J, Vokes EE. Chemotherapy with or without maintenance sunitinib for untreated extensive-stage small-cell lung cancer: A randomized, double-blind, placebo-controlled phase II study-CALGB 30504 (Alliance). J Clin Oncol. 2015 May 20;33(15):1660-5. Epub 2015 Mar 2. [https://doi.org/10.1200/JCO.2014.57.3105 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4429175/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25732163 PubMed] NCT00453154
+#'''JCOG1108:''' Nakajima TE, Yamaguchi K, Boku N, Hyodo I, Mizusawa J, Hara H, Nishina T, Sakamoto T, Shitara K, Shinozaki K, Katayama H, Nakamura S, Muro K, Terashima M. Randomized phase II/III study of 5-fluorouracil/l-leucovorin versus 5-fluorouracil/l-leucovorin plus paclitaxel administered to patients with severe peritoneal metastases of gastric cancer (JCOG1108/WJOG7312G). Gastric Cancer. 2020 Jul;23(4):677-688. Epub 2020 Feb 8. [https://doi.org/10.1007/s10120-020-01043-x link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/32036492/ PubMed] UMIN000010949
-=Relapsed or refractory disease=
+==Irinotecan monotherapy {{#subobject:41e063|Regimen=1}}==
-==Amrubicin monotherapy {{#subobject:35370b|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:514e41|Variant=1}}===
+===Regimen {{#subobject:9fb427|Variant=1}}===
-{| class="wikitable sortable" style="width: 100%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-!style="width: 20%"|Study
+!style="width: 33%"|Study
-!style="width: 20%"|Years of enrollment
+!style="width: 33%"|Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+|-
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|[http://link.springer.com/article/10.1007/s10620-005-3038-2 Enzinger et al. 2005]
+|NR in abstract
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+''Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m<sup>2</sup> IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."''
+''Study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GEJ and 33% distal esophagus)''
+''Regimen showed a 14% response rate and 53% disease control rate.''
+====Chemotherapy====
+*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
+'''42-day cycles'''
+</div></div>
+===References===
+#Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007/s10620-005-3038-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16416165 PubMed]
+==OLF {{#subobject:98b4fa|Regimen=1}}==
+OLF: '''<u>O</u>'''xaliplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
+<br>FLO: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:3d7273|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2013.54.5392 von Pawel et al. 2014 (ACT-1)]
+|[https://doi.org/10.1200/jco.2007.13.9378 Al-Batran et al. 2008]
-|2007-2010
+|2003-2006
 | style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Topotecan_monotherapy|Topotecan]]
+|[[#CLF|FLP]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of OS<br>Median OS: 7.5 vs 7.8 mo<br>(HR 0.88, 95% CI 0.73-1.06)
+| style="background-color:#d9ef8b" |Might have superior PFS<br>Median PFS: 5.8 vs 3.9 mo
-|-
-|[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)]
-|2015-2017
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy|Nivolumab]]
-| style="background-color:#fee08b" |Might have inferior OS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Patients: 100% adenocarcinoma histology (20% esophagogastric junction, 80% gastric'').
 ====Chemotherapy====
-*[[Amrubicin (Calsed)]] 40 mg/m<sup>2</sup> IV over 5 minutes once per day on days 1 to 3
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours, started on days 1, 15, 29, 43 (total dose per cycle: 10,400 mg/m<sup>2</sup>)
 ====Supportive therapy====
-*"Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
+*[[Category:Emesis prevention|Antiemetic medications]] per "local protocols"
-'''21-day cycle for at least 6 cycles'''
+'''8-week cycles'''
 </div></div>
 ===References===
-<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
+#Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [https://doi.org/10.1200/jco.2007.13.9378 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18349393 PubMed]
-# '''ACT-1:''' von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. [https://doi.org/10.1200/jco.2013.54.5392 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25385727 PubMed] NCT00547651
+==Paclitaxel & S-1 {{#subobject:a88c2a|Regimen=1}}==
-# '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] NCT02481830
-==Bendamustine monotherapy {{#subobject:6ed7fe|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:35da2b|Variant=1}}===
+===Regimen {{#subobject:82ca09|Variant=1}}===
-{| class="wikitable sortable" style="width: 80%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 25%"|Study
+! style="width: 20%" |Study
-!style="width: 25%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 25%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 20%" |Comparator
-|-
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990869/ Lammers et al. 2014 (VICC THO 0920)]
-|2009-2012
-| style="background-color:#91cf61" |Phase 2
-|ORR: 33% (95% CI, 14-52%)
 |-
+|[https://doi.org/10.1200/JCO.2018.77.8613 Ishigami et al. 2018 (PHOENIX-GC)]
+|2011-2013
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]
+| style="background-color:#d9ef8b" |Might have superior OS<br>Median OS: 17.7 vs 15.2 mo<br>(HR 0.72, 95% CI 0.49-1.04)
 |}
+''Note: Inclusion criteria for PHOENIX-GC included patients with peritoneal metastasis who had received less than or equal to 2 months of prior chemotherapy without disease progression, see link for further details''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Bendamustine]] 120 mg/m<sup>2</sup> IV once per day on days 1 & 2
+*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV once per day on days 1 and 8
-'''21-day cycle for up to 6 cycles'''
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 14
+**BSA 1.25 to less than 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 14
+**BSA more than 1.5 m<sup>2</sup>: 60 mg PO twice per day on days 1 to 14
+*[[Paclitaxel (Taxol)]] 20 mg/m<sup>2</sup> IP once per day over 1 hour on days 1 and 8
+====Supportive therapy====
+*500 mL of normal saline was given prior to intraperitoneal [[Paclitaxel (Taxol)]]
+'''35-day cycles'''
 </div></div>
 ===References===
-# '''VICC THO 0920:''' Lammers PE, Shyr Y, Li CI, Hutchison AS, Sandler A, Carbone DP, Johnson DH, Keedy VL, Horn L. Phase II study of bendamustine in relapsed chemotherapy sensitive or resistant small-cell lung cancer. J Thorac Oncol. 2014 Apr;9(4):559-62. [https://doi.org/10.1097/jto.0000000000000079 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3990869/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24736081 PubMed] NCT00984542
+#'''PHOENIX-GC:''' Ishigami H, Fujiwara Y, Fukushima R, Nashimoto A, Yabusaki H, Imano M, Imamoto H, Kodera Y, Uenosono Y, Amagai K, Kadowaki S, Miwa H, Yamaguchi H, Yamaguchi T, Miyaji T, Kitayama J. Phase III trial comparing intraperitoneal and intravenous paclitaxel plus S-1 versus cisplatin plus S-1 in patients with gastric cancer with peritoneal metastasis: PHOENIX-GC trial. J Clin Oncol. 2018 Jul 1;36(19):1922-1929. Epub 2018 May 10. [https://doi.org/10.1200/JCO.2018.77.8613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29746229 PubMed] UMIN000005930
-==Carboplatin & Etoposide (CE) {{#subobject:dobzc6|Regimen=1}}==
+==Pembrolizumab monotherapy==
-EC: '''<u>E</u>'''toposide & '''<u>C</u>'''arboplatin
-<br>EP: '''<u>E</u>'''toposide & '''<u>P</u>'''araplatin (Carboplatin)
-<br>CE: '''<u>C</u>'''arboplatin & '''<u>E</u>'''toposide
-<br>Ca/E: '''<u>Ca</u>'''rboplatin & '''<u>E</u>'''toposide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8ac106|Variant=1}}===
+===Regimen===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|rowspan=2|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ Shitara et al. 2020 (KEYNOTE-062)]
+|rowspan=2|2015-2017
+|rowspan=2 style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+|1. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|CF]]<br>2. [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]]
+| style="background-color:#eeee01" |Non-inferior OS<sup>1</sup>
 |-
-|[https://doi.org/10.1016/s1470-2045(20)30461-7 Baize et al. 2020 (GFPC 01-2013)]
+|3. [[#Cisplatin_.26_Fluorouracil_.28CF.29_.26_Pembrolizumab|CF & Pembrolizumab]]<br>4. [[#Capecitabine_.26_Cisplatin_.28CX.29_.26_Prembrolizumab_99|CX & Pembrolizumab]]
-|2013-2018
+| style="background-color:#d3d3d3" |Not reported
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[#Topotecan_monotherapy|Topotecan]]
-| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 4.7 vs 2.7 mo<br>(HR 0.57, 90% CI 0.41-0.73)
 |-
 |}
+''<sup>1</sup>Reported efficacy is for patients with PD-L1 CPS score of 1 or more. Improved OS was seen in patients with PD-L1 CPS score of 10 or more (HR: 0.62) but was not tested per analysis plan.''<br>
+''KEYNOTE-062 included patients with GEJ malignancy.''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+PD-L1 CPS score of 1 or more
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Immunotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''21-day cycles'''
-'''21-day cycle for 6 cycles'''
 </div></div>
 ===References===
-#'''GFPC 01-2013:''' Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. [https://doi.org/10.1016/s1470-2045(20)30461-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32888454 PubMed] NCT02738346
+<!-- #'''Abstract:''' Tabernero J, Van Cutsem E, Yung-Jue B, Fuchs CS, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Salguero HR, Mansoor W, Freitas MI, Brachiroli M, Goekkurt E, Chao J, Wainberg ZA, Kher U, Shah S, Kang SP, Shitara K. Pembrolizumab with or without chemotherapy versus chemotherapy for advanced gastric or gastroesophgeal junction (G/GEJ) adenocarcinoma: The phase III KEYNOTE-062 study. 2019 American Society of Clinical Oncology annual meeting. [[https://doi.org/10.1200/JCO.2019.37.18_suppl.LBA4007 link to abstract] -->
-==Cisplatin & Etoposide (EP) {{#subobject:eb644a|Regimen=1}}==
+#'''KEYNOTE-062:''' Shitara K, Van Cutsem E, Bang YJ, Fuchs C, Wyrwicz L, Lee KW, Kudaba I, Garrido M, Chung HC, Lee J, Castro HR, Mansoor W, Braghiroli MI, Karaseva N, Caglevic C, Villanueva L, Goekkurt E, Satake H, Enzinger P, Alsina M, Benson A, Chao J, Ko AH, Wainberg ZA, Kher U, Shah S, Kang SP, Tabernero J. Efficacy and Safety of Pembrolizumab or Pembrolizumab Plus Chemotherapy vs Chemotherapy Alone for Patients With First-line, Advanced Gastric Cancer: The KEYNOTE-062 Phase 3 Randomized Clinical Trial. JAMA Oncol. 2020 Oct 1;6(10):1571-1580. Epub 2020 Sep 3. [https://doi.org/10.1001/jamaoncol.2020.3370 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7489405/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32880601 PubMed] NCT02494583
-EP: '''<u>E</u>'''toposide, '''<u>P</u>'''latinol (Cisplatin)
+==S-1 monotherapy {{#subobject:a12a2a|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:159cb4|Variant=1}}===
+===Regimen variant #1, BSA-based {{#subobject:86c009|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1002/1097-0142(19900215)65:4%3C856::AID-CNCR2820650404%3E3.0.CO;2-6 O'Bryan et al. 1990 (SWOG S8215)]
+| rowspan="2" |[https://doi.org/10.1016/S1470-2045(09)70259-1 Boku et al. 2009 (JCOG 9912)]
-|NR
+| rowspan="2" |2000-2006
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[Stub#BTOC|BTOC]]
+|1. [[#Cisplatin_.26_Irinotecan_88|Cisplatin & Irinotecan]]
-| style="background-color:#ffffbf" |Did not meet efficacy endpoints
+| style="background-color:#d3d3d3" |Not reported
 |-
-|[http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 Ettinger et al. 2002 (ECOG E1588)]
+|2. [[#Fluorouracil_monotherapy|5-FU]]
-|1988-1990
+| style="background-color:#eeee01" |Non-inferior OS
-| style="background-color:#91cf61" |Non-randomized portion of phase 3 RCT
-| style="background-color:#d3d3d3" |
-| style="background-color:#d3d3d3" |
 |-
 |}
-<div class="toccolours" style="background-color:#cbd5e8">
+<div class="toccolours" style="background-color:#b3e2cd">
-====Preceding treatment====
-*ECOG E1588: [[Small_cell_lung_cancer_-_historical#CAV_2|CAV]] versus [[#Ifosfamide_monotherapy|ifosfamide]] versus [[#Teniposide_monotherapy|teniposide]], with progression
-</div>
-<div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Tegafur, gimeracil, oteracil (S-1)]] 40 mg/m<sup>2</sup> PO twice per day on days 1 to 28
