Revision as of 20:20, 7 July 2017

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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.

56 regimens on this page 74 variants on this page

Guidelines

CAP/ASCP/ASCO

HER2 Testing and Clinical Decision Making in Gastroesophageal Adenocarcinoma (2017) PubMed

ESMO

Oesophageal cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up (2016) PubMed

NCCN

NCCN Guidelines - Esophageal and Esophagogastric Junction Cancers

Neoadjuvant therapy

Capecitabine, Carboplatin, Paclitaxel, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Czito et al. 2006	Pilot, <20 pts

The primary reference did not specify whether patients were intended to proceed to surgery.

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 1.5 IV once per day on days 2, 9, 16, 23, 30
Paclitaxel (Taxol) 45 mg/m² IV over 1 hour on days 2, 9, 16, 23, 30
Capecitabine (Xeloda) 600 mg/m² PO BID, starting on day 1 and finishing the evening of the last day of radiation therapy
Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total dose of 50.4 Gy, starting on day 1

6-week course

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 contains verified protocol PubMed

Capecitabine, Cisplatin, RT

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RT: Radiation Therapy

Regimen

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.

Chemoradiotherapy

Cisplatin (Platinol) 30 mg/m² IV over 1 hour on day 1; given before the first dose of capecitabine
Capecitabine (Xeloda) 800 mg/m² PO BID, 5 days per week while radiation is being given
Concurrent radiation therapy, total of 54 Gy given (dose per fraction and total duration of treatment was not specified)

References

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 contains verified protocol--please see note above, as patients in this study did not undergo surgery PubMed

Capecitabine, Docetaxel, RT

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RT: Radiation Therapy

Regimen

Note: No primary reference could be found for this regimen; the reference below is for reference purposes only.

Chemoradiotherapy

Docetaxel (Taxotere) 20 mg/m² IV once per day on days 1, 8, 15, 22, 29
Capecitabine (Xeloda) 625-825 mg/m² PO BID on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Concurrent radiation therapy not defined

5-week course

References

Phase I: 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 SD article PubMed

Capecitabine, Docetaxel, Oxaliplatin, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Spigel et al. 2010	Phase I/II

Chemoradiotherapy

Capecitabine (Xeloda) 1000 mg/m² PO BID 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
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions, for a total dose of 45 Gy. Patients who were no longer surgical candidates received additional radiation therapy to a total dose of 64.8 Gy.

Supportive medications

Dexamethasone (Decadron) 4 mg PO every 12 hours before, at the time of, and after Docetaxel (Taxotere); first dose the evening before Docetaxel (Taxotere)
"Routine antiemetics"

5-week course of therapy

Endoscopy, CT scan, and--if available--endoscopic ultrasound for restaging 2 to 4 weeks after finishing chemoradiation. Surgical resection for appropriate candidates during weeks 9 to 12.

References

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 contains verified protocol PubMed

Capecitabine, Oxaliplatin, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Javle et al. 2009	Phase I

Chemoradiotherapy

Capecitabine (Xeloda) 625 mg/m² PO BID 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
Concurrent radiation therapy, total dose of 50.4 Gy

5-week course

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 contains protocol PubMed

Capecitabine, Paclitaxel, RT

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RT: Radiation Therapy

Regimen

Note: No primary reference could be found for this regimen.

Chemoradiotherapy

Capecitabine (Xeloda) 625 to 825 mg/m² PO BID 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
Concurrent radiation therapy not defined

5-week course

Carboplatin, Fluorouracil, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Zemanoa et al. 2009	Non-randomized

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 6 IV once per day on days 1 & 22
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion on days 1 to 42
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting on day 1, for a total dose of 45 Gy. If surgery was contraindicated, total dose was increased to 50.4 to 56.8 Gy.
Upper endoscopy and CT chest and abdomen was performed after completion of chemoradiation

42-day course

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 contains verified protocol PubMed

Carboplatin, Paclitaxel, RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
van Meerten et al. 2006	Phase II
van Hagen et al. 2012 (CROSS)	Phase III	Surgery alone	Superior OS

Chemoradiotherapy

Carboplatin (Paraplatin) AUC 2 IV once per day on days 1, 8, 15, 22, 29; given second
Paclitaxel (Taxol) 50 mg/m² IV over 1 hour once per day on days 1, 8, 15, 22, 29; given first
Concurrent radiation therapy, 1.8 Gy fractions x 23 fractions given 5 days per week, starting on day 1, for a total dose of 41.4 Gy

Supportive medications

Dexamethasone (Decadron) 10 mg IV 30 minutes prior to Paclitaxel (Taxol)
Ranitidine (Zantac) 50 mg IV 30 minutes prior to Paclitaxel (Taxol)
Clemastine (Tavist) 2 mg IV 30 minutes prior to Paclitaxel (Taxol)
Between paclitaxel & carboplatin: 100 mL NS given over 30 minutes, then Ondansetron (Zofran) 8 mg in 100 mL NS given over 30 minutes

5-week course

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.

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 PMC article contains verified protocol PubMed
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 contains verified protocol link to appendix with details about administration PubMed

Cisplatin & Docetaxel -> Cisplatin, Docetaxel, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Ruhstaller et al. 2009 (SAKK 75/02)	Phase II

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, followed by:

Chemoradiotherapy

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
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting on day 1, for a total dose of 45 Gy

5-week course

Surgery planned to be done 3 to 8 weeks after finishing chemoradiation.

References

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 (SAKK). 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 contains verified protocol PubMed

Cisplatin, Fluorouracil, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Tepper et al. 2008 (CALGB 9781)	Phase III	Surgery alone	Superior OS

Chemoradiotherapy

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 once per day on days 1 to 4, 29 to 32; given after cisplatin (total dose 8000 mg/m²)
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, then a 5.4 Gy final boost, for a total dose of 50.4 Gy, starting within 24 hours of chemotherapy

5.5-week course

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.

Regimen #2

Study	Evidence	Comparator	Efficacy
Bedenne et al. 2007 (FFCD 9102)	Phase III	Cisplatin, Fluorouracil, RT (no surgery)	Seems to have equivalent OS

Chemoradiotherapy

Cisplatin (Platinol) 15 mg/m² IV over 1 hour once per day on days 1 to 5
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion over 120 hours on days 1 to 5 (total dose per cycle: 4000 mg/m²)
Conventional radiation therapy, 2 Gy fractions x 23 fractions given 5 days per week, for a total dose of 46 Gy
- Earlier in the study, some patients instead received split-course radiation therapy, 3 Gy fractions x 5 fractions given on days 1 to 5. 15 Gy per cycle; total dose after 2 cycles is 30 Gy.

Supportive medications

1 liter NS IV over 2 hours before and after Cisplatin (Platinol)

21-day cycle for 2 cycles

Surgery to be done 50 to 60 days after start of chemoradiation.

References

Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. link to original article PubMed
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 contains verified protocol PubMed
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 contains verified protocol PubMed

Cisplatin & Etoposide

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Regimen

Study	Evidence	Comparator	Efficacy
Boonstra et al. 2011	Phase III	Surgery alone	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 4 hours once on day 1
Etoposide (Vepesid) 100 mg/m²/day IV over 2 hours once on day 1, then 200 mg/m²/day PO once per day on days 3 & 5

21-day cycle for 2 to 4 cycles, followed by surgery

References

Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011 May 19;11:181. link to original article contains verified protocol PubMed

Cisplatin & Fluorouracil

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Regimen

Study	Evidence	Comparator	Efficacy
Ancona et al. 2001	Phase III	Surgery alone	Seems not superior

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continous infusion on days 1 to 5 (total dose per cycle: 5000 mg/m²)

28-day cycle for 2 or 3 cycles, followed by surgery

References

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 PubMed
1. 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 PubMed
Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001 Jun 1;91(11):2165-74. contains protocol PubMed
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 PubMed
1. 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 PubMed
Burmeister BH, Thomas JM, Burmeister EA, Walpole ET, Harvey JA, Thomson DB, Barbour AP, Gotley DC, Smithers BM. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011 Feb;47(3):354-60. link to original article PubMed

Cisplatin & Fluorouracil -> Fluorouracil, Paclitaxel, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Ajani et al. 2006 (RTOG 9904)	Phase II

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV once per day on days 1 & 5
Fluorouracil (5-FU) 200 mg/m²/day IV continous infusion on days 1 to 21 (total dose: 4200 mg/m²)

28-day cycle for 2 cycles, followed by:

Chemoradiotherapy

Paclitaxel (Taxol) 45 mg/m² IV once per day on days 1, 8, 15, 22, 29
Fluorouracil (5-FU) 300 mg/m²/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy

5-week course

References

Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. link to original article contains verified protocol PubMed

Cisplatin & Irinotecan -> Cisplatin, Irinotecan, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence
Ilson et al. 2011	Phase II

Chemotherapy

Cisplatin (Platinol) 30 mg/m² IV over 30 minutes once per day on days 1 & 8; given before irinotecan
Irinotecan (Camptosar) 65 mg/m² IV over 30 minutes once per day on days 1 & 8; given after cisplatin

21-day cycle for 2 cycles, followed by:

Chemoradiotherapy

Cisplatin (Platinol) 30 mg/m² IV over 30 minutes once per day on days 1 & 8; given before irinotecan
Irinotecan (Camptosar) 65 mg/m² IV over 30 minutes once per day on days 1 & 8; given after cisplatin
Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total of 50.4 Gy given

Supportive medications

Dexamethasone (Decadron) 20 mg PO/IV prior to chemotherapy
Granisetron (Kytril) 2 mg PO or Ondansetron (Zofran) 32 mg IV prior to chemotherapy
At least 500 mL D5NS or NS as supportive hydration
Atropine 0.5 to 1 mg IV prn cholinergic symptoms

21-day cycle for 2 cycles

Surgery performed 4 to 8 weeks after chemoradiation.

Regimen #2

Study	Evidence
Rivera et al. 2009	Phase II

Chemotherapy

Cisplatin (Platinol) 30 mg/m² IV once per day on days 1, 8, 22, 29
Irinotecan (Camptosar) 65 mg/m² IV once per day on days 1, 8, 22, 29

21-day cycle for 2 cycles, followed by:

Chemoradiotherapy

Cisplatin (Platinol) 30 mg/m² IV once per day on days 1, 8, 15, 22
Irinotecan (Camptosar) 65 mg/m² IV once per day on days 1, 8, 15, 22
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.

5-week course

Surgery done 5 to 8 weeks after finishing chemoradiation.

Regimen #3

Study	Evidence
Sharma et al. 2009	Pilot

This regimen is being prospectively evaluated in CALGB 80302.

Chemoradiotherapy

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
Concurrent radiation therapy, 1.8 Gy fractions x 25 to 28 fractions, for a total of 45 to 50.4 Gy given

21-day cycle for 2 cycles

References

Retrospective Abstract:' R. Sharma, G. Y. Yang, H. R. Nava, T. L. Demmy, C. E. Nwogu, S. S. Yendamuri, D. Lamonica, W. Tan, R. V. Iyer, N. I. Khushalani. A single institution experience with neoadjuvant chemoradiation (CRT) with irinotecan (I) and cisplatin (C) in locally advanced esophageal carcinoma (LAEC). 2009 ASCO Annual Meeting abstract e15619. link to abstract
Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. link to original article contains verified protocol PubMed
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. 2011 Oct 11. link to original article contains verified protocol PubMed

Cisplatin, Irinotecan, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Yoon et al. 2011	Phase II

Chemoradiotherapy

Cisplatin (Platinol) 30 mg/m² IV once per day on days 1, 8, 22, 29
Irinotecan (Camptosar) 65 mg/m² IV once per day on days 1, 8, 22, 29
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.

5-week course

Surgery done at least 28 days after finishing chemoradiation, then begin adjuvant cisplatin & irinotecan at least 28 days after surgical resection.

References

Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol PubMed

Cisplatin, Paclitaxel, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence
Yoon et al. 2011	Phase II

Chemoradiotherapy

Cisplatin (Platinol) 30 mg/m² IV once per day on days 1, 8, 15, 22, 29
Paclitaxel (Taxol) 50 mg/m² IV over 1 hour on days 1, 8, 15, 22, 29
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.

5-week course

Surgery done at least 28 days after finishing chemoradiation, then begin adjuvant cisplatin & paclitaxel at least 28 days after surgical resection.

Regimen #2

Study	Evidence
Urba et al. 2003	Phase II

Chemoradiotherapy

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
Concurrent radiation therapy, 1.5 Gy 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 45 Gy

Supportive medications

Dexamethasone (Decadron) 20 mg PO given 12 and 6 hours before Paclitaxel (Taxol)
Diphenhydramine (Benadryl) 50 mg IV 30 minutes prior to Paclitaxel (Taxol)
Cimetidine (Tagamet) 300 mg IV 30 minutes prior to Paclitaxel (Taxol)
1 liter D5NS and mannitol 12.5 g bolus IV prior to Cisplatin (Platinol)
Mannitol 25 g in 1 liter D5NS IV over 4 hours after Cisplatin (Platinol)
Filgrastim (Neupogen) 5 mcg/kg SC once per day, starting 24 hours after the fourth dose of Paclitaxel (Taxol), continuing until absolute neutrophil count greater than 10,000

4-week course of therapy

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 contains verified protocol PubMed
Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol PubMed

Docetaxel, Fluorouracil, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence
Hihara et al. 2007	Phase II

Chemoradiotherapy

Docetaxel (Taxotere) 7.5 mg/m² IV over 1 hour once per day on days 1, 8, 22, 29
Fluorouracil (5-FU) 250 mg/m²/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45
Concurrent radiation therapy, 2 Gy fractions x 30 to 33 fractions given 5 days per week (i.e., on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45), for a total dose of 60 to 66 Gy, starting on day 1

Supportive medications

Dexamethasone (Decadron) 8 mg IV 30 minutes prior to Docetaxel (Taxotere)

7-week course

Regimen #2

Note: No primary reference could be found for this regimen.

Chemoradiotherapy

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 on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
Concurrent radiation therapy not defined

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 contains verified protocol PubMed

Fluorouracil, Oxaliplatin, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence
Lorenzen et al. 2008	Phase I/II

Chemoradiotherapy

Fluorouracil (5-FU) 225 mg/m²/day IV continuous infusion over days 1 to 33
Oxaliplatin (Eloxatin) 45 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy

35-day course

Surgery 4 to 6 weeks after finishing chemoradiation.

Regimen #2

Study	Evidence
Khushalani et al. 2002	Phase II

Chemoradiotherapy

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 days 8 to 42
Concurrent radiation therapy, 1.8 Gy fractions x 20 to 22 fractions, for an initial total dose of 36 to 39.6 Gy, started on day 8
- Followed by off-cord conformal oblique fields, 5.4 to 9 Gy given to the clinical target volume (CTV). A second off-cord phase to the gross tumor volume (GTV) of 5.4 Gy was then given, for a total dose delivered of 50.4 Gy to the GTV.
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.

6-week cycle for 1 initial cycle (see above)

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 contains verified protocol PubMed
Lorenzen S, Brücher B, Zimmermann F, Geinitz H, Riera J, Schuster T, Roethling N, Höfler H, Ott K, Peschel C, Siewert JR, Molls M, Lordick F. Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial. Br J Cancer. 2008 Oct 7;99(7):1020-6. Epub 2008 Sep 16. link to PMC article contains verified protocol PubMed
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 PMC article PubMed

PLF

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PLF: Platinol (Cisplatin), Leucovorin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Stahl et al. 2009	Phase III	PLF -> Cisplatin, Etoposide, RT	Might have inferior OS

Note: this regimen is given for 2.5 cycles, which is a highly unusual instruction.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 1 hour once per day on days 1, 15, 29
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
Fluorouracil (5-FU) 2000 mg/m² IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36

6-week cycle for 2.5 cycles, followed in 3 to 4 weeks by surgery

References

Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article contains verified protocol PubMed

PLF -> Cisplatin, Etoposide, RT

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PLF: Platinol (Cisplatin), Leucovorin, Fluorouracil
RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Stahl et al. 2009	Phase III	PLF	Might have superior OS

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 1 hour once per day on days 1, 15, 29
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
Fluorouracil (5-FU) 2000 mg/m² IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36

6-week cycle for 2 cycles, followed in 2 weeks by:

Chemoradiotherapy

Cisplatin (Platinol) 50 mg/m² IV over 1 hour once per day on days 1 & 8
Etoposide (Vepesid) 80 mg/m² IV over 1 hour once per day on days 3 to 5
Concurrent radiation therapy, 2.0 Gy fractions x 15 fractions, five days per week, for a target dose of 30 Gy

Followed in 3 to 4 weeks by surgery

References

Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. link to original article contains verified protocol PubMed

Perioperative chemotherapy

Cisplatin & Fluorouracil

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Regimen

Study	Evidence	Comparator	Efficacy
Ychou et al. 2011	Phase III	Surgery alone	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV once on day 1
Fluorouracil (5-FU) 800 mg/m²/day IV continous infusion on days 1 to 5 (total dose per cycle: 4000 mg/m²)

28-day cycle for 2 or 3 cycles, followed by surgery, followed by 3 to 4 more cycles

References

Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. link to original article contains verified protocol PubMed

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2006 (MAGIC)	Phase III	Surgery alone	Superior OS

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion on days 1 to 21

Supportive medications

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

21-day cycle for 3 cycles preoperatively, with surgery 3 to 6 weeks after completing cycle 3. The 3 cycles of postoperative chemotherapy are started 6 to 12 weeks after surgery.

References

Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains verified protocol PubMed

ECX

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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2017 (UK MRC ST03)	Phase III	ECX & Bevacizumab	Seems not superior

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 625 mg/m² PO BID on days 1 to 21

21-day cycle for 3 cycles preoperatively and 3 cycles postoperatively

References

Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. link to original article contains protocol PubMed

EOF

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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 on days 1 to 21

Supportive medications

Dexamethasone (Decadron) 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
5HT3 antagonist prior to chemotherapy
Metoclopramide (Reglan) 10 mg PO TID x 3 days after day 1 chemotherapy
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 NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used

EOX

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EOX: Epirubicin, Oxaliplatin, Xeloda (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 BID on days 1 to 21

Supportive medications

Dexamethasone (Decadron) 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
5HT3 antagonist prior to chemotherapy
Metoclopramide (Reglan) 10 mg PO TID x 3 days after day 1 chemotherapy
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 NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used

Surgery alone

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Regimen

Study	Evidence	Comparator	Efficacy
Macdonald et al. 2001	Phase III	Adjuvant 5-FU & Leucovorin -> 5-FU, Leucovorin, RT -> 5-FU & Leucovorin	Inferior OS
Cunningham et al. 2006 (MAGIC)	Phase III	Perioperative ECF	Inferior OS
Tepper et al. 2008 (CALGB 9781)	Phase III	Neoadjuvant Cisplatin, Fluorouracil, RT	Inferior OS
van Hagen et al. 2012 (CROSS)	Phase III	Neoadjuvant Carboplatin, Paclitaxel, RT	Inferior OS

Surgery as primary therapy; used as a comparator arm and here for reference purposes only.

References

Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. link to original article PubMed
Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, Lozach P, Ollier JC, Pavy JJ, Mercier M, Sahmoud T. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997 Jul 17;337(3):161-7. link to original article PubMed
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 PubMed
1. 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 PubMed
Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001 Jan 15;19(2):305-13. link to original article PubMed
Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001 Jun 1;91(11):2165-74. contains protocol PubMed
Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. link to original article contains verified protocol PubMed
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 PubMed
1. 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 PubMed
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 PubMed
Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. link to original article contains verified protocol PubMed
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 contains verified protocol PubMed
Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. link to original article contains verified protocol PubMed
Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011 May 19;11:181. link to original article PubMed
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 contains verified protocol link to appendix with details about administration PubMed
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 PubMed

Adjuvant therapy

5-FU & Leucovorin -> 5-FU, Leucovorin, RT -> 5-FU & Leucovorin

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RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Macdonald et al. 2001	Phase III	Surgery alone	Superior OS

Chemotherapy, part 1

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

28-day cycle, followed by:

Chemoradiotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
Folinic acid (Leucovorin) 20 mg/m² IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
Concurrent radiation therapy starting cycle 2 day 1 with 180 cGy, 5 days per week; 25 fractions given over 5 weeks for a total of 4500 cGy

35-day cycle, followed by:

Chemotherapy, part 2

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

28-day cycle for 2 cycles

Regimen #2

Note: No primary reference could be found for this regimen.

Chemotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus on EITHER days 1 & 15 OR days 1, 2, 15, 16
Fluorouracil (5-FU) 1200 mg/m² IV continuous infusion on days 1, 2, 15, 16
Folinic acid (Leucovorin) 400 mg/m² IV on EITHER days 1 & 15 OR days 1, 2, 15, 16

28-day cycle for 3 total cycles (1 cycle given before radiation, and 2 cycles to be given after radiation)

References

Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. link to original article contains verified protocol PubMed

Cisplatin & Irinotecan

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Regimen

Study	Evidence
Yoon et al. 2011	Phase II

Treatment preceded by neoadjuvant cisplatin, irinotecan, RT and surgery.

