Esophageal adenocarcinoma
Page editor | Section editor | ||
---|---|---|---|
Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL |
Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL |
Note: these are regimens tested in histology-specific populations, please see the main esophageal cancer page for other regimens.
42 regimens on this page
47 variants on this page
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Neoadjuvant induction therapy
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol (Cisplatin)
Regimen variant #1, 40/4200
Study | Evidence |
---|---|
Ajani et al. 2006 (RTOG 9904) | Phase II |
Patients: 100% adenocarcinoma histology. The majority of patients had gastric adenocarcinoma. Although gastroesophageal junction was involved, percentages were not included.
Chemotherapy
- Cisplatin (Platinol) 20 mg/m2 IV once per day on days 1 & 5
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
28-day cycle for 2 cycles
Subsequent treatment
Regimen variant #2, 80/4000, 4 day 5-FU infusion
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Alderson et al. 2017 (UK MRC OE05) | 2005-2011 | Phase III (C) | ECX | Did not meet primary endpoint of OS |
UK MRC OE05 patients: 100% adenocarcinoma of the esophagus (including Siewert types 1 and 2 gastroesophageal junction tumors)
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
21-day cycle for 2 cycles
Subsequent treatment
Regimen variant #4, 100/4000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ychou et al. 2011 (ACCORD 07) | 1995-2003 | Phase III (E-esc) | Surgery alone | Seems to have superior OS |
This is the neoadjuvant portion of pre-planned perioperative chemotherapy. It is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Patients: 100% adenocarcinoma histology (65% esophagogastric junction, 10% lower esophageal, 25% gastric adenocarcinoma)
Chemotherapy
- Cisplatin (Platinol) 100 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)
28-day cycle for 2 or 3 cycles
Subsequent treatment
- Surgery, then adjuvant CF
References
- RTOG 9904: Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. link to original article contains verified protocol 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. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. link to original article contains verified protocol PubMed NCT00002883
- UK MRC OE05: Alderson D, Cunningham D, Nankivell M, Blazeby JM, Griffin SM, Crellin A, Grabsch HI, Langer R, Pritchard S, Okines A, Krysztopik R, Coxon F, Thompson J, Falk S, Robb C, Stenning S, Langley RE. Neoadjuvant cisplatin and fluorouracil versus epirubicin, cisplatin, and capecitabine followed by resection in patients with oesophageal adenocarcinoma (UK MRC OE05): an open-label, randomised phase 3 trial. Lancet Oncol. 2017 Sep;18(9):1249-1260. Epub 2017 Aug 4. link to original article link to PMC article contains verified protocol PubMed ISRCTN01852072
Cisplatin & Irinotecan (IC)
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IC: Irinotecan & Cisplatin
Regimen
Study | Evidence |
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Rivera et al. 2009 | Phase II |
Rivera et al. patients: 100% adenocarcinoma histology (43% gastroesophageal junction, 57% gastric adenocarcinoma)
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
- Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
Supportive medications
- Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1 & 8, prior to chemotherapy
- One of the following:
- Granisetron 2 mg PO once per day on days 1 & 8, prior to chemotherapy
- Ondansetron (Zofran) 32 mg IV once per day on days 1 & 8, prior to chemotherapy
- At least 500 mL D5NS or NS as supportive hydration
- Atropine (Atropen) 0.5 to 1 mg IV prn cholinergic symptoms
21-day cycle for 2 cycles
Subsequent treatment
References
- Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. link to original article contains verified protocol PubMed
CLF
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CLF: Cisplatin, Leucovorin (Folinic acid), Fluorouracil
PLF: Platinol (Cisplatin), Leucovorin (Folinic acid), Fluorouracil
Regimen variant #1, 12 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Stahl et al. 2009 (POET) | 2000-2005 | Phase III (C) | See link | See link |
Patients: 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1, 15, 29
- Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m2 )
42-day cycle for 2 cycles
Subsequent treatment
Regimen variant #2, 15 weeks
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stahl et al. 2009 (POET) | 2000-2005 | Phase III (C) | PLF x 12 wk, then EP & RT | Might have inferior OS |
Note: this regimen is given for 2.5 cycles, which is a highly unusual instruction; total duration of treatment is 15 weeks.
Patients: 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.