-*[[Etoposide (Vepesid)]] 120 mg/m<sup>2</sup> IV once per day on days 1 to 3
+'''42-day cycles'''
-'''21-day cycles'''
+</div></div><br>
-</div></div>
-===References===
-# '''SWOG S8215:''' O'Bryan RM, Crowley JJ, Kim PN, Epstein RB, Neilan B, Coltman CA Jr, Stuckey WJ, Pazdur R. Comparison of etoposide and cisplatin with bis-chloro-ethylnitrosourea, thiotepa, vincristine, and cyclophosphamide for salvage treatment in small cell lung cancer: a Southwest Oncology Group Study. Cancer. 1990 Feb 15;65(4):856-60. [https://doi.org/10.1002/1097-0142(19900215)65:4%3C856::AID-CNCR2820650404%3E3.0.CO;2-6 link to original article] [https://pubmed.ncbi.nlm.nih.gov/2153435 PubMed]
-# '''ECOG E1588:''' Ettinger DS, Finkelstein DM, Ritch PS, Lincoln ST, Blum RH; [[Study_Groups#ECOG|ECOG]]. Study of either ifosfamide or teniposide compared to a standard chemotherapy for extensive disease small cell lung cancer: an Eastern Cooperative Oncology Group randomized study (E1588). Lung Cancer. 2002 Sep;37(3):311-8. [http://www.lungcancerjournal.info/article/S0169-5002%2802)00074-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12234701 PubMed]
-==Cisplatin, Etoposide, Irinotecan {{#subobject:11d584|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:e7a275|Variant=1}}===
+===Regimen variant #2, weight-based {{#subobject:f90b1b|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1016/S1470-2045(08)70035-4 Koizumi et al. 2008 (SPIRITS)]
+|2002-2004
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_S-1|Cisplatin & S-1]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056989/ Narahara et al. 2011 (TOP-002)]
+|2004-2005
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#IRIS_99|IRIS]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ Koizumi et al. 2013 (START<sub>gastric</sub>)]
+|2005-2008
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Docetaxel_.26_S-1|Docetaxel & S-1]]
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
-|[https://doi.org/10.1016/S1470-2045(16)30104-8 Goto et al. 2016 (JCOG0605)]
+|[https://www.ejcancer.com/article/S0959-8049(16)32267-5 Yoshino et al. 2016 (JFMC36-0701)]
-|2007-2012
+|2007-2010
-| style="background-color:#1a9851" |Phase 3 (E-esc)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Topotecan_monotherapy|Topotecan]]
+|[[#Lentinan_.26_S-1_77|Lentinan & S-1]]
-| style="background-color:#1a9850" |Superior OS<br>Median OS: 18.2 vs 12.5 mo<br>(HR 0.67, 90% CI 0.51-0.88)
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+''Note: there is another trial named START in NSCLC.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 25 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Tegafur, gimeracil, oteracil (S-1)]] by the following criteria:
-*[[Etoposide (Vepesid)]] 60 mg/m<sup>2</sup> IV once per day on days 1 to 3
+**BSA less than 1.25 m<sup>2</sup>: 40 mg PO twice per day on days 1 to 28
-*[[Irinotecan (Camptosar)]] 90 mg/m<sup>2</sup> IV once on day 8
+**BSA between 1.25 and 1.5 m<sup>2</sup>: 50 mg PO twice per day on days 1 to 28
-====Supportive therapy====
+**BSA 1.5 m<sup>2</sup> or more: 60 mg PO twice per day on days 1 to 28
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]], started on cycle 1 day 9: (dose not specified) SC once per day, continued throughout except for days of chemotherapy
+'''42-day cycles'''
-'''14-day cycle for 5 cycles'''
 </div></div>
 ===References===
-# '''JCOG0605:''' Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. [https://doi.org/10.1016/S1470-2045(16)30104-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27312053 PubMed] UMIN000000828
+#'''SPIRITS:''' Koizumi W, Narahara H, Hara T, Takagane A, Akiya T, Takagi M, Miyashita K, Nishizaki T, Kobayashi O, Takiyama W, Toh Y, Nagaie T, Takagi S, Yamamura Y, Yanaoka K, Orita H, Takeuchi M. S-1 plus cisplatin versus S-1 alone for first-line treatment of advanced gastric cancer (SPIRITS trial): a phase III trial. Lancet Oncol. 2008 Mar;9(3):215-21. Epub 2008 Feb 20. [https://doi.org/10.1016/S1470-2045(08)70035-4 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/18282805 PubMed] NCT00150670
-==Docetaxel monotherapy {{#subobject:5918ce|Regimen=1}}==
+#'''JCOG 9912:''' Boku N, Yamamoto S, Fukuda H, Shirao K, Doi T, Sawaki A, Koizumi W, Saito H, Yamaguchi K, Takiuchi H, Nasu J, Ohtsu A; Gastrointestinal Oncology Study Group of the Japan Clinical Oncology Group. Fluorouracil versus combination of irinotecan plus cisplatin versus S-1 in metastatic gastric cancer: a randomised phase 3 study. Lancet Oncol. 2009 Nov;10(11):1063-9. Epub 2009 Oct 7. [https://doi.org/10.1016/S1470-2045(09)70259-1 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/19818685 PubMed] NCT00142350
+#'''TOP-002:''' Narahara H, Iishi H, Imamura H, Tsuburaya A, Chin K, Imamoto H, Esaki T, Furukawa H, Hamada C, Sakata Y. Randomized phase III study comparing the efficacy and safety of irinotecan plus S-1 with S-1 alone as first-line treatment for advanced gastric cancer (study GC0301/TOP-002). Gastric Cancer. 2011 Mar;14(1):72-80. Epub 2011 Feb 23. [https://doi.org/10.1007/s10120-011-0009-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3056989/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21340666 PubMed] JapicCTI-050083
+#'''START:''' Koizumi W, Kim YH, Fujii M, Kim HK, Imamura H, Lee KH, Hara T, Chung HC, Satoh T, Cho JY, Hosaka H, Tsuji A, Takagane A, Inokuchi M, Tanabe K, Okuno T, Ogura M, Yoshida K, Takeuchi M, Nakajima T; JACCRO; KCSG. Addition of docetaxel to S-1 without platinum prolongs survival of patients with advanced gastric cancer: a randomized study (START). J Cancer Res Clin Oncol. 2014 Feb;140(2):319-28. Epub 2013 Dec 24. [https://doi.org/10.1007/s00432-013-1563-5 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3895196/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24366758 PubMed] NCT00287768
+#'''JFMC36-0701:''' Yoshino S, Nishikawa K, Morita S, Takahashi T, Sakata K, Nagao J, Nemoto H, Murakami N, Matsuda T, Hasegawa H, Shimizu R, Yoshikawa T, Osanai H, Imano M, Naitoh H, Tanaka A, Tajiri T, Gochi A, Suzuki M, Sakamoto J, Saji S, Oka M. Randomised phase III study of S-1 alone versus S-1 plus lentinan for unresectable or recurrent gastric cancer (JFMC36-0701). Eur J Cancer. 2016 Sep;65:164-71. Epub 2016 Aug 5. [https://www.ejcancer.com/article/S0959-8049(16)32267-5 link to original article] [https://pubmed.ncbi.nlm.nih.gov/27501505 PubMed] UMIN000000574
+#'''RESCUE-GC:''' NCT02867839
+==UFTM {{#subobject:96e8bf|Regimen=1}}==
+UFTM: '''<u>UFT</u>''' (Tegafur and uracil) & '''<u>M</u>'''itomycin
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:a6b72f|Variant=1}}===
+===Regimen {{#subobject:3a603b|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+| rowspan="2" |[https://doi.org/10.1200/jco.2003.04.130 Ohtsu et al. 2003 (JCOG 9205)]
+| rowspan="2" |1992-1995
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-esc)
+|1. [[#Fluorouracil_monotherapy|Fluorouracil]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://doi.org/10.1016/0959-8049(94)90455-3 Smyth et al. 1994]
+|2. [[#Cisplatin_.26_Fluorouracil_.28CF.29_3|FP]]
-| style="background-color:#91cf61" |Phase 2
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
 |}
+''Note: this arm of the study was terminated early. Study included patients with PFS of 2 (9.6%). Mitomycin was interrupted for 1 month after patients received a total cumulative dose of 60 mg.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+*[[Tegafur and uracil (UFT)]] 187.5 mg/m<sup>2</sup> PO twice per day
-'''21-day cycles'''
+*[[Mitomycin (Mutamycin)]] 5 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+'''28-day cycles (see note)'''
 </div></div>
 ===References===
-# Smyth JF, Smith IE, Sessa C, Schoffski P, Wanders J, Franklin H, Kaye SB; Early Clinical Trials Group of the EORTC. Activity of docetaxel (Taxotere) in small cell lung cancer. Eur J Cancer. 1994;30A(8):1058-60. [https://doi.org/10.1016/0959-8049(94)90455-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/7654428 PubMed]
+#'''JCOG 9205:''' Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; [[Study_Groups#JCOG|JCOG]]. Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: the Japan Clinical Oncology Group study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [https://doi.org/10.1200/jco.2003.04.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12506170 PubMed]
-==Etoposide monotherapy {{#subobject:4ae4d4|Regimen=1}}==
+=Maintenance after first-line therapy=
+==Capecitabine monotherapy {{#subobject:c6df5d|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:4970d7|Variant=1}}===
+===Regimen {{#subobject:878a56|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://pubmed.ncbi.nlm.nih.gov/2154857 Einhorn et al. 1990]
+|[https://doi.org/10.1200/JCO.2011.36.2236 Ohtsu et al. 2011 (AVAGAST)]
-| style="background-color:#91cf61" |Phase 2
+|2007-2008
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
-|[https://doi.org/10.1200/jco.1990.8.10.1613 Johnson et al. 1990]
+|[https://www.ejcancer.com/article/S0959-8049(14)00884-3 Kim et al. 2014 (SMC 2008-12-019)]
-| style="background-color:#91cf61" |Phase 2
+|2009-2012
+| style="background-color:#91cf61" |Non-randomized portion of RCT
 |-
 |}
-''Note: Oral etoposide to be taken on an empty stomach.''
+''AVAGAST patients: 86% gastric and 14% GEJ.  5.4% of patients had an ECOG of 2.''
+''SMC 2008-12-019 patients: 79% gastric, 5% GEJ, and 16% unknown. 2% of patients had an ECOG of 2.''
+<div class="toccolours" style="background-color:#cbd5e8">
+====Preceding treatment====
+*AVAGAST: [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]] x 6
+*SMC 2008-12-019: [[#Capecitabine_.26_Cisplatin_.28CX.29_3|CX]] x 8
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Etoposide (Vepesid)]] 50 mg/m<sup>2</sup> PO once per day
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO twice per day on days 1 to 14
 '''21-day cycles'''
 </div></div>
 ===References===
-# Einhorn LH, Pennington K, McClean J; Hoosier Oncology Group. Phase II trial of daily oral VP-16 in refractory small cell lung cancer: a Hoosier Oncology Group study. Semin Oncol. 1990 Feb;17(1 Suppl 2):32-5. '''Not available online; abstract contains protocol''' [https://pubmed.ncbi.nlm.nih.gov/2154857 PubMed]
+#'''AVAGAST:''' Ohtsu A, Shah MA, Van Cutsem E, Rha SY, Sawaki A, Park SR, Lim HY, Yamada Y, Wu J, Langer B, Starnawski M, Kang YK. Bevacizumab in combination with chemotherapy as first-line therapy in advanced gastric cancer: a randomized, double-blind, placebo-controlled phase III study. J Clin Oncol. 2011 Oct 20;29(30):3968-76. Epub 2011 Aug 15. [https://doi.org/10.1200/JCO.2011.36.2236 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21844504 PubMed] NCT00548548
-# Johnson DH, Greco FA, Strupp J, Hande KR, Hainsworth JD. Prolonged administration of oral etoposide in patients with relapsed or refractory small-cell lung cancer: a phase II trial. J Clin Oncol. 1990 Oct;8(10):1613-7. [https://doi.org/10.1200/jco.1990.8.10.1613 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/2170589 PubMed]
+#'''SMC 2008-12-019:''' Kim ST, Kang JH, Lee J, Park SH, Park JO, Park YS, Lim HY, Hwang IG, Lee SC, Park KW, Lee HR, Kang WK. Simvastatin plus capecitabine-cisplatin versus placebo plus capecitabine-cisplatin in patients with previously untreated advanced gastric cancer: a double-blind randomised phase 3 study. Eur J Cancer. 2014 Nov;50(16):2822-30. Epub 2014 Sep 15. [https://www.ejcancer.com/article/S0959-8049(14)00884-3 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25218337 PubMed] NCT01099085
-==Epirubicin & Ifosfamide {{#subobject:3661d7|Regimen=1}}==
+=Metastatic or locally advanced disease, subsequent lines of therapy=
-EI: '''<u>E</u>'''pirubicin, '''<u>I</u>'''fosfamide
+==Apatinib monotherapy {{#subobject:ao594c|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:c74edb|Variant=1}}===
+===Regimen {{#subobject:913ap2|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
+! style="width: 20%" |Comparator
-|[http://www.lungcancerjournal.info/article/S0169-5002%2811)00386-2 Jacot et al. 2012]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
-|1992-2010
-| style="background-color:#91cf61" |Phase 2
 |-
+|Awaiting publication (ANGEL)
+|2017-2018
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric cancer_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''ANGEL included patients with GEJ malignancy''