Chemotherapy

Cisplatin (Platinol) 30 mg/m² IV once per day on days 1 & 8
Irinotecan (Camptosar) 65 mg/m² IV once per day on days 1 & 8

21-day cycle for 3 cycles

References

Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol PubMed

Cisplatin & Paclitaxel

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Regimen

Study	Evidence
Yoon et al. 2011	Phase II

Treatment preceded by neoadjuvant cisplatin, paclitaxel, RT and surgery.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycle for 3 cycles

References

Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. link to original article contains verified protocol PubMed

FP -> Capecitabine & RT -> FP

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FP: Fluorouracil, Platinol (Cisplatin)
RT: Radiation Therapy

Regimen

Study	Evidence
Lee et al. 2006	Phase II

Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without FP cycles 1, 3, 4, 5. Dosage of Capecitabine (Xeloda) was listed as 625 to 825 mg/m² PO BID on days 1 to 5 or 1 to 7 while radiation is being given. FP starts 3 weeks after surgery.

Chemotherapy, part 1

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 5

21-day cycle, followed immediately by:

Chemoradiotherapy

Capecitabine (Xeloda) 825 mg/m² (1650 mg/m²/day) PO every 12 hours
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy

5-week course, followed 4 weeks later by:

Chemotherapy, part 2

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 5

21-day cycle for 3 cycles

References

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

ECF -> 5-FU & RT -> ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil
RT: Radiation Therapy

Regimen

Study	Evidence
Leong et al. 2010	Phase II

Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without ECF cycles 1, 3, 4. Dosage of Fluorouracil (5-FU) was listed as 200 to 250 mg/m²/day IV continuous infusion on days 1 to 5 or 1 to 7 while radiation is being given.

Chemotherapy, part 1

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion on days 1 to 21

21-day cycle, followed immediately by:

Chemoradiotherapy

Fluorouracil (5-FU) 225 mg/m²/day IV continuous infusion on days 1 to 35
Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week for a total dose of 45 Gy, starting on day 1

5-week course, followed 1 month later by:

Chemotherapy, part 2

Epirubicin (Ellence) 50 mg/m² IV bolus once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 200 mg/m²/day IV continuous infusion on days 1 to 21

21-day cycle for 2 cycles

References

Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):690-5. Epub 2010 May 14. link to original article contains verified protocol PubMed

Definitive chemoradiation (no surgery)

Capecitabine & Cisplatin -> Capecitabine, Cisplatin, RT

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RT: Radiation Therapy

Regimen

Study	Evidence
Lee et al. 2007	Retrospective

The study was for patients with stage IV disease.

Patients with M1b disease (visceral metastases) received the chemotherapy only part until progression of disease or unacceptable toxicity.
Patients with M1a or M1b (non-viscertal 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.

Chemotherapy

Cisplatin (Platinol) 60 mg/m² IV over 1 hour on day 1; given before the first dose of capecitabine
Capecitabine (Xeloda) 1000 mg/m² PO BID on days 1 to 14

21-day cycles

Chemoradiotherapy

Cisplatin (Platinol) 30 mg/m² IV over 1 hour on day 1; given before the first dose of capecitabine
Capecitabine (Xeloda) 800 mg/m² PO BID, 5 days per week while radiation is being given
Concurrent radiation therapy, total of 54 Gy given. Dose per fraction and total duration of treatment were not specified, but based on other regimens, it is suspected to be either 1.8 Gy x 30 fractions or 2 Gy x 27 fractions.

1-week cycles until radiation therapy is complete

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 contains verified protocol PubMed

Capecitabine, Cisplatin, RT

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RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Crosby et al. 2013 (SCOPE1)	Phase III	Capecitabine, Cisplatin, Cetuximab, RT	Seems to have superior OS

Note: total number of days per cycle is not specified in the abstract.

Chemoradiotherapy

Cisplatin (Platinol) 60 mg/m² IV once on day 1
Capecitabine (Xeloda) 615 mg/m² PO BID on days 1 to 21
Concurrent radiation therapy, total of 50 Gy given in 25 fractions with cycles 3 & 4

4 cycles

References

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. link to original article contains protocol PubMed

Capecitabine, Docetaxel, RT

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See Docetaxel (Taxotere) & Capecitabine (Xeloda).

Capecitabine, Docetaxel, Oxaliplatin, RT

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See Oxaliplatin (Eloxatin), Docetaxel (Taxotere), Capecitabine (Xeloda).

Capecitabine, Oxaliplatin, RT

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See Oxaliplatin (Eloxatin) & Capecitabine (Xeloda).

Capecitabine, Paclitaxel, RT

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See Paclitaxel (Taxol) & Capecitabine (Xeloda).

Carboplatin, Paclitaxel, RT

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See Carboplatin, Paclitaxel, RT, except patients did not undergo surgery.

Cisplatin, Docetaxel, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence
Li et al. 2009	Phase II

Chemoradiotherapy

Cisplatin (Platinol) 80 mg/m² IV once per day on days 1 & 22
Docetaxel (Taxotere) 60 mg/m² IV once per day on days 1 & 22
Concurrent radiation therapy, 1.8 to 2.0 Gy fractions, 5 days per week, to start within 24 hours of the day 1 of chemotherapy
- Patients with stage I to III disease received a total dose of 60 to 64 Gy over 4 to 6 weeks
- Patients with stage IV disease (lymph node only) received a total dose of 50 to 56 Gy

Supportive medications

Dexamethasone (Decadron) 10 mg PO/IV the day before Docetaxel (Taxotere), 30 minutes prior to Docetaxel (Taxotere), and the day after Docetaxel (Taxotere)
Diphenhydramine (Benadryl) 40 mg IV prior to chemotherapy
Cimetidine (Tagamet) 40 mg IV prior to chemotherapy
Granisetron (Kytril) 2 mg IV prior to chemotherapy
1.5 to 2.0 liters fluids before Cisplatin (Platinol)

1 course

Regimen #2

Study	Evidence
Day et al. 2010	Phase I

Note: The NCCN, Esophageal Cancer version 2.2011, suggests 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.

Chemoradiotherapy

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
Concurrent radiation therapy, 2 Gy fractions x 25 fractions, 5 days per week, for a total dose of 50 Gy, to start within 4 hours after the first dose of chemotherapy.

Supportive medications

"Steroid and anti-emetic pre-medication"

5-week course

References

Li QQ, Liu MZ, Hu YH, Liu H, He ZY, Lin HX. Definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous esophageal carcinoma. Dis Esophagus. 2010 Apr;23(3):253-9. Epub 2009 Aug 28. link to original article contains verified protocol PubMed
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 PMC article contains verified protocol PubMed

Cisplatin, Fluorouracil, RT

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RT: Radiation Therapy

Regimen #1

Study	Evidence	Comparator	Efficacy
Minsky et al. 2002 (RTOG 94-05)	Phase III	Cisplatin, 5-FU, high-dose RT	Seems not superior

Chemoradiotherapy

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 on days 1 to 4
Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, starting on day 1, for a total dose of 50.4 Gy.

28-day cycle for 2 cycles, followed by:

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 on days 1 to 4

28-day cycle for 2 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Herskovic et al. 1992 (RTOG 85-01)	Phase III	Radiation therapy	Superior OS

Chemoradiotherapy

Cisplatin (Platinol) 75 mg/m² IV once per day on the first day of week 1, 5, 8, 11 (day 1, 29, 50, 71)
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion over 96 hours on the first 4 days of week 1, 5, 8, 11 (days 1 to 4, 29 to 32, 50 to 53, 71 to 74)
Concurrent radiation therapy: starting on day 1, 2.0 Gy fractions x 15 fractions given 5 days per week x 3 weeks; then 2.0 Gy fractions x 10 fractions x 2 weeks to the initial tumor length plus a 5 cm margin, for a total dose of 50.0 Gy.

11-week course of therapy

References

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 contains verified protocol PubMed
1. 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 contains verified protocol PubMed
2. 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. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. link to original article contains verified protocol PubMed
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 contains verified protocol PubMed
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 PubMed
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 PubMed
Conroy T, Yataghène Y, Etienne PL, Michel P, Senellart H, Raoul JL, Mineur L, Rives M, Mirabel X, Lamezec B, Rio E, Le Prisé E, Peiffert D, Adenis A. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010 Oct 26;103(9):1349-55. Epub 2010 Oct 12. link to PMC article contains verified protocol PubMed
Burmeister BH, Thomas JM, Burmeister EA, Walpole ET, Harvey JA, Thomson DB, Barbour AP, Gotley DC, Smithers BM. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011 Feb;47(3):354-60. link to original article PubMed
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. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article PubMed
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 PubMed

Cisplatin, Irinotecan, RT

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See Cisplatin (Platinol) & Irinotecan (Camptosar) Regimen #1, Ilson et al. 2011 & Regimen #2, Sharma et al. 2009.

Cisplatin, Paclitaxel, RT

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See Cisplatin (Platinol) & Paclitaxel (Taxol), except patients did not undergo surgery.

Docetaxel, Fluorouracil, RT

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See Docetaxel (Taxotere) & Fluorouracil (5-FU) Regimen #1, Hihara et al. 2007 & Regimen #2.

Fluorouracil, Oxaliplatin, RT

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See Oxaliplatin (Eloxatin) & Fluorouracil (5-FU) Regimen #1, Lorenzen et al. 2008. Note: Regimen #1 was a neoadjuvant regimen, but is also listed under definitive chemoradiation by the NCCN, Esophageal Cancer version 2.2011. See Oxaliplatin (Eloxatin) & Fluorouracil (5-FU) Regimen #2, Khushalani et al. 2002.

FOLFOX 4 & RT -> FOLFOX 4

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin
RT: Radiation Therapy

Regimen

Study	Evidence	Comparator	Efficacy
Conroy et al. 2010	Phase III	Cisplatin, 5-FU, RT	Not reported

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of leucovorin as 400 mg/m².

Chemoradiotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus, then 600 mg/m²/day IV over 22 hours on days 1 & 2, given last
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV over 2 hours once on day 1
Concurrent radiation therapy, 2 Gy fractions x 25 fractions given 5 days per week, for a total dose of 50 Gy

14-day cycle for 3 cycles, followed by:

Chemotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus, then 600 mg/m²/day IV over 22 hours on days 1 & 2, given last
Folinic acid (Leucovorin) 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

Conroy T, Yataghène Y, Etienne PL, Michel P, Senellart H, Raoul JL, Mineur L, Rives M, Mirabel X, Lamezec B, Rio E, Le Prisé E, Peiffert D, Adenis A. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010 Oct 26;103(9):1349-55. Epub 2010 Oct 12. link to PMC article contains verified protocol PubMed
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. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. link to original article PubMed

Radiation therapy

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Regimen

Study	Evidence	Comparator	Efficacy
Herskovic et al. 1992 (RTOG 85-01)	Phase III	Cisplatin, 5-FU, RT	Inferior OS

Radiation as primary therapy; used as a comparator arm and here for reference purposes only.

References

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 contains verified protocol PubMed
1. 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 contains verified protocol PubMed
2. 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. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. link to original article contains verified protocol PubMed

Chemotherapy for metastatic or locally advanced disease (non-radiation/surgery candidate)

Capecitabine (Xeloda)

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Regimen

Study	Evidence
Hong et al. 2004	Phase II

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of capecitabine as 1000 mg/m².

Chemotherapy

Capecitabine (Xeloda) 1250 mg/m² PO BID on days 1 to 14

21-day cycle for up to 6 cycles

References

Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. link to original article contains verified protocol PubMed

Capecitabine & Irinotecan

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XI: Xeloda (Capecitabine) and Irinotecan

Regimen

Study	Evidence
Leary et al. 2008	Phase II

Chemotherapy

Capecitabine (Xeloda) 1000 mg/m² PO BID on days 1 to 14
Irinotecan (Camptosar) 250 mg/m² IV over 30 to 90 minutes once on day 1

Supportive medications

Atropine (Atropen) 0.25 mg SC before Irinotecan (Camptosar) as prophylaxis against cholinergic symptoms
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 BID 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 contains verified protocol PubMed
Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie, Germany. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. link to original article PubMed

Carboplatin & Paclitaxel

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Regimen

Study	Evidence
Philip et al. 1997	Phase II
Gadgeel et al. 2003	Phase II

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of carboplatin as AUC 6.

Chemotherapy

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

21-day cycles

References

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

Cetuximab (Erbitux)

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Regimen

Study	Evidence
Gold et al. 2010 (SWOG S0415)	Phase II

Chemotherapy

Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m² IV over 120 minutes on day 1, then 250 mg/m² IV over 60 minutes once per day on days 8, 15, 22
- Cycle 2 onwards: 250 mg/m² IV once per day on days 1, 8, 15, 22

Supportive medications

Diphenhydramine (Benadryl) 50 mg PO/IV 30 to 60 minutes prior to cetuximab

28-day cycles, given until progression of disease or unacceptable toxicity

References

Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. link to PMC article contains verified protocol PubMed

DC; TC

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

Regimen #1

Study	Evidence	Comparator	Efficacy
Roth et al. 2007	Randomized Phase II	ECF	Not reported
Roth et al. 2007	Randomized Phase II	TCF	Might have inferior ORR

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

Chemotherapy

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

Supportive medications

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

21-day cycle for up to 8 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Ajani et al. 2005	Randomized Phase II	DCF	Seems to have inferior ORR

Chemotherapy

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

Supportive medications

Dexamethasone (Decadron) 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (6 total doses)
Dexamethasone (Decadron) 20 mg IV before Cisplatin (Platinol) and 8 hours after Cisplatin (Platinol)
Ondansetron (Zofran) 8 mg IV before Cisplatin (Platinol), 4 hours after Cisplatin (Platinol), and 8 hours after Cisplatin (Platinol)
"Hydration was administered in a standard manner"

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #3

Study	Evidence
Kim et al. 2009	Phase II

Chemotherapy

Docetaxel (Taxotere) 70 mg/m² IV over 1 hour once on day 1, given 3 hours before cisplatin
Cisplatin (Platinol) 70 mg/m² IV over 1 hour once on day 1

Supportive medications

Dexamethasone (Decadron) 8 mg PO BID x 1 day, starting 1 day before Docetaxel (Taxotere) administration
At least 3 liters hydration (with mannitol, magnesium, and potassium chloride)
"Antiemetic treatment"

21-day cycle for up to 6 cycles, progression of disease, or unacceptable toxicity

References

Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. link to original article contains verified protocol PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains verified protocol PubMed
Kim JY, Do YR, Park KU, Kim MK, Lee KH, Bae SH, Ryoo HM, Baek JH, Song HS. A multi-center phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer. Cancer Chemother Pharmacol. 2010 May;66(1):31-6. Epub 2009 Sep 18. link to original article contains verified protocol PubMed

CF; FP

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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol

Regimen #1

Study	Evidence	Comparator	Efficacy
Van Cutsem et al. 2006 (V325 Study Group)	Phase III	DCF	Seems to have inferior OS
Dank et al. 2008	Phase III	IF	Seems not superior

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 1 to 3 hours once on day 1, given before Fluorouracil (5-FU)
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 5, started after cisplatin

Supportive medications, as described in Dank et al. 2008:

"Hyperhydration" for 2 to 3 days with each infusion
Ondansetron (Zofran) IV for antiemetic prophylaxis
Dexamethasone (Decadron) IV for antiemetic prophylaxis, then PO for 2 to 3 days
Metoclopramide (Reglan) for antiemetic prophylaxis
Filgrastim (Neupogen) SC once per day, starting on day 4, to be continued until ANC greater than 1 x 10⁹/L for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
Atropine (Atropen) prn cholinergic symptoms
Loperamide (Imodium) prn delayed diarrhea

28-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study	Evidence	Comparator	Efficacy
Lorenzen et al. 2009	Randomized Phase II	CF & Cetuximab	Seems not superior

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on day 1, given before Fluorouracil (5-FU)
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 5, started after cisplatin

29-day cycle for up to 6 cycles

Regimen #3

Study	Evidence	Comparator	Efficacy
Kang et al. 2009	Phase III	CX	Non-inferior PFS
Bang et al. 2010 (ToGA)	Phase III	CF & Trastuzumab	Inferior OS

Patients in ToGA had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion on days 1 to 5

Supportive medications

"Hyperhydration" for Cisplatin (Platinol)

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #4

Study	Evidence	Comparator	Efficacy
Ohtsu et al. 2003 (JCOG9205)	Phase III	Fluorouracil	Superior PFS
Ohtsu et al. 2003 (JCOG9205)	Phase III	UFTM	Seems not superior

Chemotherapy

Cisplatin (Platinol) 20 mg/m² IV over 30 minutes once per day on days 1 to 5
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion on days 1 to 5

28-day cycle for up to 6 cycles

References

Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. link to original article contains verified protocol PubMed
Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. link to original article contains verified protocol PubMed
Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. link to original article contains verified protocol PubMed
Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains verified protocol PubMed
Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. link to original article contains verified protocol PubMed
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed

CF-C

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CF-C: Cisplatin, Fluorouracil, Cetuximab

Regimen

Study	Evidence	Comparator	Efficacy
Lorenzen et al. 2009	Randomized Phase II	CF	Seems not superior

Chemotherapy

Cisplatin (Platinol) 100 mg/m² IV over 60 minutes once on day 1, given before fluorouracil
Fluorouracil (5-FU) 1000 mg/m²/day IV continuous infusion on days 1 to 5, given after cisplatin
Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m² IV over 120 minutes once on day 1, then 250 mg/m² IV over 60 minutes once per day on days 8, 15, 22
- Cycles 2 to 6: 250 mg/m² IV once per day on days 1, 8, 15, 22

Supportive medications

"Standard antiemetic prophylaxis and pre- and post- Cisplatin (Platinol) hydration"

29-day cycle for up to 6 cycles

References

Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. link to original article contains verified protocol PubMed

CF & Trastuzumab

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CF: Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Bang et al. 2010 (ToGA)	Phase III	CF	Superior OS

Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion on days 1 to 5
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Subsequent cycles: 6 mg/kg IV once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

References

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed

Cisplatin, Doxorubicin liposomal, Fluorouracil

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Regimen

Study	Evidence	Comparator	Efficacy
Cascinu et al. 2010	Randomized Phase II	MCF	Seems to have superior OS

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV once on day 1
Doxorubicin liposomal (Doxil) 20 mg/m² IV once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus, then 600 mg/m²/day IV continuous infusion on days 1 to 2

14-day cycles, given until progression of disease or unacceptable toxicity

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 contains verified protocol PubMed

Cisplatin & Irinotecan (CI)

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CI: Cisplatin, Irinotecan

Regimen #1

Study	Evidence
Ilson et al. 2004	Phase II

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011 lists cisplatin 25 mg/m² as an alternate dosage.

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 #2

Study	Evidence
Ilson et al. 1999	Phase II

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 medications

Dexamethasone (Decadron) 20 mg IV prior to chemotherapy
Granisetron (Kytril) 2 mg PO prior to chemotherapy
At least 500 mL D5NS IV over 30 to 60 minutes before Cisplatin (Platinol)
Atropine (Atropen) used as pretreatment medication if there was diarrhea or abdominal cramps within 1 hour of Irinotecan (Camptosar)

6-week cycle for 1 to 3 cycles, or until disease progression or unacceptable toxicity.

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 contains verified protocol PubMed
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 contains protocol PubMed

CLF; FLP

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

Regimen #1

Study	Evidence	Comparator	Efficacy
Al-Batran et al. 2008	Phase III	FLO	Might have inferior PFS

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists Fluorouracil (5-FU) as being given every 2 weeks rather than the schedule below.

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once per day on days 1, 15, 29, 43
Fluorouracil (5-FU) 2000 mg/m² IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36

Supportive medications

Up to 3 liters normal saline as hydration with Cisplatin (Platinol)
Antiemetic medications per "local protocols"

8-week cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study	Evidence	Comparator
Bouché et al. 2004 (FFCD 9803)	Randomized Phase II	LV5FU2 LV5FU2 & Irinotecan

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

Chemotherapy

Cisplatin (Platinol) 50 mg/m² IV over 1 hour once on either day 1 or 2
Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus, then 600 mg/m²/day IV continuous infusion over 22 hours on days 1 to 2

Supportive medications

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

14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity

References

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

Cisplatin & Paclitaxel

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Regimen #1

Study	Evidence
Zhang et al. 2008	Phase II

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV over 2 hours once on day 1
Paclitaxel (Taxol) 175 mg/m² IV once on day 1

21-day cycles

Regimen #2

Study	Evidence
Ilson et al. 2000	Phase II

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists 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.

