Esophageal cancer

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Are you looking for a regimen but can't find it here? 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. If you still can't find it, please let us know so we can add it!.
Please be aware that some regimens listed here are studies for gastric cancer, not esophageal cancer, reflecting the overlap between treatments of esophageal and gastric cancer.
There are several related dedicated pages:
*Histology-specific:
**Esophageal adenocarcinoma
**Esophageal squamous cell carcinoma
*Biomarker-specific:
**HER2 positive gastroesophageal cancer
Last updated on 2024-09-06:56 regimens on this page
75 variants on this page
=Guidelines=
Given the rapid change in evidence in many areas of hematology/oncology, readers are encouraged to consider any guideline published 5+ years ago to be for historical purposes, only.
==ASCO==
*2023: Shah et al. Immunotherapy and Targeted Therapy for Advanced Gastroesophageal Cancer: ASCO Guideline EuroPMC
*2021: Shah et al. Immunotherapy in Patients With Locally Advanced Esophageal Carcinoma: ASCO Treatment of Locally Advanced Esophageal Carcinoma Guideline Rapid Recommendation Update EuroPMC
**2020: Shah et al. Treatment of Locally Advanced Esophageal Carcinoma: ASCO Guideline EuroPMC
==ESMO==
*2022: Obermannová et al. Oesophageal cancer: ESMO Clinical Practice Guideline for diagnosis, treatment and follow-up EuroPMC
**2016: Lordick et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2013: Stahl et al. Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2010: Stahl et al. Esophageal cancer: Clinical Practice Guidelines for diagnosis, treatment and follow-up EuroPMC
**2009: Stahl & Oliveira. Esophageal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2008: Stahl & Oliveira. Esophageal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
**2007: Stahl. Esophageal cancer: ESMO clinical recommendations for diagnosis, treatment and follow-up EuroPMC
*2019: Muro et al. Pan-Asian adapted ESMO Clinical Practice Guidelines for the management of patients with metastatic oesophageal cancer: a JSMO-ESMO initiative endorsed by CSCO, KSMO, MOS, SSO and TOS EuroPMC
==NCCN==
*NCCN Guidelines - Esophageal and Esophagogastric Junction Cancers
*2015: Ajani et al. Esophageal and Esophagogastric Junction Cancers, Version 1.2015 EuroPMC
*2011: Ajani et al. Esophageal and esophagogastric junction cancers. EuroPMC
*2008: Ajani et al. Esophageal cancer. EuroPMC
*2006: Ajani et al. Esophageal Cancer Clinical Practice Guidelines. EuroPMC
*2003: Ajani et al. Esophageal cancer. Clinical practice guidelines in oncology. EuroPMC
==STS/ASTRO==
*2024: Worrell et al. The Society of Thoracic Surgeons/American Society for Radiation Oncology updated clinical practice guidelines on multimodality therapy for locally advanced cancer of the esophagus or gastroesophageal junction EuroPMC
=Neoadjuvant induction therapy=
==Capecitabine & Cisplatin (CX)==
CX: Cisplatin & Xeloda (Capecitabine)
XP: Xeloda (Capecitabine) & Platinol (Cisplatin)
===Regimen===
Study 	Dates of enrollment	Evidence
Lee et al. 2007esoph	2003-01 to 2005-12 	Retrospective
Note: Patients had 97% adenocarcinoma, 3% squamous cell histology; 3% with ECOG PS of 2. Patients with M1b disease (visceral metastases) received the chemotherapy only part until progression of disease or unacceptable toxicity. Patients with M1a or M1b (non-visceral metastases) received 2 cycles of the chemotherapy only part, underwent treatment with chemoradiation, and then treatment continued with--presumably, but not outright specified in the paper--chemotherapy only until progression of disease or unacceptable toxicity.
====Eligibility criteria====
*Stage IV disease
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
*Cisplatin (Platinol) 60 mg/m2 IV over 60 minutes once on day 1, given first
21-day cycles (see note)
====Subsequent treatment====
*Lee et al. 2007esoph, patients with M1a or M1b (non-visceral) disease: Definitive CX & RT
===References===
#Retrospective: Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007 Nov;37(11):829-35. Epub 2007 Oct 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Docetaxel (DC)==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ruhstaller et al. 2009 (SAKK 75/02)	2003-07 to 2006-06 	Phase 2 	 	
Ruhstaller et al. 2018 (SAKK 75/08)	2010-2013 	Phase 3 (C)	DC & Cetuximab	Did not meet primary endpoint of PFSMedian PFS: 2 vs 2.9 y(HR 1.27, 95% CI 0.93-1.72)
Note: SAKK 75/02 patients had 55% adenocarcinoma, 45% squamous cell histology
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Docetaxel (Taxotere) 75 mg/m2 IV once on day 1
21-day cycle for 2 cycles
====Subsequent treatment====
*Neoadjuvant DC & RT, then surgery
===References===
#SAKK 75/02: Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, von Moos R, Borner M, Pestalozzi BC, Balmermajno S, Köberle D, Terraciano L, Schnider A, Bodis S, Popescu R; Swiss Group for Clinical Cancer Research. Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009 Sep;20(9):1522-8. Epub 2009 May 22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#SAKK 75/08: Ruhstaller T, Thuss-Patience P, Hayoz S, Schacher S, Knorrenschild JR, Schnider A, Plasswilm L, Budach W, Eisterer W, Hawle H, Mariette C, Hess V, Mingrone W, Montemurro M, Girschikofsky M, Schmidt SC, Bitzer M, Bedenne L, Brauchli P, Stahl M; Swiss Group for Clinical Cancer Research; German Esophageal Cancer Study Group; Arbeitsgemeinschaft Medikamentöse Tumortherapie; Fédération Francophone de Cancérologie Digestive. Neoadjuvant chemotherapy followed by chemoradiation and surgery with and without cetuximab in patients with resectable esophageal cancer: a randomized, open-label, phase III trial (SAKK 75/08). Ann Oncol. 2018 Jun 1;29(6):1386-1393. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01107639
==Cisplatin & Fluorouracil (CF)==
CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol (Cisplatin)
===Regimen variant #1, 80/4000, 4 day 5-FU infusion===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Girling et al. 2002 (UK MRC OE02)	1992-1998 	Phase 3 (E-esc)	Surgery alone	Seems to have longer OS1 (primary endpoint)OS60: 23% vs 17.1%(HR 0.84, 95% CI 0.72-0.98)
1Reported efficacy for UK MRC OE02 is based on the 2009 update.
====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====
*Surgery
===Regimen variant #2, 100/5000===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Kelsen et al. 1998 (RTOG 8911)	1990-1995 	Phase 3 (E-esc)	Surgery alone	Did not meet primary endpoint of OSMedian OS: 14.9 vs 16.1 mo(HR 1.07, 95% CI 0.87-1.32)
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
====Chemotherapy====
*Cisplatin (Platinol) 100 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: see note)
28-day cycle for 3 cycles
====Subsequent treatment====
*Surgery, then adjuvant CF
===References===
#RTOG 8911: Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Update: Kelsen DP, Winter KA, Gunderson LL, Mortimer J, Estes NC, Haller DG, Ajani JA, Kocha W, Minsky BD, Roth JA, Willett CG; Radiation Therapy Oncology Group; USA Intergroup. Long-term results of RTOG trial 8911 (USA Intergroup 113): a random assignment trial comparison of chemotherapy followed by surgery compared with surgery alone for esophageal cancer. J Clin Oncol. 2007 Aug 20;25(24):3719-25. link to original article EuroPMC
#UK MRC OE02: Girling DJ, Bancewicz J, Clark PI, Smith DB, Donnelly RJ, Fayers PM, Weeden S, Hutchinson T, Harvey A, Lyddiard J; Medical Research Council Oesophageal Cancer Working Group. Surgical resection with or without preoperative chemotherapy in oesophageal cancer: a randomised controlled trial. Lancet. 2002 May 18;359(9319):1727-33. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
##Update: Allum WH, Stenning SP, Bancewicz J, Clark PI, Langley RE. Long-term results of a randomized trial of surgery with or without preoperative chemotherapy in esophageal cancer. J Clin Oncol. 2009 Oct 20;27(30):5062-7. Epub 2009 Sep 21. link to original article EuroPMC
==Cisplatin & Irinotecan (IC)==
IC: Irinotecan & Cisplatin
===Regimen===
Study 	Dates of enrollment	Evidence
Ilson et al. 2011	2002-12 to 2005-10 	Phase 2
Note: Ilson et al. 2011 patients had 75% adenocarcinoma, 22% squamous cell, 3% poorly differentiated histology; 33% gastroesophageal junction.
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes once per day on days 1 & 8, given first
*Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV or PO once per day on days 1 & 8, prior to chemotherapy
*One of the following:
**Granisetron 2 mg PO once per day on days 1 & 8, prior to chemotherapy
**Ondansetron (Zofran) 32 mg IV once per day on days 1 & 8, prior to chemotherapy
*At least 500 mL D5NS or NS as supportive hydration
*Atropine (Atropen) 0.5 to 1 mg IV prn cholinergic symptoms
21-day cycle for 2 cycles
====Subsequent treatment====
*Neoadjuvant cisplatin, irinotecan, RT, then surgery
===References===
#Ilson DH, Minsky BD, Ku GY, Rusch V, Rizk N, Shah M, Kelsen DP, Capanu M, Tang L, Campbell J, Bains M. Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer. 2012 Jun 1;118(11):2820-7. Epub 2011 Oct 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==EOF==
EOF: Epirubicin, Oxaliplatin, Fluorouracil
===Regimen===
Note: This regimen is sometimes listed as a perioperative option, but it is not clearly described as one by the primary reference to the REAL-2 study. Study participants could have had either locally advanced or metastatic disease, and the primary reference did not list a uniform policy about what patients underwent surgery and its timing--although a few patients were mentioned to undergo surgery.
====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 over 21 days, started on day 1 (total dose per cycle: 4200 mg/m2)
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg IV once on day 1, prior to chemotherapy, then 4 mg PO three times per day on days 2 & 3
*5-HT3 antagonist once on day 1, prior to chemotherapy
*Metoclopramide (Reglan) 10 mg PO three times per day on days 2 to 4
*Warfarin (Coumadin) 1 mg PO once per day as thrombosis prophylaxis, started on day -1
21-day cycle for up to 8 cycles; for perioperative use per some guidelines, 3 cycles preoperatively and 3 cycles postoperatively would be used
===References===
==EOX==
EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)
EOC: Epirubicin, Oxaliplatin, Capecitabine
===Regimen===
Note: This regimen is sometimes listed as a perioperative option, but it is not clearly described as one by the primary reference to the REAL-2 study. Study participants could have had either locally advanced or metastatic disease, and the primary reference did not list a uniform policy about what patients underwent surgery and its timing--although a few patients were mentioned to undergo surgery.