-====Chemotherapy====
+====Targeted therapy====
-*[[Epirubicin (Ellence)]] 90 mg/m<sup>2</sup> IV once on day 1
+*[[Apatinib (Aitan)]] 700 mg once per day
-*[[Ifosfamide (Ifex)]] 3000 mg/m<sup>2</sup> IV once per day on days 1 & 2
+'''28-day cycles'''
-====Supportive therapy====
-*[[Mesna (Mesnex)]] (dose/route/schedule not specified) on days 1 & 2
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion
-'''28-day cycle for up to 6 cycles'''
 </div></div>
 ===References===
-# Jacot W, Pujol JL, Chakra M, Molinier O, Bozonnat MC, Gervais R, Quantin X. Epirubicin and ifosfamide in relapsed or refractory small cell lung cancer patients. Lung Cancer. 2012 Feb;75(2):213-6. Epub 2011 Aug 9. [http://www.lungcancerjournal.info/article/S0169-5002%2811)00386-2 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21831476 PubMed]
+#'''ANGEL:''' NCT03042611
-==Gemcitabine monotherapy {{#subobject:9a9c65|Regimen=1}}==
+##'''Abstract:''' Kang Y, Kang WK, Di Bartolomeo M, Chau I, Yoon HH, Cascinu S, Ryu M, Kim JG, Lee K, Oh SC, Takashima A, Kryzhanivska A, Chao Y, Vladimirov V, Evesque L, Schenker M, McGinn A, Sankar N, Wyrwicz L, Boku N. Randomized Phase 3 ANGEL study of rivoceranib (apatinib) + best supportive care (BSC) vs placebo + BSC in patients with advanced/metastatic gastric cancer. 2019 European Society of Medical Oncology annual meeting. Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394 [https://doi.org/10.1093/annonc/mdz394.034 link to abstract]
+==Docetaxel monotherapy {{#subobject:4f3230|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 5 cycles {{#subobject:5efd8c|Variant=1}}===
+===Regimen variant #1, 60 mg/m<sup>2</sup> {{#subobject:577cd6|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1023/a:1011104509759 van der Lee et al. 2001]
+|[https://doi.org/10.1200/jco.2011.39.4585 Kang et al. 2012 (SMC 2008-08-055)]
-| style="background-color:#91cf61" |Phase 2
+|2008-2010
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.3 vs 3.8 mo<br>(HR 0.66, 95% CI 0.485-0.89)
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
-'''28-day cycle for up to 5 cycles'''
+'''21-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, indefinite {{#subobject:5a9c6c|Variant=1}}===
+===Regimen variant #2, 75 mg/m<sup>2</sup> x 6 {{#subobject:3b4816|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1200/jco.2003.09.130 Masters et al. 2003 (ECOG E1597)]
+|[https://doi.org/10.1016/S1470-2045(13)70549-7 Ford et al. 2014 (COUGAR-02)]
-| style="background-color:#91cf61" |Phase 2
+|2008-2012
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.2 vs 3.6 mo<br>(HR 0.67, 95% CI 0.49-0.92)
 |-
 |}
-''Note: dose escalation was carried out if patients had less than grade 2 toxicity with cycle 1.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] as follows:
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-**Cycle 1: 1000 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
+'''21-day cycle for up to 6 cycles'''
-**Cycle 2 onwards: 1250 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15
-'''28-day cycles'''
 </div></div>
 ===References===
-# van der Lee I, Smit EF, van Putten JW, Groen HJ, Schlösser NJ, Postmus PE, Schramel FM. Single-agent gemcitabine in patients with resistant small-cell lung cancer. Ann Oncol. 2001 Apr;12(4):557-61. [https://doi.org/10.1023/a:1011104509759 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/11398892 PubMed]
+#'''SMC 2008-08-055:''' Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [https://doi.org/10.1200/jco.2011.39.4585 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/22412140 PubMed] NCT00821990
-# '''ECOG E1597:''' Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, Johnson D; [[Study_Groups#ECOG|ECOG]]. Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003 Apr 15;21(8):1550-5. [https://doi.org/10.1200/jco.2003.09.130 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/12697880 PubMed]
+#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://doi.org/10.1093/annonc/mdt002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23406728 PubMed] NCT00813072
-==Ifosfamide monotherapy {{#subobject:a1f3a|Regimen=1}}==
+#'''COUGAR-02:''' Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [https://doi.org/10.1016/S1470-2045(13)70549-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24332238 PubMed] NCT00978549
+#'''INTEGRATEIIb:''' NCT04879368
+==Fluorouracil, Folinic acid, Mitomycin {{#subobject:b4ca9d|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:d82a3f|Variant=1}}===
+===Regimen {{#subobject:672b28|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://doi.org/10.1016/0277-5379(88)90242-8 Cantwell et al. 1988]
+|[http://www.karger.com/Article/Abstract/64319 Hofheinz et al. 2002]
-| style="background-color:#91cf61" |Phase 2
+|1998-2000
+| style="background-color:#ffffbe" |Phase 2, <20 pts in this subgroup
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Ifosfamide (Ifex)]] 5000 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 days 1, 8, 15, 22, 29, 36 (total dose per cycle: 15,600 mg/m<sup>2</sup>)
-====Supportive therapy====
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
-*[[Mesna (Mesnex)]] 5000 mg/m<sup>2</sup> IV once on day 1
+*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 22
-'''21-day cycles'''
+'''56-day cycle for 2 cycles'''
 </div></div>
 ===References===
-# Cantwell BM, Bozzino JM, Corris P, Harris AL. The multidrug resistant phenotype in clinical practice; evaluation of cross resistance to ifosfamide and mesna after VP16-213, doxorubicin and vincristine (VPAV) for small cell lung cancer. Eur J Cancer Clin Oncol. 1988 Feb;24(2):123-9. [https://doi.org/10.1016/0277-5379(88)90242-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/2833398 PubMed]
+#Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer: a phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/12119460 PubMed]
-# '''Review:''' Marangolo M, Giovanis P. Ifosfamide in small cell lung cancer. Oncology. 2003;65 Suppl 2:46-9. Review. [http://www.karger.com/Article/FullText/73358 link to original article] [https://pubmed.ncbi.nlm.nih.gov/14586147 PubMed]
+==Irinotecan monotherapy {{#subobject:6df2c0|Regimen=1}}==
-==Ifosfamide & Paclitaxel {{#subobject:6540a2|Regimen=1}}==
-PI: '''<u>P</u>'''aclitaxel, '''<u>I</u>'''fosfamide
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:8e22a|Variant=1}}===
+===Regimen variant #1, 125 mg/m<sup>2</sup>, 4 weeks out of 6 {{#subobject:9fb427|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
-! style="width: 50%" |Study
+!style="width: 33%"|Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[http://www.lungcancerjournal.info/article/S0169-5002%2807)00325-X Park et al. 2007a]
+|[http://link.springer.com/article/10.1007/s10620-005-3038-2 Enzinger et al. 2005]
+|NR in abstract
 | style="background-color:#91cf61" |Phase 2
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Note: In contrast to the primary references, some guidelines list a dosing schedule of 125 mg/m<sup>2</sup> IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."''
+''Study included patients with GE junction and distal esophageal malignancy as well (~59% gastric, 9% GE junction and 33% distal esophagus)''
+''Regimen showed a 14% response rate and 53% disease control rate.''
 ====Chemotherapy====
-*[[Ifosfamide (Ifex)]] 2500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1 & 2
+*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15, 22
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+'''42-day cycles'''
-====Supportive therapy====
-*[[Mesna (Mesnex)]] 500 mg/m<sup>2</sup> IV three times per day on days 1 & 2, '''given 15 minutes before, 4 hours after, and 8 hours after ifosfamide''' (total dose per cycle: 3000 mg/m<sup>2</sup>)
-'''21-day cycles'''
-</div></div>
-===References===
-# Park S, Ahn MJ, Ahn JS, Lee J, Hong YS, Park BB, Lee SC, Hwang IG, Park JO, Lim H, Kang WK, Park K. Combination chemotherapy with paclitaxel and ifosfamide as the third-line regimen in patients with heavily pretreated small cell lung cancer. Lung Cancer. 2007 Oct;58(1):116-22. Epub 2007 Jul 12. [http://www.lungcancerjournal.info/article/S0169-5002%2807)00325-X link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17624473 PubMed]
-==Irinotecan monotherapy {{#subobject:344d89|Regimen=1}}==
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, weekly {{#subobject:c0a7e0|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://doi.org/10.1200/jco.1992.10.8.1225 Masuda et al. 1992]
-| style="background-color:#ffffbe" |Phase 2, <20 pts
-|-
-|}
-<div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 100 mg/m<sup>2</sup> IV over 90 minutes once per day on days 1, 8, 15
-====Supportive therapy====
-*No routine prophylaxis against diarrhea, nausea, or vomiting used.
-'''21-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, q3wk {{#subobject:cu88e0|Variant=1}}===
+===Regimen variant #2, 150 mg/m<sup>2</sup> q2wk {{#subobject:fa1ef9|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 20%"|Comparator
+! style="width: 20%" |Comparator
-!style="width: 20%"|[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|rowspan=2|[https://doi.org/10.1016/j.lungcan.2022.03.003 Edelman et al. 2022 (DISTINCT)]
+|[https://doi.org/10.1200/JCO.2012.48.5805 Hironaka et al. 2013 (WJOG 4007)]
-|rowspan=2|2017-NR in abstract
+|2007-2010
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|1. [[#Irinotecan_.26_Dinutuximab_99|Irinotecan & Dinutuximab]]
+|[[#Paclitaxel_monotherapy|Paclitaxel]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|2. [[#Topotecan_monotherapy|Topotecan]]
+|[https://www.ejcancer.com/article/S0959-8049(15)00209-9 Nishikawa et al. 2015 (TRICS)]
-| style="background-color:#d3d3d3" |Not reported
+|2007-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|}
+|[https://doi.org/10.1200/jco.2011.39.4585 Kang et al. 2012 (SMC 2008-08-055)]
-<div class="toccolours" style="background-color:#b3e2cd">
+|2008-2010
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.3 vs 3.8 mo<br>(HR 0.66, 95% CI 0.485-0.89)
+|-
+|[https://www.ejcancer.com/article/S0959-8049(14)00093-8 Higuchi et al. 2014 (BIRIP)]
+|2008-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Cisplatin_.26_Irinotecan_.28IC.29|Cisplatin & Irinotecan]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
+|-
+|[https://doi.org/10.1093/annonc/mdv265 Tanabe et al. 2015 (JACCRO GC-05)]
+|2008-2011
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Irinotecan_.26_S-1_77|Irinotecan & S-1]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ Bang et al. 2018 (JAVELIN Gastric 300)]
+|2015-2017
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Avelumab_monotherapy_99|Avelumab]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS
+|-
+|}
+''Hironaka et al patients: 3.7% patients with an ECOG PS of 2''
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 350 mg/m<sup>2</sup> IV once on day 1
+*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycles'''
+'''14-day cycles'''
-</div></div>
+</div></div><br>
-===References===
-# Masuda N, Fukuoka M, Kusunoki Y, Matsui K, Takifuji N, Kudoh S, Negoro S, Nishioka M, Nakagawa K, Takada M. CPT-11: a new derivative of camptothecin for the treatment of refractory or relapsed small-cell lung cancer. J Clin Oncol. 1992 Aug;10(8):1225-9. [https://doi.org/10.1200/jco.1992.10.8.1225 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/1321891 PubMed]
-#'''DISTINCT:''' Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. [https://doi.org/10.1016/j.lungcan.2022.03.003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35278766/ PubMed] NCT03098030
-==Lurbinectedin monotherapy {{#subobject:7167f3|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen {{#subobject:bef45d|Variant=1}}===
+===Regimen variant #3, 300 mg/m<sup>2</sup> q3wk {{#subobject:c410d|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 20%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
-!style="width: 25%"|[[Levels_of_Evidence#Efficacy|Efficacy]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://doi.org/10.1016/s1470-2045(20)30068-1 Trigo et al. 2020 (PM1183-B-005-14)]
+|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)]
-|2015-2019
+|2008-2010
-| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#1a9851" |Randomized Phase 2 (C)