Chemotherapy

Cisplatin (Platinol) 75 mg/m² IV once on day 2, given after paclitaxel
Paclitaxel (Taxol) 200 mg/m² IV over 24 hours once on day 1

Supportive medications

"Granulocyte colony stimulating factor support"

21-day cycles

Regimen #3

Study	Evidence
Petrasch et al. 1998	Phase II

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 medications

Dexamethasone (Decadron) 20 mg IV 30 minutes prior to Paclitaxel (Taxol)
Cimetidine (Tagamet) 300 mg IV 30 minutes prior to Paclitaxel (Taxol)
Clemastine (Tavist) 2 mg IV 30 minutes prior to Paclitaxel (Taxol)
Ondansetron (Zofran) 8 mg IV 30 minutes prior to Paclitaxel (Taxol)
"Adequate pre- and posthydration" for Cisplatin (Platinol)

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 PMC article contains verified protocol PubMed
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. contains protocol PubMed
Zhang X, Shen L, Li J, Li Y, Li J, Jin M. A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. Am J Clin Oncol. 2008 Feb;31(1):29 to 33. link to original article contains protocol PubMed

CX; XP

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

Regimen

Study	Evidence	Comparator	Efficacy
Kang et al. 2009	Phase III	CF	Non-inferior PFS
Bang et al. 2010 (ToGA)	Phase III	CX & Trastuzumab	Inferior OS
Lordick et al. 2013 (EXPAND)	Phase III	CX & Cetuximab	Seems not superior

Patients in ToGA had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO BID on days 1 to 14
- Lordick et al. 2013 gave Capecitabine (Xeloda) 1000 mg/m² PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)

Supportive medications

per Kang et al. 2009:
"Hyperhydration" for Cisplatin (Platinol)

21-day cycles, given until progression of disease or unacceptable toxicity

References

Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. link to original article contains verified protocol PubMed
Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie, Germany. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. link to original article PubMed
Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed
Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed

CX-C

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CX-C: Cisplatin, Xeloda (Capecitabine), Cetuximab

Regimen

Study	Evidence	Comparator	Efficacy
Lordick et al. 2013 (EXPAND)	Phase III	CX	Seems not superior

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV over 2 hours once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)
Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m² IV once on day 1
- Subsequently: 250 mg/m² IV once per week

21-day cycles, given until progression of disease or unacceptable toxicity

References

Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. link to original article contains verified protocol PubMed

CX & Trastuzumab

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CX: Cisplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence	Comparator	Efficacy
Bang et al. 2010 (ToGA)	Phase III	CX	Superior OS

Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.

Chemotherapy

Cisplatin (Platinol) 80 mg/m² IV once on day 1
Capecitabine (Xeloda) 1000 mg/m² PO BID on days 1 to 14
Trastuzumab (Herceptin) as follows:
- Cycle 1: 8 mg/kg IV once on day 1
- Subsequent cycles: 6 mg/kg IV once on day 1

21-day cycles, given until progression of disease or unacceptable toxicity

References

Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. link to original article contains verified protocol PubMed

Docetaxel (Taxotere)

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Regimen #1

Study	Evidence	Comparator	Efficacy
Ford et al. 2013 (COUGAR-2)	Phase III	Active symptom control	Superior OS

Chemotherapy

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

21-day cycle for up to 6 cycles

Regimen #2

Study	Evidence
Albertsson et al. 2007	Phase II

Chemotherapy

Docetaxel (Taxotere) 100 mg/m² IV over 1 hour 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 contains protocol PubMed
Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article PubMed
Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. link to original article contains verified protocol PubMed

DCF; TCF

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

Regimen #1

Study	Evidence	Comparator	Efficacy
Ajani et al. 2005	Randomized Phase II	DC	Seems to have superior ORR
Van Cutsem et al. 2006 (V325 Study Group)	Phase III	CF	Seems to have superior OS

Note: In contrast to the original references, the NCCN, Esophageal Cancer version 2.2011, lists each cycle as lasting 28 days.

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 1 to 3 hours once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion on days 1 to 5

Supportive medications

(varied depending on reference):
Dexamethasone (Decadron) 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (6 total doses)
Dexamethasone (Decadron) 20 mg IV before Cisplatin (Platinol) and 8 hours after Cisplatin (Platinol)
Ondansetron (Zofran) 8 mg IV before Cisplatin (Platinol), 4 hours after Cisplatin (Platinol), and 8 hours after Cisplatin (Platinol)
"Hydration [was] administered in a standard manner"

21-day cycles, given until progression of disease or unacceptable toxicity

Regimen #2

Study	Evidence	Comparator	Efficacy
Roth et al. 2007	Randomized Phase II	ECF	Not reported
Roth et al. 2007	Randomized Phase II	TC	Might have superior ORR

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

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV over 1 hour once on day 1
Cisplatin (Platinol) 75 mg/m² IV over 4 hours once on day 1
Fluorouracil (5-FU) 300 mg/m²/day IV continuous infusion on days 1 to 14

Supportive medications

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

21-day cycle for up to 8 cycles

References

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

mDCF

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mDCF: modified Docetaxel, Cisplatin, Fluorouracil

Regimen #1

Study	Evidence
Ozal et al. 2010	Phase II

Chemotherapy

Docetaxel (Taxotere) 60 mg/m² IV once on day 1
Cisplatin (Platinol) 60 mg/m² IV once on day 1
Fluorouracil (5-FU) 750 mg/m²/day IV continuous infusion on days 1 to 4

21-day cycles

Regimen #2

Study	Evidence
Shah et al. 2010	Phase II

Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab.

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV over 1 hour on days 1, 15, 29
Cisplatin (Platinol) 40 mg/m² IV over 1 to 3 hours once per day on days 3, 17, 31
Folinic acid (Leucovorin) 400 mg/m² IV once per day on days 1, 15, 29
Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1, 15, 29, then 1000 mg/m²/day IV continuous infusion on days 1 & 2, 15 & 16, 29 & 30

Supportive medications

"Standard premedication and delayed emesis regimens"

42-day cycles, given until progression of disease or unacceptable toxicity

References

Abstract: G. Ozal, M. Dogan, H. Akbulut, B. Yalcin, G. Utkan, Y. Urun, F. Icli. The safety and efficacy of modified-dose docetaxel, cisplatin, and 5-fluorouracil (mDCF) combination in the front-line treatment of advanced gastric cancer. 2010 Gastrointestinal Cancers Symposium abstract 113. link to abstract
Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. link to original article contains verified protocol PubMed

mDCF & Bevacizumab

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mDCF: modified Docetaxel, Cisplatin, Fluorouracil

Regimen

Study	Evidence
Shah et al. 2010	Phase II

Chemotherapy

Docetaxel (Taxotere) 40 mg/m² IV over 1 hour on days 1, 15, 29
Cisplatin (Platinol) 40 mg/m² IV over 1 to 3 hours once per day on days 3, 17, 31
Folinic acid (Leucovorin) 400 mg/m² IV once per day on days 1, 15, 29
Fluorouracil (5-FU) 400 mg/m² IV bolus once per day on days 1, 15, 29, then 1000 mg/m²/day IV continuous infusion on days 1 to 2, 15 to 16, 29 to 30
Bevacizumab (Avastin) 10 mg/kg IV once per day on days 1, 15, 29

Supportive medications

"Standard premedication and delayed emesis regimens"

42-day cycles, given until progression of disease or unacceptable toxicity

References

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

Docetaxel, Carboplatin, Fluorouracil

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Regimen

Study	Evidence
Elkerm et al. 2008	Phase II

Chemotherapy

Docetaxel (Taxotere) 75 mg/m² IV once on day 1
Carboplatin (Paraplatin) AUC 6 IV once on day 2
Fluorouracil (5-FU) 1200 mg/m²/day IV continuous infusion on days 1 to 3

Supportive medications

Filgrastim (Neupogen) 5 mcg/kg SC once per day on days 4 to 9

21-day cycles

References

Abstract: Y. M. Elkerm, A. Elsaid, S. AL-Batran, C. Pauligk. Final results of a phase II trial of docetaxel-carboplatin-FU in locally advanced gastric carcinoma. 2008 Gastrointestinal Cancers Symposium abstract 38. link to abstract

Docetaxel & Irinotecan

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Regimen

Study	Evidence
Burtness et al. 2009	Phase II

Chemotherapy

Docetaxel (Taxotere) 35 mg/m² IV over 1 hour 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 medications

Dexamethasone (Decadron) 8 mg PO given 12 hours before Docetaxel (Taxotere), then 10 mg IV within 1 hour before chemotherapy

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 contains verified protocol PubMed

DOF

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DOF: Docetaxel, Oxaliplatin, Fluorouracil

Regimen

Study	Evidence
Shankaran et al. 2009	Phase II

Chemotherapy

Docetaxel (Taxotere) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV once on day 1
Fluorouracil (5-FU) 1200 mg/m²/day IV continuous infusion over 46 hours on days 1 to 2 (total dose: 2400 mg/m²)

14-day cycles

References

Abstract: V. Shankaran, M. F. Mulcahy, H. S. Hochster, T. Ryan, H. Choi, A. B. Benson. Docetaxel, oxaliplatin, and 5-fluorouracil for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinomas: Preliminary results of a phase II study. 2009 Gastrointestinal Cancers Symposium abstract 47. link to abstract

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Findlay et al. 1994	Phase II
Ross et al. 2002	Phase III	MCF	Seems to have noninferior OS
Roth et al. 2007	Randomized Phase II	TC TCF	Not reported
Cunningham et al. 2008 (REAL-2)	Phase III	ECX	Non-inferior OS
		EOF	Non-inferior OS
		EOX	Seems to have inferior OS

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

Supportive medications

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

21-day cycle for up to 8 cycles

References

Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, et al. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. link to original article contains verified protocol PubMed
Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. link to original article contains verified protocol PubMed
Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. link to original article contains verified protocol PubMed
Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed

ECX

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ECX: Epirubicin, Cisplatin, Xeloda (Capecitabine)

Regimen

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2008 (REAL-2)	Phase III	ECF	Non-inferior OS
Cunningham et al. 2008 (REAL-2)	Phase III	EOF EOX	Non-inferior OS

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 BID on days 1 to 21

Supportive medications

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

21-day cycle for up to 8 cycles

References

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed
Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. Epub 2014 Jun 22. link to original article PubMed
Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. link to original article PubMed

EOF

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EOF: Epirubicin, Oxaliplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2008 (REAL-2)	Phase III	ECF ECX	Non-inferior OS
Cunningham et al. 2008 (REAL-2)	Phase III	EOX	Non-inferior OS

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 on days 1 to 21

Supportive medications

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

21-day cycle for up to 8 cycles

References

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

EOX; EOC

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

Regimen #1

Study	Evidence	Comparator	Efficacy
Waddell et al. 2013 (REAL3)	Phase III	mEOC+P	Seems to have superior OS

Chemotherapy

Epirubicin (Ellence) 50 mg/m² IV once on day 1
Oxaliplatin (Eloxatin) 130 mg/m² IV once on day 1
Capecitabine (Xeloda) 1250 mg/m²/day PO (it is assumed this daily dose was divided into two doses per day) on days 1 to 21

21-day cycle for up to 8 cycles

Regimen #2

Study	Evidence	Comparator	Efficacy
Cunningham et al. 2008 (REAL-2)	Phase III	ECF	Seems to have superior OS
		ECX	Non-inferior OS
		EOF	Non-inferior OS

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) 625 mg/m² PO BID on days 1 to 21

Supportive medications

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

21-day cycle for up to 8 cycles

References

Cunningham D, Starling N, Rao S, Iveson T, Nicolson M, Coxon F, Middleton G, Daniel F, Oates J, Norman AR; Upper Gastrointestinal Clinical Studies Group of the National Cancer Research Institute of the United Kingdom. Capecitabine and oxaliplatin for advanced esophagogastric cancer. N Engl J Med. 2008 Jan 3;358(1):36-46. link to original article contains verified protocol PubMed content property of HemOnc.org
Waddell T, Chau I, Cunningham D, Gonzalez D, Frances A, 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 PMC article contains verified protocol PubMed

Erlotinib (Tarceva)

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Regimen

Study	Evidence
Dragovich et al. 2006 (SWOG 0127)	Phase II
Ilson et al. 2010	Phase II

Chemotherapy

Erlotinib (Tarceva) 150 mg PO once per day on days 1 to 28, at least 1 hour before a meal, or 2 hours after a meal

28-day cycles

References

Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. link to original article contains verified protocol PubMed
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 contains verified protocol PubMed

Etoposide (Vepesid)

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Regimen

Study	Evidence
Harstrick et al. 1992	Phase II

Note: this is higher than the dose usually employed in modern settings.

Chemotherapy

Etoposide (Vepesid) 200 mg/m² (route not specified) once per day on days 1 to 3

21-day cycles

References

Harstrick A, Bokemeyer C, Preusser P, Köhne-Wömpner CH, Meyer HJ, Stahl M, Knipp H, Schmoll HJ, Wilke H. Phase II study of single-agent etoposide in patients with metastatic squamous-cell carcinoma of the esophagus. Cancer Chemother Pharmacol. 1992;29(4):321-2. link to original article contains protocol PubMed

Fluorouracil (5-FU)

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Regimen

Study	Evidence	Comparator	Efficacy
Ohtsu et al. 2003 (JCOG9205)	Phase III	FP	Inferior PFS
Ohtsu et al. 2003 (JCOG9205)	Phase III	UFTM	Seems not superior

Chemotherapy

Fluorouracil (5-FU) 800 mg/m²/day IV continuous infusion on days 1 to 5

28-day cycles

References

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

Fluorouracil & Folinic acid (LV5FU2)

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Regimen

Study	Evidence	Comparator
Bouché et al. 2004 (FFCD 9803)	Randomized Phase II	LV5FU2 & Cisplatin LV5FU2 & Irinotecan

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

Chemotherapy

Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus, then 600 mg/m²/day IV continuous infusion over 22 hours on days 1 to 2

14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity

References

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

Fluorouracil, Folinic acid, Mitomycin

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Regimen

Study	Evidence
Hofheinz et al. 2002	Phase II

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36; given after folinic acid
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36; given before fluorouracil
Mitomycin (Mutamycin) 10 mg/m² IV once per day on days 1 & 22

56-day cycle for 2 cycles

References

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

FLOT

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

Regimen

Study	Evidence
Al-Batran et al. 2008	Phase II

Chemotherapy

Fluorouracil (5-FU) 2600 mg/m² IV continuous 24-hour infusion on day 1, given last
Folinic acid (Leucovorin) 200 mg/m² IV over 1 to 2 hours once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV over 1 to 2 hours once on day 1
Docetaxel (Taxotere) 50 mg/m² IV over 1 to 2 hours once on day 1

Supportive medications

Dexamethasone (Decadron) 8 mg PO once per day on days 0 to 3 of every cycle

14-day cycle for up to 8 (or more) cycles

References

Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. link to original article contains verified protocol PubMed

FOLFIRI

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

Regimen #1, "IF"

Study	Evidence	Comparator	Efficacy
Dank et al. 2008	Phase III	CF	Seems not superior

Chemotherapy

Fluorouracil (5-FU) 2000 mg/m²/day IV continuous 22-hour infusion on days 1, 8, 15, 22, 29, 36; given last
Folinic acid (Leucovorin) 500 mg/m² IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36; given second
Irinotecan (Camptosar) 80 mg/m² IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36; given first

Supportive medications

Ondansetron (Zofran) for antiemetic prophylaxis
Dexamethasone (Decadron) for antiemetic prophylaxis
Filgrastim (Neupogen) SC once per day, starting on day 4, to be continued until ANC greater than 1 x 10⁹/L for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
Atropine (Atropen) prn cholinergic symptoms
Loperamide (Imodium) prn delayed diarrhea

7-week cycles

Regimen #2, LV5FU2 & Irinotecan

Study	Evidence	Comparator
Bouché et al. 2004 (FFCD 9803)	Randomized Phase II	LV5FU2 LV5FU2 & Cisplatin

Chemotherapy

Folinic acid (Leucovorin) 200 mg/m² IV over 2 hours once on day 1
Fluorouracil (5-FU) 400 mg/m² IV bolus, then 600 mg/m²/day IV continuous infusion over 22 hours on days 1 to 2
Irinotecan (Camptosar) 180 mg/m² IV over 90 minutes once on day 1

14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity (primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used)

Regimen #3

Study	Evidence
Samalin et al. 2010	Retrospective

Chemotherapy

Folinic acid (Leucovorin) 400 mg/m² IV over 2 hours once on day 1, given second
Fluorouracil (5-FU) 400 mg/m² IV bolus, then 1200 mg/m²/day IV continuous infusion over 46 hours on days 1 to 2 (total dose per cycle: 2400 mg/m²)
Irinotecan (Camptosar) 180 mg/m² IV over 90 minutes once on day 1, given first

14-day cycles

References

Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. link to original article contains verified protocol PubMed
Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. link to original article contains verified protocol PubMed
Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. link to original article contains protocol PubMed
Retrospective: Samalin E, Afchain P, Thézenas S, Abbas F, Romano O, Guimbaud R, Bécouarn Y, Desseigne F, Edeline J, Mitry E, Bouché O, Adenis A, Aparicio T, Dorval E, Kramar A, Ychou M. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Gastroenterol Clin Biol. 2011 Jan;35(1):48-54. Epub 2010 Oct 28. link to original article contains verified protocol PubMed
Retrospective: Samalin E, Afchain P, Thézenas S, Abbas F, Romano O, Guimbaud R, Bécouarn Y, Desseigne F, Edeline J, Mitry E, Bouché O, Adenis A, Aparicio T, Dorval E, Kramar A, Ychou M. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Clin Res Hepatol Gastroenterol. 2011 Jan;35(1):48-54. contains protocol PubMed
Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. link to original article PubMed

FOLFOX-C

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FOLFOX-C: FOLinic acid, Fluorouracil, OXaliplatin, Cetuximab

Regimen

Study	Evidence	Comparator
Enziger et al. 2016 (CALGB 80403/ECOG E1206)	Randomized Phase II	ECF-C IC-C

Chemotherapy

Fluorouracil (5-FU) 400 mg/m² IV bolus, then 2400 mg/m² IV continuous infusion over 46 to 48 hours, given after oxaliplatin and folinic acid (total dose per cycle: 2800 mg/m²)
Folinic acid (Leucovorin) 400 mg/m² IV over 2 hours once on day 1
Oxaliplatin (Eloxatin) 85 mg/m² IV over 2 hours once on day 1
Cetuximab (Erbitux) 400 mg/m² IV over 120 minutes once on day 1 of the first cycle and then 250 mg/m² IV over 60 minutes once per week

14-day cycles

References

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 contains verified protocol PubMed

Gemcitabine, Fluorouracil, Folinic acid

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Regimen

Study	Evidence
Morgan-Meadows et al. 2005	Phase II

Chemotherapy

Gemcitabine (Gemzar) 1000 mg/m² IV once per day on days 1, 8, 15
Fluorouracil (5-FU) 600 mg/m² IV once per day on days 1, 8, 15
Folinic acid (Leucovorin) 25 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 contains protocol PubMed

Irinotecan (Camptosar)

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Regimen #1, q3wk dosing

Study	Evidence	Comparator	Efficacy
Thuss-Patience et al. 2011	Phase III	Best supportive care	Seems to have superior OS

Chemotherapy

Irinotecan (Camptosar) as follows:
- Cycle 1: 250 mg/m² (capped at BSA = 2 m²) IV over 30 minutes once on day 1
- Cycles 2 to 10 (depending on toxicity): 350 mg/m² IV over 30 minutes once on day 1

Supportive medications

Atropine (Atropen) 0.25 mg SC before irinotecan as prophylaxis against cholinergic symptoms
"5-HT3 antagonists and dexamethasone"

21-day cycle for up to 10 cycles

Regimen #2, alternate q3wk dosing

Study	Evidence	Comparator
Roy et al. 2013	Randomized Phase II	Docetaxel Irinotecan liposome

Chemotherapy

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

21-day cycles

Regimen #3, q2wk dosing

Study	Evidence	Comparator	Efficacy
Kang et al. 2012	Phase III	Best supportive care	Superior OS

Note: This regimen was listed by the NCCN, Esophageal Cancer version 2.2011 as 180 mg/m² dosing, but no primary reference could be found for esophageal cancer at this dose level. This regimen is a gastric cancer regimen.

Chemotherapy

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

14-day cycles

Regimen #4, 4 weeks on, 2 weeks off dosing

Study	Evidence
Mühr-Wilkenshoff et al. 2003	Phase II, <20 patients
Enzinger et al. 2005	Phase II

Note: In contrast to the primary references, the NCCN, Esophageal Cancer version 2.2011, lists a dosing schedule of 125 mg/m² IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV over 60 minutes (Mühr-Wilkenshoff et al. 2003) or 90 minutes (Enzinger et al. 2005) once per day on days 1, 8, 15, 22

6-week 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 PubMed
Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. link to original article PubMed
Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. link to original article PubMed

Irinotecan & Mitomycin

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Regimen #1

Study	Evidence	Comparator
Lustberg et al. 2010	Randomized Phase II	Irinotecan & Mitomycin

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV once per day on days 2 & 9
Mitomycin (Mutamycin) 6 mg/m² IV once on day 1

Supportive medications

Ondansetron (Zofran) or Granisetron (Kytril) and Dexamethasone (Decadron) premedication
Loperamide (Imodium) started with first episode of diarrhea
Erythropoietin for hemoglobin less than 10 g/dL permitted

28-day cycle for up to 6 cycles

Regimen #2

Study	Evidence
Giuliani et al. 2005	Phase II

Chemotherapy

Irinotecan (Camptosar) 150 mg/m² IV once per day on days 1 & 15
Mitomycin (Mutamycin) 8 mg/m² IV once on day 1

28-day cycles

Regimen #3

Study	Evidence
Bamias et al. 2003	Phase II

Chemotherapy

Irinotecan (Camptosar) 125 mg/m² IV once on day 1
Mitomycin (Mutamycin) 5 mg/m² IV once on day 1

14-day cycles, given until progression of disease or unacceptable toxicity

References

Bamias A, Papamichael D, Syrigos K, Pavlidis N. Phase II study of irinotecan and mitomycin C in 5-fluorouracil-pretreated patients with advanced colorectal and gastric cancer. J Chemother. 2003 Jun;15(3):275-81. link to original article contains protocol PubMed
Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. link to original article contains protocol PubMed
Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. link to original article contains verified protocol PubMed

MCF

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MCF: Mitomycin, Cisplatin, Fluorouracil

Regimen

Study	Evidence	Comparator	Efficacy
Ross et al. 2002	Phase III	ECF	Seems to have noninferior OS
Cascinu et al. 2010	Randomized Phase II	Cisplatin, Doxorubicin liposomal, Fluorouracil	Seems to have inferior OS

Chemotherapy

Mitomycin (Mutamycin) 7 mg/m² (maximum dose of 14 mg per cycle) 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 on days 1 to 42

Supportive medications

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

42-day cycle for up to 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 contains verified protocol PubMed
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 contains verified protocol PubMed

OLF; FLO

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

Regimen

Study	Evidence	Comparator	Efficacy
Al-Batran et al. 2008	Phase III	FLP	Might have superior PFS

Chemotherapy

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

Supportive medications

Antiemetic medications per "local protocols"

8-week cycles, given until progression of disease or unacceptable toxicity

References

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

Paclitaxel (Taxol)

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Regimen #1

Study	Evidence
Ilson et al. 2007	Phase II

Chemotherapy

Paclitaxel (Taxol) 80 mg/m² IV over 1 hour on days 1, 8, 15, 22

Supportive medications

Dexamethasone (Decadron) 20 mg IV 30 to 60 minutes before paclitaxel
Cimetidine (Tagamet) 300 mg IV 30 to 60 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV 30 to 60 minutes prior to paclitaxel

28-day cycles

Regimen #2

Study	Evidence
Ajani et al. 1994	Phase II

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of paclitaxel as 135 to 175 mg/m².