Chemotherapy
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1, 15, 29
- Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
- Fluorouracil (5-FU) 2000 mg/m2 IV continuous infusion over 24 hours, started on days 1, 8, 15, 22, 29, 36 (total dose per cycle: 12,000 mg/m2 )
42-day cycle for 2.5 cycles
Subsequent treatment
- Surgery, in 3 to 4 weeks
References
- POET: Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article contains verified protocol PubMed
- Update: Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. link to original article PubMed
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2006 (MAGIC) | 1994-2002 | Phase III (E-esc) | See link | See link |
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase II/III (C) | See link | See link |
This is the neoadjuvant portion of pre-planned perioperative chemotherapy.
Cunningham et al. Patients: 100% adenocarcinoma histology. 75% gastric adenocarcinoma, 15% lower esophagus, 11% gastroesophageal junction.
Al-Batran et. al Patients: 100% adenocarcinoma histology of the gastroesophageal junction (AEG I-III) or the stomach.
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2 )
Supportive medications
- MAGIC: Warfarin (Coumadin) 1 mg PO once per day recommended for thrombosis prophylaxis
21-day cycle for 3 cycles
Subsequent treatment
- Surgery occurs 3 to 6 weeks after completing cycle 3, then adjuvant ECF is started 6 to 12 weeks after surgery
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 verified protocol PubMed
- FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed NCT01216644
- Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. link to original article PubMed
ECX
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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Cunningham et al. 2017 (UK MRC ST03) | 2007-2014 | Phase III (C) | ECX & Bevacizumab | Did not meet primary endpoint of OS |
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase II/III (C) | See link | See link |
This is the neoadjuvant portion of pre-planned perioperative chemotherapy.
Cunningham et al. Patients: 100% adenocarcinoma histology (36% gastric, 14% lower esophageal, 50% gastroesophageal junction).
Al-Batran et al. Patients: 100% adenocarcinoma histology including gastroesophageal junction (AEG I-III) or the stomach.
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 on days 1 to 21
21-day cycle for 3 cycles
Subsequent treatment
- Surgery, then adjuvant ECX
References
- FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed NCT01216644
- Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. link to original article PubMed
- UK MRC ST03: Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. link to original article contains protocol link to PMC article PubMed NCT00450203
FLOT
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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase II/III (E-switch-ic) | See link | See link |
This is the neoadjuvant portion of pre-planned perioperative chemotherapy.
Patients: 100% adenocarcinoma histology of the gastroesophageal junction (AEG I-III) or the stomach
Chemotherapy
- 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
Subsequent treatment
- Surgery, then adjuvant FLOT
References
- FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed NCT01216644
- Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. link to original article PubMed
Neoadjuvant chemoradiotherapy
Note: while these regimens are listed as neoadjuvant (pre-operative), in some cases they are also used as definitive therapy in patients that are not surgical candidates.
Cisplatin, Etoposide, RT
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EP & RT: Etoposide, Platinol (Cisplatin), Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Stahl et al. 2009 (POET) | 2000-2005 | Phase III (E-esc) | See link | See link |
Patients: 100% adenocarcinoma histology. 55% Siewert classification Type I, 45% Siewert classification Types II &III.
Preceding treatment
- PLF x 12 wk
Chemotherapy, to start 2 weeks after the last day of PLF
- Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once per day on days 1 & 8
- Etoposide (Vepesid) 80 mg/m2 IV over 60 minutes once per day on days 3 to 5
Radiotherapy
- Concurrent radiation therapy, 2.0 Gy fractions x 15 fractions (target dose of 30 Gy)
3-week course
Subsequent treatment
- Surgery, in 3 to 4 weeks
References
- POET: Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article contains verified protocol PubMed
- Update: Stahl M, Walz MK, Riera-Knorrenschild J, Stuschke M, Sandermann A, Bitzer M, Wilke H, Budach W. Preoperative chemotherapy versus chemoradiotherapy in locally advanced adenocarcinomas of the oesophagogastric junction (POET): long-term results of a controlled randomised trial. Eur J Cancer. 2017 Aug;81:183-190. link to original article PubMed
Cisplatin, Fluorouracil, RT
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CF & RT: Cisplatin, Fluourouracil, Radiation Therapy
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Walsh et al. 1996 | 1990-1995 | Randomized Phase II (E-esc) | Surgery alone | Superior OS |
Note: of historic interest only.