====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
*Capecitabine (Xeloda) 500 to 625 mg/m2 PO twice per day on days 1 to 21
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg IV once on day 1, prior to chemotherapy, then 4 mg PO three times per day on days 2 & 3
*5-HT3 antagonist once on day 1, prior to chemotherapy
*Metoclopramide (Reglan) 10 mg PO three times per day on days 2 to 4
21-day cycle for up to 8 cycles; for perioperative use per some guidelines, 3 cycles preoperatively and 3 cycles postoperatively would be used
===References===
==PCF==
PCF: Paclitaxel, Cisplatin, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence
Zhao et al. 2015 (ZY-01)	2005-2007 	Non-randomized part of phase 3 RCT
====Chemotherapy====
*Paclitaxel (Taxol) 100 mg/m2 IV over 3 hours once on day 1
*Cisplatin (Platinol) 60 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 700 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 3500 mg/m2)
21-day cycle for 2 cycles
====Subsequent treatment====
*Surgery, then adjuvant PCF x 2 versus no further treatment
===References===
#ZY-01: Zhao Y, Dai Z, Min W, Sui X, Kang H, Zhang Y, Ren H, Wang XJ. Perioperative versus Preoperative Chemotherapy with Surgery in Patients with Resectable Squamous Cell Carcinoma of Esophagus: A Phase III Randomized Trial. J Thorac Oncol. 2015 Sep;10(9):1349-1356. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT01225523
=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.
==Capecitabine, Carboplatin, Paclitaxel, RT==
Capecitabine, Carboplatin, Paclitaxel, RT: Capecitabine, Carboplatin, Paclitaxel, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Czito et al. 2006	2003-07 to 2005-07 	Pilot, fewer than 20 pts
Note: The primary reference did not specify whether patients were intended to proceed to surgery. Patients had 77% adenocarcinoma, 23% squamous cell histology. 54% lower thoracic, 23% midthoracic, 23% gastroesophageal junction.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 1.5 IV once per day on days 2, 9, 16, 23, 30
*Paclitaxel (Taxol) 45 mg/m2 IV over 60 minutes once per day on days 2, 9, 16, 23, 30
*Capecitabine (Xeloda) 600 mg/m2 PO twice per day, starting on day 1 and finishing the evening of the last day of radiation therapy
====Radiotherapy====
*Concurrent radiation therapy: 180 cGy fractions x 28 fractions, for a total dose of 5040 cGy
6-week course
====Subsequent treatment====
*Czito et al. 2006, surgical candidates: surgery, performed 6 to 8 weeks after chemoradiotherapy completion. Patients could receive adjuvant chemotherapy, beginning 4 to 12 weeks postoperatively
===References===
#Phase I: Czito BG, Kelsey CR, Hurwitz HI, Willett CG, Morse MA, Blobe GC, Fernando NH, D'Amico TA, Harpole DH, Honeycutt W, Yu D, Bendell JC. A Phase I study of capecitabine, carboplatin, and paclitaxel with external beam radiation therapy for esophageal carcinoma. Int J Radiat Oncol Biol Phys. 2007 Mar 15;67(4):1002-7. Epub 2006 Dec 29. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Capecitabine, Cisplatin, RT==
CX & RT: Cisplatin, Xeloda (Capecitabine), Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Lee et al. 2007esoph	2003-01 to 2005-12 	Retrospective
Note: This study was for patients with stage IV disease. Please reference the original paper, as there were no patients who only received this neoadjuvant treatment, and they did not undergo surgical resection of disease. Patients had 3% adenocarcinoma, 97% squamous cell histology; 3% with ECOG PS of 2.
====Preceding treatment====
*Induction Capecitabine & Cisplatin
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV over 60 minutes once on day 1, given first
*Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5, given second
7-day cycles until radiation therapy is complete
====Radiotherapy====
*Concurrent radiation therapy, total of 5400 cGy given (dose per fraction and total duration of treatment was not specified)
One course
===References===
#Retrospective: Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007 Nov;37(11):829-35. Epub 2007 Oct 19. link to original article dosing details in manuscript have been reviewed by our editors--please see note above, as patients in this study did not undergo surgery EuroPMC
==Capecitabine, Docetaxel, RT==
Capecitabine, Docetaxel, RT: Capecitabine, Docetaxel, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Wood et al. 2013 (D-9939)	Not reported 	Phase 1
Note: Some guidelines recommend different dosing but this is the only publication that we could locate with dosing details. Treatment is assumed to begin on a Monday.
====Chemotherapy====
*Docetaxel (Taxotere) 15 mg/m2 IV once per day on days 1, 8, 15, 22, 29
*Capecitabine (Xeloda) 3500 mg PO once per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, given prior to radiation
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (5040 cGy in 28 fractions)
5-week course
===References===
#D-9939: Wood MD, Zaki BI, Gordon SR, Sutton JE Jr, Lisovsky M, Gui J, Bubis JA, Dragnev KH, Rigas JR. Trimodality therapy for stage II-III carcinoma of the esophagus: a dose-ranging study of concurrent capecitabine, docetaxel, and thoracic radiotherapy. J Thorac Oncol. 2013 Apr;8(4):487-94. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00153881
==Capecitabine, Docetaxel, Oxaliplatin, RT==
Capecitabine, Docetaxel, Oxaliplatin, RT: Capecitabine, Docetaxel, Oxaliplatin, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Spigel et al. 2010 (SCRI GI 57)	2005-2008 	Phase 1/2
Note: Patients had 69% adenocarcinoma, 18% squamous cell, 12% not otherwise specified. 69% distal esophagus, 16% midesophagus, 14% gastroesophageal junction.
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 7, 15 to 21, 29 to 35
*Docetaxel (Taxotere) 20 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22, 29
*Oxaliplatin (Eloxatin) 40 mg/m2 IV over 2 hours once per day on days 1, 8, 15, 22, 29
====Supportive therapy====
*Dexamethasone (Decadron) 4 mg PO every 12 hours before, at the time of, and after docetaxel; first dose the evening prior to docetaxel
*"Routine antiemetics"
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
5-week course
====Subsequent treatment====
*Endoscopy, CT scan, and--if available--endoscopic ultrasound for restaging 2 to 4 weeks after finishing chemoradiation, with subsequent treatment by the following response-based criteria:
**SCRI GI 57, surgical candidates: Surgical resection sometime during weeks 9 to 12
**SCRI GI 57, patients who were no longer surgical candidates: Additional radiation therapy to a total dose of 6480 cGy
===References===
#SCRI GI 57: Spigel DR, Greco FA, Meluch AA, Lane CM, Farley C, Gray JR, Clark BL, Burris HA 3rd, Hainsworth JD. Phase I/II trial of preoperative oxaliplatin, docetaxel, and capecitabine with concurrent radiation therapy in localized carcinoma of the esophagus or gastroesophageal junction. J Clin Oncol. 2010 May 1;28(13):2213-9. Epub 2010 Mar 29. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00193128
==Capecitabine, Oxaliplatin, RT==
CapeOx & RT: Capecitabine, Oxaliplatin, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Javle et al. 2009	Not reported 	Phase 1b
====Chemotherapy====
*Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
*Oxaliplatin (Eloxatin) 85 mg/m2 IV once per day on days 1, 15, 29
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (total dose of 5040 cGy)
5-week course
====Subsequent treatment====
*Surgery
===References===
#Phase I: Javle MM, Yang G, Nwogu CE, Wilding GE, O'Malley L, Vinjamaram S, Schiff MD, Nava HR, LeVea C, Clark KR, Prey JD, Smith PF, Pendyala L. Capecitabine, oxaliplatin and radiotherapy: a phase IB neoadjuvant study for esophageal cancer with gene expression analysis. Cancer Invest. 2009 Feb;27(2):193-200. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Capecitabine, Paclitaxel, RT==
Capecitabine, Paclitaxel, RT: Capecitabine, Paclitaxel, Radiation Therapy
===Regimen===
Note: No primary reference could be found for this regimen.
====Chemotherapy====
*Capecitabine (Xeloda) 625 to 825 mg/m2 PO twice per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
*Paclitaxel (Taxol) 45 to 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy not defined on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
5-week course
===References===
==Carboplatin, Fluorouracil, RT==
Carboplatin, Fluorouracil, RT: Carboplatin, Fluorouracil, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Zemanoa et al. 2009	2001-01 to 2005-08 	Non-randomized
Note: Patients had 86% squamous cell, 8% adenocarcinoma, 6% other histology. 3% ECOG PS of 2.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 6 IV once per day on days 1 & 22
*Fluorouracil (5-FU) 200 mg/m2/day IV continuous infusion, started on days 1 & 22 (total dose: 8400 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy by the following criteria:
**Surgery indicated: 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
**If surgery was contraindicated: total dose was increased to 5040 to 5680 cGy.
5-week course
====Subsequent treatment====
*Upper endoscopy and CT chest and abdomen was performed after completion of chemoradiation
*Surgery planned to be done 4 to 6 weeks after finishing chemoradiation
===References===
#Zemanova M, Petruzelka L, Pazdro A, Kralova D, Smejkal M, Pazdrova G, Honova H. Prospective non-randomized study of preoperative concurrent platinum plus 5-fluorouracil-based chemoradiotherapy with or without paclitaxel in esophageal cancer patients: long-term follow-up. Dis Esophagus. 2010 Feb;23(2):160-7. Epub 2009 Jun 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Carboplatin & Paclitaxel (CP) & RT==
CP & RT: Carboplatin, Paclitaxel, Radiation Therapy
ESMO-preferred for squamous cell carcinoma (I-A, 2016)
===Regimen variant #1, 5 weeks of chemotherapy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
van Meerten et al. 2006 	2001-2004 	Phase 2 	 	
van Hagen et al. 2012 (CROSS)	2004-2008 	Phase 3 (E-esc)	Surgery alone	Longer OS1 (primary endpoint)OS120: 38% vs 25%(HR 0.70, 95% CI 0.55-0.89)
1Reported efficacy for CROSS is based on the 2021 update.
Note: van Meerten et al. patients had 76% adenocarcinoma, 22% squamous cell, 2% large cell histology. 91% lower esophagus, 9% thoracic esophagus. CROSS patients had 75% adenocarcinoma, 23% squamous cell, 2% other histology. 24% gastroesophageal junction.