-|ORR: 35.2% (95% CI, 26.2-45.2%)
+|1. [[#Docetaxel_monotherapy|Docetaxel]]<br> 2. [[#Irinotecan_liposomal_monotherapy|Irinotecan liposomal]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Study included patients with GE junction malignancy (77% gastric, 23% GE junction) and included patients with ECOG of 2''
 ====Chemotherapy====
-*[[Lurbinectedin (Zepzelca)]] 3.2 mg/m<sup>2</sup> IV over 60 minutes once on day 1
+*[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
-====Supportive therapy====
+'''21-day cycles'''
-*"All patients received antiemetic prophylaxis."
+</div></div><br>
-'''21-day cycles'''
-</div></div>
-===References===
-# '''PM1183-B-005-14:''' Trigo J, Subbiah V, Besse B, Moreno V, López R, Sala MA, Peters S, Ponce S, Fernández C, Alfaro V, Gómez J, Kahatt C, Zeaiter A, Zaman K, Boni V, Arrondeau J, Martínez M, Delord JP, Awada A, Kristeleit R, Olmedo ME, Wannesson L, Valdivia J, Rubio MJ, Anton A, Sarantopoulos J, Chawla SP, Mosquera-Martinez J, D'Arcangelo M, Santoro A, Villalobos VM, Sands J, Paz-Ares L. Lurbinectedin as second-line treatment for patients with small-cell lung cancer: a single-arm, open-label, phase 2 basket trial. Lancet Oncol. 2020 May;21(5):645-654. [https://doi.org/10.1016/s1470-2045(20)30068-1 link to original article] '''contains dosing details in manuscript''' Epub 2020 Mar 27. [https://pubmed.ncbi.nlm.nih.gov/32224306/ PubMed] NCT02454972
-==Paclitaxel monotherapy {{#subobject:e71ce6|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, every 3 weeks {{#subobject:dbac57|Variant=1}}===
+===Regimen variant #4, 350 mg/m<sup>2</sup> q3wk {{#subobject:160f2f|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ Smit et al. 1998]
+|[https://www.ejcancer.com/article/S0959-8049(11)00396-0 Thuss-Patience et al. 2011]
-| style="background-color:#91cf61" |Phase 2
+|2002-2006
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Best_supportive_care_2|Best supportive care]]
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 4 vs 2.4 mo<br>(HR 0.48, 95% CI 0.25-0.92)
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''Thuss-Patience et al. 2011 included patients with GE junction malignancy (~58% gastric, 43% GE junction) and included patients with ECOG of 2''
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV over 3 hours once on day 1
+*[[Irinotecan (Camptosar)]] as follows:
+**Cycle 1: 250 mg/m<sup>2</sup> (maximum dose of 500 mg) IV over 30 minutes once on day 1
+**Cycles 2 to 10 (depending on toxicity): 350 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 ====Supportive therapy====
-*[[Dexamethasone (Decadron)]] 8 mg PO given twice on day 1; 12 and 6 hours prior to [[Paclitaxel (Taxol)]]
+*[[Atropine (Atropen)]] 0.25 mg SC once on day 1, given prior to [[Irinotecan (Camptosar)]]
-*[[Clemastine (Tavist)]] 2 mg IV push once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]]
-*One of the following H2 blockers:
+*[[Dexamethasone (Decadron)]]
-**[[Cimetidine (Tagamet)]] 300 mg IV push once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
+'''21-day cycle for up to 10 cycles'''
-**[[Ranitidine (Zantac)]] 50 mg IV push once on day 1; 30 minutes prior to [[Paclitaxel (Taxol)]]
+</div></div>
-'''21-day cycle for up to 5 cycles'''
+===References===
-</div></div><br>
+#Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007/s10620-005-3038-2 link to original article] [https://pubmed.ncbi.nlm.nih.gov/16416165 PubMed]
+#Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [https://www.ejcancer.com/article/S0959-8049(11)00396-0 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/21742485 PubMed] NCT00144378
+#'''SMC 2008-08-055:''' Kang JH, Lee SI, Lim DH, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [https://doi.org/10.1200/jco.2011.39.4585 link to original article] [https://pubmed.ncbi.nlm.nih.gov/22412140 PubMed] NCT00821990
+#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://doi.org/10.1093/annonc/mdt002 link to original article] [https://pubmed.ncbi.nlm.nih.gov/23406728 PubMed] NCT00813072
+#'''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://doi.org/10.1200/JCO.2012.48.5805 link to original artile] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24190112 PubMed] UMIN000001252
+#'''BIRIP:''' Higuchi K, Tanabe S, Shimada K, Hosaka H, Sasaki E, Nakayama N, Takeda Y, Moriwaki T, Amagai K, Sekikawa T, Sakuyama T, Kanda T, Sasaki T, Azuma M, Takahashi F, Takeuchi M, Koizumi W; Tokyo Cooperative Oncology Group. Biweekly irinotecan plus cisplatin versus irinotecan alone as second-line treatment for advanced gastric cancer: a randomised phase III trial (TCOG GI-0801/BIRIP trial). Eur J Cancer. 2014 May;50(8):1437-45. Epub 2014 Feb 20. [https://www.ejcancer.com/article/S0959-8049(14)00093-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24560487 PubMed] UMIN000001028
+#'''TRICS:''' Nishikawa K, Fujitani K, Inagaki H, Akamaru Y, Tokunaga S, Takagi M, Tamura S, Sugimoto N, Shigematsu T, Yoshikawa T, Ishiguro T, Nakamura M, Morita S, Miyashita Y, Tsuburaya A, Sakamoto J, Tsujinaka T. Randomised phase III trial of second-line irinotecan plus cisplatin versus irinotecan alone in patients with advanced gastric cancer refractory to S-1 monotherapy: TRICS trial. Eur J Cancer. 2015 May;51(7):808-16. Epub 2015 Mar 18. [https://www.ejcancer.com/article/S0959-8049(15)00209-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/25797356 PubMed] UMIN000002571
+#'''JACCRO GC-05:''' Tanabe K, Fujii M, Nishikawa K, Kunisaki C, Tsuji A, Matsuhashi N, Takagane A, Ohno T, Kawase T, Kochi M, Yoshida K, Kakeji Y, Ichikawa W, Chin K, Terashima M, Takeuchi M, Nakajima T; JACCRO. Phase II/III study of second-line chemotherapy comparing irinotecan-alone with S-1 plus irinotecan in advanced gastric cancer refractory to first-line treatment with S-1 (JACCRO GC-05). Ann Oncol. 2015 Sep;26(9):1916-22. Epub 2015 Jun 24. [https://doi.org/10.1093/annonc/mdv265 link to original article] [https://pubmed.ncbi.nlm.nih.gov/26109630 PubMed] NCT00639327
+#'''JAVELIN Gastric 300:''' Bang YJ, Yanez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://doi.org/10.1093/annonc/mdy264 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30052729 PubMed] NCT02625623
+#'''INTEGRATEIIb:''' NCT04879368
+==Irinotecan liposomal monotherapy {{#subobject:9a99c8|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, weekly paclitaxel {{#subobject:658a5f|Variant=1}}===
+===Regimen {{#subobject:c50e15|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://ar.iiarjournals.org/content/26/1B/777.long Yamamoto et al. 2006]
+|[https://doi.org/10.1093/annonc/mdt002 Roy et al. 2013 (PEP0206)]
-| style="background-color:#91cf61" |Phase 2
+|2008-2010
+| style="background-color:#1a9851" |Randomized Phase 2 (E-switch-ic)
+|1. [[#Docetaxel_monotherapy|Docetaxel]]<br> 2. [[#Irinotecan_monotherapy|Irinotecan]]
+| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
+*[[Irinotecan liposome (Onivyde)]] 120 mg/m<sup>2</sup> IV over 90 minutes once on day 1
-====Supportive therapy====
+'''21-day cycles'''
-*[[Dexamethasone (Decadron)]] 20 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to [[Paclitaxel (Taxol)]]
-*[[Ranitidine (Zantac)]] 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to [[Paclitaxel (Taxol)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV once per day on days 1, 8, 15, 22, 29, 36; 30 minutes prior to [[Paclitaxel (Taxol)]]
-*If ANC less than 1000/uL or WBC count less than 2 x 10<sup>9</sup>/L, [[:Category:Granulocyte colony-stimulating factors|G-CSF]] (type not specified) 2 mcg/kg SC once per day is given until WBC count greater than or equal to 10 x 10<sup>9</sup>/L, except on days that paclitaxel is given
-'''8-week cycles'''
 </div></div>
 ===References===
-# Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77(2):347-51. [https://doi.org/10.1038/bjc.1998.54 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2151229/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/9461009 PubMed]
+#'''PEP0206:''' Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [https://doi.org/10.1093/annonc/mdt002 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/23406728 PubMed] NCT00813072
-# Yamamoto N, Tsurutani J, Yoshimura N, Asai G, Moriyama A, Nakagawa K, Kudoh S, Takada M, Minato Y, Fukuoka M. Phase II study of weekly paclitaxel for relapsed and refractory small cell lung cancer. Anticancer Res. 2006 Jan-Feb;26(1B):777-81. [http://ar.iiarjournals.org/content/26/1B/777.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16739353 PubMed]
+==Nivolumab monotherapy {{#subobject:7011e1|Regimen=1}}==
-==Temozolomide monotherapy {{#subobject:693cf4|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 75 mg/m<sup>2</sup>/d, 21 out of 28 days {{#subobject:96a285|Variant=1}}===
+===Regimen {{#subobject:#f2fd8e|Variant=1}}===
-{| class="wikitable" style="width: 60%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 33%"|Study
+! style="width: 20%" |Study
-!style="width: 33%"|Years of enrollment
+! style="width: 20%" |Years of enrollment
-!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[http://clincancerres.aacrjournals.org/content/18/4/1138.long Pietanza et al. 2012]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ Janjigian et al. 2018 (CheckMate 032)]
-|2008-2010
+|2013-2015
 | style="background-color:#91cf61" |Phase 2
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
 |-
-|}
+|[https://doi.org/10.1016/S0140-6736(17)31827-5 Kang et al. 2017 (ATTRACTION-2)]
-<div class="toccolours" style="background-color:#b3e2cd">
+|2014-2016
-====Chemotherapy====
+| style="background-color:#1a9851" |Phase 3 (E-esc)
-*[[Temozolomide (Temodar)]] 75 mg/m<sup>2</sup> PO once per day on days 1 to 21, with no food 2 hours before or 1 hour after temozolomide
+|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
-====Supportive therapy====
+| style="background-color:#1a9850" |Superior OS<sup>1</sup><br>Median OS: 5.3 vs 4.1 mo<br>(HR 0.62, 95% CI 0.50-0.75)
-*[[Ondansetron (Zofran)]] 8 mg PO once per day on days 1 to 21, prior to [[Temozolomide (Temodar)]] prn nausea
-*Patients with at least grade 3 lymphopenia received prophylaxis for Pneumocystis carinii pneumonia (no specific medication/dose/schedule listed)
-'''28-day cycles'''
-</div></div><br>
-<div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 200 mg/m<sup>2</sup>/d, 5 out of 28 days {{#subobject:792fd1|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
-! style="width: 50%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ Zauderer et al. 2014 (MSKCC 08-065)]
-| style="background-color:#91cf61" |Phase 2
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''<sup>1</sup>Reported efficacy is based on the 2021 update.''<br>
-====Chemotherapy====
+''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''
-*[[Temozolomide (Temodar)]] 200 mg/m<sup>2</sup> PO once per day on days 1 to 5
+====Immunotherapy====
-====Supportive therapy====
+*[[Nivolumab (Opdivo)]] 3 mg/kg IV once on day 1
-*[[Ondansetron (Zofran)]] 8 mg PO once per day on days 1 to 5; 30 minutes prior to [[Temozolomide (Temodar)]]
+'''14-day cycles'''
-'''28-day cycles'''
 </div></div>
 ===References===
-# Pietanza MC, Kadota K, Huberman K, Sima CS, Fiore JJ, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Chan TA, Rizvi NA, Azzoli CG, Riely GJ, Kris MG, Krug LM. Phase II trial of temozolomide in patients with relapsed sensitive or refractory small cell lung cancer, with assessment of methylguanine-DNA methyltransferase as a potential biomarker. Clin Cancer Res. 2012 Feb 15;18(4):1138-45. Epub 2012 Jan 6. [http://clincancerres.aacrjournals.org/content/18/4/1138.long link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/22228633 PubMed]
+#'''ATTRACTION-2:''' Kang YK, Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Chen LT. Nivolumab in patients with advanced gastric or gastro-oesophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2017 Dec 2;390(10111):2461-2471. Epub 2017 Oct 6. [https://doi.org/10.1016/S0140-6736(17)31827-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/28993052 PubMed] NCT02267343