Chemotherapy
Radiotherapy
- Concurrent radiation therapy
Subsequent treatment
References
- Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. link to original article contains verified protocol PubMed
Cisplatin, Irinotecan, RT
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Cisplatin, Irinotecan, RT: Cisplatin, Irinotecan, Radiation Therapy
Regimen variant #1, 60/130 x 2 + 45 Gy
Study | Evidence |
---|---|
Yoon et al. 2011 | Phase II |
Patients: 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycle for 2 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
5-week course
Subsequent treatment
- Yoon et al. 2011: surgery at least 28 days after finishing chemoradiation, then begin adjuvant IC at least 28 days after surgical resection
Regimen variant #2
Study | Evidence |
---|---|
Rivera et al. 2009 | Phase II |
Patients: 100% adenocarcinoma histology (43% gastroesophageal junction, 57% gastric adenocarcinoma)
Preceding treatment
- IC induction x 2
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1, 8, 15, 22
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
5-week course
Subsequent treatment
- Surgery, 5 to 8 weeks after finishing chemoradiation
References
- Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. link to original article contains verified protocol PubMed
- Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol link to PMC article PubMed
Cisplatin, Paclitaxel, RT
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Cisplatin, Paclitaxel, RT: Cisplatin, Paclitaxel, Radiation Therapy
Regimen variant #1, weekly cisplatin
Study | Evidence |
---|---|
Yoon et al. 2011 | Phase II |
Patients: 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29
- Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
5-week course
Subsequent treatment
- Surgery at least 28 days after finishing chemoradiation, then adjuvant cisplatin & paclitaxel at least 28 days after surgical resection
References
- Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol link to PMC article PubMed
Fluorouracil, Paclitaxel, RT
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Fluorouracil, Paclitaxel, RT: Fluorouracil, Paclitaxel, Radiation Therapy
Regimen
Study | Evidence |
---|---|
Ajani et al. 2006 (RTOG 9904) | Phase II |
Patients: 100% adenocarcinoma histology. The majority of patients had gastric adenocarcinoma. Although gastroesophageal junction was involved, percentages were not included.
Preceding treatment
- CF induction x 2
Chemotherapy
- Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 1500 mg/m2)
- Paclitaxel (Taxol) 45 mg/m2 IV once on day 1
7-day cycle for 5 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy
5-week course
Subsequent treatment
References
- RTOG 9904: Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. link to original article contains verified protocol PubMed
Adjuvant therapy
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol
Regimen variant #3, 100/4000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ychou et al. 2011 (ACCORD 07) | 1995-2003 | Phase III (E-esc) | Observation | Seems to have superior OS |
This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
Patients: 100% adenocarcinoma histology (65% gastroesophageal junction, 10% lower esophageal, 25% gastric adenocarcinoma)
Preceding treatment
- Neoadjuvant CF, then surgery
Chemotherapy
- Cisplatin (Platinol) 100 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)
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. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. link to original article contains verified protocol PubMed NCT00002883
Cisplatin & Irinotecan (IC)
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Regimen
Study | Evidence |
---|---|
Yoon et al. 2011 | Phase II |
Patients: 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1 & 8
- Irinotecan (Camptosar) 65 mg/m2 IV once per day on days 1 & 8
21-day cycle for 3 cycles
References
- Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol link to PMC article PubMed
Cisplatin & Paclitaxel
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Regimen
Study | Evidence |
---|---|
Yoon et al. 2011 | Phase II |
Patients: 100% adenocarcinoma of the esophagus or gastroesophageal junction (tumor extension < 2cm into gastric cardia)
Preceding treatment
Chemotherapy
- Cisplatin (Platinol) 75 mg/m2 IV once on day 1
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
21-day cycle for 3 cycles
References
- Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM; ECOG. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol link to PMC article PubMed
ECF
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ECF: Epirubicin, Cisplatin, Fluorouracil
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2006 (MAGIC) | 1994-2002 | Phase III (E-esc) | See link | See link |
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase II/III (C) | See link | See link |
This is the adjuvant portion of pre-planned perioperative chemotherapy.
Cunningham et al. Patients: 100% adenocarcinoma histology (75% gastric adenocarcinoma, 15% lower esophagus, 11% gastroesophageal junction).
Al-Batran et. al Patients: 100% adenocarcinoma histology of the gastroesophageal junction (AEG I-III) or the stomach.