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15, 22, 29, given second
*Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, given first
====Supportive therapy====
*Dexamethasone (Decadron) 10 mg IV once per day on days 1, 8, 15, 22, 29, given 30 minutes prior to paclitaxel
*Ranitidine (Zantac) 50 mg IV once per day on days 1, 8, 15, 22, 29, given 30 minutes prior to paclitaxel
*Clemastine (Tavist) 2 mg IV once per day on days 1, 8, 15, 22, 29, given 30 minutes prior to paclitaxel
*100 mL NS given over 30 minutes once per day on days 1, 8, 15, 22, 29, given between paclitaxel & carboplatin
*Ondansetron (Zofran) 8 mg in 100 mL NS given over 30 minutes once per day on days 1, 8, 15, 22, 29, given between paclitaxel & carboplatin
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 31 (23 fractions, for a total dose of 4140 cGy)
5-week course
====Subsequent treatment====
*Surgery planned to be done within 6 weeks of finishing chemoradiation; van Hagen et al. 2012 said surgery was done as soon as possible after finishing chemoradiotherapy, preferably within 4 to 6 weeks
===Regimen variant #2, 6 weeks of chemotherapy===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Safran et al. 2022 (RTOG 1010)	2010-2015 	Phase 3 (C)	CP, Trastuzumab, RT	Did not meet primary endpoint of DFSMedian DFS: 14.2 vs 19.6 mo(HR 1.01, 95% CI 0.72-1.41)
====Biomarker eligibility criteria====
*HER2+
====Chemotherapy====
*Carboplatin (Paraplatin) AUC 2 IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, 29, 36
*Paclitaxel (Taxol) 50 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22, 29, 36
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions, for a total dose of 5040 cGy)
6-week course
===References===
#van Meerten E, Muller K, Tilanus HW, Siersema PD, Eijkenboom WM, van Dekken H, Tran TC, van der Gaast A. Neoadjuvant concurrent chemoradiation with weekly paclitaxel and carboplatin for patients with oesophageal cancer: a phase II study. Br J Cancer. 2006 May 22;94(10):1389-94. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
#CROSS: van Hagen P, Hulshof MC, van Lanschot JJ, Steyerberg EW, van Berge Henegouwen MI, Wijnhoven BP, Richel DJ, Nieuwenhuijzen GA, Hospers GA, Bonenkamp JJ, Cuesta MA, Blaisse RJ, Busch OR, ten Kate FJ, Creemers GJ, Punt CJ, Plukker JT, Verheul HM, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJ, Rozema T, Biermann K, Beukema JC, Piet AH, van Rij CM, Reinders JG, Tilanus HW, van der Gaast A; CROSS Group. Preoperative chemoradiotherapy for esophageal or junctional cancer. N Engl J Med. 2012 May 31;366(22):2074-84. link to original article dosing details in manuscript have been reviewed by our editors link to appendix with details about administration EuroPMC NTR487
##Update: Shapiro J, van Lanschot JJB, Hulshof MCCM, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch ORC, Ten Kate FJW, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Spillenaar Bilgen EJ, van Dekken H, van der Sangen MJC, Rozema T, Biermann K, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS study group. Neoadjuvant chemoradiotherapy plus surgery versus surgery alone for oesophageal or junctional cancer (CROSS): long-term results of a randomised controlled trial. Lancet Oncol. 2015 Sep;16(9):1090-1098. Epub 2015 Aug 5. link to original article EuroPMC
##Update: Eyck BM, van Lanschot JJB, Hulshof MCCM, van der Wilk BJ, Shapiro J, van Hagen P, van Berge Henegouwen MI, Wijnhoven BPL, van Laarhoven HWM, Nieuwenhuijzen GAP, Hospers GAP, Bonenkamp JJ, Cuesta MA, Blaisse RJB, Busch OR, Creemers GM, Punt CJA, Plukker JTM, Verheul HMW, Spillenaar Bilgen EJ, van der Sangen MJC, Rozema T, Ten Kate FJW, Beukema JC, Piet AHM, van Rij CM, Reinders JG, Tilanus HW, Steyerberg EW, van der Gaast A; CROSS Study Group. Ten-Year Outcome of Neoadjuvant Chemoradiotherapy Plus Surgery for Esophageal Cancer: The Randomized Controlled CROSS Trial. J Clin Oncol. 2021 Jun 20;39(18):1995-2004. Epub 2021 Apr 23. link to original article EuroPMC
#RTOG 1010: Safran HP, Winter K, Ilson DH, Wigle D, DiPetrillo T, Haddock MG, Hong TS, Leichman LP, Rajdev L, Resnick M, Kachnic LA, Seaward S, Mamon H, Diaz Pardo DA, Anderson CM, Shen X, Sharma AK, Katz AW, Salo J, Leonard KL, Moughan J, Crane CH. Trastuzumab with trimodality treatment for oesophageal adenocarcinoma with HER2 overexpression (NRG Oncology/RTOG 1010): a multicentre, randomised, phase 3 trial. Lancet Oncol. 2022 Feb;23(2):259-269. Epub 2022 Jan 14. link to original article link to PMC article dosing details in abstract have been reviewed by our editors EuroPMC NCT01196390
==Cisplatin & Docetaxel (DC) & RT==
DC & RT: Docetaxel, Cisplatin, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Ruhstaller et al. 2009 (SAKK 75/02)	2003-07 to 2006-06 	Phase 2
Note: Patients had 55% adenocarcinoma, 45% squamous cell histology
====Preceding treatment====
*Induction Cisplatin & Docetaxel x 2
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1, 8, 15, 22, 29
*Docetaxel (Taxotere) 20 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
5-week course
====Subsequent treatment====
*Surgery, 3 to 8 weeks after finishing chemoradiation
===References===
#SAKK 75/02: Ruhstaller T, Widmer L, Schuller JC, Roth A, Hess V, Mingrone W, von Moos R, Borner M, Pestalozzi BC, Balmermajno S, Köberle D, Terraciano L, Schnider A, Bodis S, Popescu R; Swiss Group for Clinical Cancer Research. Multicenter phase II trial of preoperative induction chemotherapy followed by chemoradiation with docetaxel and cisplatin for locally advanced esophageal carcinoma (SAKK 75/02). Ann Oncol. 2009 Sep;20(9):1522-8. Epub 2009 May 22. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Fluorouracil (CF) & RT==
CF & RT: Cisplatin, Fluourouracil, Radiation Therapy
===Regimen variant #1, 75/3200 x 2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Mariette et al. 2014 (FFCD 9901)	2000-2009 	Phase 3 (E-esc)	Surgery alone	Did not meet primary endpoint of OSOS36: 47.5% vs 53%(HR 0.99, 95% CI 0.69-1.40)
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once per day on either day 1 or 2 & 29
*Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose: 6400 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 4500 cGy)
5-week course
====Subsequent treatment====
*Surgery
===Regimen variant #2, 75/4000 x 2===
Study 	Dates of enrollment	Evidence
Bedenne et al. 2007 (FFCD 9102)	1993-2000 	Non-randomized part of phase 3 RCT
Note: Patients had 89% epidermoid, 11% glandular histology.
====Chemotherapy====
*Cisplatin (Platinol) 15 mg/m2 IV over 60 minutes once per day on days 1 to 5, 22 to 26
*Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 120 hours, started on days 1 & 22 (total dose: 8000 mg/m2)
====Supportive therapy====
*1 liter NS IV over 2 hours twice per day on days 1 to 5, 22 to 26, before and after cisplatin
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 31 (23 fractions, for a total dose of 4600 cGy)
**Earlier in the study, some patients instead received split-course radiation therapy, 300 cGy fractions x 5 fractions given on days 1 to 5. 1500 cGy per cycle; total dose after 2 cycles is 3000 cGy.
5-week course
====Subsequent treatment====
*Definitive Cisplatin, Fluorouracil, RT (no surgery) x 3 (5 cycles total) versus surgery, 50 to 60 days after start of chemoradiation
===Regimen variant #3, 80/3200===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Burmeister et al. 2005	1994-2000 	Phase 3 (E-esc)	Surgery alone	Did not meet primary endpoint of PFSMedian PFS: 16 vs 12 mo(HR 0.82, 95% CI 0.61-1.10)
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority.
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 800 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose: 3200 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy 233 cGy per day on days 1 to 5, 8 to 12, 15 to 19 (15 fractions for a total dose of 3500 cGy)
3-week course
====Subsequent treatment====
*Surgery
===Regimen variant #4, 100/4000 x 2===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Tepper et al. 2008 (CALGB 9781)	1997-2000 	Phase 3 (E-esc)	Surgery alone	Longer OS (primary endpoint)Median OS: 4.48 vs 1.79 y(HR NR, 95% CI 0.18-0.68)
Note: Patients had 75% adenocarcinoma, 25% squamous cell histology. 5% with ECOG PS of 2. 
====Chemotherapy====
*Cisplatin (Platinol) 100 mg/m2 IV over 30 minutes once per day on days 1 & 29, given first
*Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on days 1 & 29, given second (total dose: 8000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, then a 540 cGy final boost, for a total dose of 5040 cGy), starting within 24 hours of start of chemotherapy
5-week course
====Subsequent treatment====
*EGD and CT chest and abdomen done within 4 weeks after finishing radiation therapy. Only patients who still had resectable disease that was stable or responded would proceed to surgery. Surgery was planned to be done 3 to 8 weeks after finishing chemoradiation.
===References===
#Burmeister BH, Smithers BM, Gebski V, Fitzgerald L, Simes RJ, Devitt P, Ackland S, Gotley DC, Joseph D, Millar J, North J, Walpole ET, Denham JW; Trans-Tasman Radiation Oncology Group; Australasian Gastro-Intestinal Trials Group. Surgery alone versus chemoradiotherapy followed by surgery for resectable cancer of the oesophagus: a randomised controlled phase III trial. Lancet Oncol. 2005 Sep;6(9):659-68. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#FFCD 9102: Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, Pezet D, Roullet B, Seitz JF, Herr JP, Paillot B, Arveux P, Bonnetain F, Binquet C. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007 Apr 1;25(10):1160-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#CALGB 9781: Tepper J, Krasna MJ, Niedzwiecki D, Hollis D, Reed CE, Goldberg R, Kiel K, Willett C, Sugarbaker D, Mayer R. Phase III trial of trimodality therapy with cisplatin, fluorouracil, radiotherapy, and surgery compared with surgery alone for esophageal cancer: CALGB 9781. J Clin Oncol. 2008 Mar 1;26(7):1086-92. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00003118
#FFCD 9901: Mariette C, Dahan L, Mornex F, Maillard E, Thomas PA, Meunier B, Boige V, Pezet D, Robb WB, Le Brun-Ly V, Bosset JF, Mabrut JY, Triboulet JP, Bedenne L, Seitz JF. Surgery alone versus chemoradiotherapy followed by surgery for stage I and II esophageal cancer: final analysis of randomized controlled phase III trial FFCD 9901. J Clin Oncol. 2014 Aug 10;32(23):2416-22. Epub 2014 Jun 30. link to original article EuroPMC NCT00047112
#KEYNOTE-975: NCT04210115
==Cisplatin, Irinotecan, RT==
Cisplatin, Irinotecan, RT: Cisplatin, Irinotecan, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Ilson et al. 2011	2002-12 to 2005-10 	Phase 2
Note: Patients had 75% adenocarcinoma, 22% squamous cell, 3% poorly differentiated history; 33% gastroesophageal junction.