-# '''MSKCC 08-065:''' Zauderer MG, Drilon A, Kadota K, Huberman K, Sima CS, Bergagnini I, Sumner DK, Travis WD, Heguy A, Ginsberg MS, Holodny AI, Riely GJ, Kris MG, Krug LM, Pietanza MC. Trial of a 5-day dosing regimen of temozolomide in patients with relapsed small cell lung cancers with assessment of methylguanine-DNA methyltransferase. Lung Cancer. 2014 Nov;86(2):237-40. Epub 2014 Aug 17. [https://www.lungcancerjournal.info/article/S0169-5002(14)00349-3 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4497567/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/25194640 PubMed] NCT00740636
+##'''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]
-==Topotecan monotherapy {{#subobject:6e9625|Regimen=1}}==
+##'''Update:''' Chen LT, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Sameshima H, Kang YK, Boku N. A phase 3 study of nivolumab in previously treated advanced gastric or gastroesophageal junction cancer (ATTRACTION-2): 2-year update data. Gastric Cancer. 2020 May;23(3):510-519. Epub 2019 Dec 20. [https://doi.org/10.1007/s10120-019-01034-7 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc7165140/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/31863227/ PubMed]
+##'''Update:''' Boku N, Satoh T, Ryu MH, Chao Y, Kato K, Chung HC, Chen JS, Muro K, Kang WK, Yeh KH, Yoshikawa T, Oh SC, Bai LY, Tamura T, Lee KW, Hamamoto Y, Kim JG, Chin K, Oh DY, Minashi K, Cho JY, Tsuda M, Nishiyama T, Chen LT, Kang YK. Nivolumab in previously treated advanced gastric cancer (ATTRACTION-2): 3-year update and outcome of treatment beyond progression with nivolumab. Gastric Cancer. 2021 Jul;24(4):946-958. Epub 2021 Mar 20. [https://doi.org/10.1007/s10120-021-01173-w link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8205916/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/33743112/ PubMed]
+#'''CheckMate 032:''' Janjigian YY, Bendell J, Calvo E, Kim JW, Ascierto PA, Sharma P, Ott PA, Peltola K, Jaeger D, Evans J, de Braud F, Chau I, Harbison CT, Dorange C, Tschaika M, Le DT. CheckMate 032 Study: Efficacy and Safety of Nivolumab and Nivolumab Plus Ipilimumab in Patients With Metastatic Esophagogastric Cancer. J Clin Oncol. 2018 Oct 1;36(28):2836-2844. Epub 2018 Aug 15. [https://doi.org/10.1200/JCO.2017.76.6212 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161834/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30110194 PubMed] NCT01928394
+==Paclitaxel monotherapy {{#subobject:2dcad9|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 1 mg/m<sup>2</sup> {{#subobject:a060a6|Variant=1}}===
+===Regimen variant #1, 70 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:gg21e8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1016/S1470-2045(16)30104-8 Goto et al. 2016 (JCOG0605)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324622/ Lee et al. 2018 (KCSG ST10-01)]
-|2007-2012
+|2011-2015
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Cisplatin.2C_Etoposide.2C_Irinotecan|Cisplatin, Etoposide, Irinotecan]]
+|[[#Irinotecan_monotherapy_2|Irinotecan]]
-| style="background-color:#d73027" |Inferior OS
+| style="background-color:#ffffbf" |Inconclusive whether non-inferior PFS
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Topotecan (Hycamtin)]] 1 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
+*[[Paclitaxel (Taxol)]] 70 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-'''21-day cycle for 4 cycles'''
+'''28-day cycles'''
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 1.5 mg/m<sup>2</sup> {{#subobject:a08066|Variant=1}}===
+===Regimen variant #2, 80 mg/m<sup>2</sup> weekly {{#subobject:0e8f41|Variant=1}}===
+{| class="wikitable sortable" style="width: 60%; text-align:center;"
+!style="width: 33%"|Study
+!style="width: 33%"|Years of enrollment
+!style="width: 33%"|[[Levels_of_Evidence#Evidence|Evidence]]
+|-
+|[http://ar.iiarjournals.org/content/27/4C/2667.long Kodera et al. 2007 (CCOG0302)]
+|2003-2006
+| style="background-color:#91cf61" |Phase 2
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+'''21-day cycles'''
+</div></div><br>
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen variant #3, 80 mg/m<sup>2</sup>, 3 out of 4 weeks {{#subobject:dd21e8|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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/10.1007/s10120-005-0351-6 Hironaka et al. 2006]
+|2002-2004
+| style="background-color:#91cf61" |Non-randomized
+| style="background-color:#d3d3d3" |
+| style="background-color:#d3d3d3" |
 |-
-|[https://doi.org/10.1200/jco.1999.17.2.658 von Pawel et al. 1999]
+|[https://doi.org/10.1200/JCO.2012.48.5805 Hironaka et al. 2013 (WJOG 4007)]
-|NR
+|2007-2010
-| style="background-color:#1a9851" |Phase 3 (E-RT-de-esc)
+| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
-|[[Small_cell_lung_cancer_-_historical#CAV_3|CAV]]
+|[[#Irinotecan_monotherapy_2|Irinotecan]]
-| style="background-color:#ffffbf" |Did not meet primary endpoints of ORR/DOR
+| style="background-color:#ffffbf" |Did not meet primary endpoint of OS <br>(HR 0.88, 95% CI 0.67-1.16)
 |-
-|[https://doi.org/10.1200/jco.2006.08.3998 Eckardt et al. 2007]
+|[https://doi.org/10.1016/S1470-2045%2814%2970420-6 Wilke et al. 2014 (RAINBOW)]
-|1999-2001
+|2010-2012
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Topotecan_monotherapy|Topotecan]]; oral
+|[[#Paclitaxel_.26_Ramucirumab|Paclitaxel & Ramucirumab]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+| style="background-color:#fc8d59" |Seems to have inferior OS
 |-
-|[https://doi.org/10.1200/jco.2013.54.5392 von Pawel et al. 2014 (ACT-1)]
+|[https://doi.org/10.1002/ijc.33025 Lorenzen et al. 2020 (RADPAC)]
-|2007-2010
+|2011-2015
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Amrubicin_monotherapy|Amrubicin]]
+|[[#Everolimus_.26_Paclitaxel_99|Everolimus & Paclitaxel]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)]
+| rowspan="2" |[https://doi.org/10.1016/S2468-1253(16)30219-9 Shitara et al. 2017 (ABSOLUTE)]
-|2015-2017
+| rowspan="2" |2013-2015
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (C)
+|1. [[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]] weekly
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|2. [[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]] q3wk
+| style="background-color:#d9ef8b" |Might have superior OS
+|-
+|[https://doi.org/10.1016/S1470-2045(17)30682-4 Bang et al. 2017 (GOLD)]
+|2013-2016
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy|Nivolumab]]
+|[[#Olaparib_.26_Paclitaxel_88|Olaparib & Paclitaxel]]
 | style="background-color:#fee08b" |Might have inferior OS
 |-
-|[https://doi.org/10.1016/j.jtho.2021.02.009 Blackhall et al. 2021 (TAHOE)]
+|[https://doi.org/10.1016/S0140-6736(18)31257-1 Shitara et al. 2018 (KEYNOTE-061)]
-|2017-2018
+|2015-2016
 | style="background-color:#1a9851" |Phase 3 (C)
-|[[#Rovalpituzumab_tesirine_monotherapy_77|Rovalpituzumab tesirine]]
+|[[#Pembrolizumab_monotherapy|Pembrolizumab]]
-| style="background-color:#1a9850" |Superior OS
+| style="background-color:#fc8d59" |Seems to have inferior OS<sup>1</sup>
 |-
-|rowspan=2|[https://doi.org/10.1016/j.lungcan.2022.03.003 Edelman et al. 2022 (DISTINCT)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ Bang et al. 2018 (JAVELIN Gastric 300)]
-|rowspan=2|2017-NR in abstract
+|2015-2017
-|rowspan=2 style="background-color:#1a9851" |Phase 3 (C)
+| style="background-color:#1a9851" |Phase 3 (C)
-|1. [[#Irinotecan_.26_Dinutuximab_99|Irinotecan & Dinutuximab]]
+|[[#Avelumab_monotherapy_99|Avelumab]]
 | style="background-color:#ffffbf" |Did not meet primary endpoint of OS
 |-
-|2. [[#Irinotecan_monotherapy|Irinotecan]]
+|[https://doi.org/10.1002/cncr.34019 Chung et al. 2021 (KEYNOTE-063)]
-| style="background-color:#d3d3d3" |Not reported
+|2017-2018
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Pembrolizumab_monotherapy|Pembrolizumab]]
+| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 4 vs 2 mo<br>(HR 0.62, 95% CI 0.40-0.96)
+|-
+|[https://doi.org/10.1016/s2468-1253(21)00313-7 Xu et al. 2021 (RAINBOW-Asia)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (C)
+|[[#Paclitaxel_.26_Ramucirumab|Paclitaxel & Ramucirumab]]
+| style="background-color:#fc8d59" |Seems to have inferior PFS
 |-
 |}
-<div class="toccolours" style="background-color:#b3e2cd">
+''<sup>1</sup>Reported efficacy is based on the 2021 update, for the CPS ≥ 1 group.''<br>
+''Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."''
+''RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction)''
+''Satoh et al. patients: 98.5% gastric. 1.5 other''
+''Hironaka et al patients: 3.7% patients with a PFS of 2''
 ====Chemotherapy====
-*[[Topotecan (Hycamtin)]] 1.5 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 60 minutes once per day on days 1, 8, 15
-====Supportive therapy====
+'''28-day cycles'''
-*(varies depending on reference):
-*[[:Category:Granulocyte colony-stimulating factors|G-CSF]] use per physician discretion
-*In von Pawel et al. 2014 (ACT-1), "Prophylactic antibiotics were recommended for patients at high risk of infectious complications."
-'''21-day cycles'''
-''Duration varies depending on reference:''
-*In von Pawel et al. 1999 treatment is given until progression of disease, unacceptable toxicity, or 6 cycles beyond maximal response. Patients with stable disease after 4 cycles could have treatment discontinued at physician discretion.
-*In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles therapy.
-*In ACT-1, treatment was given for 6 cycles or until progression of disease. Patients who had at least stable disease by cycle 6 could receive another 6 cycles of treatment.
 </div></div><br>
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #3, oral route {{#subobject:cb27be|Variant=1}}===
+===Regimen variant #4, 175 mg/m<sup>2</sup> q3wk {{#subobject:a4bdf6|Variant=1}}===
 {| class="wikitable sortable" style="width: 100%; text-align:center;"
-!style="width: 20%"|Study
+! style="width: 20%" |Study
-!style="width: 20%"|Years of enrollment
+! style="width: 20%" |Years 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.2006.08.3998 Eckardt et al. 2007]
+|[https://doi.org/10.1093/annonc/mdy055 Kang et al. 2018 (DREAM)]
-|1999-2001
+|2013-2015
-| style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Topotecan_monotherapy|Topotecan]]; IV (1.5 mg/m<sup>2</sup>)
+|[[#DHP107_monotherapy_77|DHP107]]
-| style="background-color:#ffffbf" |Did not meet primary endpoint of ORR
+| style="background-color:#eeee01" |Non-inferior PFS
-|-
-|[https://doi.org/10.1200/jco.2006.06.5821 O'Brien et al. 2006 (GSK 104864/478)]
-|2000-2004
-| style="background-color:#1a9851" |Phase 3 (E-esc)
-|[[Small_cell_lung_cancer_-_null_regimens#Best_supportive_care|Best supportive care]]
-| style="background-color:#91cf60" |Seems to have superior OS
-|-
-|[https://doi.org/10.1016/s1470-2045(20)30461-7 Baize et al. 2020 (GFPC 01-2013)]
-|2013-2018
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[#Carboplatin_.26_Etoposide_.28CE.29_3|Carboplatin & Etoposide]]
-| style="background-color:#d73027" |Inferior PFS
-|-
-|[https://doi.org/10.1016/j.annonc.2021.01.071 Spigel et al. 2021 (CheckMate 331)]
-|2015-2017
-| style="background-color:#1a9851" |Phase 3 (C)
-|[[Small_cell_lung_cancer_-_historical#Nivolumab_monotherapy|Nivolumab]]
-| style="background-color:#fee08b" |Might have inferior OS
 |-
 |}
-''Note: Duration of treatment details vary depending on reference. In GSK 104864/478, treatment is given for at least 4 cycles, though this depended on tolerability and response. In Eckardt et al. 2007, patients with complete or partial response continued treatment progression of disease or 2 cycles beyond best response. Patients with stable disease received at least 4 cycles of therapy. Patients enrolled in GFPC 01-2013 received 6 cycles.''
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Topotecan (Hycamtin)]] 2.3 mg/m<sup>2</sup> PO once per day on days 1 to 5
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycle for 4 or more cycles (see note)'''
+'''21-day cycles'''
 </div></div>
 ===References===
-# von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, Stewart DJ, Clark PI, Palmer MC, Depierre A, Carmichael J, Krebs JB, Ross G, Lane SR, Gralla R. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent small-cell lung cancer. J Clin Oncol. 1999 Feb;17(2):658-67. [https://doi.org/10.1200/jco.1999.17.2.658 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/10080612 PubMed]
+#Hironaka S, Zenda S, Boku N, Fukutomi A, Yoshino T, Onozawa Y. Weekly paclitaxel as second-line chemotherapy for advanced or recurrent gastric cancer. Gastric Cancer. 2006;9(1):14-8. [https://doi.org/10.1007/s10120-005-0351-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/16557431 PubMed]