Chemotherapy

Paclitaxel (Taxol) 250 mg/m² IV over 24 hours on day 1; dosage adjusted based on toxicity down to 150 or 200 mg/m², or up to 280 mg/m²

Supportive medications

Dexamethasone (Decadron) 20 mg PO 14 hours and 7 hours before paclitaxel
Cimetidine (Tagamet) 300 mg IV 60 minutes prior to paclitaxel
Diphenhydramine (Benadryl) 50 mg IV 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

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 contains verified protocol PubMed
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 contains verified protocol PubMed
Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article PubMed

Placebo

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Regimen

Study	Evidence	Comparator	Efficacy
Thuss-Patience et al. 2011	Phase III	Irinotecan	Seems to have inferior OS
Fuchs et al. 2013 (REGARD)	Phase III	Ramucirumab	Seems to have inferior OS
Ford et al. 2013 (COUGAR-2)	Phase III	Docetaxel	Inferior OS

Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."

No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.

References

Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. link to original article contains verified protocol PubMed
Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. link to original article PubMed
Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. link to original article contains verified protocol PubMed
Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. link to original article contains verified protocol PubMed

Ramucirumab (Cyramza)

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Fuchs et al. 2013 (REGARD)	Phase III	3%	Placebo	3%	Seems to have superior OS	Chemo exposed

Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."

Chemotherapy

Ramucirumab (Cyramza) 8 mg/kg IV once every 2 weeks

Given until progression of disease, unacceptable toxicity, or death

References

Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. link to original article contains verified protocol PubMed

Ramucirumab & Paclitaxel

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Regimen

Study	Evidence	ORR	Comparator	Comparator ORR	Efficacy	Pt Population
Wilke et al. 2014 (RAINBOW)	Phase III	28% (95% CI 23-33%)	Paclitaxel	16% (95% CI 13-20%)	Seems to have superior OS	Chemo exposed

Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."

Chemotherapy

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

28-day cycles, given until progression of disease or unacceptable toxicity

References

Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. link to original article contains verified protocol PubMed

UFTM

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UFTM: UFT (Tegafur-uracil), Mitomycin

Regimen

Study	Evidence	Comparator	Efficacy
Ohtsu et al. 2003 (JCOG9205)	Phase III	Fluorouracil	Seems not superior
Ohtsu et al. 2003 (JCOG9205)	Phase III	FP	Seems not superior

Chemotherapy

Tegafur-uracil (UFT) 375 mg/m²/day PO divided into two doses given BID
Mitomycin (Mutamycin) 5 mg/m² IV once per week
- "Mitomycin was interrupted for 1 month after patients received a total dose of 60 mg."