====Preceding treatment====
*IC induction x 2
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes once per day on days 1, 8, 22, 29 given first
*Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1, 8, 22, 29, given second
====Radiotherapy====
*Concurrent radiation therapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 38 (28 fractions, for a total of 5040 cGy)
5.5-week course
====Subsequent treatment====
*Surgery, performed 4 to 8 weeks after chemoradiation
===References===
#Ilson DH, Minsky BD, Ku GY, Rusch V, Rizk N, Shah M, Kelsen DP, Capanu M, Tang L, Campbell J, Bains M. Phase 2 trial of induction and concurrent chemoradiotherapy with weekly irinotecan and cisplatin followed by surgery for esophageal cancer. Cancer. 2012 Jun 1;118(11):2820-7. Epub 2011 Oct 11. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Paclitaxel (TP) & RT==
TP & RT: Taxol (Paclitaxel), Platinol (Cisplatin), Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence
Urba et al. 2003	1995-01 to 1997-09 	Phase 2
Note: Patients had 83% adenocarcinoma, 14% squamous cell, 3% undifferentiated histology
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 2 hours once on day 1
*Paclitaxel (Taxol) 60 mg/m2 IV over 3 hours once per day on days 1, 8, 15, 22
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg PO twice per day on days 1, 8, 15, 22; 12 and 6 hours prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22; 30 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15, 22; 30 minutes prior to paclitaxel
*1 liter D5NS and mannitol 12.5 g bolus IV once on day 1, prior to cisplatin
*Mannitol 25 g in 1 liter D5NS IV over 4 hours once on day 1, after cisplatin
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting on day 23, continuing until ANC greater than 10,000/μL
====Radiotherapy====
*Concurrent radiation therapy, 150 cGy fractions given twice per day on days 1 to 5, 8 to 12, 15 to 19, with at least 6 hours between fractions, for a total dose of 4500 cGy
4-week course
====Subsequent treatment====
*Barium swallow and CT chest and abdomen done about 1 week prior to surgery to rule out metastatic disease. Surgery to be done on approximately day 50
===References===
#Urba SG, Orringer MB, Ianettonni M, Hayman JA, Satoru H. Concurrent cisplatin, paclitaxel, and radiotherapy as preoperative treatment for patients with locoregional esophageal carcinoma. Cancer. 2003 Nov 15;98(10):2177-83. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Docetaxel, Fluorouracil, RT==
Docetaxel, Fluorouracil, RT: Docetaxel, Fluorouracil, Radiation Therapy
===Regimen variant #1, 15/4000 x 2===
Study 	Dates of enrollment 	Evidence
Hihara et al. 2007	2004-04-21 to 2005-04-07	Phase 1
Note: Patients had 86% squamous cell, 14% carcinosarcoma histology
====Chemotherapy====
*Docetaxel (Taxotere) 7.5 mg/m2 IV over 60 minutes once per day on days 1, 8, 29, 36
*Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 29, 36, 43 (total dose: 8000 mg/m2)
====Supportive therapy====
*Dexamethasone (Decadron) 8 mg IV once per day on days 1, 8, 29, 36; 30 minutes prior to docetaxel
====Radiotherapy====
*Concurrent radiation therapy 200 cGy fractions x 30 to 33 fractions, for a total dose of 60 to 6600 cGy
6- to 6.5-week course
===Regimen variant #2===
Note: No primary reference could be found for this regimen.
====Chemotherapy====
*Docetaxel (Taxotere) 20 mg/m2 IV once per day on days 1, 8, 15, 22, 29
*Fluorouracil (5-FU) 200 to 300 mg/m2/day IV continuous infusion over 120 hours, started on days 1, 8, 15, 22, 29 (total dose: 5000 to 7500 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy not defined on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
5-week course
===References===
#Phase I: Hihara J, Yoshida K, Hamai Y, Emi M, Yamaguchi Y, Wadasaki K. Phase I study of docetaxel (TXT) and 5-fluorouracil (5-FU) with concurrent radiotherapy in patients with advanced esophageal cancer. Anticancer Res. 2007 Jul-Aug;27(4C):2597-603. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Fluorouracil, Oxaliplatin, RT==
Fluorouracil, Oxaliplatin, RT: Fluorouracil, Oxaliplatin, Radiation Therapy
===Regimen variant #1, 5040 cGy, bi-weekly oxaliplatin===
Study 	Dates of enrollment	Evidence
Khushalani et al. 2002	2000-02 to 2001-05 	Phase 2
Note: 58% of patients had stage IV disease
====Chemotherapy====
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once per day on days 1, 15, 29
*Fluorouracil (5-FU) 180 mg/m2/day IV continuous infusion over 35 days, started on day 8 (total dose: 6300 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy, 180 cGy fractions x 20 to 22 fractions, for an initial total dose of 36 to 3960 cGy, started on day 8
**Followed by off-cord conformal oblique fields, 540 to 900 cGy given to the clinical target volume (CTV). A second off-cord phase to the gross tumor volume (GTV) of 540 cGy was then given, for a total dose delivered of 5040 cGy to the GTV.
6-week course
====Subsequent treatment====
*Upper GI endoscopy and CT chest, abdomen, and pelvis were done after completion of chemoradiation, and patients without progressive stage II-III disease were offered surgery followed by another cycle of oxaliplatin and 5-FU. Patients who could not proceed to surgery were given another 1 to 2 cycles of oxaliplatin and 5-FU within 2 weeks.
===Regimen variant #2, 5040 cGy, weekly oxaliplatin===
Study 	Dates of enrollment	Evidence
Ajani et al. 2013 (MDACC 2004-0703)	2005-2011 	Non-randomized part of phase 2 RCT
Note: it is unclear how long the 5-FU continuous infusions were in this regimen; the authors have been contacted for clarification. Treatment is assumed to start on a Monday.
====Preceding treatment====
*FUOX versus no induction chemotherapy
====Chemotherapy====
*Oxaliplatin (Eloxatin) 40 mg/m2 IV once per day on days 1, 8, 15, 22, 29
*Fluorouracil (5-FU) 250 mg/m2/day IV continuous infusion over 96 hours, started on days 1, 8, 15, 22, 29 (total dose: 5000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy: 5040 cGy of proton or photon (intensity modulated) radiation in 28 fractions
5-week course
====Subsequent treatment====
*Surgery
===References===
#Khushalani NI, Leichman CG, Proulx G, Nava H, Bodnar L, Klippenstein D, Litwin A, Smith J, Nava E, Pendyala L, Smith P, Greco W, Berdzik J, Douglass H, Leichman L. Oxaliplatin in combination with protracted-infusion fluorouracil and radiation: report of a clinical trial for patients with esophageal cancer. J Clin Oncol. 2002 Jun 15;20(12):2844-50. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#MDACC 2004-0703: Ajani JA, Xiao L, Roth JA, Hofstetter WL, Walsh G, Komaki R, Liao Z, Rice DC, Vaporciyan AA, Maru DM, Lee JH, Bhutani MS, Eid A, Yao JC, Phan AP, Halpin A, Suzuki A, Taketa T, Thall PF, Swisher SG. A phase II randomized trial of induction chemotherapy versus no induction chemotherapy followed by preoperative chemoradiation in patients with esophageal cancer. Ann Oncol. 2013 Nov;24(11):2844-9. Epub 2013 Aug 23. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00525915
=Definitive therapy=
==Capecitabine, Cisplatin, RT==
CX & RT: Cisplatin, Xeloda (Capecitabine), Radiation Therapy
===Regimen variant #1, 1250/60/50===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Crosby et al. 2013 (SCOPE-1)	2008-2012 	Phase 3 (C)	Capecitabine, Cisplatin, Cetuximab, RT	Did not meet primary endpoint of OS1Median OS: 34.5 vs 24.7 mo(HR 0.80, 95% CI 0.59-1.08)
1Reported efficacy is based on the 2017 update.
Note: Patients had 25% adenocarcinoma, 73% squamous cell, 2% undifferentiated histology
====Chemotherapy====
*Capecitabine (Xeloda) as follows:
**Cycles 1 & 2: 625 mg/m2 PO twice per day on days 1 to 21
**Cycle 3 (chemoradiation): 625 mg/m2 PO twice per day on days 1 to 42
*Cisplatin (Platinol) as follows:
**Cycles 1 & 2: 60 mg/m2 IV once on day 1
**Cycle 3 (chemoradiation): 60 mg/m2 IV once per day on days 1 & 22
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3 (chemoradiation): 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (total of 5000 cGy given in 25 fractions)
21-day cycle for 2 cycles, then 6-week course
===Regimen variant #2, 1600/30/54===
Study 	Evidence
Lee et al. 2007esoph	Retrospective
Note: Patients had 97% adenocarcinoma, 3% squamous cell histology; 3% with ECOG PS of 2.
====Preceding treatment====
*Induction XP x 2
====Chemotherapy====
*Capecitabine (Xeloda) 800 mg/m2 PO twice per day on days 1 to 5
*Cisplatin (Platinol) 30 mg/m2 IV over 60 minutes once on day 1, given first
7-day cycles until radiation therapy is complete
====Radiotherapy====
*Concurrent radiation therapy, total of 5400 cGy given. Dose per fraction and total duration of treatment were not specified, but based on other regimens, it is suspected to be either 180 cGy x 30 fractions or 200 cGy x 27 fractions.
One course
===References===
#Retrospective: Lee SS, Kim SB, Park SI, Kim YH, Ryu JS, Song HY, Shin JH, Jung HY, Lee GH, Choi KD, Cho KJ, Kim JH. Capecitabine and cisplatin chemotherapy (XP) alone or sequentially combined chemoradiotherapy containing XP regimen in patients with three different settings of stage IV esophageal cancer. Jpn J Clin Oncol. 2007 Nov;37(11):829-35. Epub 2007 Oct 19. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#SCOPE-1: Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, Ray R, Bashir N, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013 Jun;14(7):627-37. Epub 2013 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN47718479
##Update: Crosby T, Hurt CN, Falk S, Gollins S, Staffurth J, Ray R, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G, Mukherjee S. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer. Br J Cancer. 2017 Mar 14;116(6):709-716. Epub 2017 Feb 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
==Cisplatin & Docetaxel (DC) & RT==
DC & RT: Docetaxel, Cisplatin, Radiation Therapy
===Regimen variant #1===
Study 	Dates of enrollment	Evidence
Day et al. 2010	2001-05 to 2007-01 	Phase 1
Note: Patients had 46% squamous cell, 54% adenocarcinoma histology. Some guidelines suggest a wider dose range of 20 to 30 mg/m2 for both cisplatin and docetaxel. The primary reference also investigated these dose levels, but ultimately recommended 30 mg/m2 dosages for both cisplatin and docetaxel.
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29
*Docetaxel (Taxotere) 30 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Supportive therapy====
*"Steroid and anti-emetic pre-medication"
====Radiotherapy====
*Concurrent radiation therapy, 200 cGy fractions x 25 fractions, for a total dose of 5000 cGy, to start within 4 hours after the first dose of chemotherapy.
5-week course
===References===
#Phase I: Day FL, Leong T, Ngan S, Thomas R, Jefford M, Zalcberg JR, Rischin D, McKendick J, Milner AD, Di Iulio J, Matera A, Michael M. Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer. Br J Cancer. 2011 Jan 18;104(2):265-71. Epub 2010 Dec 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Cisplatin & Fluorouracil (CF) & RT==
CF & RT: Cisplatin, Fluorouracil, Radiation Therapy
FP & RT: Fluorouracil, Platinol (Cisplatin), Radiation Therapy
===Regimen variant #1, 60/4725 x 4 (5000 cGy)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Crosby et al. 2013 (SCOPE-1)	2008-2012 	Phase 3 (C)	Capecitabine, Cisplatin, Cetuximab, RT	Did not meet primary endpoint of OS1Median OS: 34.5 vs 24.7 mo(HR 0.80, 95% CI 0.59-1.08)
1Reported efficacy is based on the 2017 update.