-<!-- Presented in part at the International Association for the Study of Lung Cancer’s 11th World Conference on Lung Cancer, Barcelona, Spain, July 3-6, 2005. -->
+#'''CCOG0302:''' Kodera Y, Ito S, Mochizuki Y, Fujitake S, Koshikawa K, Kanyama Y, Matsui T, Kojima H, Takase T, Ohashi N, Fujiwara M, Sakamoto J, Akimasa N; Chubu Clinical Cancer Group. A phase II study of weekly paclitaxel as second-line chemotherapy for advanced gastric cancer (CCOG0302 study). Anticancer Res. 2007 Jul-Aug;27(4C):2667-71. [http://ar.iiarjournals.org/content/27/4C/2667.long link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/17695430 PubMed]
-# '''GSK 104864/478:''' O'Brien ME, Ciuleanu TE, Tsekov H, Shparyk Y, Cuceviá B, Juhasz G, Thatcher N, Ross GA, Dane GC, Crofts T. Phase III trial comparing supportive care alone with supportive care with oral topotecan in patients with relapsed small-cell lung cancer. J Clin Oncol. 2006 Dec 1;24(34):5441-7. [https://doi.org/10.1200/jco.2006.06.5821 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17135646 PubMed] NCT00276276
+#'''WJOG 4007:''' Hironaka S, Ueda S, Yasui H, Nishina T, Tsuda M, Tsumura T, Sugimoto N, Shimodaira H, Tokunaga S, Moriwaki T, Esaki T, Nagase M, Fujitani K, Yamaguchi K, Ura T, Hamamoto Y, Morita S, Okamoto I, Boku N, Hyodo I. Randomized, open-label, phase III study comparing irinotecan with paclitaxel in patients with advanced gastric cancer without severe peritoneal metastasis after failure of prior combination chemotherapy using fluoropyrimidine plus platinum: WJOG 4007 trial. J Clin Oncol. 2013 Dec 10;31(35):4438-44. Epub 2013 Nov 4. [https://doi.org/10.1200/JCO.2012.48.5805 link to original artile] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/24190112 PubMed] UMIN000001252
-<!-- Presented in part at the 39th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, May 31 to June 3, 2003. -->
+#'''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. Epub 2014 Sep 17. [https://doi.org/10.1016/S1470-2045%2814%2970420-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25240821 PubMed] NCT01170663
-# Eckardt JR, von Pawel J, Pujol JL, Papai Z, Quoix E, Ardizzoni A, Poulin R, Preston AJ, Dane G, Ross G. Phase III study of oral compared with intravenous topotecan as second-line therapy in small-cell lung cancer. J Clin Oncol. 2007 May 20;25(15):2086-92. [https://doi.org/10.1200/jco.2006.08.3998 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/17513814 PubMed]
+#'''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://doi.org/10.1016/S2468-1253(16)30219-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28404157 PubMed] JapicCTI-132059
-<!-- Presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, June 3-7, 2011, and 14th World Conference on Lung Cancer, Amsterdam, the Netherlands, July 3-7, 2011. -->
+#'''GOLD:''' Bang YJ, Xu RH, Chin K, Lee KW, Park SH, Rha SY, Shen L, Qin S, Xu N, Im SA, Locker G, Rowe P, Shi X, Hodgson D, Liu YZ, Boku N. Olaparib in combination with paclitaxel in patients with advanced gastric cancer who have progressed following first-line therapy (GOLD): a double-blind, randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2017 Dec;18(12):1637-1651. Epub 2017 Nov 2. [https://doi.org/10.1016/S1470-2045(17)30682-4 link to original article] [https://pubmed.ncbi.nlm.nih.gov/29103871 PubMed] NCT01924533
-# '''ACT-1:''' von Pawel J, Jotte R, Spigel DR, O'Brien ME, Socinski MA, Mezger J, Steins M, Bosquée L, Bubis J, Nackaerts K, Trigo JM, Clingan P, Schütte W, Lorigan P, Reck M, Domine M, Shepherd FA, Li S, Renschler MF. Randomized phase III trial of amrubicin versus topotecan as second-line treatment for patients with small-cell lung cancer. J Clin Oncol. 2014 Dec 10;32(35):4012-9. Epub 2014 Nov 10. [https://doi.org/10.1200/jco.2013.54.5392 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25385727 PubMed] NCT00547651
+#'''DREAM:''' Kang YK, Ryu MH, Park SH, Kim JG, Kim JW, Cho SH, Park YI, Park SR, Rha SY, Kang MJ, Cho JY, Kang SY, Roh SY, Ryoo BY, Nam BH, Jo YW, Yoon KE, Oh SC. Efficacy and safety findings from DREAM: a phase III study of DHP107 (oral paclitaxel) versus IV paclitaxel in patients with advanced gastric cancer after failure of first-line chemotherapy. Ann Oncol. 2018 May 1;29(5):1220-1226. [https://doi.org/10.1093/annonc/mdy055 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/29438463 PubMed] NCT01839773
-# '''JCOG0605:''' Goto K, Ohe Y, Shibata T, Seto T, Takahashi T, Nakagawa K, Tanaka H, Takeda K, Nishio M, Mori K, Satouchi M, Hida T, Yoshimura N, Kozuki T, Imamura F, Kiura K, Okamoto H, Sawa T, Tamura T; JCOG. Combined chemotherapy with cisplatin, etoposide, and irinotecan versus topotecan alone as second-line treatment for patients with sensitive relapsed small-cell lung cancer (JCOG0605): a multicentre, open-label, randomised phase 3 trial. Lancet Oncol. 2016 Aug;17(8):1147-57. Epub 2016 Jun 14. [https://doi.org/10.1016/S1470-2045(16)30104-8 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/27312053 PubMed] UMIN000000828
+#'''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://doi.org/10.1016/S0140-6736(18)31257-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29880231 PubMed] NCT02370498
-#'''GFPC 01-2013:''' Baize N, Monnet I, Greillier L, Geier M, Lena H, Janicot H, Vergnenegre A, Crequit J, Lamy R, Auliac JB, Letreut J, Le Caer H, Gervais R, Dansin E, Madroszyk A, Renault PA, Le Garff G, Falchero L, Berard H, Schott R, Saulnier P, Chouaid C; Groupe Français de Pneumo-Cancérologie. Carboplatin plus etoposide versus topotecan as second-line treatment for patients with sensitive relapsed small-cell lung cancer: an open-label, multicentre, randomised, phase 3 trial. Lancet Oncol. 2020 Sep;21(9):1224-1233. [https://doi.org/10.1016/s1470-2045(20)30461-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32888454 PubMed] NCT02738346
+##'''Update:''' Fuchs CS, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. Epub 2021 Sep 1. [https://doi.org/10.1007/s10120-021-01227-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8732941/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34468869/ PubMed]
-# '''CheckMate 331:''' Spigel DR, Vicente D, Ciuleanu TE, Gettinger S, Peters S, Horn L, Audigier-Valette C, Pardo Aranda N, Juan-Vidal O, Cheng Y, Zhang H, Shi M, Luft A, Wolf J, Antonia S, Nakagawa K, Fairchild J, Baudelet C, Pandya D, Doshi P, Chang H, Reck M. Second-line nivolumab in relapsed small-cell lung cancer: CheckMate 331. Ann Oncol. 2021 May;32(5):631-641. Epub 2021 Feb 1. [https://doi.org/10.1016/j.annonc.2021.01.071 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/33539946/ PubMed] NCT02481830
+#'''KCSG ST10-01:''' Lee KW, Maeng CH, Kim TY, Zang DY, Kim YH, Hwang IG, Oh SC, Chung JS, Song HS, Kim JW, Jeong SJ, Cho JY. A phase III study to compare the efficacy and safety of paclitaxel versus irinotecan in patients with metastatic or recurrent gastric cancer who failed in first-line therapy (KCSG ST10-01). Oncologist. 2019 Jan;24(1):18-e24. Epub 2018 Aug 20. [http://theoncologist.alphamedpress.org/content/24/1/18.long link to original article] '''contains dosing details in abstract''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6324622/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/30126861 PubMed] NCT01224652
-#'''TAHOE:''' Blackhall F, Jao K, Greillier L, Cho BC, Penkov K, Reguart N, Majem M, Nackaerts K, Syrigos K, Hansen K, Schuette W, Cetnar J, Cappuzzo F, Okamoto I, Erman M, Langer SW, Kato T, Groen H, Sun Z, Luo Y, Tanwani P, Caffrey L, Komarnitsky P, Reinmuth N. Efficacy and Safety of Rovalpituzumab Tesirine Compared With Topotecan as Second-Line Therapy in DLL3-High SCLC: Results From the Phase 3 TAHOE Study. J Thorac Oncol. 2021 Sep;16(9):1547-1558. Epub 2021 Feb 16. [https://doi.org/10.1016/j.jtho.2021.02.009 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/33607312/ PubMed] NCT03061812
+#'''JAVELIN Gastric 300:''' Bang YJ, Yanez Ruiz E, Van Cutsem E, Lee KW, Wyrwicz L, Schenker M, Alsina M, Ryu MH, Chung HC, Evesque L, Al-Batran SE, Park SH, Lichinitser M, Boku N, Moehler MH, Hong J, Xiong H, Hallwachs R, Conti I, Taieb J. Phase III, randomised trial of avelumab versus physician's choice of chemotherapy as third-line treatment of patients with advanced gastric or gastro-oesophageal junction cancer: primary analysis of JAVELIN Gastric 300. Ann Oncol. 2018 Oct 1;29(10):2052-2060. [https://doi.org/10.1093/annonc/mdy264 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6225815/ link to PMC article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30052729 PubMed] NCT02625623
-#'''DISTINCT:''' Edelman MJ, Dvorkin M, Laktionov K, Navarro A, Juan-Vidal O, Kozlov V, Golden G, Jordan O, Deng CQ, Bentsion D, Chouaid C, Dechev H, Dowlati A, Fernández Núñez N, Ivashchuk O, Kiladze I, Kortua T, Leighl N, Luft A, Makharadze T, Min Y, Quantin X; DISTINCT study investigators. Randomized phase 3 study of the anti-disialoganglioside antibody dinutuximab and irinotecan vs irinotecan or topotecan for second-line treatment of small cell lung cancer. Lung Cancer. 2022 Apr;166:135-142. Epub 2022 Mar 4. [https://doi.org/10.1016/j.lungcan.2022.03.003 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/35278766/ PubMed] NCT03098030
+#'''RADPAC:''' Lorenzen S, Knorrenschild JR, Pauligk C, Hegewisch-Becker S, Seraphin J, Thuss-Patience P, Kopp HG, Dechow T, Vogel A, Luley KB, Pink D, Stahl M, Kullmann F, Hebart H, Siveke J, Egger M, Homann N, Probst S, Goetze TO, Al-Batran SE. Phase III randomized, double-blind study of paclitaxel with and without everolimus in patients with advanced gastric or esophagogastric junction carcinoma who have progressed after therapy with a fluoropyrimidine/platinum-containing regimen (RADPAC). Int J Cancer. 2020 Nov 1;147(9):2493-2502. Epub 2020 May 7. [https://doi.org/10.1002/ijc.33025 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/32339253/ PubMed] NCT01248403
-==Vinorelbine monotherapy {{#subobject:4177e0|Regimen=1}}==
+#'''RAINBOW-Asia:''' Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. Epub 2021 Oct 6. Epub ahead of print. [https://doi.org/10.1016/s2468-1253(21)00313-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34626550/ PubMed] NCT02898077
+#'''KEYNOTE-063:''' Chung HC, Kang YK, Chen Z, Bai Y, Wan Ishak WZ, Shim BY, Park YL, Koo DH, Lu J, Xu J, Chon HJ, Bai LY, Zeng S, Yuan Y, Chen YY, Gu K, Zhong WY, Kuang S, Shih CS, Qin SK. Pembrolizumab versus paclitaxel for previously treated advanced gastric or gastroesophageal junction cancer (KEYNOTE-063): A randomized, open-label, phase 3 trial in Asian patients. Cancer. 2022 Mar 1;128(5):995-1003. Epub 2021 Dec 8. [https://doi.org/10.1002/cncr.34019 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/34878659/ PubMed] NCT03019588
+#'''INTEGRATEIIb:''' NCT04879368
+==nab-Paclitaxel monotherapy {{#subobject:8f6227|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #1, 25 mg/m<sup>2</sup> {{#subobject:be1346|Variant=1}}===
+===Regimen {{#subobject:fe2978|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
-! style="width: 50%" |Study
+! style="width: 20%" |Study
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
 |-
-|[https://www.karger.com/Article/Abstract/227555 Furuse et al. 1996a]
+| rowspan="2" |[https://doi.org/10.1016/S2468-1253(16)30219-9 Shitara et al. 2017 (ABSOLUTE)]
-| style="background-color:#91cf61" |Phase 2
+| rowspan="2" |2013-2015
+| rowspan="2" style="background-color:#1a9851" |Phase 3 (E-switch-ic)
+|1. [[#Paclitaxel_monotherapy|Paclitaxel]]; weekly
+| style="background-color:#eeee01" |Non-inferior OS
+|-
+|2. [[#nab-Paclitaxel_monotherapy|nab-Paclitaxel]]; q3wk
+| style="background-color:#d3d3d3" |Not reported
 |-
 |}
 <div class="toccolours" style="background-color:#b3e2cd">
 ====Chemotherapy====
-*[[Vinorelbine (Navelbine)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Paclitaxel, nanoparticle albumin-bound (Abraxane)]] 100 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-'''21-day cycles'''
+'''28-day cycles'''
-</div></div><br>
+</div></div>
+===References===