References

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

@@ Line 3: / Line 3: @@
 Is there a regimen missing from this list? Would you like to share a different dosage/schedule or an additional reference for a regimen? Have you noticed an error? Do you have an idea that will help the site grow to better meet your needs and the needs of many others? You are [[How_to_contribute|invited to contribute to the site]].
-'''Please be aware that some regimens listed here are studies for gastric cancer, not esophageal cancer.''' These regimens were listed as options by the NCCN - Esophageal Cancer, and their inclusion here reflects the overlap between treatments of esophageal and gastric cancer.
+'''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.
 {| class="wikitable" style="float:right; margin-right: 5px;"
@@ Line 57: / Line 57: @@
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen {{#subobject:eccd56|Variant=1}}===
-''Note: This is listed as a neoadjuvant regimen by the NCCN, Esophageal Cancer version 2.2011, but the 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.''
+''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.''
 ====Chemoradiotherapy====
 *[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 1 hour on day 1; given before the first dose of capecitabine
@@ Line 73: / Line 73: @@
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen {{#subobject:d49e8|Variant=1}}===
-''Note: Neither of the references cited for this regimen by the NCCN, Esophageal Cancer version 2.2011, actually contained this regimen. No primary reference could be found for this regimen.''
+''Note: No primary reference could be found for this regimen; the reference below is for reference purposes only.''
 ====Chemoradiotherapy====
 *[[Docetaxel (Taxotere)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
@@ Line 80: / Line 80: @@
 '''5-week course'''
+===References===
+# '''Phase I:''' 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. [http://www.sciencedirect.com/science/article/pii/S1556086415327945 link to SD article] [https://www.ncbi.nlm.nih.gov/pubmed/23370365 PubMed]
 ==Capecitabine, Docetaxel, Oxaliplatin, RT {{#subobject:312400|Regimen=1}}==
@@ Line 145: / Line 148: @@
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
 ===Regimen {{#subobject:c6f9f5|Variant=1}}===
-''Note: Neither of the references cited for this regimen by the NCCN, Esophageal Cancer version 2.2011, actually contained this regimen. No primary reference could be found for this regimen.''
+''Note: No primary reference could be found for this regimen.''
 ====Chemoradiotherapy====
 *[[Capecitabine (Xeloda)]] 625 to 825 mg/m<sup>2</sup> PO BID on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
@@ Line 312: / Line 315: @@
 ===References===
+# Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. [http://www.nejm.org/doi/full/10.1056/NEJM199608153350702 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8672151 PubMed]
 # 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. [http://jco.ascopubs.org/content/25/10/1160.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17401004 PubMed]
 # 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. [http://jco.ascopubs.org/content/26/7/1086.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18309943 PubMed]
-==Cisplatin & Fluorouracil -> Fluorouracil, Paclitaxel, RT {{#subobject:52e768|Regimen=1}}==
+==Cisplatin & Etoposide {{#subobject:5a71ff|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:f93c95|Variant=1}}===
-===Regimen {{#subobject:f8576f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/24/24/3953.long Ajani et al. 2006 (RTOG 9904)]
+|[https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-181 Boonstra et al. 2011]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#Surgery_alone|Surgery alone]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 & 5
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 4 hours once on day 1
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continous infusion on days 1 to 21 (total dose: 4200 mg/m<sup>2</sup>)
+*[[Etoposide (Vepesid)]] 100 mg/m<sup>2</sup>/day IV over 2 hours once on day 1, then 200 mg/m<sup>2</sup>/day PO once per day on days 3 & 5
-'''28-day cycle for 2 cycles, followed by:'''
-====Chemoradiotherapy====
-*[[Paclitaxel (Taxol)]] 45 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
-*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
-'''5-week course'''
+'''21-day cycle for 2 to 4 cycles, followed by surgery'''
 ===References===
-# Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. [http://jco.ascopubs.org/content/24/24/3953.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16921048 PubMed]
+# Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011 May 19;11:181. [https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-181 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21595951 PubMed]
-==Cisplatin & Irinotecan -> Cisplatin, Irinotecan, RT {{#subobject:500b44|Regimen=1}}==
+==Cisplatin & Fluorouracil {{#subobject:37e6ba|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:e6fe90|Variant=1}}===
-===Regimen #1 {{#subobject:927613|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.26591/full Ilson et al. 2011]
+|[https://www.ncbi.nlm.nih.gov/pubmed/11391598 Ancona et al. 2001]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#Surgery_alone|Surgery alone]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given before irinotecan'''
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given after cisplatin'''
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continous infusion on days 1 to 5 (total dose per cycle: 5000 mg/m<sup>2</sup>)
-'''21-day cycle for 2 cycles, followed by:'''
+'''28-day cycle for 2 or 3 cycles, followed by surgery'''
-====Chemoradiotherapy====
+===References===
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given before irinotecan'''
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199812313392704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9869669 PubMed]
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given after cisplatin'''
+## '''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. [http://ascopubs.org/doi/abs/10.1200/JCO.2006.10.4760 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17704421 PubMed]
-*Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total of 50.4 Gy given
+# Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001 Jun 1;91(11):2165-74. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11391598 PubMed]
+# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)08651-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12049861 PubMed]
+## '''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. [http://ascopubs.org/doi/abs/10.1200/JCO.2009.22.2083 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19770374 PubMed]
+# Burmeister BH, Thomas JM, Burmeister EA, Walpole ET, Harvey JA, Thomson DB, Barbour AP, Gotley DC, Smithers BM. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011 Feb;47(3):354-60. [http://www.ejcancer.com/article/S0959-8049(10)00874-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21084184 PubMed]
-====Supportive medications====
+==Cisplatin & Fluorouracil -> Fluorouracil, Paclitaxel, RT {{#subobject:52e768|Regimen=1}}==
-*[[Dexamethasone (Decadron)]] 20 mg PO/IV prior to chemotherapy
+{| class="wikitable" style="float:right; margin-left: 5px;"
-*[[Granisetron (Kytril)]] 2 mg PO or [[Ondansetron (Zofran)]] 32 mg IV prior to chemotherapy
+|-
-*At least 500 mL D5NS or NS as supportive hydration
+|[[#top|back to top]]
-*Atropine 0.5 to 1 mg IV prn cholinergic symptoms
+|}
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-'''21-day cycle for 2 cycles'''
+===Regimen {{#subobject:f8576f|Variant=1}}===
-''Surgery performed 4 to 8 weeks after chemoradiation.''
-===Regimen #2 {{#subobject:1a3475|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.redjournal.org/article/S0360-3016(09)00362-9/abstract Rivera et al. 2009]
+|[http://jco.ascopubs.org/content/24/24/3953.long Ajani et al. 2006 (RTOG 9904)]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV once per day on days 1 & 5
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continous infusion on days 1 to 21 (total dose: 4200 mg/m<sup>2</sup>)
-'''21-day cycle for 2 cycles, followed by:'''
+'''28-day cycle for 2 cycles, followed by:'''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+*[[Paclitaxel (Taxol)]] 45 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
+*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
 '''5-week course'''
-''Surgery done 5 to 8 weeks after finishing chemoradiation.''
-===Regimen #3 {{#subobject:3a82b6|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://meetinglibrary.asco.org/content/34782-65 Sharma et al. 2009]
-|style="background-color:#ff0000"|Pilot
-|-
-|}
-''This regimen is being prospectively evaluated in CALGB 80302.''
-====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 to 28 fractions, for a total of 45 to 50.4 Gy given
-'''21-day cycle for 2 cycles''' (2 cycles per NCCN, Esophageal Cancer version 2.2011; abstract did not specify number of cycles)
 ===References===
-# '''Retrospective Abstract:'''' R. Sharma, G. Y. Yang, H. R. Nava, T. L. Demmy, C. E. Nwogu, S. S. Yendamuri, D. Lamonica, W. Tan, R. V. Iyer, N. I. Khushalani. A single institution experience with neoadjuvant chemoradiation (CRT) with irinotecan (I) and cisplatin (C) in locally advanced esophageal carcinoma (LAEC). 2009 ASCO Annual Meeting abstract e15619. [http://meetinglibrary.asco.org/content/34782-65 link to abstract]
+# Ajani JA, Winter K, Okawara GS, Donohue JH, Pisters PW, Crane CH, Greskovich JF, Anne PR, Bradley JD, Willett C, Rich TA. Phase II trial of preoperative chemoradiation in patients with localized gastric adenocarcinoma (RTOG 9904): quality of combined modality therapy and pathologic response. J Clin Oncol. 2006 Aug 20;24(24):3953-8. [http://jco.ascopubs.org/content/24/24/3953.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16921048 PubMed]
-# Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. [http://www.redjournal.org/article/S0360-3016(09)00362-9/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19540072 PubMed]
-# 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. 2011 Oct 11. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.26591/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21990000 PubMed]
-==Cisplatin, Irinotecan, RT {{#subobject:4932b1|Regimen=1}}==
+==Cisplatin & Irinotecan -> Cisplatin, Irinotecan, RT {{#subobject:500b44|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 434: / Line 415: @@
 |}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen {{#subobject:eac274|Variant=1}}===
+===Regimen #1 {{#subobject:927613|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
+|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.26591/full Ilson et al. 2011]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of preoperative irinotecan as 50 mg/m<sup>2</sup>.''
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given before irinotecan'''
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given after cisplatin'''
+'''21-day cycle for 2 cycles, followed by:'''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given before irinotecan'''
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8; '''given after cisplatin'''
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
+*Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, for a total of 50.4 Gy given
-'''5-week course'''
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg PO/IV prior to chemotherapy
+*[[Granisetron (Kytril)]] 2 mg PO or [[Ondansetron (Zofran)]] 32 mg IV prior to chemotherapy
+*At least 500 mL D5NS or NS as supportive hydration
+*Atropine 0.5 to 1 mg IV prn cholinergic symptoms
-''Surgery done at least 28 days after finishing chemoradiation, then begin [[#Cisplatin_.26_Irinotecan|adjuvant cisplatin & irinotecan]] at least 28 days after surgical resection.''
+'''21-day cycle for 2 cycles'''
-===References===
+''Surgery performed 4 to 8 weeks after chemoradiation.''
-# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
-==Cisplatin, Paclitaxel, RT {{#subobject:3d8eaa|Regimen=1}}==
+===Regimen #2 {{#subobject:1a3475|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:5a433d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
+|[http://www.redjournal.org/article/S0360-3016(09)00362-9/abstract Rivera et al. 2009]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
+'''21-day cycle for 2 cycles, followed by:'''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV over 1 hour on days 1, 8, 15, 22, 29
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 *Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
 '''5-week course'''
-''Surgery done at least 28 days after finishing chemoradiation, then begin [[#Cisplatin_.26_Paclitaxel|adjuvant cisplatin & paclitaxel]] at least 28 days after surgical resection.''
+''Surgery done 5 to 8 weeks after finishing chemoradiation.''
-===Regimen #2 {{#subobject:32166d|Variant=1}}===
+===Regimen #3 {{#subobject:3a82b6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11759/full Urba et al. 2003]
+|[http://meetinglibrary.asco.org/content/34782-65 Sharma et al. 2009]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#ff0000"|Pilot
 |-
 |}
+''This regimen is being prospectively evaluated in CALGB 80302.''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Paclitaxel (Taxol)]] 60 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 8, 15, 22
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*Concurrent radiation therapy, 1.5 Gy 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 45 Gy
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 to 28 fractions, for a total of 45 to 50.4 Gy given
-====Supportive medications====
+'''21-day cycle for 2 cycles'''
-*[[Dexamethasone (Decadron)]] 20 mg PO given 12 and 6 hours before [[Paclitaxel (Taxol)]]
-*[[Diphenhydramine (Benadryl)]] 50 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
-*[[Cimetidine (Tagamet)]] 300 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
-*1 liter D5NS and mannitol 12.5 g bolus IV prior to [[Cisplatin (Platinol)]]
-*Mannitol 25 g in 1 liter D5NS IV over 4 hours after [[Cisplatin (Platinol)]]
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting 24 hours after the fourth dose of [[Paclitaxel (Taxol)]], continuing until absolute neutrophil count greater than 10,000
-'''4-week course of therapy'''
-''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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11759/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14601087 PubMed]
+# '''Retrospective Abstract:'''' R. Sharma, G. Y. Yang, H. R. Nava, T. L. Demmy, C. E. Nwogu, S. S. Yendamuri, D. Lamonica, W. Tan, R. V. Iyer, N. I. Khushalani. A single institution experience with neoadjuvant chemoradiation (CRT) with irinotecan (I) and cisplatin (C) in locally advanced esophageal carcinoma (LAEC). 2009 ASCO Annual Meeting abstract e15619. [http://meetinglibrary.asco.org/content/34782-65 link to abstract]
-# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
+# Rivera F, Galán M, Tabernero J, Cervantes A, Vega-Villegas ME, Gallego J, Laquente B, Rodríguez E, Carrato A, Escudero P, Massutí B, Alonso-Orduña V, Cardenal A, Sáenz A, Giralt J, Yuste AL, Antón A, Aranda E; Spanish Cooperative Group for Digestive Tumor Therapy. Phase II trial of preoperative irinotecan-cisplatin followed by concurrent irinotecan-cisplatin and radiotherapy for resectable locally advanced gastric and esophagogastric junction adenocarcinoma. Int J Radiat Oncol Biol Phys. 2009 Dec 1;75(5):1430-6. Epub 2009 Jun 18. [http://www.redjournal.org/article/S0360-3016(09)00362-9/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19540072 PubMed]
+# 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. 2011 Oct 11. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.26591/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21990000 PubMed]
-==Docetaxel, Fluorouracil, RT {{#subobject:956374|Regimen=1}}==
+==Cisplatin, Irinotecan, RT {{#subobject:4932b1|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 516: / Line 497: @@
 |}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:c112ab|Variant=1}}===
+===Regimen {{#subobject:eac274|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://ar.iiarjournals.org/content/27/4C/2597.long Hihara et al. 2007]
+|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemoradiotherapy====
-*[[Docetaxel (Taxotere)]] 7.5 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 8, 22, 29
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
-*[[Fluorouracil (5-FU)]] 250 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1, 8, 22, 29
-*Concurrent radiation therapy, 2 Gy fractions x 30 to 33 fractions given 5 days per week (i.e., on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45), for a total dose of 60 to 66 Gy, starting on day 1
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
-====Supportive medications====
+'''5-week course'''
-*[[Dexamethasone (Decadron)]] 8 mg IV 30 minutes prior to [[Docetaxel (Taxotere)]]
-'''7-week course'''
+''Surgery done at least 28 days after finishing chemoradiation, then begin [[#Cisplatin_.26_Irinotecan|adjuvant cisplatin & irinotecan]] at least 28 days after surgical resection.''
-===Regimen #2 {{#subobject:8dd58b|Variant=1}}===
-''Note: Neither of the references cited for this regimen by the NCCN, Esophageal Cancer version 2.2011, actually contained this regimen. No primary reference could be found for this regimen.''
-====Chemoradiotherapy====
-*[[Docetaxel (Taxotere)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
-*[[Fluorouracil (5-FU)]] 200 to 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
-*Concurrent radiation therapy not defined
-'''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. [http://ar.iiarjournals.org/content/27/4C/2597.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17695421 PubMed]
+# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
-==Fluorouracil, Oxaliplatin, RT {{#subobject:94b79a|Regimen=1}}==
+==Cisplatin, Paclitaxel, RT {{#subobject:3d8eaa|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 553: / Line 524: @@
 |}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:bbd435|Variant=1}}===
+===Regimen #1 {{#subobject:5a433d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567089 Lorenzen et al. 2008]
+|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
-|style="background-color:#eeee00"|Phase I/II
+|style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemoradiotherapy====
-*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over days 1 to 33
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
-*[[Oxaliplatin (Eloxatin)]] 45 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29
+*[[Paclitaxel (Taxol)]] 50 mg/m<sup>2</sup> IV over 1 hour on days 1, 8, 15, 22, 29
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, starting within 24 hours of the first dose of chemotherapy, for a total dose of 45 Gy.
-'''35-day course'''
+'''5-week course'''
-''Surgery 4 to 6 weeks after finishing chemoradiation.''
+''Surgery done at least 28 days after finishing chemoradiation, then begin [[#Cisplatin_.26_Paclitaxel|adjuvant cisplatin & paclitaxel]] at least 28 days after surgical resection.''
-===Regimen #2 {{#subobject:ae22de|Variant=1}}===
+===Regimen #2 {{#subobject:32166d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://jco.ascopubs.org/content/20/12/2844.long Khushalani et al. 2002]
+|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.11759/full Urba et al. 2003]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011 lists [[Fluorouracil (5-FU)]] as being given on days 1 to 33.''
 ====Chemoradiotherapy====
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Fluorouracil (5-FU)]] 180 mg/m<sup>2</sup>/day IV continuous infusion over days 8 to 42
+*[[Paclitaxel (Taxol)]] 60 mg/m<sup>2</sup> IV over 3 hours once per day on days 1, 8, 15, 22
-*Concurrent radiation therapy, 1.8 Gy fractions x 20 to 22 fractions, for an initial total dose of 36 to 39.6 Gy, started on day 8
+*Concurrent radiation therapy, 1.5 Gy 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 45 Gy
-**Followed by off-cord conformal oblique fields, 5.4 to 9 Gy given to the clinical target volume (CTV). A second off-cord phase to the gross tumor volume (GTV) of 5.4 Gy was then given, for a total dose delivered of 50.4 Gy to the GTV.
-*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.
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg PO given 12 and 6 hours before [[Paclitaxel (Taxol)]]
+*[[Diphenhydramine (Benadryl)]] 50 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Cimetidine (Tagamet)]] 300 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*1 liter D5NS and mannitol 12.5 g bolus IV prior to [[Cisplatin (Platinol)]]
+*Mannitol 25 g in 1 liter D5NS IV over 4 hours after [[Cisplatin (Platinol)]]
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting 24 hours after the fourth dose of [[Paclitaxel (Taxol)]], continuing until absolute neutrophil count greater than 10,000
+'''4-week course of therapy'''
-'''6-week cycle for 1 initial cycle (see above)'''
+''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===
-# 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. [http://jco.ascopubs.org/content/20/12/2844.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065561 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.11759/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/14601087 PubMed]
-# Lorenzen S, Brücher B, Zimmermann F, Geinitz H, Riera J, Schuster T, Roethling N, Höfler H, Ott K, Peschel C, Siewert JR, Molls M, Lordick F. Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial. Br J Cancer. 2008 Oct 7;99(7):1020-6. Epub 2008 Sep 16. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567089 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18797462 PubMed]
+# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
-=Perioperative chemotherapy=
+==Docetaxel, Fluorouracil, RT {{#subobject:956374|Regimen=1}}==
-==ECF {{#subobject:87a09a|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen {{#subobject:d40982|Variant=1}}===
+===Regimen #1 {{#subobject:c112ab|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)]
+|[http://ar.iiarjournals.org/content/27/4C/2597.long Hihara et al. 2007]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#Surgery_alone|Surgery alone]]
-|style="background-color:#00cd00"|Superior OS
 |-
 |}
-====Chemotherapy====
+====Chemoradiotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Docetaxel (Taxotere)]] 7.5 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 8, 22, 29
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 250 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
+*Concurrent radiation therapy, 2 Gy fractions x 30 to 33 fractions given 5 days per week (i.e., on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33, 36 to 40, 43 to 45), for a total dose of 60 to 66 Gy, starting on day 1
 ====Supportive medications====
-*[[Warfarin (Coumadin)]] 1 mg PO once per day recommended for thrombosis prophylaxis
+*[[Dexamethasone (Decadron)]] 8 mg IV 30 minutes prior to [[Docetaxel (Taxotere)]]
+'''7-week course'''
+===Regimen #2 {{#subobject:8dd58b|Variant=1}}===
+''Note: No primary reference could be found for this regimen.''
+====Chemoradiotherapy====
+*[[Docetaxel (Taxotere)]] 20 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+*[[Fluorouracil (5-FU)]] 200 to 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, 8 to 12, 15 to 19, 22 to 26, 29 to 33
+*Concurrent radiation therapy not defined
-'''21-day cycle for 3 cycles preoperatively, with surgery 3 to 6 weeks after completing cycle 3. The 3 cycles of postoperative chemotherapy are started 6 to 12 weeks after surgery.'''
+'''5-week course'''
 ===References===
-# Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [http://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
+# '''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. [http://ar.iiarjournals.org/content/27/4C/2597.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17695421 PubMed]
-==ECX {{#subobject:c8ab0e|Regimen=1}}==
+==Fluorouracil, Oxaliplatin, RT {{#subobject:94b79a|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen {{#subobject:27f848|Variant=1}}===
+===Regimen #1 {{#subobject:bbd435|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30043-8/fulltext Cunningham et al. 2017 (UK MRC ST03)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567089 Lorenzen et al. 2008]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase I/II
-|ECX & Bevacizumab
-|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-====Chemotherapy====
+====Chemoradiotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion over days 1 to 33
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 45 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29
-*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO BID on days 1 to 21
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
-'''21-day cycle for 3 cycles preoperatively and 3 cycles postoperatively'''
+'''35-day course'''
-===References===
+''Surgery 4 to 6 weeks after finishing chemoradiation.''
-# Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30043-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28163000 PubMed]
-==EOF {{#subobject:ae4e32|Regimen=1}}==
+===Regimen #2 {{#subobject:ae22de|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://jco.ascopubs.org/content/20/12/2844.long Khushalani et al. 2002]
+|style="background-color:#eeee00"|Phase II
 |-
-|[[#top|back to top]]
 |}
-EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
+====Chemoradiotherapy====
-===Regimen {{#subobject:e532ea|Variant=1}}===
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29
-''Note: This regimen is listed as a perioperative option by the NCCN, Esophageal Cancer version 2.2011, 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.''
+*[[Fluorouracil (5-FU)]] 180 mg/m<sup>2</sup>/day IV continuous infusion over days 8 to 42
-====Chemotherapy====
+*Concurrent radiation therapy, 1.8 Gy fractions x 20 to 22 fractions, for an initial total dose of 36 to 39.6 Gy, started on day 8
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+**Followed by off-cord conformal oblique fields, 5.4 to 9 Gy given to the clinical target volume (CTV). A second off-cord phase to the gross tumor volume (GTV) of 5.4 Gy was then given, for a total dose delivered of 50.4 Gy to the GTV.
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*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.
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
-====Supportive medications====
+'''6-week cycle for 1 initial cycle (see above)'''
-*[[Dexamethasone (Decadron)]] 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
-*[[:Category:Serotonin_5-HT3_antagonists|5HT3 antagonist]] prior to chemotherapy
-*[[Metoclopramide (Reglan)]] 10 mg PO TID x 3 days after day 1 chemotherapy
-*[[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 NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used'''
+===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. [http://jco.ascopubs.org/content/20/12/2844.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12065561 PubMed]
+# Lorenzen S, Brücher B, Zimmermann F, Geinitz H, Riera J, Schuster T, Roethling N, Höfler H, Ott K, Peschel C, Siewert JR, Molls M, Lordick F. Neoadjuvant continuous infusion of weekly 5-fluorouracil and escalating doses of oxaliplatin plus concurrent radiation in locally advanced oesophageal squamous cell carcinoma: results of a phase I/II trial. Br J Cancer. 2008 Oct 7;99(7):1020-6. Epub 2008 Sep 16. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2567089 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18797462 PubMed]
+# 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3937600/ link to PMC article] [https://www.ncbi.nlm.nih.gov/pubmed/23975663 PubMed]
-==EOX {{#subobject:891a3e|Regimen=1}}==
+==PLF {{#subobject:74dca8|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
+PLF: '''<u>P</u>'''latinol (Cisplatin), '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:6941e|Variant=1}}===
+===Regimen {{#subobject:cf9923|Variant=1}}===
-''Note: This regimen is listed as a perioperative option by the NCCN, Esophageal Cancer version 2.2011, 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.''
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0506 Stahl et al. 2009]
+|style="background-color:#00cd00"|Phase III
+|PLF -> Cisplatin, Etoposide, RT
+|style="background-color:#ff0000"|Might have inferior OS
+|-
+|}
+''Note: this regimen is given for 2.5 cycles, which is a highly unusual instruction.''
 ====Chemotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 15, 29
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
-*[[Capecitabine (Xeloda)]] 500 to 625 mg/m<sup>2</sup> PO BID on days 1 to 21
+*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36
+'''6-week cycle for 2.5 cycles, followed in 3 to 4 weeks by surgery'''
-====Supportive medications====
+===References===
-*[[Dexamethasone (Decadron)]] 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
+# Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0506 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19139439 PubMed]
-*[[:Category:Serotonin_5-HT3_antagonists|5HT3 antagonist]] prior to chemotherapy
-*[[Metoclopramide (Reglan)]] 10 mg PO TID x 3 days after day 1 chemotherapy