Note: This regimen was an alternative for patients who could not swallow pills. Patients had 25% adenocarcinoma, 73% squamous cell, 2% undifferentiated histology
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 & 2: 60 mg/m2 IV once on day 1
**Cycle 3 (chemoradiation): 60 mg/m2 IV once per day on days 1 & 22
*Fluorouracil (5-FU) as follows:
**Cycles 1 & 2: 225 mg/m2/day IV continuous infusion over 21 days, started on day 1 (total dose per cycle: 4725 mg/m2)
**Cycle 3 (chemoradiation): 225 mg/m2/day IV continuous infusion over 42 days, started on day 1 (total dose during chemoradiation: 9450 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 3 (chemoradiation): 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (total of 5000 cGy given in 25 fractions)
21-day cycle for 2 cycles, then 5-week course
===Regimen variant #2, 75/4000 x 2 (5040 cGy)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Minsky et al. 2002 (RTOG 94-05) 	1995-1999 	Phase 3 (C)	CF & RT; high-dose RT	Did not meet primary endpoint of OS24
Conroy et al. 2014 (PRODIGE5/ACCORD17)	2004-2011 	Phase 3 (C)	See link 	See link
Note: RTOG 94-05 included both adenocarcinoma and squamous cell histology
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes once per day on days 1 & 29
*Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose: 8000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy by the following study-specific criteria:
**RTOG 94-05: 180 cGy fractions x 28 fractions, for a total dose of 5040 cGy
**PRODIGE5/ACCORD17: 200 cGy fractions x 25 fractions, for a total dose of 5000 cGy
5- to 5.5-week course
====Subsequent treatment====
*CF consolidation
===Regimen variant #3, 75/4000 x 3 (6600 cGy)===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Bedenne et al. 2007 (FFCD 9102)	1993-2000 	Phase 3 (E-switch-ooc)	Surgery 	Equivalent OS (primary endpoint)
Note: Patients had 89% epidermoid, 11% glandular histology. Note that this was not a formal non-inferiority study but the study met its primary endpoint of equivalence. Earlier in the study, some patients instead received split-course radiation therapy.
====Preceding treatment====
*Induction CF & RT x 2
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycle 1: 15 mg/m2 IV over 60 minutes once per day on days 1 to 5
**Cycles 2 & 3: 15 mg/m2 IV over 60 minutes once per day on days 1 to 5
*Fluorouracil (5-FU) as follows:
**Cycle 1: 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
**Cycles 2 & 3: 800 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
====Supportive therapy====
*1 liter NS IV over 2 hours before and after cisplatin
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 1: 200 cGy per day on days 1 to 5, 8 to 12 (10 fractions, for a total dose of 6600 cGy, including the initial 4600 cGy)
3-week course, then 28-day cycle for 2 cycles
===Regimen variant #4, 75/4000 x 4 (5000 cGy)===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Herskovic et al. 1992 (RTOG 85-01)	1986-1990 	Phase 3 (E-esc)	Radiation therapy	Longer OS
Note: Patients had 88% squamous cell, 12% adenocarcinoma histology. 7% karnofsky performance scale of 50-60.
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycle 1 (chemoradiation): 75 mg/m2 IV once per day on days 1 & 29
**Cycles 2 & 3: 75 mg/m2 IV once on day 1
*Fluorouracil (5-FU) as follows:
**Cycle 1 (chemoradiation): 1000 mg/m2/day IV continuous infusion over 96 hours, started on days 1 & 29 (total dose during chemoradiation: 8000 mg/m2)
**Cycles 2 & 3: 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2)
====Radiotherapy====
*Concurrent radiation therapy as follows:
**Cycle 1 (chemoradiation): 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19 to the tumor, then 200 cGy per day on days 22 to 26, 29 to 33 to the initial tumor length plus a 5 cm margin (25 fractions for a total dose of 5000 cGy)
7-week course, then 21-day cycle for 2 cycles
===References===
#RTOG 85-01: Herskovic A, Martz K, al-Sarraf M, Leichman L, Brindle J, Vaitkevicius V, Cooper J, Byhardt R, Davis L, Emami B. Combined chemotherapy and radiotherapy compared with radiotherapy alone in patients with cancer of the esophagus. N Engl J Med. 1992 Jun 11;326(24):1593-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Update: al-Sarraf M, Martz K, Herskovic A, Leichman L, Brindle JS, Vaitkevicius VK, Cooper J, Byhardt R, Davis L, Emami B. Progress report of combined chemoradiotherapy versus radiotherapy alone in patients with esophageal cancer: an intergroup study. J Clin Oncol. 1997 Jan;15(1):277-84. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
##Update: Cooper JS, Guo MD, Herskovic A, Macdonald JS, Martenson JA Jr, Al-Sarraf M, Byhardt R, Russell AH, Beitler JJ, Spencer S, Asbell SO, Graham MV, Leichman LL; Radiation Therapy Oncology Group. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). JAMA. 1999 May 5;281(17):1623-7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#RTOG 94-05: Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002631
#FFCD 9102: Bedenne L, Michel P, Bouché O, Milan C, Mariette C, Conroy T, Pezet D, Roullet B, Seitz JF, Herr JP, Paillot B, Arveux P, Bonnetain F, Binquet C. Chemoradiation followed by surgery compared with chemoradiation alone in squamous cancer of the esophagus: FFCD 9102. J Clin Oncol. 2007 Apr 1;25(10):1160-8. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#SCOPE-1: Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, Ray R, Bashir N, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013 Jun;14(7):627-37. Epub 2013 Apr 25. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN47718479
##Update: Crosby T, Hurt CN, Falk S, Gollins S, Staffurth J, Ray R, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G, Mukherjee S. Long-term results and recurrence patterns from SCOPE-1: a phase II/III randomised trial of definitive chemoradiotherapy +/- cetuximab in oesophageal cancer. Br J Cancer. 2017 Mar 14;116(6):709-716. Epub 2017 Feb 14. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
#PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Epub 2014 Feb 18. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00861094
##HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article EuroPMC
#KEYNOTE-975: NCT04210115
==Cisplatin & Paclitaxel (TP) & RT==
TP & RT: Taxol (Paclitaxel), Platinol (Cisplatin), Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Suntharalingam et al. 2017 (RTOG 0436)	2008-2013 	Phase 3 (C)	TP, Cetuximab, RT	Did not meet primary endpoint of OSOS36: 28% vs 34%(HR 1.11, 95% CI 0.86-1.43)
Note: patients had 62% adenocarcinoma, 38% squamous cell histology. 14% with M1a disease. 6% with Zubrod PS score 2.
====Chemotherapy====
*Cisplatin (Platinol) 25 mg/m2 IV once per day on days 1, 8, 15, 22, 29
*Paclitaxel (Taxol) 50 mg/m2 IV once per day on days 1, 8, 15, 22, 29
====Radiotherapy====
*Concurrent radiation therapy, 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 35 to 37 (28 fractions, for a total dose of 5040 cGy)
6-week course
===References===
#RTOG 0436: Suntharalingam M, Winter K, Ilson D, Dicker AP, Kachnic L, Konski A, Chakravarthy AB, Anker CJ, Thakrar H, Horiba N, Dubey A, Greenberger JS, Raben A, Giguere J, Roof K, Videtic G, Pollock J, Safran H, Crane CH. Effect of the addition of cetuximab to paclitaxel, cisplatin, and radiation therapy for patients with esophageal cancer: The NRG Oncology RTOG 0436 phase 3 randomized clinical trial. JAMA Oncol. 2017 Nov 1;3(11):1520-1528. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00655876
==FOLFOX4 & RT==
FOLFOX4 & RT: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Radiation Therapy
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Conroy et al. 2014 (PRODIGE5/ACCORD17)	2004-2011 	Phase 3 (E-switch-ic)	See link 	See link
Note: In contrast to the original reference, some guidelines list the dosage of leucovorin as 400 mg/m2. Despite being a non-superior experimental arm, this regimen is recommended by some guidelines such as ESMO.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once per day on days 1, 15, 29, then 1600 mg/m2 IV continuous infusion over 46 hours, started on days 1, 15, 29 given third (total dose: 6000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once per day on days 1, 15, 29, given first
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once per day on days 1, 15, 29, given first
====Radiotherapy====
*Concurrent radiation therapy 200 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33 (25 fractions, for a total dose of 5000 cGy)
5-week course
====Subsequent treatment====
*FOLFOX4 consolidation x 3
===References===
#PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Epub 2014 Feb 18. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00861094
##HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article EuroPMC
#KEYNOTE-975: NCT04210115
==S-1 & RT==
S-1 & RT: S-1 & Radiation Therapy
===Regimen===
Study 	Dates of enrollment 	Evidence 	Comparator 	Comparative Efficacy
Ji et al. 2021 (ZJCH-E-E)	2016-06-01 to 2018-08-31	Phase 3 (E-esc)	RT x 6000 cGy	Higher OS24 (primary endpoint)OS24: 53.2% vs 35.8%(HR 0.63, 95% CI 0.47-0.85)
====Chemotherapy====
*Tegafur, gimeracil, oteracil (S-1) 70 mg/m2/day PO on days 1 to 14, 29 to 42 (rounded down to the nearest 20 mg)
====Radiotherapy====
*External beam radiotherapy 180 cGy per day on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40 (30 fractions for a total dose of 5400 cGy)
6-week course
===References===
#ZJCH-E-E: Ji Y, Du X, Zhu W, Yang Y, Ma J, Zhang L, Li J, Tao H, Xia J, Yang H, Huang J, Bao Y, Du D, Liu D, Wang X, Li C, Yang X, Zeng M, Liu Z, Zheng W, Pu J, Chen J, Hu W, Li P, Wang J, Xu Y, Zheng X, Chen J, Wang W, Tao G, Cai J, Zhao J, Zhu J, Jiang M, Yan Y, Xu G, Bu S, Song B, Xie K, Huang S, Zheng Y, Sheng L, Lai X, Chen Y, Cheng L, Hu X, Ji W, Fang M, Kong Y, Yu X, Li H, Li R, Shi L, Shen W, Zhu C, Lv J, Huang R, He H, Chen M. Efficacy of Concurrent Chemoradiotherapy With S-1 vs Radiotherapy Alone for Older Patients With Esophageal Cancer: A Multicenter Randomized Phase 3 Clinical Trial. JAMA Oncol. 2021 Oct 1;7(10):1459-1466. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02813967
=Consolidation after definitive therapy=
==Cisplatin & Fluorouracil (CF)==
CF: Cisplatin & Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Minsky et al. 2002 (RTOG 94-05) 	1995-1999 	Non-randomized part of phase 3 RCT	 	
Conroy et al. 2014 (PRODIGE5/ACCORD17)	2004-2011 	Phase 3 (C) 	See link 	See link
Note: study included both adenocarcinoma and squamous cell histology
====Preceding treatment====
*RTOG 94-05: Definitive CF & RT; standard dose versus CF & RT; high-dose
*PRODIGE5/ACCORD17: Definitive CF & RT
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes 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)
28-day cycle for 2 cycles
===References===
#RTOG 94-05: Minsky BD, Pajak TF, Ginsberg RJ, Pisansky TM, Martenson J, Komaki R, Okawara G, Rosenthal SA, Kelsen DP. INT 0123 (Radiation Therapy Oncology Group 94-05) phase III trial of combined-modality therapy for esophageal cancer: high-dose versus standard-dose radiation therapy. J Clin Oncol. 2002 Mar 1;20(5):1167-74. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00002631
#PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Epub 2014 Feb 18. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00861094
##HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article EuroPMC
==FOLFOX4==
FOLFOX4: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin 4
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Conroy et al. 2014 (PRODIGE5/ACCORD17)	2004-2011 	Phase 3 (E-switch-ic)	See link 	See link
Note: In contrast to the original reference, some guidelines list the dosage of leucovorin as 400 mg/m2. Despite being a non-superior experimental arm, this regimen is recommended by some guidelines such as ESMO.