Preceding treatment
- Neoadjuvant ECF x 3, then surgery
Chemotherapy, to start 6 to 12 weeks after surgery
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
Supportive medications
- MAGIC: Warfarin (Coumadin) 1 mg PO once per day recommended for thrombosis prophylaxis
21-day cycle for 3 cycles
References
- MAGIC: Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ; MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains verified protocol PubMed
- FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed NCT01216644
- Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. link to original article PubMed
ECF/5-FU & RT
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ECF/5-FU & RT: Epirubicin, Cisplatin, Fluorouracil alternating with 5-FluoroUracil & Radiation Therapy
Protocol
Study | Evidence |
---|---|
Leong et al. 2010 | Phase II |
Note: In contrast to the primary reference, some guidelines list this regimen without ECF cycles 1, 3, 4.
Patients: 100% adenocarcinoma (6% gastroesophageal junction, 94% gastric origin).
Preceding treatment
- Surgery, within 10 weeks
Chemotherapy, part 1
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on day 1 (total dose: 4200 mg/m2)
21-day cycle, followed 1 to 3 weeks later by:
Chemotherapy, part 2
- Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion, started on day 1 (total dose: 7875 mg/m2)
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions for a total dose of 45 Gy
5-week course, followed 1 month later by:
Chemotherapy, part 3
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 4200 mg/m2)
21-day cycle for 2 cycles
References
- Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M; Trans-Tasman Radiation Oncology Group. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):690-5. Epub 2010 May 14. link to original article contains verified protocol PubMed
ECX
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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Cunningham et al. 2017 (UK MRC ST03) | 2007-2014 | Phase III (C) | ECX & Bevacizumab | Did not meet primary endpoint of OS |
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase II/III (C) | See link | See link |
This is the adjuvant portion of pre-planned perioperative chemotherapy.
Cunningham et al. Patients: 100% adenocarcinoma histology (36% gastric, 14% lower esophageal, 50% gastroesophageal junction).
Al-Batran et al. Patients: 100% adenocarcinoma histology including gastroesophageal junction (AEG I-III) or the stomach.
Preceding treatment
- Neoadjuvant ECX x 3, then surgery
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 on days 1 to 21
21-day cycle for 3 cycles
References
- FLOT4-AIO: Al-Batran SE, Hofheinz RD, Pauligk C, Kopp HG, Haag GM, Luley KB, Meiler J, Homann N, Lorenzen S, Schmalenberg H, Probst S, Koenigsmann M, Egger M, Prasnikar N, Caca K, Trojan J, Martens UM, Block A, Fischbach W, Mahlberg R, Clemens M, Illerhaus G, Zirlik K, Behringer DM, Schmiegel W, Pohl M, Heike M, Ronellenfitsch U, Schuler M, Bechstein WO, Königsrainer A, Gaiser T, Schirmacher P, Hozaeel W, Reichart A, Goetze TO, Sievert M, Jäger E, Mönig S, Tannapfel A. Histopathological regression after neoadjuvant docetaxel, oxaliplatin, fluorouracil, and leucovorin versus epirubicin, cisplatin, and fluorouracil or capecitabine in patients with resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4-AIO): results from the phase 2 part of a multicentre, open-label, randomised phase 2/3 trial. Lancet Oncol. 2016 Dec;17(12):1697-1708. Epub 2016 Oct 22. link to original article PubMed NCT01216644
- Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. link to original article PubMed
- UK MRC ST03: Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. link to original article contains protocol link to PMC article PubMed NCT00450203
FLOT
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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Al-Batran et al. 2016 (FLOT4-AIO) | 2010-2015 | Phase II/III (E-switch-ic) | See link | See link |
This is the adjuvant portion of pre-planned perioperative chemotherapy.
Patients: 100% adenocarcinoma histology including gastroesophageal junction (AEG I-III) or the stomach.