+#'''ABSOLUTE:''' Shitara K, Takashima A, Fujitani K, Koeda K, Hara H, Nakayama N, Hironaka S, Nishikawa K, Makari Y, Amagai K, Ueda S, Yoshida K, Shimodaira H, Nishina T, Tsuda M, Kurokawa Y, Tamura T, Sasaki Y, Morita S, Koizumi W. Nab-paclitaxel versus solvent-based paclitaxel in patients with previously treated advanced gastric cancer (ABSOLUTE): an open-label, randomised, non-inferiority, phase 3 trial. Lancet Gastroenterol Hepatol. 2017 Apr;2(4):277-287. Epub 2017 Jan 19. [https://doi.org/10.1016/S2468-1253(16)30219-9 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/28404157 PubMed] JapicCTI-132059
+==Paclitaxel & Ramucirumab {{#subobject:fdd93f|Regimen=1}}==
 <div class="toccolours" style="background-color:#eeeeee">
-===Regimen variant #2, 30 mg/m<sup>2</sup> {{#subobject:f20f90|Variant=1}}===
+===Regimen {{#subobject:f66446|Variant=1}}===
-{| class="wikitable" style="width: 40%; text-align:center;"
+{| class="wikitable" style="color:white; background-color:#404040"
-! style="width: 50%" |Study
+|<small>'''FDA-recommended dose'''</small>
-! style="width: 50%" |[[Levels_of_Evidence#Evidence|Evidence]]
 |-
-|[https://www.ejcancer.com/article/0959-8049(93)90112-S/pdf Jassem et al. 1993]
+|}
-| style="background-color:#91cf61" |Phase 2
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045%2814%2970420-6 Wilke et al. 2014 (RAINBOW)]
+|2010-2012
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[#Paclitaxel_monotherapy|Paclitaxel]]
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 9.6 vs 7.4 mo<br>(HR 0.81, 95% CI 0.68-0.96)
+|-
+|[https://doi.org/10.1016/s2468-1253(21)00313-7 Xu et al. 2021 (RAINBOW-Asia)]
+|2017-2020
+| style="background-color:#1a9851" |Phase 3 (E-esc)
+|[[#Paclitaxel_monotherapy|Paclitaxel]]
+| style="background-color:#91cf60" |Seems to have superior PFS<br>Median PFS: 4.1 vs 3.15 mo <br>(HR 0.77, 95% CI 0.61-0.955)
+|-
+|}
+''Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."''
+''RAINBOW included patients with GE junction malignancy (79% gastric, 21% GE junction).''
+====Targeted therapy====
+*[[Ramucirumab (Cyramza)]] 8 mg/kg IV over 60 minutes once per day on days 1 & 15, '''given first'''
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, '''given second'''
+'''28-day cycles'''
+</div></div>
+===References===
+#'''RAINBOW:''' Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. Epub 2014 Sep 17. [https://doi.org/10.1016/S1470-2045%2814%2970420-6 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/25240821 PubMed] NCT01170663
+#'''RAINBOW-Asia:''' Xu RH, Zhang Y, Pan H, Feng J, Zhang T, Liu T, Qin Y, Qin S, Yin X, Liu B, Ba Y, Yang N, Voon PJ, Tanasanvimon S, Zhou C, Zhang WL, Shen L. Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial. Lancet Gastroenterol Hepatol. 2021 Dec;6(12):1015-1024. Epub 2021 Oct 6. [https://doi.org/10.1016/s2468-1253(21)00313-7 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/34626550/ PubMed] NCT02898077
+#'''RAMIRIS:''' NCT03081143
+==Pembrolizumab monotherapy {{#subobject:88c665|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:ac7d94|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885175/ Fuchs et al. 2018 (KEYNOTE-059)]
+|2015-2016
+| style="background-color:#91cf61" |Phase 2 (RT)
+| style="background-color:#d3d3d3" |
+|ORR: 12% (95% CI 8-16)
+|-
+|[https://doi.org/10.1016/S0140-6736(18)31257-1 Shitara et al. 2018 (KEYNOTE-061)]
+|2015-2016
+| style="background-color:#1a9851" |Phase 3 (E-switch-ooc)
+|[[#Paclitaxel_monotherapy|Paclitaxel]]
+| style="background-color:#91cf60" |Seems to have superior OS<sup>1</sup><br>Median OS: 9.1 vs 8.3 mo<br>(HR 0.81, 95% CI 0.66-1.00)
 |-
 |}
+''<sup>1</sup>Reported efficacy is based on the 2021 update, for the CPS ≥ 1 group.''<br>
+''Both studies included patients with GE junction malignancy:''
+*''KEYNOTE-059: 48.3% gastric, 51.4% GE junction and 57.1% of patients had a PD-L1 CPS score of at least 1''
+*''KEYNOTE-061: 68.8% gastric, 31.2% GE junction and 66% of all patients receiving pembrolizumab had a PD-L1 CPS score of at least 1''
+<div class="toccolours" style="background-color:#fdcdac">
+====Biomarker eligibility criteria====
+PD-L1 (combined positive score > 1%) as determined by an FDA-approved test.
+</div>
 <div class="toccolours" style="background-color:#b3e2cd">
-====Chemotherapy====
+====Immunotherapy====
-*[[Vinorelbine (Navelbine)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Pembrolizumab (Keytruda)]] 200 mg IV once on day 1
-'''21-day cycles'''
+'''21-day cycle for up to 35 cycles (2 years)'''
+</div></div>
+===References===
+<!-- # '''Abstract:''' Charles S. Fuchs, Toshihiko Doi, Raymond Woo-Jun Jang, Kei Muro, Taroh Satoh, Manuela Machado, ...Weijing Sun, Shadia Ibrahim Jalal, Manish A. Shah, Jean-Philippe Metges, Marcelo Garrido, Talia Golan, Mario Mandala, Zev A. Wainberg, Daniel V.T. Catenacci, Yung-Jue Bang, Jiangdian Wang, Minori Koshiji, Rita P. Dalal, Harry H. Yoon (2017). KEYNOTE-059 cohort 1: Efficacy and safety of pembrolizumab (pembro) monotherapy in patients with previously treated advanced gastric cancer. Journal of Clinical Oncology 35, no. 15_suppl (May 2017) 4003-4003. [https://doi.org/10.1200/JCO.2017.35.15_suppl.4003 link to abstract] -->
+#'''KEYNOTE-059:''' Fuchs CS, Doi T, Jang RW, Muro K, Satoh T, Machado M, Sun W, Jalal SI, Shah MA, Metges JP, Garrido M, Golan T, Mandala M, Wainberg ZA, Catenacci DV, Ohtsu A, Shitara K, Geva R, Bleeker J, Ko AH, Ku G, Philip P, Enzinger PC, Bang YJ, Levitan D, Wang J, Rosales M, Dalal RP, Yoon HH. Safety and efficacy of pembrolizumab monotherapy in patients with previously treated advanced gastric and gastroesophageal junction cancer: phase 2 clinical KEYNOTE-059 trial. JAMA Oncol. 2018 May 10;4(5):e180013. Epub 2018 May 10. [https://jamanetwork.com/journals/jamaoncology/fullarticle/2675013 link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5885175/ link to PMC article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29543932 PubMed] NCT02335411
+#'''KEYNOTE-061:''' Shitara K, Özgüroğlu M, Bang YJ, Di Bartolomeo MD, Mandalà M, Ryu MH, Fornaro L, Olesiński T, Caglevic C, Chung HC, Muro K, Goekkurt E, Mansoor W, McDermott RS, Shacham-Shmueli E, Chen X, Mayo C, Kang SP, Ohtsu A, Fuchs CS; KEYNOTE-061 investigators. Pembrolizumab versus paclitaxel for previously treated, advanced gastric or gastro-oesophageal junction cancer (KEYNOTE-061): a randomised, open-label, controlled, phase 3 trial. Lancet. 2018 Jul 14;392(10142):123-133. Epub 2018 Jun 4. [https://doi.org/10.1016/S0140-6736(18)31257-1 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/29880231 PubMed] NCT02370498
+##'''Update:''' Fuchs CS, Özgüroğlu M, Bang YJ, Di Bartolomeo M, Mandala M, Ryu MH, Fornaro L, Olesinski T, Caglevic C, Chung HC, Muro K, Van Cutsem E, Elme A, Thuss-Patience P, Chau I, Ohtsu A, Bhagia P, Wang A, Shih CS, Shitara K. Pembrolizumab versus paclitaxel for previously treated PD-L1-positive advanced gastric or gastroesophageal junction cancer: 2-year update of the randomized phase 3 KEYNOTE-061 trial. Gastric Cancer. 2022 Jan;25(1):197-206. Epub 2021 Sep 1. [https://doi.org/10.1007/s10120-021-01227-z link to original article] [https://www.ncbi.nlm.nih.gov/pmc/articles/pmc8732941/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/34468869/ PubMed]
+==Ramucirumab monotherapy {{#subobject:425b15|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:813cff|Variant=1}}===
+{| class="wikitable" style="color:white; background-color:#404040"
+|<small>'''FDA-recommended dose'''</small>
+|-
+|}
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S0140-6736(13)61719-5 Fuchs et al. 2013 (REGARD)]
+|2009-2012
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#91cf60" |Seems to have superior OS<br>Median OS: 5.2 vs 3.8 mo<br>(HR 0.78, 95% CI 0.60-0.998)
+|-
+|}
+''Patients in REGARD previously had "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."''
+''Study includes patients with GE junction malignancy (75% gastric, 25% GE junction).''
+====Targeted therapy====
+*[[Ramucirumab (Cyramza)]] 8 mg/kg IV over 60 minutes once on day 1
+'''14-day cycles'''
+</div></div>
+===References===
+#'''REGARD:''' Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. [https://doi.org/10.1016/S0140-6736(13)61719-5 link to original article] '''contains dosing details in manuscript''' [https://pubmed.ncbi.nlm.nih.gov/24094768 PubMed] NCT00917384
+==Regorafenib monotherapy {{#subobject:022ef0|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:5f203f|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ Pavlakis et al. 2016 (INTEGRATE)]
+|2012-2014
+| style="background-color:#1a9851" |Randomized Phase 2 (E-esc)
+|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior PFS<br>Median PFS: 2.6 vs 0.9 mo<br>(HR 0.40, 95% CI 0.28-0.59)
+|-
+|}
+''INTEGRATE included patients with GEJ malignancy: 62% stomach or other, 38% GEJ''
+====Targeted therapy====
+*[[Regorafenib (Stivarga)]] 160 mg PO once per day on days 1 to 21
+'''28-day cycles'''
+</div></div>
+===References===
+#'''INTEGRATE:''' Pavlakis N, Sjoquist KM, Martin AJ, Tsobanis E, Yip S, Kang YK, Bang YJ, Alcindor T, O'Callaghan CJ, Burnell MJ, Tebbutt NC, Rha SY, Lee J, Cho JY, Lipton LR, Wong M, Strickland A, Kim JW, Zalcberg JR, Simes J, Goldstein D. Regorafenib for the treatment of advanced gastric cancer (INTEGRATE): A multinational placebo-controlled phase II trial. J Clin Oncol. 2016 Aug 10;34(23):2728-35. Epub 2016 Jun 20. [https://doi.org/10.1200/JCO.2015.65.1901 link to original article] '''contains dosing details in manuscript''' [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5019744/ link to PMC article] [https://pubmed.ncbi.nlm.nih.gov/27325864 PubMed] ANZCTR12612000239864
+==Trifluridine and tipiracil monotherapy {{#subobject:938bf3|Regimen=1}}==
+<div class="toccolours" style="background-color:#eeeeee">
+===Regimen {{#subobject:cfc20c|Variant=1}}===
+{| class="wikitable sortable" style="width: 100%; text-align:center;"
+! style="width: 20%" |Study
+! style="width: 20%" |Years of enrollment
+! style="width: 20%" |[[Levels_of_Evidence#Evidence|Evidence]]
+! style="width: 20%" |Comparator
+! style="width: 20%" |[[Levels_of_Evidence#Comparative_efficacy|Comparative Efficacy]]
+|-
+|[https://doi.org/10.1016/S1470-2045(18)30739-3 Shitara et al. 2018 (TAGS)]
+|2016-2018
+| style="background-color:#1a9851" |Phase 3 (E-RT-esc)
+|[[Gastric_cancer_-_null_regimens#Placebo|Placebo]]
+| style="background-color:#1a9850" |Superior OS<br>Median OS: 5.7 vs 3.6 mo<br>(HR 0.69, 95% CI 0.56-0.85)
+|-
+|}
+<div class="toccolours" style="background-color:#b3e2cd">
+====Chemotherapy====
+*[[Trifluridine and tipiracil (Lonsurf)]] 35 mg/m<sup>2</sup> PO twice per day on days 1 to 5, 8 to 12
+'''28-day cycles'''
 </div></div>
 ===References===
-# Jassem J, Karnicka-Mlodkowska H, van Pottelsberghe C, van Glabbeke M, Noseda MA, Ardizzoni A, Gozzelino F, Planting A, van Zandwijk N; [[Study_Groups#EORTC|EORTC]] Lung Cancer Cooperative Group. Phase II study of vinorelbine (Navelbine) in previously treated small cell lung cancer patients. Eur J Cancer. 1993;29A(12):1720-2. [https://www.ejcancer.com/article/0959-8049(93)90112-S/pdf link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8398301 PubMed]
+#'''TAGS:''' Shitara K, Doi T, Dvorkin M, Mansoor W, Arkenau HT, Prokharau A, Alsina M, Ghidini M, Faustino C, Gorbunova V, Zhavrid E, Nishikawa K, Hosokawa A, Yalçın Ş, Fujitani K, Beretta GD, Van Cutsem E, Winkler RE, Makris L, Ilson DH, Tabernero J. Trifluridine/tipiracil versus placebo in patients with heavily pretreated metastatic gastric cancer (TAGS): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet Oncol. 2018 Nov 1;19(11):1437-48. Epub 2018 Oct 18. [https://doi.org/10.1016/S1470-2045(18)30739-3 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/30355453 PubMed] NCT02500043
-# Furuse K, Kubota K, Kawahara M, Takada M, Kimura I, Fujii M, Ohta M, Hasegawa K, Yoshida K, Nakajima S, Ogura T, Niitani H; Japan Lung Cancer Vinorelbine Study Group. Phase II study of vinorelbine in heavily previously treated small cell lung cancer. Oncology. 1996 Mar-Apr;53(2):169-72. [https://www.karger.com/Article/Abstract/227555 link to original article] '''contains dosing details in abstract''' [https://pubmed.ncbi.nlm.nih.gov/8604245 PubMed]
+#'''INTEGRATEIIb:''' NCT04879368
-[[Category:Small cell lung cancer regimens]]
+[[Category:Gastric cancer regimens]]
 [[Category:Disease-specific pages]]
-[[Category:Lung cancers]]
+[[Category:Gastroesophageal cancers]]