====Preceding treatment====
*Definitive FOLFOX4 & RT
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 1600 mg/m2 IV continuous infusion over 46 hours, given third (total dose per cycle: 2000 mg/m2)
*Leucovorin (Folinic acid) 200 mg/m2 IV over 2 hours once on day 1
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1
14-day cycle for 3 cycles
===References===
#PRODIGE5/ACCORD17: Conroy T, Galais MP, Raoul JL, Bouché O, Gourgou-Bourgade S, Douillard JY, Etienne PL, Boige V, Martel-Lafay I, Michel P, Llacer-Moscardo C, François E, Créhange G, Abdelghani MB, Juzyna B, Bedenne L, Adenis A; Fédération Francophone de Cancérologie Digestive and UNICANCER-GI Group. Definitive chemoradiotherapy with FOLFOX versus fluorouracil and cisplatin in patients with oesophageal cancer (PRODIGE5/ACCORD17): final results of a randomised, phase 2/3 trial. Lancet Oncol. 2014 Mar;15(3):305-14. Epub 2014 Feb 18. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT00861094
##HRQoL analysis: Bascoul-Mollevi C, Gourgou S, Galais MP, Raoul JL, Bouché O, Douillard JY, Adenis A, Etienne PL, Juzyna B, Bedenne L, Conroy T. Health-related quality of life results from the PRODIGE 5/ACCORD 17 randomised trial of FOLFOX versus fluorouracil-cisplatin regimen in oesophageal cancer. Eur J Cancer. 2017 Oct;84:239-249. Epub 2017 Aug 19. link to original article EuroPMC
=Adjuvant therapy=
==Cisplatin & Fluorouracil (CF)==
CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol
===Regimen===
Study 	Dates of enrollment	Evidence
Kelsen et al. 1998 (RTOG 8911)	1990-1995 	Non-randomized part of phase 3 RCT
Note: This was an experimental arm that did not meet its primary endpoint; included here because other variants of this regimen have demonstrated comparative superiority. This is a component of a sequential treatment protocol; to our knowledge there are no references to support using it as a stand-alone treatment.
====Preceding treatment====
*Neoadjuvant CF, then surgery
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 1
*Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: see note)
28-day cycle for 3 cycles
===References===
#RTOG 8911: Kelsen DP, Ginsberg R, Pajak TF, Sheahan DG, Gunderson L, Mortimer J, Estes N, Haller DG, Ajani J, Kocha W, Minsky BD, Roth JA. Chemotherapy followed by surgery compared with surgery alone for localized esophageal cancer. N Engl J Med. 1998 Dec 31;339(27):1979-84. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Nivolumab monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Kelly et al. 2021 (CheckMate 577)	2016-2019 	Phase 3 (E-RT-esc)	Placebo 	Longer DFS (primary endpoint)Median DFS: 22.4 vs 11 mo(HR 0.69, 96.4% CI 0.56-0.86)
====Preceding treatment====
*Neoadjuvant chemoradiotherapy (not specified), then surgery, with residual pathologic disease
====Immunotherapy====
*Nivolumab (Opdivo) as follows:
**Cycles 1 to 8: 240 mg IV over 30 minutes once on day 1
**Cycles 9 to 17: 480 mg IV over 30 minutes once on day 1
14-day cycle for 8 cycles, then 28-day cycle for 9 cycles (1 year total)
===References===
#CheckMate 577: Kelly RJ, Ajani JA, Kuzdzal J, Zander T, Van Cutsem E, Piessen G, Mendez G, Feliciano J, Motoyama S, Lièvre A, Uronis H, Elimova E, Grootscholten C, Geboes K, Zafar S, Snow S, Ko AH, Feeney K, Schenker M, Kocon P, Zhang J, Zhu L, Lei M, Singh P, Kondo K, Cleary JM, Moehler M; CheckMate 577 Investigators. Adjuvant Nivolumab in Resected Esophageal or Gastroesophageal Junction Cancer. N Engl J Med. 2021 Apr 1;384(13):1191-1203. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02743494
=Metastatic or locally advanced disease, first-line=
==Carboplatin & Paclitaxel (CP)==
===Regimen===
Study 	Dates of enrollment 	Evidence
Philip et al. 1997	Not reported in abstract	Phase 2
Note: In contrast to the original reference, some guidelines list the dosage of carboplatin as AUC 6. The full manuscript was not available for review.
====Eligibility criteria====
*Locally advanced metastatic or recurrent esophageal or gastric cancer
====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. dosing details in abstract have been reviewed by our editors EuroPMC
==Cisplatin & Fluorouracil (CF)==
CF: Cisplatin & Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Sun et al. 2021 (KEYNOTE-590)	2017-2019 	Phase 3 (C)	CF & Pembrolizumab	Shorter OS (co-primary endpoint)Median OS: 9.8 vs 12.4 mo(HR 1.37, 95% CI 1.16-1.61)
Note: to our knowledge, this regimen variant was not tested as an experimental arm in an RCT in this context, prior to becoming a standard comparator arm. 73% of patients had squamous histology. 
====Chemotherapy====
*Cisplatin (Platinol) 80 mg/m2 IV over 2 hours 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 6 cycles
===References===
#KEYNOTE-590: Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03189719
##HRQoL analysis: Mansoor W, Joo S, Norquist JM, Kato K, Sun JM, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Sunpaweravong P, Alsina M, Goekkurt E, Suryawanshi S, Shah S, Shen L. Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer. Oncologist. 2024 Oct 3;29(10):e1324-e1335. Erratum in: Oncologist. 2024 Aug 5;29(8):e1100. link to original article link to PMC article EuroPMC
==Cisplatin & Fluorouracil (CF) & Pembrolizumab==
CF & Pembrolizumab: Cisplatin, Fluorouracil, Pembrolizumab
===Regimen===
FDA-recommended dose
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Sun et al. 2021 (KEYNOTE-590)	2017-2019 	Phase 3 (E-RT-esc)	CF 	Longer OS (co-primary endpoint)Median OS: 12.4 vs 9.8 mo(HR 0.73, 95% CI 0.62-0.86)
Note: 73% of patients had squamous histology. MCBS score is for all patients, regardless of CPS status. 
====Immunotherapy====
*Pembrolizumab (Keytruda) 200 mg IV once on day 1
====Chemotherapy====
*Cisplatin (Platinol) as follows:
**Cycles 1 to 6: 80 mg/m2 IV over 2 hours once on day 1
*Fluorouracil (5-FU) as follows:
**Cycles 1 to 6: 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 up to 35 cycles (2 years)
===References===
#KEYNOTE-590: Sun JM, Shen L, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Mansoor W, Li SH, Sunpaweravong P, Maqueda MA, Goekkurt E, Hara H, Antunes L, Fountzilas C, Tsuji A, Oliden VC, Liu Q, Shah S, Bhagia P, Kato K; KEYNOTE-590 Investigators. Pembrolizumab plus chemotherapy versus chemotherapy alone for first-line treatment of advanced oesophageal cancer (KEYNOTE-590): a randomised, placebo-controlled, phase 3 study. Lancet. 2021 Aug 28;398(10302):759-771. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC NCT03189719
##HRQoL analysis: Mansoor W, Joo S, Norquist JM, Kato K, Sun JM, Shah MA, Enzinger P, Adenis A, Doi T, Kojima T, Metges JP, Li Z, Kim SB, Cho BC, Sunpaweravong P, Alsina M, Goekkurt E, Suryawanshi S, Shah S, Shen L. Health-related quality-of-life analysis from KEYNOTE-590: pembrolizumab plus chemotherapy versus chemotherapy for advanced esophageal cancer. Oncologist. 2024 Oct 3;29(10):e1324-e1335. Erratum in: Oncologist. 2024 Aug 5;29(8):e1100. link to original article link to PMC article EuroPMC
==Cisplatin & Irinotecan (IC)==
IC: Irinotecan & Cisplatin
CI: Cisplatin & Irinotecan
===Regimen variant #1===
Study 	Dates of enrollment	Evidence
Ilson 2004	Not reported 	Phase 2
Note: In contrast to the original reference, some guidelines list cisplatin 25 mg/m2 as an alternate dosage. Patients had 26% squamous cell, 74% adenocarcinoma histology. 85% metastatic disease.
====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 cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Ilson et al. 1999	1997-07 to 1998-09 	Phase 2
Note: Patients had 66% adenocarcinoma, 34% squamous cell histology. Did not receive any prior chemotherapy. 97% with metastatic disease. 
====Chemotherapy====
*Cisplatin (Platinol) 30 mg/m2 IV bolus once per day on days 1, 8, 15, 22
*Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes once per day on days 1, 8, 15, 22
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22, prior to chemotherapy
*Granisetron 2 mg PO once per day on days 1, 8, 15, 22, prior to chemotherapy
*At least 500 mL D5NS IV over 30 to 60 minutes once per day on days 1, 8, 15, 22, prior to cisplatin
*Atropine (Atropen) used as pretreatment medication if there was diarrhea or abdominal cramps within 1 hour of irinotecan
42-day cycles 
===References===
#Ilson DH, Saltz L, Enzinger P, Huang Y, Kornblith A, Gollub M, O'Reilly E, Schwartz G, DeGroff J, Gonzalez G, Kelsen DP. Phase II trial of weekly irinotecan plus cisplatin in advanced esophageal cancer. J Clin Oncol. 1999 Oct;17(10):3270-5. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Ilson DH. Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. Oncology (Williston Park). 2004 Dec;18(14 Suppl 14):22-5. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==Cisplatin & Paclitaxel (TP)==
===Regimen variant #1===
Study 	Dates of enrollment 	Evidence
Ilson et al. 2000	Not reported in abstract	Phase 2
Note: In contrast to the original reference, some guidelines list the paclitaxel dose as 135 mg/m2. No primary reference could be found for the 135 mg/m2 dosage. The protocol reported here was amended to change the original dose of 250 mg/m2 to 200 mg/m2 based on toxicity and treatment-related deaths. Patients had 87% adenocarcinoma, 13% squamous cell histology. Included both gastroesophageal junction and esophageal patients. 95% with metastatic disease. None had received prior chemotherapy. The full manuscript was not available for review.
====Chemotherapy====
*Cisplatin (Platinol) 75 mg/m2 IV once on day 2, given second
*Paclitaxel (Taxol) 200 mg/m2 IV continuous infusion over 24 hours, started on day 1
====Supportive therapy====
*"Granulocyte colony stimulating factor support"
21-day cycles
===Regimen variant #2===
Study 	Dates of enrollment	Evidence
Petrasch et al. 1998	Not reported 	Phase 2
Note: Patients had 25% adenocarcinoma, 75% squamous cell histology. Consisting of unresectable stage III disease, recurrent or metastatic tumors of esophageal origin. 