-*[[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 NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used'''
-==Surgery alone==
+==PLF -> Cisplatin, Etoposide, RT {{#subobject:9f350d|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+PLF: '''<u>P</u>'''latinol (Cisplatin), '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
-===Regimen===
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:e3d573|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 711: / Line 700: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa010187 Macdonald et al. 2001]
+|[http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0506 Stahl et al. 2009]
-|style="background-color:#00cd00"|Phase III
-|[[#5-FU_.26_Leucovorin_-.3E_5-FU.2C_Leucovorin.2C_RT_-.3E_5-FU_.26_Leucovorin|Adjuvant 5-FU & Leucovorin -> 5-FU, Leucovorin, RT -> 5-FU & Leucovorin]]
-|style="background-color:#ff0000"|Inferior OS
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)]
-|style="background-color:#00cd00"|Phase III
-|[[#ECF|Perioperative ECF]]
-|style="background-color:#ff0000"|Inferior OS
-|-
-|[http://jco.ascopubs.org/content/26/7/1086.long Tepper et al. 2008 (CALGB 9781)]
-|style="background-color:#00cd00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_RT|Neoadjuvant Cisplatin, Fluorouracil, RT]]
-|style="background-color:#ff0000"|Inferior OS
-|-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa1112088 van Hagen et al. 2012 (CROSS)]
 |style="background-color:#00cd00"|Phase III
-|[[#Carboplatin.2C_Paclitaxel.2C_RT|Neoadjuvant Carboplatin, Paclitaxel, RT]]
+|[[#PLF|PLF]]
-|style="background-color:#ff0000"|Inferior OS
+|style="background-color:#00cd00"|Might have superior OS
 |-
 |}
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 1 hour once per day on days 1, 15, 29
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36
+*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36
-''Surgery as primary therapy; used as a comparator arm and here for reference purposes only.''
+'''6-week cycle for 2 cycles, followed in 2 weeks by:'''
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 1 hour once per day on days 1 & 8
+*[[Etoposide (Vepesid)]] 80 mg/m<sup>2</sup> IV over 1 hour once per day on days 3 to 5
+*Concurrent radiation therapy, 2.0 Gy fractions x 15 fractions, five days per week, for a target dose of 30 Gy
+'''Followed in 3 to 4 weeks by surgery'''
 ===References===
-# Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [http://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
+# Stahl M, Walz MK, Stuschke M, Lehmann N, Meyer HJ, Riera-Knorrenschild J, Langer P, Engenhart-Cabillic R, Bitzer M, Königsrainer A, Budach W, Wilke H. Phase III comparison of preoperative chemotherapy compared with chemoradiotherapy in patients with locally advanced adenocarcinoma of the esophagogastric junction. J Clin Oncol. 2009 Feb 20;27(6):851-6. Epub 2009 Jan 12. [http://ascopubs.org/doi/full/10.1200/JCO.2008.17.0506 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19139439 PubMed]
-# Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [http://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
-# 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. [http://jco.ascopubs.org/content/26/7/1086.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18309943 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1112088 link to original article] '''contains verified protocol''' [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1112088/suppl_file/nejmoa1112088_appendix.pdf link to appendix with details about administration] [https://www.ncbi.nlm.nih.gov/pubmed/22646630 PubMed]
-=Adjuvant therapy=
+=Perioperative chemotherapy=
-==5-FU & Leucovorin -> 5-FU, Leucovorin, RT -> 5-FU & Leucovorin {{#subobject:f6b345|Regimen=1}}==
+==Cisplatin & Fluorouracil {{#subobject:e35a6c|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:d61794|Variant=1}}===
-===Regimen #1 {{#subobject:5cd826|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 755: / Line 736: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJMoa010187 Macdonald et al. 2001]
+|[http://ascopubs.org/doi/full/10.1200/JCO.2010.33.0597 Ychou et al. 2011]
 |style="background-color:#00cd00"|Phase III
 |[[#Surgery_alone|Surgery alone]]
-|style="background-color:#00cd00"|Superior OS
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
-====Chemotherapy, part 1====
+====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continous infusion on days 1 to 5 (total dose per cycle: 4000 mg/m<sup>2</sup>)
-'''28-day cycle, followed by:'''
+'''28-day cycle for 2 or 3 cycles, followed by surgery, followed by 3 to 4 more cycles'''
-====Chemoradiotherapy====
+===References===
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
+# Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.0597 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
-*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
-*Concurrent radiation therapy starting cycle 2 day 1 with 180 cGy, 5 days per week; 25 fractions given over 5 weeks for a total of 4500 cGy
-'''35-day cycle, followed by:'''
+==ECF {{#subobject:87a09a|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
-====Chemotherapy, part 2====
+|-
-*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+|[[#top|back to top]]
-*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
+|}
+ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-'''28-day cycle for 2 cycles'''
+===Regimen {{#subobject:d40982|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)]
+|style="background-color:#00cd00"|Phase III
+|[[#Surgery_alone|Surgery alone]]
+|style="background-color:#00cd00"|Superior OS
+|-
+|}
+====Chemotherapy====
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
-===Regimen #2 {{#subobject:c3cc1c|Variant=1}}===
+====Supportive medications====
-''Note: This regimen was listed by the NCCN, Esophageal Cancer version 2.2011, but the reference cited, [http://jco.ascopubs.org/content/25/24/3732.long André T et al. 2007] ([https://www.ncbi.nlm.nih.gov/pubmed/17704423 PubMed]), was for colon cancer, did not include radiation, and did not match this regimen. No primary reference could be found for this regimen.''
+*[[Warfarin (Coumadin)]] 1 mg PO once per day recommended for thrombosis prophylaxis
-====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus on EITHER days 1 & 15 OR days 1, 2, 15, 16
-*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup> IV continuous infusion on days 1, 2, 15, 16
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV on EITHER days 1 & 15 OR days 1, 2, 15, 16
-'''28-day cycle for 3 total cycles (1 cycle given before radiation, and 2 cycles to be given after radiation)'''
+'''21-day cycle for 3 cycles preoperatively, with surgery 3 to 6 weeks after completing cycle 3. The 3 cycles of postoperative chemotherapy are started 6 to 12 weeks after surgery.'''
 ===References===
-# Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [http://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
+# Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [http://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
-==Cisplatin & Irinotecan {{#subobject:308dd0|Regimen=1}}==
+==ECX {{#subobject:c8ab0e|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:507e9f|Variant=1}}===
+ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+===Regimen {{#subobject:27f848|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30043-8/fulltext Cunningham et al. 2017 (UK MRC ST03)]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|ECX & Bevacizumab
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''Treatment preceded by [[#Cisplatin.2C_Irinotecan.2C_RT|neoadjuvant cisplatin, irinotecan, RT]] and surgery.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO BID on days 1 to 21
-'''21-day cycle for 3 cycles'''
+'''21-day cycle for 3 cycles preoperatively and 3 cycles postoperatively'''
 ===References===
-# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
+# Cunningham D, Stenning SP, Smyth EC, Okines AF, Allum WH, Rowley S, Stevenson L, Grabsch HI, Alderson D, Crosby T, Griffin SM, Mansoor W, Coxon FY, Falk SJ, Darby S, Sumpter KA, Blazeby JM, Langley RE. Peri-operative chemotherapy with or without bevacizumab in operable oesophagogastric adenocarcinoma (UK Medical Research Council ST03): primary analysis results of a multicentre, open-label, randomised phase 2-3 trial. Lancet Oncol. 2017 Mar;18(3):357-370. Epub 2017 Feb 3. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(17)30043-8/fulltext link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/28163000 PubMed]
-==Cisplatin & Paclitaxel {{#subobject:b40afb|Regimen=1}}==
+==EOF {{#subobject:ae4e32|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:c15e56|Variant=1}}===
+EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
-{| border="1" style="text-align:center;" !align="left"
+===Regimen {{#subobject:e532ea|Variant=1}}===
-|'''Study'''
+''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.''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
-|style="background-color:#eeee00"|Phase II
-|-
-|}
-''Treatment preceded by [[#Cisplatin.2C_Paclitaxel.2C_RT|neoadjuvant cisplatin, paclitaxel, RT]] and surgery.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
-'''21-day cycle for 3 cycles'''
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
+*[[:Category:Serotonin_5-HT3_antagonists|5HT3 antagonist]] prior to chemotherapy
+*[[Metoclopramide (Reglan)]] 10 mg PO TID x 3 days after day 1 chemotherapy
+*[[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 NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used'''
+==EOX {{#subobject:891a3e|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
+===Regimen {{#subobject:6941e|Variant=1}}===
+''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/m<sup>2</sup> IV bolus once on day 1
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Capecitabine (Xeloda)]] 500 to 625 mg/m<sup>2</sup> PO BID on days 1 to 21
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
+*[[:Category:Serotonin_5-HT3_antagonists|5HT3 antagonist]] prior to chemotherapy
+*[[Metoclopramide (Reglan)]] 10 mg PO TID x 3 days after day 1 chemotherapy
+*[[Warfarin (Coumadin)]] 1 mg PO once per day as thrombosis prophylaxis, started on day -1
-===References===
+'''21-day cycle for up to 8 cycles; for perioperative use per NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used'''
-# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
-==FP -> Capecitabine & RT -> FP {{#subobject:778727|Regimen=1}}==
+==Surgery alone==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol (Cisplatin)
-<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen===
-===Regimen {{#subobject:20ea7f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa010187 Macdonald et al. 2001]
+|style="background-color:#00cd00"|Phase III
+|[[#5-FU_.26_Leucovorin_-.3E_5-FU.2C_Leucovorin.2C_RT_-.3E_5-FU_.26_Leucovorin|Adjuvant 5-FU & Leucovorin -> 5-FU, Leucovorin, RT -> 5-FU & Leucovorin]]
+|style="background-color:#ff0000"|Inferior OS
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa055531 Cunningham et al. 2006 (MAGIC)]
+|style="background-color:#00cd00"|Phase III
+|[[#ECF|Perioperative ECF]]
+|style="background-color:#ff0000"|Inferior OS
 |-
-|[http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm Lee et al. 2006]
+|[http://jco.ascopubs.org/content/26/7/1086.long Tepper et al. 2008 (CALGB 9781)]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#Cisplatin.2C_Fluorouracil.2C_RT|Neoadjuvant Cisplatin, Fluorouracil, RT]]
+|style="background-color:#ff0000"|Inferior OS
+|-
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa1112088 van Hagen et al. 2012 (CROSS)]
+|style="background-color:#00cd00"|Phase III
+|[[#Carboplatin.2C_Paclitaxel.2C_RT|Neoadjuvant Carboplatin, Paclitaxel, RT]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |}
-''Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without FP cycles 1, 3, 4, 5. Dosage of [[Capecitabine (Xeloda)]] was listed as 625 to 825 mg/m<sup>2</sup> PO BID on days 1 to 5 or 1 to 7 while radiation is being given. FP starts 3 weeks after surgery.''
-====Chemotherapy, part 1====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-'''21-day cycle, followed immediately by:'''
+''Surgery as primary therapy; used as a comparator arm and here for reference purposes only.''
-====Chemoradiotherapy====
+===References===
-*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> (1650 mg/m<sup>2</sup>/day) PO every 12 hours
+# Walsh TN, Noonan N, Hollywood D, Kelly A, Keeling N, Hennessy TP. A comparison of multimodal therapy and surgery for esophageal adenocarcinoma. N Engl J Med. 1996 Aug 15;335(7):462-7. Erratum in: N Engl J Med 1999 Jul 29;341(5):384. [http://www.nejm.org/doi/full/10.1056/NEJM199608153350702 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/8672151 PubMed]
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
+# Bosset JF, Gignoux M, Triboulet JP, Tiret E, Mantion G, Elias D, Lozach P, Ollier JC, Pavy JJ, Mercier M, Sahmoud T. Chemoradiotherapy followed by surgery compared with surgery alone in squamous-cell cancer of the esophagus. N Engl J Med. 1997 Jul 17;337(3):161-7. [http://www.nejm.org/doi/full/10.1056/NEJM199707173370304 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9219702 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199812313392704 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/9869669 PubMed]
+## '''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. [http://ascopubs.org/doi/abs/10.1200/JCO.2006.10.4760 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17704421 PubMed]
+# Urba SG, Orringer MB, Turrisi A, Iannettoni M, Forastiere A, Strawderman M. Randomized trial of preoperative chemoradiation versus surgery alone in patients with locoregional esophageal carcinoma. J Clin Oncol. 2001 Jan 15;19(2):305-13. [http://ascopubs.org/doi/abs/10.1200/JCO.2001.19.2.305 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/11208820 PubMed]
+# Ancona E, Ruol A, Santi S, Merigliano S, Sileni VC, Koussis H, Zaninotto G, Bonavina L, Peracchia A. Only pathologic complete response to neoadjuvant chemotherapy improves significantly the long term survival of patients with resectable esophageal squamous cell carcinoma: final report of a randomized, controlled trial of preoperative chemotherapy versus surgery alone. Cancer. 2001 Jun 1;91(11):2165-74. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11391598 PubMed]
+# Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [http://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
+# 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. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(02)08651-8/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12049861 PubMed]
+## '''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. [http://ascopubs.org/doi/abs/10.1200/JCO.2009.22.2083 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19770374 PubMed]
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70288-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16129366 PubMed]
+# Cunningham D, Allum WH, Stenning SP, Thompson JN, Van de Velde CJ, Nicolson M, Scarffe JH, Lofts FJ, Falk SJ, Iveson TJ, Smith DB, Langley RE, Verma M, Weeden S, Chua YJ, MAGIC Trial Participants. Perioperative chemotherapy versus surgery alone for resectable gastroesophageal cancer. N Engl J Med. 2006 Jul 6;355(1):11-20. [http://www.nejm.org/doi/full/10.1056/NEJMoa055531 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16822992 PubMed]
+# 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. [http://jco.ascopubs.org/content/26/7/1086.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18309943 PubMed]
+# Ychou M, Boige V, Pignon JP, Conroy T, Bouché O, Lebreton G, Ducourtieux M, Bedenne L, Fabre JM, Saint-Aubert B, Genève J, Lasser P, Rougier P. Perioperative chemotherapy compared with surgery alone for resectable gastroesophageal adenocarcinoma: an FNCLCC and FFCD multicenter phase III trial. J Clin Oncol. 2011 May 1;29(13):1715-21. Epub 2011 Mar 28. [http://ascopubs.org/doi/full/10.1200/JCO.2010.33.0597 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21444866 PubMed]
+# Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011 May 19;11:181. [https://bmccancer.biomedcentral.com/articles/10.1186/1471-2407-11-181 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21595951 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa1112088 link to original article] '''contains verified protocol''' [http://www.nejm.org/doi/suppl/10.1056/NEJMoa1112088/suppl_file/nejmoa1112088_appendix.pdf link to appendix with details about administration] [https://www.ncbi.nlm.nih.gov/pubmed/22646630 PubMed]
+# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2013.53.6532 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24982463 PubMed]
-'''5-week course, followed 4 weeks later by:'''
+=Adjuvant therapy=
+==5-FU & Leucovorin -> 5-FU, Leucovorin, RT -> 5-FU & Leucovorin {{#subobject:f6b345|Regimen=1}}==
-====Chemotherapy, part 2====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-'''21-day cycle for 3 cycles'''
-===References===
-# Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. [http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16489675 PubMed]
-==ECF -> 5-FU & RT -> ECF {{#subobject:7f3e93|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen #1 {{#subobject:5cd826|Variant=1}}===
-===Regimen {{#subobject:53c380|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.redjournal.org/article/S0360-3016(09)03613-X/abstract Leong et al. 2010]
+|[http://www.nejm.org/doi/full/10.1056/NEJMoa010187 Macdonald et al. 2001]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#Surgery_alone|Surgery alone]]
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
-''Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without ECF cycles 1, 3, 4. Dosage of [[Fluorouracil (5-FU)]] was listed as 200 to 250 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5 or 1 to 7 while radiation is being given.''
 ====Chemotherapy, part 1====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
-'''21-day cycle, followed immediately by:'''
+'''28-day cycle, followed by:'''
 ====Chemoradiotherapy====
-*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 35
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
-*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week for a total dose of 45 Gy, starting on day 1
+*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 4 and the last 3 days of radiation therapy
+*Concurrent radiation therapy starting cycle 2 day 1 with 180 cGy, 5 days per week; 25 fractions given over 5 weeks for a total of 4500 cGy
-'''5-week course, followed 1 month later by:'''
+'''35-day cycle, followed by:'''
 ====Chemotherapy, part 2====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Fluorouracil (5-FU)]] 425 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Folinic acid (Leucovorin)]] 20 mg/m<sup>2</sup> IV bolus once per day on days 1 to 5
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
+'''28-day cycle for 2 cycles'''
+===Regimen #2 {{#subobject:c3cc1c|Variant=1}}===
+''Note: No primary reference could be found for this regimen.''
+====Chemotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus on EITHER days 1 & 15 OR days 1, 2, 15, 16
+*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup> IV continuous infusion on days 1, 2, 15, 16
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV on EITHER days 1 & 15 OR days 1, 2, 15, 16
-'''21-day cycle for 2 cycles'''
+'''28-day cycle for 3 total cycles (1 cycle given before radiation, and 2 cycles to be given after radiation)'''
 ===References===
-# Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):690-5. Epub 2010 May 14. [http://www.redjournal.org/article/S0360-3016(09)03613-X/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20472363 PubMed]
+# Macdonald JS, Smalley SR, Benedetti J, Hundahl SA, Estes NC, Stemmermann GN, Haller DG, Ajani JA, Gunderson LL, Jessup JM, Martenson JA. Chemoradiotherapy after surgery compared with surgery alone for adenocarcinoma of the stomach or gastroesophageal junction. N Engl J Med. 2001 Sep 6;345(10):725-30. [http://www.nejm.org/doi/full/10.1056/NEJMoa010187 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11547741 PubMed]
-=Definitive chemoradiation (no surgery)=
+==Cisplatin & Irinotecan {{#subobject:308dd0|Regimen=1}}==
-==Capecitabine & Cisplatin -> Capecitabine, Cisplatin, RT {{#subobject:ce2bbb|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:507e9f|Variant=1}}===
-===Regimen {{#subobject:f7a6c1|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://jjco.oxfordjournals.org/content/37/11/829.long Lee et al. 2007]
+|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
-|style="background-color:#ff0000"|Retrospective
+|style="background-color:#eeee00"|Phase II
 |-
 |}
-''The study was for patients with stage IV disease.''
+''Treatment preceded by [[#Cisplatin.2C_Irinotecan.2C_RT|neoadjuvant cisplatin, irinotecan, RT]] and surgery.''
-*Patients with M1b disease (visceral metastases) received the chemotherapy only part until progression of disease or unacceptable toxicity.
+====Chemotherapy====
-*Patients with M1a or M1b (non-viscertal 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.
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
-====Chemotherapy====
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 1 hour on day 1; given before the first dose of capecitabine
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
-'''21-day cycles'''
+'''21-day cycle for 3 cycles'''
-====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 1 hour on day 1; given before the first dose of capecitabine
-*[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO BID, 5 days per week while radiation is being given
-*Concurrent radiation therapy, total of 54 Gy given. Dose per fraction and total duration of treatment were not specified, but based on other regimens, it is suspected to be either 1.8 Gy x 30 fractions or 2 Gy x 27 fractions.
-'''1-week cycles until radiation therapy is complete'''
 ===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. [http://jjco.oxfordjournals.org/content/37/11/829.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17951334 PubMed]
+# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
-==Capecitabine, Cisplatin, RT {{#subobject:dfe688|Regimen=1}}==
+==Cisplatin & Paclitaxel {{#subobject:b40afb|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:c15e56|Variant=1}}===
-===Regimen {{#subobject:4beb7f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract Crosby et al. 2013 (SCOPE1)]
+|[http://www.springerlink.com/content/v4g0257025185531/ Yoon et al. 2011]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|Capecitabine, Cisplatin, Cetuximab, RT
-|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
-''Note: total number of days per cycle is not specified in the abstract.''
+''Treatment preceded by [[#Cisplatin.2C_Paclitaxel.2C_RT|neoadjuvant cisplatin, paclitaxel, RT]] and surgery.''
-====Chemoradiotherapy====
+====Chemotherapy====
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Capecitabine (Xeloda)]] 615 mg/m<sup>2</sup> PO BID on days 1 to 21
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-*Concurrent radiation therapy, total of 50 Gy given in 25 fractions with cycles 3 & 4
-'''4 cycles'''
+'''21-day cycle for 3 cycles'''
 ===References===
-# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23623280 PubMed]
+# Yoon HH, Catalano P, Gibson MK, Skaar TC, Philips S, Montgomery EA, Hafez MJ, Powell M, Liu G, Forastiere AA, Benson AB, Kleinberg LR, Murphy KM. Genetic variation in radiation and platinum pathways predicts severe acute radiation toxicity in patients with esophageal adenocarcinoma treated with cisplatin-based preoperative radiochemotherapy: results from the Eastern Cooperative Oncology Group. Cancer Chemother Pharmacol. 2011 Oct;68(4):863-70. Epub 2011 Feb 1. [http://www.springerlink.com/content/v4g0257025185531/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21286719 PubMed]
-==Capecitabine, Docetaxel, RT {{#subobject:9fbb10|Regimen=1}}==
+==FP -> Capecitabine & RT -> FP {{#subobject:778727|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-See [[#Docetaxel_.28Taxotere.29_.26_Capecitabine_.28Xeloda.29|Docetaxel (Taxotere) & Capecitabine (Xeloda)]].
+FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol (Cisplatin)
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-==Capecitabine, Docetaxel, Oxaliplatin, RT {{#subobject:6c2946|Regimen=1}}==
+===Regimen {{#subobject:20ea7f|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[[#top|back to top]]
+|[http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm Lee et al. 2006]
-|}
+|style="background-color:#eeee00"|Phase II
-See [[#Oxaliplatin_.28Eloxatin.29.2C_Docetaxel_.28Taxotere.29.2C_Capecitabine_.28Xeloda.29|Oxaliplatin (Eloxatin), Docetaxel (Taxotere), Capecitabine (Xeloda)]].
-==Capecitabine, Oxaliplatin, RT {{#subobject:22577b|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[[#top|back to top]]
 |}
-See [[#Oxaliplatin_.28Eloxatin.29_.26_Capecitabine_.28Xeloda.29|Oxaliplatin (Eloxatin) & Capecitabine (Xeloda)]].
+''Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without FP cycles 1, 3, 4, 5. Dosage of [[Capecitabine (Xeloda)]] was listed as 625 to 825 mg/m<sup>2</sup> PO BID on days 1 to 5 or 1 to 7 while radiation is being given. FP starts 3 weeks after surgery.''
+====Chemotherapy, part 1====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-==Capecitabine, Paclitaxel, RT {{#subobject:56dddf|Regimen=1}}==
+'''21-day cycle, followed immediately by:'''
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
+====Chemoradiotherapy====
-|[[#top|back to top]]
+*[[Capecitabine (Xeloda)]] 825 mg/m<sup>2</sup> (1650 mg/m<sup>2</sup>/day) PO every 12 hours
-|}
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
-See [[#Paclitaxel_.28Taxol.29_.26_Capecitabine_.28Xeloda.29|Paclitaxel (Taxol) & Capecitabine (Xeloda)]].
+'''5-week course, followed 4 weeks later by:'''
+====Chemotherapy, part 2====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
+'''21-day cycle for 3 cycles'''
-==Carboplatin, Paclitaxel, RT {{#subobject:d4831|Regimen=1}}==
+===References===
-{| class="wikitable" style="float:right; margin-left: 5px;"
+# Lee HS, Choi Y, Hur WJ, Kim HJ, Kwon HC, Kim SH, Kim JS, Lee JH, Jung GJ, Kim MC. Pilot study of postoperative adjuvant chemoradiation for advanced gastric cancer: adjuvant 5-FU/cisplatin and chemoradiation with capecitabine. World J Gastroenterol. 2006 Jan 28;12(4):603-7. [http://www.wjgnet.com/1007-9327/full/v12/i4/603.htm link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16489675 PubMed]
-|-
-|[[#top|back to top]]
-|}
-See [[#Carboplatin.2C_Paclitaxel.2C_RT|Carboplatin, Paclitaxel, RT]], except patients did not undergo surgery.
-==Cisplatin, Docetaxel, RT {{#subobject:21719f|Regimen=1}}==
+==ECF -> 5-FU & RT -> ECF {{#subobject:7f3e93|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen #1 {{#subobject:7b3f9c|Variant=1}}===
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:53c380|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1111/j.1442-2050.2009.01003.x/full Li et al. 2009]
+|[http://www.redjournal.org/article/S0360-3016(09)03613-X/abstract Leong et al. 2010]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
-====Chemoradiotherapy====
+''Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without ECF cycles 1, 3, 4. Dosage of [[Fluorouracil (5-FU)]] was listed as 200 to 250 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5 or 1 to 7 while radiation is being given.''
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 22
+====Chemotherapy, part 1====
-*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 22
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*Concurrent radiation therapy, 1.8 to 2.0 Gy fractions, 5 days per week, to start within 24 hours of the day 1 of chemotherapy
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-**Patients with stage I to III disease received a total dose of 60 to 64 Gy over 4 to 6 weeks
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
-**Patients with stage IV disease (lymph node only) received a total dose of 50 to 56 Gy
-====Supportive medications====
+'''21-day cycle, followed immediately by:'''
-*[[Dexamethasone (Decadron)]] 10 mg PO/IV the day before [[Docetaxel (Taxotere)]], 30 minutes prior to [[Docetaxel (Taxotere)]], and the day after [[Docetaxel (Taxotere)]]
-*[[Diphenhydramine (Benadryl)]] 40 mg IV prior to chemotherapy
-*[[Cimetidine (Tagamet)]] 40 mg IV prior to chemotherapy
-*[[Granisetron (Kytril)]] 2 mg IV prior to chemotherapy
-*1.5 to 2.0 liters fluids before [[Cisplatin (Platinol)]]
-'''1 course'''
-===Regimen #2 {{#subobject:f4800d|Variant=1}}===
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031899 Day et al. 2010]
-|style="background-color:#ff0000"|Phase I
-|-
-|}
-''Note: The NCCN, Esophageal Cancer version 2.2011, suggests a wider dose range of 20 to 30 mg/m<sup>2</sup> for both cisplatin and docetaxel. The primary reference also investigated these dose levels, but ultimately recommended 30 mg/m<sup>2</sup> dosages for both cisplatin and docetaxel.''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+*[[Fluorouracil (5-FU)]] 225 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 35