Difference between revisions of "Staging page"

Revision as of 16:46, 9 October 2022

Guidelines

ESMO

ESMO/ESSO/ESTRO

NCCN

Perioperative therapy

Capecitabine & Cisplatin (CX)

Protocol

Chemotherapy, neoadjuvant CX portion

Surgery

Chemotherapy, adjuvant CX portion

References

Cisplatin & Fluorouracil (CF)

Protocol variant #1, 80/4000

Chemotherapy, neoadjuvant CF portion

Surgery

Chemotherapy, adjuvant CF portion

Protocol variant #2, 100/4000

Chemotherapy, neoadjuvant CF portion

Surgery

Chemotherapy, adjuvant CF portion

References

ECF

Regimen

Chemotherapy, neoadjuvant ECF portion

Supportive therapy

Surgery

Chemotherapy, adjuvant ECF portion

Supportive therapy

References

ECX

Protocol

Chemotherapy, neoadjuvant ECX portion

Surgery

Chemotherapy, adjuvant ECX portion

References

EOF

Protocol

Chemotherapy, neodjuvant EOF portion

Surgery

Chemotherapy, adjuvant EOF portion

References

EOX

Protocol

Chemotherapy, neoadjuvant EOX portion

Surgery

Chemotherapy, adjuvant EOX portion

References

FLOT

Protocol variant #1, 3 + 3

Chemotherapy, neoadjuvant FLOT portion

Surgery

Chemotherapy, adjuvant FLOT portion

Protocol variant #2, 4 + 4

Chemotherapy, neoadjuvant FLOT portion

Surgery

Chemotherapy, adjuvant FLOT portion

References

SOX

Protocol

Chemotherapy, neoadjuvant SOX portion

Preceding treatment

Chemotherapy, adjuvant SOX portion

References

Neoadjuvant chemotherapy

DOS

Regimen

Chemotherapy

Subsequent treatment

References

ECF

Regimen

Chemotherapy

References

Adjuvant therapy

CapeOx

Regimen

Preceding treatment

Chemotherapy

Regimen variant #1, 2000 mg/m²/day

Regimen variant #2, 2500 mg/m²/day