Preceding treatment
- Neoadjuvant FLOT x 4, then surgery
Chemotherapy
- 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
- Update: Al-Batran SE, Homann N, Pauligk C, Goetze TO, Meiler J, Kasper S, Kopp HG, Mayer F, Haag GM, Luley K, Lindig U, Schmiegel W, Pohl M, Stoehlmacher J, Folprecht G, Probst S, Prasnikar N, Fischbach W, Mahlberg R, Trojan J, Koenigsmann M, Martens UM, Thuss-Patience P, Egger M, Block A, Heinemann V, Illerhaus G, Moehler M, Schenk M, Kullmann F, Behringer DM, Heike M, Pink D, Teschendorf C, Löhr C, Bernhard H, Schuch G, Rethwisch V, from Weikersthal LF, Hartmann JT, Kneba M, Daum S, Schulmann K, Less J, Belle S, Gaiser T, Oduncu FS, Güntner M, Hozaeel W, Reichart A, Hunter E, Kraus T, Mönig S, Bechstein WO, Schuler M, Schmalenberg H, Hofheinz RD; FLOT4-AIO Investigators. perioperative chemotherapy with fluorouracil plus leucovorin, oxaliplatin, and docetaxel versus fluorouracil or capecitabine plus cisplatin and epirubicin for locally advanced, resectable gastric or gastro-oesophageal junction adenocarcinoma (FLOT4): a randomized, phase 2/3 trial. Lancet. 2019 May 11;393(10184):1948-1957. Epub 2019 Apr 11. link to original article PubMed
FULV/FULV & RT
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FULV/FULV & RT: FluoroUracil & LeucoVorin (Folinic acid) alternating with FluoroUracil, LeucoVorin (Folinic acid) & Radiation Therapy
Protocol variant #1
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Macdonald et al. 2001 (INT-0116) | 1991-1998 | Phase III (E-esc) | Observation | Superior OS |
Preceding treatment
Chemotherapy, part 1
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5 (total dose per cycle: 2125 mg/m2)
- Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 5
28-day 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 (total dose per cycle: 2800 mg/m2)
- 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 1.8 Gy x 25 fractions for a total of 45 Gy
35-day course, followed by:
Chemotherapy, part 3, to start one month after the completion of radiotherapy
- Fluorouracil (5-FU) 425 mg/m2 IV bolus once per day on days 1 to 5 (total dose per cycle 2125 mg/m2)
- Folinic acid (Leucovorin) 20 mg/m2 IV bolus once per day on days 1 to 5
28-day cycle for 2 cycles
Regimen variant #2
Note: No primary reference could be found for this regimen.
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 400 mg/m2 IV bolus on EITHER days 1 & 15 OR days 1, 2, 15, 16
- Fluorouracil (5-FU) 1200 mg/m2 IV continuous infusion over 24 hours, started on days 1, 2, 15, 16 (total dose per cycle: 4800 mg/m2)
- Folinic acid (Leucovorin) 400 mg/m2 IV on EITHER days 1 & 15 OR days 1, 2, 15, 16
28-day cycle for 3 total cycles (1 cycle given before radiation, and 2 cycles to be given after radiation)
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 verified protocol PubMed
Metastatic or locally advanced disease, first-line
Capecitabine & Cisplatin (CX)
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CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2009 | 2003-2006 | Randomized Phase II (E-switch-ic) | XI | Did not meet primary endpoint of ORR |
Lordick et al. 2013 (EXPAND) | 2008-2010 | Phase III (C) | CX & Cetuximab | Did not meet primary endpoint of PFS |
EXPAND patients: 100% adenocarcinoma (stomach or gastroesophageal junction) locally advanced unresectable (M0) or metastatic (M1).
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Lordick et al. 2013: 1000 mg/m2 PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)
21-day cycles
References
- Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. link to original article PubMed
- EXPAND: Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed EudraCT 2007-004219-75
Capecitabine & Cisplatin (CX) & Cetuximab
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CX-C: Cisplatin, Xeloda (Capecitabine), Cetuximab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lordick et al. 2013 (EXPAND) | 2008-2010 | Phase III (E-esc) | CX | Did not meet primary endpoint of PFS |
Patients: 100% adenocarcinoma (stomach or gastroesophageal junction) locally advanced unresectable (M0) or metastatic (M1).
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 2 hours once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day from the evening of day 1 to the morning of day 15 (28 doses per cycle)
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV once on day 1
- Subsequently: 250 mg/m2 IV once per day on days 1, 8, 15
21-day cycles
References
- EXPAND: Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed EudraCT 2007-004219-75
CapeOx
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CapeOX: Capecitabine & OXaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2020 (JAVELIN Gastric 100) | 2015-2017 | Phase III (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 |
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Oxaliplatin (Eloxatin) 130 mg/m2 IV once on day 1
21-day cycles
References
- JAVELIN Gastric 100: Moehler M, Dvorkin M, Boku N, Özgüroğlu M, Ryu MH, Muntean AS, Lonardi S, Nechaeva M, Bragagnoli AC, Coşkun HS, Cubillo Gracian A, Takano T, Wong R, Safran H, Vaccaro GM, Wainberg ZA, Silver MR, Xiong H, Hong J, Taieb J, Bang YJ. Phase III Trial of Avelumab Maintenance After First-Line Induction Chemotherapy Versus Continuation of Chemotherapy in Patients With Gastric Cancers: Results From JAVELIN Gastric 100. J Clin Oncol. 2021 Mar 20;39(9):966-977. Epub 2020 Nov 16. link to original article contains verified protocol PubMed NCT02625610
CAPIRI
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CapeIRI: Capecitabine and IRInotecan
CAPIRI: CAPecitabine and IRInotecan
XELIRI: XELox (Capecitabine) and IRInotecan
XI: Xeloda (Capecitabine) and Irinotecan
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Moehler et al. 2009 | 2003-2006 | Randomized Phase II (E-switch-ic) | XP | Did not meet primary endpoint of ORR |
Patients: 45% esophageal, 38% gastroesophageal junction, 17% gastric origin. 93% adenocarcinoma, 7% squamous cell histology. 86% metastatic disease. 14% ECOG PS of 2.