====Chemotherapy====
*Cisplatin (Platinol) 50 mg/m2 IV over 60 minutes once on day 1, given second
*Paclitaxel (Taxol) 90 mg/m2 IV over 3 hours once on day 1, given first
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV once on day 1; 30 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 30 minutes prior to paclitaxel
*Clemastine (Tavist) 2 mg IV once on day 1; 30 minutes prior to paclitaxel
*Ondansetron (Zofran) 8 mg IV once on day 1; 30 minutes prior to paclitaxel
*"Adequate pre- and post- hydration" for cisplatin
14-day cycles
===References===
#Petrasch S, Welt A, Reinacher A, Graeven U, König M, Schmiegel W. Chemotherapy with cisplatin and paclitaxel in patients with locally advanced, recurrent or metastatic oesophageal cancer. Br J Cancer. 1998 Aug;78(4):511-4. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC
#Ilson DH, Forastiere A, Arquette M, Costa F, Heelan R, Huang Y, Kelsen DP. A phase II trial of paclitaxel and cisplatin in patients with advanced carcinoma of the esophagus. Cancer J. 2000 Sep-Oct;6(5):316-23. dosing details in abstract have been reviewed by our editors EuroPMC
==Docetaxel & Irinotecan==
===Regimen===
Study 	Dates of enrollment	Evidence
Burtness et al. 2009	2001-12 to 2004-10 	Phase 2
Note: Patients had 79% adenocarcinoma, 21% squamous cell histology. All patients ECOG PS of 0 or 1, and unresectable/metastatic disease.
====Chemotherapy====
*Docetaxel (Taxotere) 35 mg/m2 IV over 60 minutes once per day on days 1 & 8, given first
*Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
====Supportive therapy====
*Dexamethasone (Decadron) as follows:
**8 mg PO once per day on days 1 & 8; 12 hours prior to docetaxel
**10 mg IV once per day on days 1 & 8, within 1 hour of chemotherapy
**8 mg PO once per day on days 1 & 8; 12 hour afters chemotherapy
*Serotonin 5-HT3 antagonist IV once per day on days 1 & 8, within 1 hour before chemotherapy
*"Oral antiemetic therapy prescribed"
*Loperamide (Imodium) as needed
21-day cycles
===References===
#Burtness B, Gibson M, Egleston B, Mehra R, Thomas L, Sipples R, Quintanilla M, Lacy J, Watkins S, Murren JR, Forastiere AA. Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer. Ann Oncol. 2009 Jul;20(7):1242-8. Epub 2009 May 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==ECF==
ECF: Epirubicin, Cisplatin, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ross et al. 2002 	1995-1998 	Phase 3 (C)	MCF 	Seems to have non-inferior OS
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (C)	1. ECX 	Non-inferior OS
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (C)	2. EOF 	Non-inferior OS
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (C)	3. EOX 	Seems to have shorter OS
Note: Ross et al. patients had adenocarcinoma, squamous carcinoma, or undifferentiated carcinoma histology, all advanced esophagogastric cancer. REAL-2 patients had 35% esophageal, 25% gastroesophageal junction, 40% gastric primary site. 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, 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)
*Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis
21-day cycle for up to 8 cycles
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC
#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 dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN51678883
==ECX==
ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-RT-switch-ic)	1. ECF 	Non-inferior OS (primary endpoint)
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-RT-switch-ic)	2. EOF 3. EOX	Non-inferior OS (primary endpoint)
Note: REAL-2 patients had 35% esophageal, 25% gastroesophageal junction, 40% gastric primary site. 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
*Capecitabine (Xeloda) 625 mg/m2 PO twice per day on days 1 to 21
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 dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN51678883
==EOF==
EOF: Epirubicin, Oxaliplatin, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-switch-ic)	1. ECF2. ECX	Non-inferior OS (primary endpoint)
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-switch-ic)	3. EOX 	Non-inferior OS (primary endpoint)
Note: Patients had 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 dosing details in manuscript have been reviewed by our editors EuroPMC ISRCTN51678883
==EOX==
EOX: Epirubicin, Oxaliplatin, Xeloda (Capecitabine)
EOC: Epirubicin, Oxaliplatin, Capecitabine
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-RT-switch-ic)	1. ECF 	Seems to have longer OS
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-RT-switch-ic)	2. ECX 	Non-inferior OS (primary endpoint)
Cunningham et al. 2008 (REAL-2)	2000-2005 	Phase 3 (E-RT-switch-ic)	3. EOF 	Non-inferior OS (primary endpoint)
Waddell et al. 2013 (REAL3) 	2008-2011 	Phase 3 (C) 	mEOC+P 	Longer OS (primary endpoint)Median OS: 11.3 vs 8.8 mo(HR 0.73, 95% CI 0.57-0.93)
Note: REAL-2 patients had 35% esophageal, 25% gastroesophageal junction, 40% gastric primary site. 11% ECOG PS of 2. REAL3 patients had 99% adenocarcinoma, 1% undifferentiated histology. 39% esophagus, 31% gastroesophageal junction, 30% gastric primary site. 6% ECOG 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
===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 dosing details in manuscript have been reviewed by our editors EuroPMC 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 dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00824785
==mFOLFOX6 & Cetuximab==
mFOLFOX6 & Cetuximab: modified FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Cetuximab
FOLFOX-C: FOLinic acid (Leucovorin), Fluorouracil, OXaliplatin, Cetuximab
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Enziger et al. 2016 (CALGB 80403/ECOG E1206)	2006-2009 	Randomized Phase 2 (E-switch-ic)	1. ECF-C2. IC-C	Not powered to draw conclusions
Note: Patients had 91% adenocarcinoma, 9% squamous cell histology. 56% esophageal, 43% gastroesophageal tumors. To receive full-dose therapy in this trial, patients were required to have an absolute neutrophil count of 1,000/µL or greater, platelets of 75,000/µL or greater, and no other grade 2 or higher treatment-related toxicity.
====Chemotherapy====
*Fluorouracil (5-FU) 400 mg/m2 IV bolus once on day 1, then 2400 mg/m2 IV continuous infusion over 46 to 48 hours, given third (total dose per cycle: 2800 mg/m2)
*Leucovorin (Folinic acid) 400 mg/m2 IV over 2 hours once on day 1, given second, with oxaliplatin
*Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours once on day 1, given second, with leucovorin
====Targeted therapy====
*Cetuximab (Erbitux) as follows, given first:
**Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once on day 8
**Cycle 2 onwards: 250 mg/m2 IV over 60 minutes once per day on days 1 & 8
14-day cycles
===References===
#CALGB 80403/ECOG E1206: Enzinger PC, Burtness BA, Niedzwiecki D, Ye X, Douglas K, Ilson DH, Villaflor VM, Cohen SJ, Mayer RJ, Venook A, Benson AB 3rd, Goldberg RM. CALGB 80403 (Alliance)/E1206: a randomized phase II study of three chemotherapy regimens plus cetuximab in metastatic esophageal and gastroesophageal junction cancers. J Clin Oncol. 2016 Aug 10;34(23):2736-42. Epub 2016 Jul 5. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC NCT00381706
==FULV & Gemcitabine==
FULV & Gemcitabine: 5-FU, LeucoVorin, Gemcitabine
===Regimen===
Study 	Dates of enrollment	Evidence
Morgan-Meadows et al. 2005	1998-06 to 2001-11 	Phase 2
Note: Patients had 100% esophageal cancer (both squamous and adenocarcinoma histology). The full manuscript of Morgan-Meadows et al. 2005 was not available for review. 
====Eligibility criteria====
*No prior therapy
====Chemotherapy====
*Fluorouracil (5-FU) 600 mg/m2 IV once per day on days 1, 8, 15 (total dose per cycle: 1800 mg/m2)
*Leucovorin (Folinic acid) 25 mg/m2 IV once per day on days 1, 8, 15
*Gemcitabine (Gemzar) 1000 mg/m2 IV once per day on days 1, 8, 15
28-day cycles
===References===
#Morgan-Meadows S, Mulkerin D, Berlin JD, Kim K, Bailey H, Saphner T, Jumonville A, Hansen R, Ahuja H, McFarland T, Thomas JP. A phase II trial of gemcitabine, 5-fluorouracil and leucovorin in advanced esophageal carcinoma. Oncology. 2005;69(2):130-4. Epub 2005 Aug 23. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
==LdCF==
LdCF: Liposomal doxorubicin, Cisplatin, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Cascinu et al. 2010	2002-2005 	Randomized Phase 2 (E-switch-ic)	MCF 	Longer OS (secondary endpoint)Median OS: 12.1 vs 8.3 mo(HR 0.59, 95% CI 0.34-0.94)
Note: Patients had 11% gastroesophageal junction, 89% gastric origin. 90% metastatic. 6% with ECOG PS of 2. 
====Chemotherapy====
*Pegylated liposomal doxorubicin (Doxil) 20 mg/m2 IV once on day 1
*Cisplatin (Platinol) 50 mg/m2 IV 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)
14-day cycles
===References===
#Cascinu S, Galizia E, Labianca R, Ferraù F, Pucci F, Silva RR, Luppi G, Beretta GD, Berardi R, Scartozzi M. Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II trial. Cancer Chemother Pharmacol. 2011 Jul;68(1):37-43. Epub 2010 Sep 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==MCF==
MCF: Mitomycin, Cisplatin, Fluorouracil
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Ross et al. 2002 	1995-1998 	Phase 3 (E-switch-ic) 	ECF 	Seems to have non-inferior OS (primary endpoint)
Cascinu et al. 2010	2002-2005 	Randomized Phase 2 (C)	LdCF 	Shorter OS (secondary endpoint)Median OS: 8.3 vs 12.1 mo(HR 1.69, 95% CI 1.06-2.94)
Note: Cascinu et al. patients had 11% gastroesophageal junction, 89% gastric primary site. 90% metastatic. 6% with ECOG PS of 2. 
====Chemotherapy====
*Mitomycin (Mutamycin) 7 mg/m2 (maximum dose of 14 mg) IV once on day 1
*Cisplatin (Platinol) 60 mg/m2 IV once per day on days 1 & 22
*Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion, started on day 1 (total dose per cycle: 12,600 mg/m2)
====Supportive therapy====
*Warfarin (Coumadin) 1 mg PO once per day for catheter thrombosis prophylaxis
42-day cycle for up to 5 cycles (6 months)
===References===
#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 dosing details in manuscript have been reviewed by our editors EuroPMC
#Cascinu S, Galizia E, Labianca R, Ferraù F, Pucci F, Silva RR, Luppi G, Beretta GD, Berardi R, Scartozzi M. Pegylated liposomal doxorubicin, 5-fluorouracil and cisplatin versus mitomycin-C, 5-fluorouracil and cisplatin for advanced gastric cancer: a randomized phase II trial. Cancer Chemother Pharmacol. 2011 Jul;68(1):37-43. Epub 2010 Sep 7. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Paclitaxel monotherapy==
===Regimen variant #1, weekly===
Study 	Dates of enrollment	Evidence 	Comparator 	Comparative Efficacy
Ilson et al. 2007 	1998-01 to 2000-04 	Phase 2 	 	
Noronha et al. 2024c	2016-05 to 2020-12 	Phase 3 (E-esc)	Best supportive care	Longer OS (primary endpoint)Median OS: 9.2 vs 4.2 mo(HR 0.49, 95% CI 0.39-0.64)
Note: Patients in Ilson et al. 2007 had 100% esophageal cancers. 66% adenocarcinoma, 34% squamous cell. Median ECOG PS 1, ranging 0-2. 