-*[[Docetaxel (Taxotere)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+*Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week for a total dose of 45 Gy, starting on day 1
-*Concurrent radiation therapy, 2 Gy fractions x 25 fractions, 5 days per week, for a total dose of 50 Gy, to start within 4 hours after the first dose of chemotherapy.
-====Supportive medications====
+'''5-week course, followed 1 month later by:'''
-*"Steroid and anti-emetic pre-medication"
-'''5-week course'''
+====Chemotherapy, part 2====
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
+'''21-day cycle for 2 cycles'''
 ===References===
-# Li QQ, Liu MZ, Hu YH, Liu H, He ZY, Lin HX. Definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous esophageal carcinoma. Dis Esophagus. 2010 Apr;23(3):253-9. Epub 2009 Aug 28. [http://onlinelibrary.wiley.com/doi/10.1111/j.1442-2050.2009.01003.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19732130 PubMed]
+# Leong T, Joon DL, Willis D, Jayamoham J, Spry N, Harvey J, Di Iulio J, Milner A, Mann GB, Michael M. Adjuvant chemoradiation for gastric cancer using epirubicin, cisplatin, and 5-fluorouracil before and after three-dimensional conformal radiotherapy with concurrent infusional 5-fluorouracil: a multicenter study of the Trans-Tasman Radiation Oncology Group. Int J Radiat Oncol Biol Phys. 2011 Mar 1;79(3):690-5. Epub 2010 May 14. [http://www.redjournal.org/article/S0360-3016(09)03613-X/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20472363 PubMed]
-# '''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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031899 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21157450 PubMed]
-==Cisplatin, Fluorouracil, RT {{#subobject:2b3dbc|Regimen=1}}==
+=Definitive chemoradiation (no surgery)=
+==Capecitabine & Cisplatin -> Capecitabine, Cisplatin, RT {{#subobject:ce2bbb|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
@@ Line 1,079: / Line 1,093: @@
 |}
 RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen #1 {{#subobject:3272d5|Variant=1}}===
+===Regimen {{#subobject:f7a6c1|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/20/5/1167.long Minsky et al. 2002 (RTOG 94-05)]
+|[http://jjco.oxfordjournals.org/content/37/11/829.long Lee et al. 2007]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#ff0000"|Retrospective
-|Cisplatin, 5-FU, high-dose RT
-|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-====Chemoradiotherapy====
+''The study was for patients with stage IV disease.''
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*Patients with M1b disease (visceral metastases) received the chemotherapy only part until progression of disease or unacceptable toxicity.
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4
+*Patients with M1a or M1b (non-viscertal 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.
-*Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, starting on day 1, for a total dose of 50.4 Gy.
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 1 hour on day 1; given before the first dose of capecitabine
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
-'''28-day cycle for 2 cycles, followed by:'''
+'''21-day cycles'''
-====Chemotherapy====
+====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV over 1 hour on day 1; given before the first dose of capecitabine
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4
+*[[Capecitabine (Xeloda)]] 800 mg/m<sup>2</sup> PO BID, 5 days per week while radiation is being given
+*Concurrent radiation therapy, total of 54 Gy given. Dose per fraction and total duration of treatment were not specified, but based on other regimens, it is suspected to be either 1.8 Gy x 30 fractions or 2 Gy x 27 fractions.
+'''1-week cycles until radiation therapy is complete'''
-'''28-day cycle for 2 cycles'''
+===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. [http://jjco.oxfordjournals.org/content/37/11/829.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17951334 PubMed]
-===Regimen #2 {{#subobject:ca1b71|Variant=1}}===
+==Capecitabine, Cisplatin, RT {{#subobject:dfe688|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:4beb7f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,112: / Line 1,134: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract Crosby et al. 2013 (SCOPE1)]
 |style="background-color:#00cd00"|Phase III
-|[[#Radiation_therapy|Radiation therapy]]
+|Capecitabine, Cisplatin, Cetuximab, RT
-|style="background-color:#00cd00"|Superior OS
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
+''Note: total number of days per cycle is not specified in the abstract.''
 ====Chemoradiotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once per day on the first day of week 1, 5, 8, 11 (day 1, 29, 50, 71)
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on the first 4 days of week 1, 5, 8, 11 (days 1 to 4, 29 to 32, 50 to 53, 71 to 74)
+*[[Capecitabine (Xeloda)]] 615 mg/m<sup>2</sup> PO BID on days 1 to 21
-*Concurrent radiation therapy: starting on day 1, 2.0 Gy fractions x 15 fractions given 5 days per week x 3 weeks; then 2.0 Gy fractions x 10 fractions x 2 weeks to the initial tumor length plus a 5 cm margin, for a total dose of 50.0 Gy.
+*Concurrent radiation therapy, total of 50 Gy given in 25 fractions with cycles 3 & 4
-'''11-week course of therapy'''
+'''4 cycles'''
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1584260 PubMed]
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70136-0/abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23623280 PubMed]
-## '''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. [http://jco.ascopubs.org/content/15/1/277.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8996153 PubMed]
-## '''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. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. [http://jama.jamanetwork.com/article.aspx?articleid=189737 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10235156 PubMed]
+==Capecitabine, Docetaxel, RT {{#subobject:9fbb10|Regimen=1}}==
-# 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. [http://jco.ascopubs.org/content/20/5/1167.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11870157 PubMed]
+{| class="wikitable" style="float:right; margin-left: 5px;"
-# 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. [http://jco.ascopubs.org/content/25/10/1160.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17401004 PubMed]
+|-
-# Conroy T, Yataghène Y, Etienne PL, Michel P, Senellart H, Raoul JL, Mineur L, Rives M, Mirabel X, Lamezec B, Rio E, Le Prisé E, Peiffert D, Adenis A. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010 Oct 26;103(9):1349-55. Epub 2010 Oct 12. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990616 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20940718 PubMed]
+|[[#top|back to top]]
-# 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. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24556041 PubMed]
+|}
+See [[#Docetaxel_.28Taxotere.29_.26_Capecitabine_.28Xeloda.29|Docetaxel (Taxotere) & Capecitabine (Xeloda)]].
-==Cisplatin, Irinotecan, RT {{#subobject:c0c088|Regimen=1}}==
+==Capecitabine, Docetaxel, Oxaliplatin, RT {{#subobject:6c2946|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-See [[#Cisplatin_.28Platinol.29_.26_Irinotecan_.28Camptosar.29|Cisplatin (Platinol) & Irinotecan (Camptosar) Regimen #1, Ilson et al. 2011 & Regimen #2, Sharma et al. 2009]].
+See [[#Oxaliplatin_.28Eloxatin.29.2C_Docetaxel_.28Taxotere.29.2C_Capecitabine_.28Xeloda.29|Oxaliplatin (Eloxatin), Docetaxel (Taxotere), Capecitabine (Xeloda)]].
-==Cisplatin, Paclitaxel, RT {{#subobject:3ab15|Regimen=1}}==
+==Capecitabine, Oxaliplatin, RT {{#subobject:22577b|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-See [[#Cisplatin_.28Platinol.29_.26_Paclitaxel_.28Taxol.29|Cisplatin (Platinol) & Paclitaxel (Taxol)]], except patients did not undergo surgery.
+See [[#Oxaliplatin_.28Eloxatin.29_.26_Capecitabine_.28Xeloda.29|Oxaliplatin (Eloxatin) & Capecitabine (Xeloda)]].
-==Docetaxel, Fluorouracil, RT {{#subobject:e37962|Regimen=1}}==
+==Capecitabine, Paclitaxel, RT {{#subobject:56dddf|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-See [[#Docetaxel_.28Taxotere.29_.26_Fluorouracil_.285-FU.29|Docetaxel (Taxotere) & Fluorouracil (5-FU) Regimen #1, Hihara et al. 2007 & Regimen #2]].
+See [[#Paclitaxel_.28Taxol.29_.26_Capecitabine_.28Xeloda.29|Paclitaxel (Taxol) & Capecitabine (Xeloda)]].
-==Fluorouracil, Oxaliplatin, RT {{#subobject:ab0124|Regimen=1}}==
+==Carboplatin, Paclitaxel, RT {{#subobject:d4831|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-See [[#Oxaliplatin_.28Eloxatin.29_.26_Fluorouracil_.285-FU.29|Oxaliplatin (Eloxatin) & Fluorouracil (5-FU) Regimen #1, Lorenzen et al. 2008]]. ''Note: Regimen #1 was a neoadjuvant regimen, but is also listed under definitive chemoradiation by the NCCN, Esophageal Cancer version 2.2011.'' See [[#Oxaliplatin_.28Eloxatin.29_.26_Fluorouracil_.285-FU.29|Oxaliplatin (Eloxatin) & Fluorouracil (5-FU) Regimen #2, Khushalani et al. 2002]].
+See [[#Carboplatin.2C_Paclitaxel.2C_RT|Carboplatin, Paclitaxel, RT]], except patients did not undergo surgery.
-==FOLFOX 4 & RT -> FOLFOX 4 {{#subobject:1f91c5|Regimen=1}}==
+==Cisplatin, Docetaxel, RT {{#subobject:21719f|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-FOLFOX: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen #1 {{#subobject:7b3f9c|Variant=1}}===
-===Regimen {{#subobject:e2fc30|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990616 Conroy et al. 2010]
+|[http://onlinelibrary.wiley.com/doi/10.1111/j.1442-2050.2009.01003.x/full Li et al. 2009]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#Cisplatin.2C_Fluorouracil.2C_RT_2|Cisplatin, 5-FU, RT]]
-|style="background-color:#d3d3d3"|Not reported
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of leucovorin as 400 mg/m<sup>2</sup>.''
 ====Chemoradiotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV over 22 hours on days 1 & 2, '''given last'''
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once per day on days 1 & 22
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 22
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*Concurrent radiation therapy, 1.8 to 2.0 Gy fractions, 5 days per week, to start within 24 hours of the day 1 of chemotherapy
-*Concurrent radiation therapy, 2 Gy fractions x 25 fractions given 5 days per week, for a total dose of 50 Gy
+**Patients with stage I to III disease received a total dose of 60 to 64 Gy over 4 to 6 weeks
+**Patients with stage IV disease (lymph node only) received a total dose of 50 to 56 Gy
-'''14-day cycle for 3 cycles, followed by:'''
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 10 mg PO/IV the day before [[Docetaxel (Taxotere)]], 30 minutes prior to [[Docetaxel (Taxotere)]], and the day after [[Docetaxel (Taxotere)]]
+*[[Diphenhydramine (Benadryl)]] 40 mg IV prior to chemotherapy
+*[[Cimetidine (Tagamet)]] 40 mg IV prior to chemotherapy
+*[[Granisetron (Kytril)]] 2 mg IV prior to chemotherapy
+*1.5 to 2.0 liters fluids before [[Cisplatin (Platinol)]]
-====Chemotherapy====
+'''1 course'''
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV over 22 hours on days 1 & 2, '''given last'''
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''14-day cycle for 3 cycles'''
+===Regimen #2 {{#subobject:f4800d|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
-===References===
+|'''Study'''
-# Conroy T, Yataghène Y, Etienne PL, Michel P, Senellart H, Raoul JL, Mineur L, Rives M, Mirabel X, Lamezec B, Rio E, Le Prisé E, Peiffert D, Adenis A. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010 Oct 26;103(9):1349-55. Epub 2010 Oct 12. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990616 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20940718 PubMed]
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-# 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. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24556041 PubMed]
+|-
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031899 Day et al. 2010]
+|style="background-color:#ff0000"|Phase I
+|-
+|}
+''Note: The NCCN, Esophageal Cancer version 2.2011, suggests a wider dose range of 20 to 30 mg/m<sup>2</sup> for both cisplatin and docetaxel. The primary reference also investigated these dose levels, but ultimately recommended 30 mg/m<sup>2</sup> dosages for both cisplatin and docetaxel.''
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+*[[Docetaxel (Taxotere)]] 30 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22, 29
+*Concurrent radiation therapy, 2 Gy fractions x 25 fractions, 5 days per week, for a total dose of 50 Gy, to start within 4 hours after the first dose of chemotherapy.
+====Supportive medications====
+*"Steroid and anti-emetic pre-medication"
+'''5-week course'''
+===References===
+# Li QQ, Liu MZ, Hu YH, Liu H, He ZY, Lin HX. Definitive concomitant chemoradiotherapy with docetaxel and cisplatin in squamous esophageal carcinoma. Dis Esophagus. 2010 Apr;23(3):253-9. Epub 2009 Aug 28. [http://onlinelibrary.wiley.com/doi/10.1111/j.1442-2050.2009.01003.x/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19732130 PubMed]
+# '''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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3031899 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21157450 PubMed]
-==Radiation therapy==
+==Cisplatin, Fluorouracil, RT {{#subobject:2b3dbc|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
+RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
-===Regimen===
+===Regimen #1 {{#subobject:3272d5|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,215: / Line 1,254: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)]
+|[http://jco.ascopubs.org/content/20/5/1167.long Minsky et al. 2002 (RTOG 94-05)]
 |style="background-color:#00cd00"|Phase III
-|[[#Cisplatin.2C_Fluorouracil.2C_RT_2|Cisplatin, 5-FU, RT]]
+|Cisplatin, 5-FU, high-dose RT
-|style="background-color:#ff0000"|Inferior OS
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4
+*Concurrent radiation therapy, 1.8 Gy fractions x 28 fractions given 5 days per week, starting on day 1, for a total dose of 50.4 Gy.
-''Radiation as primary therapy; used as a comparator arm and here for reference purposes only.''
+'''28-day cycle for 2 cycles, followed by:'''
-===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1584260 PubMed]
-## '''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. [http://jco.ascopubs.org/content/15/1/277.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8996153 PubMed]
-## '''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. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. [http://jama.jamanetwork.com/article.aspx?articleid=189737 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10235156 PubMed]
-=Chemotherapy for metastatic or locally advanced disease (non-radiation/surgery candidate)=
+====Chemotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on days 1 to 4
-==Best supportive care==
+'''28-day cycle for 2 cycles'''
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen===
+===Regimen #2 {{#subobject:ca1b71|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,244: / Line 1,280: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract Thuss-Patience et al. 2011]
+|[http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)]
 |style="background-color:#00cd00"|Phase III
-|[[#Irinotecan_.28Camptosar.29|Irinotecan]]
+|[[#Radiation_therapy|Radiation therapy]]
-|style="background-color:#ff0000"|Seems to have inferior OS
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
+====Chemoradiotherapy====
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once per day on the first day of week 1, 5, 8, 11 (day 1, 29, 50, 71)
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion over 96 hours on the first 4 days of week 1, 5, 8, 11 (days 1 to 4, 29 to 32, 50 to 53, 71 to 74)
+*Concurrent radiation therapy: starting on day 1, 2.0 Gy fractions x 15 fractions given 5 days per week x 3 weeks; then 2.0 Gy fractions x 10 fractions x 2 weeks to the initial tumor length plus a 5 cm margin, for a total dose of 50.0 Gy.
-''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.''
+'''11-week course of therapy'''
 ===References===
-# Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1584260 PubMed]
-# Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
+## '''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. [http://jco.ascopubs.org/content/15/1/277.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8996153 PubMed]
+## '''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. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. [http://jama.jamanetwork.com/article.aspx?articleid=189737 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10235156 PubMed]
+# 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. [http://jco.ascopubs.org/content/20/5/1167.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11870157 PubMed]
+# 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. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(05)70288-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16129366 PubMed]
+# 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. [http://jco.ascopubs.org/content/25/10/1160.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/17401004 PubMed]
+# Conroy T, Yataghène Y, Etienne PL, Michel P, Senellart H, Raoul JL, Mineur L, Rives M, Mirabel X, Lamezec B, Rio E, Le Prisé E, Peiffert D, Adenis A. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010 Oct 26;103(9):1349-55. Epub 2010 Oct 12. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990616 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20940718 PubMed]
+# Burmeister BH, Thomas JM, Burmeister EA, Walpole ET, Harvey JA, Thomson DB, Barbour AP, Gotley DC, Smithers BM. Is concurrent radiation therapy required in patients receiving preoperative chemotherapy for adenocarcinoma of the oesophagus? A randomised phase II trial. Eur J Cancer. 2011 Feb;47(3):354-60. [http://www.ejcancer.com/article/S0959-8049(10)00874-9/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/21084184 PubMed]
+# 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. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24556041 PubMed]
+# 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. [http://ascopubs.org/doi/full/10.1200/JCO.2013.53.6532 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24982463 PubMed]
-==Capecitabine (Xeloda) {{#subobject:a9eb0b|Regimen=1}}==
+==Cisplatin, Irinotecan, RT {{#subobject:c0c088|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:b6ba4c|Variant=1}}===
+See [[#Cisplatin_.28Platinol.29_.26_Irinotecan_.28Camptosar.29|Cisplatin (Platinol) & Irinotecan (Camptosar) Regimen #1, Ilson et al. 2011 & Regimen #2, Sharma et al. 2009]].
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
+==Cisplatin, Paclitaxel, RT {{#subobject:3ab15|Regimen=1}}==
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
-|[http://annonc.oxfordjournals.org/content/15/9/1344.long Hong et al. 2004]
+|[[#top|back to top]]
-|style="background-color:#eeee00"|Phase II
+|}
+See [[#Cisplatin_.28Platinol.29_.26_Paclitaxel_.28Taxol.29|Cisplatin (Platinol) & Paclitaxel (Taxol)]], except patients did not undergo surgery.
+==Docetaxel, Fluorouracil, RT {{#subobject:e37962|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
 |-
+|[[#top|back to top]]
 |}
+See [[#Docetaxel_.28Taxotere.29_.26_Fluorouracil_.285-FU.29|Docetaxel (Taxotere) & Fluorouracil (5-FU) Regimen #1, Hihara et al. 2007 & Regimen #2]].
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of capecitabine as 1000 mg/m<sup>2</sup>.''
+==Fluorouracil, Oxaliplatin, RT {{#subobject:ab0124|Regimen=1}}==
-====Chemotherapy====
-*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO BID on days 1 to 14
-'''21-day cycle for up to 6 cycles'''
-===References===
-# Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. [http://annonc.oxfordjournals.org/content/15/9/1344.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15319239 PubMed]
-==Capecitabine & Irinotecan {{#subobject:c699c3|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:d233c0|Variant=1}}===
+See [[#Oxaliplatin_.28Eloxatin.29_.26_Fluorouracil_.285-FU.29|Oxaliplatin (Eloxatin) & Fluorouracil (5-FU) Regimen #1, Lorenzen et al. 2008]]. ''Note: Regimen #1 was a neoadjuvant regimen, but is also listed under definitive chemoradiation by the NCCN, Esophageal Cancer version 2.2011.'' See [[#Oxaliplatin_.28Eloxatin.29_.26_Fluorouracil_.285-FU.29|Oxaliplatin (Eloxatin) & Fluorouracil (5-FU) Regimen #2, Khushalani et al. 2002]].
-{| border="1" style="text-align:center;" !align="left"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://www.springerlink.com/content/8051q1q431p22662/ Leary et al. 2008]
-|style="background-color:#eeee00"|Phase II
-|-
-|}
-====Chemotherapy====
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
-*[[Irinotecan (Camptosar)]] 250 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1
-====Supportive medications====
+==FOLFOX 4 & RT -> FOLFOX 4 {{#subobject:1f91c5|Regimen=1}}==
-*[[Atropine (Atropen)]] 0.25 mg SC before [[Irinotecan (Camptosar)]] as prophylaxis against cholinergic symptoms
-*[[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 BID 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. [http://www.springerlink.com/content/8051q1q431p22662/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19104814 PubMed]
-==Carboplatin & Paclitaxel {{#subobject:4df570|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:9725d8|Variant=1}}===
+FOLFOX: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin
+<br>RT: '''<u>R</u>'''adiation '''<u>T</u>'''herapy
+===Regimen {{#subobject:e2fc30|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pubmed/9427274 Philip et al. 1997]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990616 Conroy et al. 2010]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
-|-
+|[[#Cisplatin.2C_Fluorouracil.2C_RT_2|Cisplatin, 5-FU, RT]]
-|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract Gadgeel et al. 2003]
+|style="background-color:#d3d3d3"|Not reported
-|style="background-color:#eeee00"|Phase II
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of carboplatin as AUC 6.''
+''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of leucovorin as 400 mg/m<sup>2</sup>.''
+====Chemoradiotherapy====
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV over 22 hours on days 1 & 2, '''given last'''
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*Concurrent radiation therapy, 2 Gy fractions x 25 fractions given 5 days per week, for a total dose of 50 Gy
+'''14-day cycle for 3 cycles, followed by:'''
 ====Chemotherapy====
-*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1, '''given second'''
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV over 22 hours on days 1 & 2, '''given last'''
-*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
-'''21-day cycles'''
+'''14-day cycle for 3 cycles'''
 ===References===
-# Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9427274 PubMed]
+# Conroy T, Yataghène Y, Etienne PL, Michel P, Senellart H, Raoul JL, Mineur L, Rives M, Mirabel X, Lamezec B, Rio E, Le Prisé E, Peiffert D, Adenis A. Phase II randomised trial of chemoradiotherapy with FOLFOX4 or cisplatin plus fluorouracil in oesophageal cancer. Br J Cancer. 2010 Oct 26;103(9):1349-55. Epub 2010 Oct 12. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990616 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20940718 PubMed]
-# Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12576922 PubMed]
+# 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. Erratum in: Lancet Oncol. 2014 Dec;15(13):e587. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70028-2/abstract link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24556041 PubMed]
-==Cetuximab (Erbitux) {{#subobject:5aca6d|Regimen=1}}==
+==Radiation therapy==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:b11ea0|Variant=1}}===
+===Regimen===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397 Gold et al. 2010 (SWOG S0415)]
+|[http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 Herskovic et al. 1992 (RTOG 85-01)]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#Cisplatin.2C_Fluorouracil.2C_RT_2|Cisplatin, 5-FU, RT]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |}
-====Chemotherapy====
-*[[Cetuximab (Erbitux)]] as follows:
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
-**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-====Supportive medications====
+''Radiation as primary therapy; used as a comparator arm and here for reference purposes only.''
-*[[Diphenhydramine (Benadryl)]] 50 mg PO/IV 30 to 60 minutes prior to cetuximab
-'''28-day cycles, given until progression of disease or unacceptable toxicity'''
+===References===
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJM199206113262403 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1584260 PubMed]
+## '''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. [http://jco.ascopubs.org/content/15/1/277.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/8996153 PubMed]
+## '''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. Chemoradiotherapy of locally advanced esophageal cancer: long-term follow-up of a prospective randomized trial (RTOG 85-01). Radiation Therapy Oncology Group. JAMA. 1999 May 5;281(17):1623-7. [http://jama.jamanetwork.com/article.aspx?articleid=189737 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10235156 PubMed]
-===References===
+=Chemotherapy for metastatic or locally advanced disease (non-radiation/surgery candidate)=
-# Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20631636 PubMed]
-==DC; TC {{#subobject:724868|Regimen=1}}==
+==Capecitabine (Xeloda) {{#subobject:a9eb0b|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-DC: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin
+===Regimen {{#subobject:b6ba4c|Variant=1}}===
-<br>TC: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin
-===Regimen #1 {{#subobject:cd0910|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
+|[http://annonc.oxfordjournals.org/content/15/9/1344.long Hong et al. 2004]
-|rowspan=2 style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#eeee00"|Phase II
-|[[#ECF_2|ECF]]
-|style="background-color:#d3d3d3"|Not reported
-|-
-|[[#DCF.2C_TCF|TCF]]
-|style="background-color:#ff0000"|Might have inferior ORR
 |-
 |}
-''Note: the protocol was amended to change the original dose of 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
+''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of capecitabine as 1000 mg/m<sup>2</sup>.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup> PO BID on days 1 to 14
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
-====Supportive medications====
+'''21-day cycle for up to 6 cycles'''
-*3 liters per day "hyperhydration"
-*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO BID x 4 days after [[Docetaxel (Taxotere)]]
-*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
-*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-'''21-day cycle for up to 8 cycles'''
+===References===
+# Hong YS, Song SY, Lee SI, Chung HC, Choi SH, Noh SH, Park JN, Han JY, Kang JH, Lee KS, Cho JY. A phase II trial of capecitabine in previously untreated patients with advanced and/or metastatic gastric cancer. Ann Oncol. 2004 Sep;15(9):1344-7. [http://annonc.oxfordjournals.org/content/15/9/1344.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15319239 PubMed]
-===Regimen #2 {{#subobject:f1913d|Variant=1}}===
+==Capecitabine & Irinotecan {{#subobject:c699c3|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+XI: '''<u>X</u>'''eloda (Capecitabine) and '''<u>I</u>'''rinotecan
+===Regimen {{#subobject:d233c0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/23/24/5660.long Ajani et al. 2005]
+|[http://www.springerlink.com/content/8051q1q431p22662/ Leary et al. 2008]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#eeee00"|Phase II
-|[[#DCF.2C_TCF|DCF]]
-|style="background-color:#ff0000"|Seems to have inferior ORR
 |-
 |}
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 85 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
+*[[Irinotecan (Camptosar)]] 250 mg/m<sup>2</sup> IV over 30 to 90 minutes once on day 1
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (6 total doses)
+*[[Atropine (Atropen)]] 0.25 mg SC before [[Irinotecan (Camptosar)]] as prophylaxis against cholinergic symptoms
-*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
+*[[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
-*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
+*[[Ciprofloxacin (Cipro)]] 250 mg PO BID prn diarrhea lasting longer than 24 hours despite loperamide
-*"Hydration was administered in a standard manner"
+'''21-day cycle for up to 8 cycles'''
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+===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. [http://www.springerlink.com/content/8051q1q431p22662/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19104814 PubMed]
+# Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie, Germany. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdp269 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19605504 PubMed]
-===Regimen #3 {{#subobject:6adc30|Variant=1}}===
+==Carboplatin & Paclitaxel {{#subobject:4df570|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:9725d8|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.springerlink.com/content/e131402311p276x0/ Kim et al. 2009]