Chemotherapy
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
- Irinotecan (Camptosar) 250 mg/m2 IV over 30 to 90 minutes once on day 1
Supportive medications
- Atropine (Atropen) 0.25 mg SC once on day 1, given before Irinotecan (Camptosar)
- Loperamide (Imodium) 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool
- Ciprofloxacin (Cipro) 250 mg PO twice per day prn diarrhea lasting longer than 24 hours despite loperamide
21-day cycles
References
- Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. link to original article PubMed
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Van Cutsem et al. 2006 (TAX 325) | 1999-2003 | Phase III (C) | DCF | Seems to have inferior OS |
Dank et al. 2008 | 2000-2002 | Phase III (C) | IF | Might have inferior TTP |
Van Cutsem et al Patients: 100% adenocarcinoma histology (22% gastroesophageal junction, 88% gastric origin). 97% with metastatic disease. 1% with Karnosky PS of 70.
Dank et al Patients: 100% adenocarcinoma histology (20% gastroesophageal junction, 80% gastric origin). 96% with metastatic disease. 1% with Karnofsky PS of 70.
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 1 to 3 hours once on day 1, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 5000 mg/m2 )
Supportive medications
- 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
- 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 verified protocol 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 verified protocol PubMed
ECX
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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
Regimen variant #1, 50/60/1250
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Iveson et al. 2014 (Amgen 20060317) | 2009 | Randomized Phase II (C) | ECX & Rilotumumab | Seems to have inferior PFS |
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV bolus once on day 1
- Cisplatin (Platinol) 60 mg/m2 IV over 4 hours once on day 1
- Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 21
21-day cycles
Regimen variant #2, 50/60/2000
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Guimbaud et al. 2014 (FFCD 03-07) | 2005-2008 | Phase III (C) | FOLFIRI | Inferior TTF |
Chemotherapy
- Epirubicin (Ellence) 50 mg/m2 IV over 15 minutes once on day 1
- Maximum cumulative dose allowed was 900 mg/m2
- Cisplatin (Platinol) 60 mg/m2 IV over 60 minutes once on day 1
- Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 2 to 15
21-day cycles
References
- Amgen 20060317: Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. Epub 2014 Jun 22. link to original article contains protocol PubMed NCT00719550
- FFCD 03-07: Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. link to original article contains verified protocol PubMed NCT00374036
Erlotinib monotherapy
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Regimen
Study | Evidence |
---|---|
Dragovich et al. 2006 (SWOG 0127) | Phase II |
Patients: 100% adenocarcinoma (63% gastroesophageal junction, 37% gastric origin). All with ECOG PS of 0 or 1.
Targeted therapy
- Erlotinib (Tarceva) 150 mg PO once per day, at least 1 hour before a meal, or 2 hours after a meal
28-day cycles
References
- SWOG 0127: Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. link to original article contains verified protocol PubMed NCT00032123
FLOT
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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere (Docetaxel)
Regimen
Study | Evidence |
---|---|
Al-Batran et al. 2008a | Phase II |
Patients: 100% adenocarcinoma histology (44% gastroesophageal junction, 56% gastric origin). 93% metastatic disease. 15% with ECOG 2-3.