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once on day 1, given 30 to 60 minutes prior to paclitaxel
7-day cycles
===Regimen variant #2, CI===
Study 	Dates of enrollment	Evidence
Ajani et al. 1994	1992-08 to 1993-12 	Phase 2
Note: In contrast to the original reference, some guidelines list the dosage of paclitaxel as 135 to 175 mg/m2. Patients had 100% esophageal cancer. 36% squamous cell, 64% adenocarcinoma histology.
====Chemotherapy====
*Paclitaxel (Taxol) 250 mg/m2 IV continuous infusion over 24 hours, started on day 1
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg PO for 2 doses on day 1; 14 hours and 7 hours prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once on day 1; 60 minutes prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once on day 1; 60 minutes prior to paclitaxel
*Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 24 hours after the paclitaxel infusion finishes
21-day cycles
====Dose and schedule modifications====
*Paclitaxel (Taxol) dosage adjusted based on toxicity down to 150 or 200 mg/m2, or up to 280 mg/m2
===References===
#Ajani JA, Ilson DH, Daugherty K, Pazdur R, Lynch PM, Kelsen DP. Activity of taxol in patients with squamous cell carcinoma and adenocarcinoma of the esophagus. J Natl Cancer Inst. 1994 Jul 20;86(14):1086-91. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Ilson DH, Wadleigh RG, Leichman LP, Kelsen DP. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol. 2007 May;18(5):898-902. Epub 2007 Mar 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#Noronha V, Patil VM, Menon N, Goud S, Singh A, Shah M, More S, Shah S, Yadav A, Sonawane S, Nawale K, Chowdhury OR, Kaushal RK, Ghosh-Laskar S, Agarwal JP, Yadav S, Pai T, Janu A, Mahajan A, Purandare N, Banavali S, Badwe R, Prabhash K. Phase III randomized trial comparing palliative systemic therapy to best supportive care in advanced esophageal/GEJ cancer. Int J Cancer. 2024 Dec 15;155(12):2232-2245. Epub 2024 Aug 2. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC CTRI/2016/01/006474
=Metastatic or locally advanced disease, subsequent lines of therapy=
==CAPIRI==
CapeIRI: Capecitabine and IRInotecan
CAPIRI: CAPecitabine and IRInotecan
XELIRI: XELox (Capecitabine) and IRInotecan
XI: Xeloda (Capecitabine) and Irinotecan
===Regimen===
Study 	Dates of enrollment	Evidence
Leary et al. 2008	2003-10 to 2005-09 	Phase 2
====Chemotherapy====
*Capecitabine (Xeloda) 1000 mg/m2 PO twice per day on days 1 to 14
*Irinotecan (Camptosar) 250 mg/m2 IV over 30 to 90 minutes once on day 1
====Supportive therapy====
*Atropine (Atropen) 0.25 mg SC once on day 1, given prior to irinotecan
*Loperamide (Imodium) 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool
*Ciprofloxacin (Cipro) 250 mg PO twice per day prn diarrhea lasting longer than 24 hours despite loperamide
 
21-day cycle for up to 8 cycles
===References===
#Leary A, Assersohn L, Cunningham D, Norman AR, Chong G, Brown G, Ross PJ, Costello C, Higgins L, Oates J. A phase II trial evaluating capecitabine and irinotecan as second line treatment in patients with oesophago-gastric cancer who have progressed on, or within 3 months of platinum-based chemotherapy. Cancer Chemother Pharmacol. 2009 Aug;64(3):455-62. Epub 2008 Dec 23. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
==Docetaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Albertsson et al. 2007	1997-2003 	Phase 2
Note: Patients had squamous cell or adenocarcinoma histology of the esophagus or gastric cardia.
====Chemotherapy====
*Docetaxel (Taxotere) 100 mg/m2 IV over 60 minutes once on day 1
21-day cycles
===References===
#Albertsson M, Johansson B, Friesland S, Kadar L, Letocha H, Frykholm G, Wagenius G. Phase II studies on docetaxel alone every third week, or weekly in combination with gemcitabine in patients with primary locally advanced, metastatic, or recurrent esophageal cancer. Med Oncol. 2007;24(4):407-12. link to original article dosing details in abstract have been reviewed by our editors EuroPMC
#INTEGRATE IIb: NCT04879368
==Docetaxel & Irinotecan==
===Regimen===
Study 	Dates of enrollment	Evidence
Burtness et al. 2009	2001-12 to 2004-10 	Phase 2, fewer than 20 pts in this subgroup
Note: Patients had 79% adenocarcinoma, 21% squamous cell histology. All patients ECOG PS of 0 or 1, and unresectable/metastatic disease.
====Chemotherapy====
*Docetaxel (Taxotere) 35 mg/m2 IV over 60 minutes once per day on days 1 & 8, given first
*Irinotecan (Camptosar) 50 mg/m2 IV over 30 minutes once per day on days 1 & 8, given second
====Supportive therapy====
*Dexamethasone (Decadron) as follows:
**8 mg PO once per day on days 1 & 8; 12 hours prior to docetaxel
**10 mg IV once per day on days 1 & 8, within 1 hour of chemotherapy
**8 mg PO once per day on days 1 & 8; 12 hour afters chemotherapy
*Serotonin 5-HT3 antagonist IV once per day on days 1 & 8, within 1 hour before chemotherapy
*"Oral antiemetic therapy prescribed"
*Loperamide (Imodium) as needed
21-day cycles
===References===
#Burtness B, Gibson M, Egleston B, Mehra R, Thomas L, Sipples R, Quintanilla M, Lacy J, Watkins S, Murren JR, Forastiere AA. Phase II trial of docetaxel-irinotecan combination in advanced esophageal cancer. Ann Oncol. 2009 Jul;20(7):1242-8. Epub 2009 May 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Erlotinib monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Ilson et al. 2010	2002-07 to 2005-09 	Phase 2
Note: Patients had 57% adenocarcinoma, 43% squamous cell histology. 6% proximal esophagus, 35% distal esophagus, 59% gastroesophageal junction. 
====Targeted therapy====
*Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28, taken at least 1 hour before a meal, or 2 hours after a meal
28-day cycles
===References===
#Ilson DH, Kelsen D, Shah M, Schwartz G, Levine DA, Boyd J, Capanu M, Miron B, Klimstra D. A phase 2 trial of erlotinib in patients with previously treated squamous cell and adenocarcinoma of the esophagus. Cancer. 2011 Apr 1;117(7):1409-14. Epub 2010 Nov 8. link to original article dosing details in manuscript have been reviewed by our editors link to PMC article EuroPMC
==Irinotecan monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Mühr-Wilkenshoff et al. 2003	1999-2000 	Phase 2, fewer than 20 patients
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. Ten patients had esophageal squamous cell carcinoma, three with esophageal adenocarcinoma
====Chemotherapy====
*Irinotecan (Camptosar) 125 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22
42-day cycles
===References===
#Mühr-Wilkenshoff F, Hinkelbein W, Ohnesorge I, Wolf KJ, Riecken EO, Zeitz M, Scherübl H. A pilot study of irinotecan (CPT-11) as single-agent therapy in patients with locally advanced or metastatic esophageal carcinoma. Int J Colorectal Dis. 2003 Jul;18(4):330-4. Epub 2003 Feb 1. link to original article EuroPMC
#INTEGRATE IIb: NCT04879368
==IRI-S==
IRI-S: IRInotecan & S-1
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Huang et al. 2019 (ESWN 01)	2014-2016 	Phase 3 (E-switch-ic)	S-1 	Longer PFS (primary endpoint)Median PFS: 3.8 vs 1.7 mo(HR 0.58, 95% CI 0.38-0.86)
====Chemotherapy====
*Irinotecan (Camptosar) 160 mg/m2 IV once on day 1, given first
*Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
**Less than 1.25 m2: 40 mg PO twice per day on days 1 to 10
**Between 1.25 m2 and 1.5 m2: 50 mg PO twice per day on days 1 to 10
**1.5 m2 or more: 60 mg PO twice per day on days 1 to 10
14-day cycles
===References===
#ESWN 01: Huang J, Xu B, Liu Y, Huang J, Lu P, Ba Y, Wu L, Bai Y, Zhang S, Feng J, Cheng Y, Li J, Wen L, Yuan X, Ma C, Hu C, Fan Q, Wang X. Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial. Cancer Commun (Lond). 2019 Apr 2;39(1):16. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02319187
==Paclitaxel monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence
Ilson et al. 2007	1998-01 to 2000-04 	Phase 2
Note: Patients had 100% esophageal cancers. 66% adenocarcinoma, 34% squamous cell. Median ECOG PS 1, ranging 0-2. 
====Chemotherapy====
*Paclitaxel (Taxol) 80 mg/m2 IV over 60 minutes once per day on days 1, 8, 15, 22
====Supportive therapy====
*Dexamethasone (Decadron) 20 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to paclitaxel
*Cimetidine (Tagamet) 300 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to paclitaxel
*Diphenhydramine (Benadryl) 50 mg IV once per day on days 1, 8, 15, 22; 30 to 60 minutes prior to paclitaxel
28-day cycles
===References===
#Ilson DH, Wadleigh RG, Leichman LP, Kelsen DP. Paclitaxel given by a weekly 1-h infusion in advanced esophageal cancer. Ann Oncol. 2007 May;18(5):898-902. Epub 2007 Mar 9. link to original article dosing details in manuscript have been reviewed by our editors EuroPMC
#INTEGRATE IIb: NCT04879368
==S-1 monotherapy==
===Regimen===
Study 	Dates of enrollment	Evidence 	Comparator	Comparative Efficacy
Huang et al. 2019 (ESWN 01)	2014-2016 	Phase 3 (C)	IRI-S 	Shorter PFSMedian PFS: 1.7 vs 3.8 mo(HR 1.72, 95% CI 1.16-2.63)
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====
*Tegafur, gimeracil, oteracil (S-1) by the following BSA-based criteria:
**Less than 1.25 m2: 40 mg PO twice per day on days 1 to 14
**Between 1.25 m2 and 1.5 m2: 50 mg PO twice per day on days 1 to 14
**1.5 m2 or more: 60 mg PO twice per day on days 1 to 14
21-day cycles
===References===
#ESWN 01: Huang J, Xu B, Liu Y, Huang J, Lu P, Ba Y, Wu L, Bai Y, Zhang S, Feng J, Cheng Y, Li J, Wen L, Yuan X, Ma C, Hu C, Fan Q, Wang X. Irinotecan plus S-1 versus S-1 in patients with previously treated recurrent or metastatic esophageal cancer (ESWN 01): a prospective randomized, multicenter, open-labeled phase 3 trial. Cancer Commun (Lond). 2019 Apr 2;39(1):16. link to original article link to PMC article dosing details in manuscript have been reviewed by our editors EuroPMC NCT02319187
Category:Esophageal cancer regimens
Category:Disease-specific pages
Category:Gastroesophageal cancers