Chemotherapy
- Fluorouracil (5-FU) 2600 mg/m2 IV continuous infusion over 24 hours, started on day 1, given fourth
- Folinic acid (Leucovorin) 200 mg/m2 IV over 1 to 2 hours once on day 1
- Oxaliplatin (Eloxatin) 85 mg/m2 IV over 1 to 2 hours once on day 1
- Docetaxel (Taxotere) 50 mg/m2 IV over 1 to 2 hours once on day 1
Supportive medications
- Dexamethasone (Decadron) 8 mg PO once per day on days 0 to 3
14-day cycle for up to 8 (or more) cycles
References
- Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. link to original article contains verified protocol PubMed
FOLFIRI
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FOLFIRI: FOLinic acid, Fluorouracil, IRInotecan
IF: Irinotecan & 5-Fluorouracil
Regimen
Study | Years of enrollment | Evidence |
---|---|---|
Wolff et al. 2009 | 2002-2006 | Phase II |
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 medications
- 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
References
- Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. link to original article contains protocol PubMed
Irinotecan monotherapy
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Regimen
Study | Evidence |
---|---|
Enzinger et al. 2005 | Phase II |
Note: In contrast to the primary reference, some guidelines list a dosing schedule of 125 mg/m2 IV once per day on days 1 & 8, with 21-day cycles.
Patients: 100% adenocarcinoma histology, both gastric and esophageal
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV over 90 minutes once per day on days 1, 8, 15, 22
42-day cycles
References
- Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. link to original article PubMed
Irinotecan & Mitomycin
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Lustberg et al. 2010 | 2002-2006 | Randomized Phase II (E-switch-ic) | Irinotecan & Mitomycin (alternate schedule) | No statistical comparison |
Patients: 56% lower esophageal, 44% gastroesophageal junction. 100% adenocarcinoma histology. 100% previously untreated 6% with ECOG PS = 2. 77% stage four disease.
Chemotherapy
- Irinotecan (Camptosar) 125 mg/m2 IV once per day on days 2 & 9
- Mitomycin (Mutamycin) 6 mg/m2 IV once on day 1
Supportive medications
- Ondansetron (Zofran) or Granisetron and Dexamethasone (Decadron) premedication
- Loperamide (Imodium) started with first episode of diarrhea
- Erythropoietin for hemoglobin less than 10 g/dL permitted
28-day cycle for up to 6 cycles
References
- Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. link to original article contains verified protocol link to PMC article PubMed
mFOLFOX6
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mFOLFOX6: modified FOLinic acid, Fluorouracil, OXaliplatin
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Shah et al. 2021 (GAMMA-1) | 2015-2019 | Phase III (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 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
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 verified protocol PubMed NCT02545504
mFOLFOX6 (L-Leucovorin)
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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 III (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 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
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 verified protocol PubMed NCT02545504
Metastatic or locally advanced disease, subsequent lines of therapy
Apatinib monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Li et al. 2016 | 2011-2012 | Phase III (E-esc) | Placebo | Seems to have superior OS |
Targeted therapy
- Apatinib (Aitan) 850 mg PO once per day
Continued indefinitely
References
- Li J, Qin S, Xu J, Xiong J, Wu C, Bai Y, Liu W, Tong J, Liu Y, Xu R, Wang Z, Wang Q, Ouyang X, Yang Y, Ba Y, Liang J, Lin X, Luo D, Zheng R, Wang X, Sun G, Wang L, Zheng L, Guo H, Wu J, Xu N, Yang J, Zhang H, Cheng Y, Wang N, Chen L, Fan Z, Sun P, Yu H. Randomized, double-blind, placebo-controlled phase III trial of apatinib in patients with chemotherapy-refractory advanced or metastatic adenocarcinoma of the stomach or gastroesophageal junction. J Clin Oncol. 2016 May 1;34(13):1448-54. Epub 2016 Feb 16. link to original article contains protocol PubMed
Cetuximab monotherapy
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Regimen
Study | Evidence |
---|---|
Gold et al. 2010 (SWOG S0415) | Phase II |
Patients: 100% metastatic esophageal adenocarcinoma who failed one prior chemotherapy regimen. 10% had ECOG PS of 2.
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV over 2 hours on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8, 15, 22
- Cycle 2 onwards: 250 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications
- Diphenhydramine (Benadryl) 50 mg IV or PO once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to Cetuximab (Erbitux)
28-day cycles
References
- SWOG S0415: Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. link to original article contains verified protocol link to PMC article PubMed
Docetaxel monotherapy
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Regimen variant #1, 75 mg/m2 x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Ford et al. 2013 (COUGAR-02) | 2008-2012 | Phase III (E-esc) | Active symptom control | Superior OS |
COUGAR-02 patients: 100% adenocarcinoma histology (20% esophageal, 35% gastroesophageal junction, 45% stomach) that progressed on or within 6 months of treatment with a platinum-fluoropyrimidine combination. 15% ECOG PS of 2. 12% locally advanced, 88% metastatic disease.
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 minutes once on day 1
21-day cycle for up to 6 cycles
Regimen variant #2, 75 mg/m2, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roy et al. 2013 (PEP0206) | 2008-2010 | Randomized Phase II (C) | 1. Irinotecan 2. Irinotecan liposomal |
Not powered to draw conclusions |
Chemotherapy
- Docetaxel (Taxotere) 75 mg/m2 IV over 60 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 verified protocol 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 verified protocol PubMed
Irinotecan monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roy et al. 2013 (PEP0206) | 2008-2010 | Randomized Phase II (C) | 1. Docetaxel 2. Irinotecan liposomal |
Not powered to draw conclusions |
Chemotherapy
- Irinotecan (Camptosar) 300 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 verified protocol PubMed NCT00813072
Irinotecan liposomal monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Roy et al. 2013 (PEP0206) | 2008-2010 | Randomized Phase II (E-switch-ic) | 1. Docetaxel 2. Irinotecan |
Not powered to draw conclusions |
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 verified protocol PubMed NCT00813072
Irinotecan & Mitomycin
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Regimen
Study | Evidence |
---|---|
Giuliani et al. 2005 | Phase II |
Patients: 100% gastric adenocarcinoma. Treatment given as second-line chemotherapy for pretreated patients with advanced or metastatic disease.
Chemotherapy
- Irinotecan (Camptosar) 150 mg/m2 IV once per day on days 1 & 15
- Mitomycin (Mutamycin) 8 mg/m2 IV once on day 1
28-day cycles
References
- Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale. Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. link to original article contains protocol PubMed
Nivolumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Janjigian et al. 2018 (CheckMate-032) | 2013-2015 | Phase II | ||
Kang et al. 2017 (ATTRACTION-2) | 2014-2016 | Phase III (E-esc) | Placebo | Superior OS |
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 verified protocol PubMed NCT02267343
- Subgroup analysis: Kato K, Satoh T, Muro K, Yoshikawa T, Tamura T, Hamamoto Y, Chin K, Minashi K, Tsuda M, Yamaguchi K, Machida N, Esaki T, Goto M, Komatsu Y, Nakajima TE, Sugimoto N, Yoshida K, Oki E, Nishina T, Tsuji A, Fujii H, Kunieda K, Saitoh S, Omuro Y, Azuma M, Iwamoto Y, Taku K, Fushida S, Chen LT, Kang YK, Boku N. A subanalysis of Japanese patients in a randomized, double-blind, placebo-controlled, phase 3 trial of nivolumab for patients with advanced gastric or gastro-esophageal junction cancer refractory to, or intolerant of, at least two previous chemotherapy regimens (ONO-4538-12, ATTRACTION-2). Gastric Cancer. 2019 Mar;22(2):344-354. Epub 2018 Dec 1. link to original article link to original article PubMed
- CheckMate-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
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Wilke et al. 2014 (RAINBOW) | 2010-2012 | Phase III (C) | Paclitaxel & Ramucirumab | Seems to have inferior OS |
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- RAINBOW: Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains protocol PubMed NCT01170663
Paclitaxel & Ramucirumab
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy | ORR | Comparator ORR |
---|---|---|---|---|---|---|
Wilke et al. 2014 (RAINBOW) | 2010-2012 | Phase III (E-esc) | Paclitaxel | Seems to have superior OS | 28% (95% CI 23-33%) | 16% (95% CI 13-20%) |
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."
Patients: 100% adenocarcinoma histology, 20% gastroesophageal junction, 80% gastric origin.
Targeted therapy
- Ramucirumab (Cyramza) 8 mg/kg IV once per day on days 1 & 15
Chemotherapy
- Paclitaxel (Taxol) 80 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
References
- RAINBOW: Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed NCT01170663
Ramucirumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
---|---|---|---|---|
Fuchs et al. 2013 (REGARD) | 2009-2012 | Phase III (E-esc) | Placebo | Seems to have superior OS |
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."
Patients: 100% adenocarcinoma histology (25% gastroesophageal junction, 75% gastric origin)
Targeted therapy
- Ramucirumab (Cyramza) 8 mg/kg IV 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 verified protocol PubMed