+|[https://www.ncbi.nlm.nih.gov/pubmed/9427274 Philip et al. 1997]
+|style="background-color:#eeee00"|Phase II
+|-
+|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract Gadgeel et al. 2003]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
+''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of carboplatin as AUC 6.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 70 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given 3 hours before cisplatin'''
+*[[Carboplatin (Paraplatin)]] AUC 5 IV once on day 1, '''given second'''
-*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-====Supportive medications====
+'''21-day cycles'''
-*[[Dexamethasone (Decadron)]] 8 mg PO BID x 1 day, starting 1 day before [[Docetaxel (Taxotere)]] administration
-*At least 3 liters hydration (with mannitol, magnesium, and potassium chloride)
-*"Antiemetic treatment"
-'''21-day cycle for up to 6 cycles, progression of disease, or unacceptable toxicity'''
 ===References===
-# Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
+# Philip PA, Zalupski MM, Gadgeel S, Hussain M, Shields A. A phase II study of carboplatin and paclitaxel in the treatment of patients with advanced esophageal and gastric cancer. Semin Oncol. 1997 Dec;24(6 Suppl 19):S19-86-S19-88. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9427274 PubMed]
-# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
+# Gadgeel SM, Shields AF, Heilbrun LK, Labadidi S, Zalupski M, Chaplen R, Philip PA. Phase II study of paclitaxel and carboplatin in patients with advanced gastric cancer. Am J Clin Oncol. 2003 Feb;26(1):37-41. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2003&issue=02000&article=00008&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12576922 PubMed]
-# Kim JY, Do YR, Park KU, Kim MK, Lee KH, Bae SH, Ryoo HM, Baek JH, Song HS. A multi-center phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer. Cancer Chemother Pharmacol. 2010 May;66(1):31-6. Epub 2009 Sep 18. [http://www.springerlink.com/content/e131402311p276x0/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19763571 PubMed]
-==CF; FP {{#subobject:4d9936|Regimen=1}}==
+==Cetuximab (Erbitux) {{#subobject:5aca6d|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:b11ea0|Variant=1}}===
-<br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol
-===Regimen #1 {{#subobject:10f0c6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/24/31/4991.long Van Cutsem et al. 2006 (V325 Study Group)]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397 Gold et al. 2010 (SWOG S0415)]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#DCF.2C_TCF|DCF]]
-|style="background-color:#ff0000"|Seems to have inferior OS
-|-
-|[http://annonc.oxfordjournals.org/content/19/8/1450.long Dank et al. 2008]
-|style="background-color:#00cd00"|Phase III
-|[[#FOLFIRI|IF]]
-|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given before Fluorouracil (5-FU)'''
+*[[Cetuximab (Erbitux)]] as follows:
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, '''started after cisplatin'''
+**Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
+**Cycle 2 onwards: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-Supportive medications, as described in Dank et al. 2008:
+====Supportive medications====
-*"Hyperhydration" for 2 to 3 days with each infusion
+*[[Diphenhydramine (Benadryl)]] 50 mg PO/IV 30 to 60 minutes prior to cetuximab
-*[[Ondansetron (Zofran)]] IV for antiemetic prophylaxis
-*[[Dexamethasone (Decadron)]] IV for antiemetic prophylaxis, then PO for 2 to 3 days
-*[[Metoclopramide (Reglan)]] for antiemetic prophylaxis
-*[[Filgrastim (Neupogen)]] SC once per day, starting on day 4, to be continued until ANC greater than 1 x 10<sup>9</sup>/L for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
-*[[Atropine (Atropen)]] prn cholinergic symptoms
-*[[Loperamide (Imodium)]] prn delayed diarrhea
 '''28-day cycles, given until progression of disease or unacceptable toxicity'''
-===Regimen #2 {{#subobject:fe6c13|Variant=1}}===
+===References===
+# Gold PJ, Goldman B, Iqbal S, Leichman LP, Zhang W, Lenz HJ, Blanke CD. Cetuximab as second-line therapy in patients with metastatic esophageal adenocarcinoma: a phase II Southwest Oncology Group Study (S0415). J Thorac Oncol. 2010 Sep;5(9):1472-6. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2928397 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20631636 PubMed]
+==DC; TC {{#subobject:724868|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+DC: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin
+<br>TC: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin
+===Regimen #1 {{#subobject:cd0910|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,498: / Line 1,526: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/20/10/1667.long Lorenzen et al. 2009]
+|rowspan=2|[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
-|style="background-color:#00cd00"|Randomized Phase II
+|rowspan=2 style="background-color:#00cd00"|Randomized Phase II
-|[[#CF_.26_Cetuximab|CF & Cetuximab]]
+|[[#ECF_2|ECF]]
-|style="background-color:#eeee00"|Seems not superior
+|style="background-color:#d3d3d3"|Not reported
+|-
+|[[#DCF.3B_TCF|TCF]]
+|style="background-color:#ff0000"|Might have inferior ORR
 |-
 |}
+''Note: the protocol was amended to change the original dose of 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given before Fluorouracil (5-FU)'''
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, '''started after cisplatin'''
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
+====Supportive medications====
+*3 liters per day "hyperhydration"
+*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO BID x 4 days after [[Docetaxel (Taxotere)]]
+*[[:Category:Serotonin_5-HT3_antagonists|5-HT3 antagonist]] for emesis prophylaxis
+*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-'''29-day cycle for up to 6 cycles'''
+'''21-day cycle for up to 8 cycles'''
-===Regimen #3 {{#subobject:782e95|Variant=1}}===
+===Regimen #2 {{#subobject:f1913d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,517: / Line 1,555: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/20/4/666.long Kang et al. 2009]
+|[http://jco.ascopubs.org/content/23/24/5660.long Ajani et al. 2005]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#00cd00"|Randomized Phase II
-|[[#CX.2C_XP|CX]]
+|[[#DCF.3B_TCF|DCF]]
-|style="background-color:#eeee00"|Non-inferior PFS
+|style="background-color:#ff0000"|Seems to have inferior ORR
-|-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
-|style="background-color:#00cd00"|Phase III
-|[[#CF_.26_Trastuzumab|CF & Trastuzumab]]
-|style="background-color:#ff0000"|Inferior OS
 |-
 |}
-''Patients in '''ToGA''' had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Docetaxel (Taxotere)]] 85 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
 ====Supportive medications====
-*"Hyperhydration" for [[Cisplatin (Platinol)]]
+*[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (6 total doses)
+*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
+*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
+*"Hydration was administered in a standard manner"
 '''21-day cycles, given until progression of disease or unacceptable toxicity'''
-===Regimen #4 {{#subobject:16f18e|Variant=1}}===
+===Regimen #3 {{#subobject:6adc30|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/21/1/54.long Ohtsu et al. 2003 (JCOG9205)]
+|[http://www.springerlink.com/content/e131402311p276x0/ Kim et al. 2009]
-|rowspan=2 style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#Fluorouracil_.285-FU.29|Fluorouracil]]
-|style="background-color:#00cd00"|Superior PFS
-|-
-|[[#UFTM|UFTM]]
-|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
+*[[Docetaxel (Taxotere)]] 70 mg/m<sup>2</sup> IV over 1 hour once on day 1, '''given 3 hours before cisplatin'''
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
+*[[Cisplatin (Platinol)]] 70 mg/m<sup>2</sup> IV over 1 hour once on day 1
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 8 mg PO BID x 1 day, starting 1 day before [[Docetaxel (Taxotere)]] administration
+*At least 3 liters hydration (with mannitol, magnesium, and potassium chloride)
+*"Antiemetic treatment"
-'''28-day cycle for up to 6 cycles'''
+'''21-day cycle for up to 6 cycles, progression of disease, or unacceptable toxicity'''
 ===References===
-# Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
+# Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
-# Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
+# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
-# Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [http://annonc.oxfordjournals.org/content/19/8/1450.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18558665 PubMed]
+# Kim JY, Do YR, Park KU, Kim MK, Lee KH, Bae SH, Ryoo HM, Baek JH, Song HS. A multi-center phase II study of docetaxel plus cisplatin as first-line therapy in patients with metastatic squamous cell esophageal cancer. Cancer Chemother Pharmacol. 2010 May;66(1):31-6. Epub 2009 Sep 18. [http://www.springerlink.com/content/e131402311p276x0/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19763571 PubMed]
-# Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed]
-# Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. [http://annonc.oxfordjournals.org/content/20/10/1667.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19549707 PubMed]
-# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-==CF-C {{#subobject:717dc4|Regimen=1}}==
+==CF; FP {{#subobject:4d9936|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-CF-C: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, '''<u>C</u>'''etuximab
+CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:54b7fe|Variant=1}}===
+<br>FP: '''<u>F</u>'''luorouracil, '''<u>P</u>'''latinol
+===Regimen #1 {{#subobject:10f0c6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,581: / Line 1,612: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/20/10/1667.long Lorenzen et al. 2009]
+|[http://jco.ascopubs.org/content/24/31/4991.long Van Cutsem et al. 2006 (V325 Study Group)]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#00cd00"|Phase III
-|[[#CF.2C_FP|CF]]
+|[[#DCF.3B_TCF|DCF]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|[http://annonc.oxfordjournals.org/content/19/8/1450.long Dank et al. 2008]
+|style="background-color:#00cd00"|Phase III
+|[[#FOLFIRI|IF]]
 |style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given before fluorouracil'''
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1, '''given before Fluorouracil (5-FU)'''
-*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, '''given after cisplatin'''
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, '''started after cisplatin'''
-*[[Cetuximab (Erbitux)]] as follows:
-**Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
-**Cycles 2 to 6: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
-====Supportive medications====
+Supportive medications, as described in Dank et al. 2008:
-*"Standard antiemetic prophylaxis and pre- and post- [[Cisplatin (Platinol)]] hydration"
+*"Hyperhydration" for 2 to 3 days with each infusion
+*[[Ondansetron (Zofran)]] IV for antiemetic prophylaxis
+*[[Dexamethasone (Decadron)]] IV for antiemetic prophylaxis, then PO for 2 to 3 days
+*[[Metoclopramide (Reglan)]] for antiemetic prophylaxis
+*[[Filgrastim (Neupogen)]] SC once per day, starting on day 4, to be continued until ANC greater than 1 x 10<sup>9</sup>/L for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
+*[[Atropine (Atropen)]] prn cholinergic symptoms
+*[[Loperamide (Imodium)]] prn delayed diarrhea
-'''29-day cycle for up to 6 cycles'''
+'''28-day cycles, given until progression of disease or unacceptable toxicity'''
-===References===
+===Regimen #2 {{#subobject:fe6c13|Variant=1}}===
-# Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. [http://annonc.oxfordjournals.org/content/20/10/1667.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19549707 PubMed]
-==CF & Trastuzumab {{#subobject:ca9cd1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:b2731|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,616: / Line 1,645: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
+|[http://annonc.oxfordjournals.org/content/20/10/1667.long Lorenzen et al. 2009]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#00cd00"|Randomized Phase II
-|[[#CF.2C_FP|CF]]
+|[[#CF_.26_Cetuximab|CF & Cetuximab]]
-|style="background-color:#00cd00"|Superior OS
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given before Fluorouracil (5-FU)'''
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, '''started after cisplatin'''
-*[[Trastuzumab (Herceptin)]] as follows:
-**Cycle 1: 8 mg/kg IV once on day 1
-**Subsequent cycles: 6 mg/kg IV once on day 1
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+'''29-day cycle for up to 6 cycles'''
-===References===
+===Regimen #3 {{#subobject:782e95|Variant=1}}===
-# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-==Cisplatin, Doxorubicin liposomal, Fluorouracil {{#subobject:f31fcc|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:1b58a0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,647: / Line 1,664: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.springerlink.com/content/n8477v3g21081103 Cascinu et al. 2010]
+|[http://annonc.oxfordjournals.org/content/20/4/666.long Kang et al. 2009]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#00cd00"|Phase III
-|[[#MCF|MCF]]
+|[[#CX.2C_XP|CX]]
-|style="background-color:#00cd00"|Seems to have superior OS
+|style="background-color:#eeee00"|Non-inferior PFS
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
+|style="background-color:#00cd00"|Phase III
+|[[#CF_.26_Trastuzumab|CF & Trastuzumab]]
+|style="background-color:#ff0000"|Inferior OS
 |-
 |}
+''Patients in '''ToGA''' had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Doxorubicin liposomal (Doxil)]] 20 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 2
-'''14-day cycles, given until progression of disease or unacceptable toxicity'''
+====Supportive medications====
+*"Hyperhydration" for [[Cisplatin (Platinol)]]
-===References===
+'''21-day cycles, given until progression of disease or unacceptable toxicity'''
-# 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. [http://www.springerlink.com/content/n8477v3g21081103/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20821330 PubMed]
-==Cisplatin & Irinotecan (CI) {{#subobject:ec60da|Regimen=1}}==
+===Regimen #4 {{#subobject:16f18e|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CI: '''<u>C</u>'''isplatin, '''<u>I</u>'''rinotecan
-===Regimen #1 {{#subobject:8f624d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.cancernetwork.com/oncology-journal/phase-ii-trial-weekly-irinotecan-cisplatin-advanced-esophageal-cancer Ilson et al. 2004]
+|rowspan=2|[http://jco.ascopubs.org/content/21/1/54.long Ohtsu et al. 2003 (JCOG9205)]
-|style="background-color:#eeee00"|Phase II
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[#Fluorouracil_.285-FU.29|Fluorouracil]]
+|style="background-color:#00cd00"|Superior PFS
+|-
+|[[#UFTM|UFTM]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011 lists cisplatin 25 mg/m<sup>2</sup> as an alternate dosage.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Cisplatin (Platinol)]] 20 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 to 5
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-'''21-day cycles'''
+'''28-day cycle for up to 6 cycles'''
-===Regimen #2 {{#subobject:219a1|Variant=1}}===
+===References===
+# Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
+# Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
+# Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [http://annonc.oxfordjournals.org/content/19/8/1450.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18558665 PubMed]
+# Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed]
+# Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. [http://annonc.oxfordjournals.org/content/20/10/1667.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19549707 PubMed]
+# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
+==CF-C {{#subobject:717dc4|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+CF-C: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil, '''<u>C</u>'''etuximab
+===Regimen {{#subobject:54b7fe|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/17/10/3270.full Ilson et al. 1999]
+|[http://annonc.oxfordjournals.org/content/20/10/1667.long Lorenzen et al. 2009]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Randomized Phase II
+|[[#CF.3B_FP|CF]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22
+*[[Cisplatin (Platinol)]] 100 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given before fluorouracil'''
-*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22
+*[[Fluorouracil (5-FU)]] 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5, '''given after cisplatin'''
+*[[Cetuximab (Erbitux)]] as follows:
+**Cycle 1: 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1, then 250 mg/m<sup>2</sup> IV over 60 minutes once per day on days 8, 15, 22
+**Cycles 2 to 6: 250 mg/m<sup>2</sup> IV once per day on days 1, 8, 15, 22
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 20 mg IV prior to chemotherapy
+*"Standard antiemetic prophylaxis and pre- and post- [[Cisplatin (Platinol)]] hydration"
-*[[Granisetron (Kytril)]] 2 mg PO prior to chemotherapy
-*At least 500 mL D5NS IV over 30 to 60 minutes before [[Cisplatin (Platinol)]]
-*[[Atropine (Atropen)]] used as pretreatment medication if there was diarrhea or abdominal cramps within 1 hour of [[Irinotecan (Camptosar)]]
-'''6-week cycle for 1 to 3 cycles, or until disease progression or unacceptable toxicity.'''
+'''29-day cycle for up to 6 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. [http://jco.ascopubs.org/content/17/10/3270.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10506629 PubMed]
+# Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. [http://annonc.oxfordjournals.org/content/20/10/1667.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19549707 PubMed]
-# Ilson DH. Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. Oncology (Williston Park). 2004 Dec;18(14 Suppl 14):22-5. [http://www.cancernetwork.com/oncology-journal/phase-ii-trial-weekly-irinotecan-cisplatin-advanced-esophageal-cancer link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15685830 PubMed]
-==CLF; FLP {{#subobject:b913d6|Regimen=1}}==
+==CF & Trastuzumab {{#subobject:ca9cd1|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-CLF: '''<u>C</u>'''isplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
+CF: '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-<br>FLP: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>P</u>'''latinol (Cisplatin)
-===Regimen #1 {{#subobject:beef19|Variant=1}}===
+===Regimen {{#subobject:b2731|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,724: / Line 1,763: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/26/9/1435.long Al-Batran et al. 2008]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
 |style="background-color:#00cd00"|Phase III
-|[[#OLF.2C_FLO|FLO]]
+|[[#CF.3B_FP|CF]]
-|style="background-color:#ff0000"|Might have inferior PFS
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists [[Fluorouracil (5-FU)]] as being given every 2 weeks rather than the schedule below.''
+''Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Subsequent cycles: 6 mg/kg IV once on day 1
-====Supportive medications====
+'''21-day cycles, given until progression of disease or unacceptable toxicity'''
-*Up to 3 liters normal saline as hydration with [[Cisplatin (Platinol)]]
-*Antiemetic medications per "local protocols"
-'''8-week cycles, given until progression of disease or unacceptable toxicity'''
+===References===
+# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-===Regimen #2 {{#subobject:34890|Variant=1}}===
+==Cisplatin, Doxorubicin liposomal, Fluorouracil {{#subobject:f31fcc|Regimen=1}}==
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:1b58a0|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/22/21/4319.long Bouché et al. 2004 (FFCD 9803)]
+|[http://www.springerlink.com/content/n8477v3g21081103 Cascinu et al. 2010]
 |style="background-color:#00cd00"|Randomized Phase II
-|[[#Fluorouracil_.26_Folinic_acid_.28LV5FU2.29|LV5FU2]]<br> [[#FOLFIRI|LV5FU2 & Irinotecan]]
+|[[#MCF|MCF]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
-''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 1 hour once on either day 1 or 2
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Doxorubicin liposomal (Doxil)]] 20 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion over 22 hours on days 1 to 2
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 2
-====Supportive medications====
+'''14-day cycles, given until progression of disease or unacceptable toxicity'''
-*1 liter hydration over 3 hours before and after [[Cisplatin (Platinol)]]
-*5-HT3 antagonist IV before [[Cisplatin (Platinol)]]
-*[[Methylprednisolone (Solumedrol)]] 120 mg IV 10 minutes before [[Cisplatin (Platinol)]]
-*Oral antiemetics and corticosteroids from days 2 to 5
-'''14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity'''
 ===References===
-# Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
+# 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. [http://www.springerlink.com/content/n8477v3g21081103/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20821330 PubMed]
-# Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
-==Cisplatin & Paclitaxel {{#subobject:5d50ee|Regimen=1}}==
+==Cisplatin & Irinotecan (CI) {{#subobject:ec60da|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen #1 {{#subobject:c401a9|Variant=1}}===
+CI: '''<u>C</u>'''isplatin, '''<u>I</u>'''rinotecan
+===Regimen #1 {{#subobject:8f624d|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2008&issue=02000&article=00005&type=abstract Zhang et al. 2008]
+|[http://www.cancernetwork.com/oncology-journal/phase-ii-trial-weekly-irinotecan-cisplatin-advanced-esophageal-cancer Ilson et al. 2004]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
+''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011 lists cisplatin 25 mg/m<sup>2</sup> as an alternate dosage.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV once per day on days 1 & 8
-*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV once per day on days 1 & 8
 '''21-day cycles'''
-===Regimen #2 {{#subobject:ffaa05|Variant=1}}===
+===Regimen #2 {{#subobject:219a1|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pubmed/11079171 Ilson et al. 2000]
+|[http://jco.ascopubs.org/content/17/10/3270.full Ilson et al. 1999]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
-''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the paclitaxel dose as 135 mg/m<sup>2</sup>. No primary reference could be found for the 135 mg/m<sup>2</sup> dosage. The protocol reported here was amended to change the original dose of 250 mg/m<sup>2</sup> to 200 mg/m<sup>2</sup> based on toxicity and treatment-related deaths.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 2, '''given after paclitaxel'''
+*[[Cisplatin (Platinol)]] 30 mg/m<sup>2</sup> IV bolus once per day on days 1, 8, 15, 22
-*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 24 hours once on day 1
+*[[Irinotecan (Camptosar)]] 65 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22
 ====Supportive medications====
-*"Granulocyte colony stimulating factor support"
+*[[Dexamethasone (Decadron)]] 20 mg IV prior to chemotherapy
+*[[Granisetron (Kytril)]] 2 mg PO prior to chemotherapy
+*At least 500 mL D5NS IV over 30 to 60 minutes before [[Cisplatin (Platinol)]]
+*[[Atropine (Atropen)]] used as pretreatment medication if there was diarrhea or abdominal cramps within 1 hour of [[Irinotecan (Camptosar)]]
+'''6-week cycle for 1 to 3 cycles, or until disease progression or unacceptable toxicity.'''
-'''21-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. [http://jco.ascopubs.org/content/17/10/3270.full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/10506629 PubMed]
+# Ilson DH. Phase II trial of weekly irinotecan/cisplatin in advanced esophageal cancer. Oncology (Williston Park). 2004 Dec;18(14 Suppl 14):22-5. [http://www.cancernetwork.com/oncology-journal/phase-ii-trial-weekly-irinotecan-cisplatin-advanced-esophageal-cancer link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15685830 PubMed]
-===Regimen #3 {{#subobject:a5b523|Variant=1}}===
+==CLF; FLP {{#subobject:b913d6|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+CLF: '''<u>C</u>'''isplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
+<br>FLP: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>P</u>'''latinol (Cisplatin)
+===Regimen #1 {{#subobject:beef19|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063082 Petrasch et al. 1998]
+|[http://jco.ascopubs.org/content/26/9/1435.long Al-Batran et al. 2008]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#OLF.3B_FLO|FLO]]
+|style="background-color:#ff0000"|Might have inferior PFS
 |-
 |}
+''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists [[Fluorouracil (5-FU)]] as being given every 2 weeks rather than the schedule below.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
-*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup> IV continuous 24-hour infusion on days 1, 8, 15, 22, 29, 36
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 20 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*Up to 3 liters normal saline as hydration with [[Cisplatin (Platinol)]]
-*[[Cimetidine (Tagamet)]] 300 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*Antiemetic medications per "local protocols"
-*[[Clemastine (Tavist)]] 2 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
-*[[Ondansetron (Zofran)]] 8 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
-*"Adequate pre- and posthydration" for [[Cisplatin (Platinol)]]
-'''14-day cycles'''
+'''8-week cycles, given until progression of disease or unacceptable toxicity'''
-===References===
+===Regimen #2 {{#subobject:34890|Variant=1}}===
-# 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063082 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9716036 PubMed]
-# 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. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11079171 PubMed]
-# Zhang X, Shen L, Li J, Li Y, Li J, Jin M. A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. Am J Clin Oncol. 2008 Feb;31(1):29 to 33. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2008&issue=02000&article=00005&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18376224 PubMed]
-==CX; XP {{#subobject:c58325|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
-<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
-===Regimen, & {{#subobject:130681|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/20/4/666.long Kang et al. 2009]
+|[http://jco.ascopubs.org/content/22/21/4319.long Bouché et al. 2004 (FFCD 9803)]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#00cd00"|Randomized Phase II
-|[[Esophageal_cancer#CF.2C_FP|CF]]
+|[[#Fluorouracil_.26_Folinic_acid_.28LV5FU2.29|LV5FU2]]<br> [[#FOLFIRI|LV5FU2 & Irinotecan]]
-|style="background-color:#eeee00"|Non-inferior PFS
-|-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
-|style="background-color:#00cd00"|Phase III
-|[[#CX_.26_Trastuzumab|CX & Trastuzumab]]
-|style="background-color:#ff0000"|Inferior OS
-|-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract Lordick et al. 2013 (EXPAND)]
-|style="background-color:#00cd00"|Phase III
-|[[#CX_.26_Cetuximab|CX & Cetuximab]]
-|style="background-color:#eeee00"|Seems not superior
 |-
 |}
-''Patients in '''ToGA''' had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
+''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more regular schedule was used.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 1 hour once on either day 1 or 2
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
-**Lordick et al. 2013 gave [[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion over 22 hours on days 1 to 2
 ====Supportive medications====
-*per Kang et al. 2009:
+*1 liter hydration over 3 hours before and after [[Cisplatin (Platinol)]]
-*"Hyperhydration" for [[Cisplatin (Platinol)]]
+*5-HT3 antagonist IV before [[Cisplatin (Platinol)]]
+*[[Methylprednisolone (Solumedrol)]] 120 mg IV 10 minutes before [[Cisplatin (Platinol)]]
+*Oral antiemetics and corticosteroids from days 2 to 5
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+'''14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity'''
 ===References===
-# Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed]
+# Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
-# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
+# Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
-# Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594786 PubMed]
-==CX-C {{#subobject:318959|Regimen=1}}==
+==Cisplatin & Paclitaxel {{#subobject:5d50ee|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-CX-C: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), '''<u>C</u>'''etuximab
+===Regimen #1 {{#subobject:c401a9|Variant=1}}===
-===Regimen {{#subobject:afe6a1|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract Lordick et al. 2013 (EXPAND)]
+|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2008&issue=02000&article=00005&type=abstract Zhang et al. 2008]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[Esophageal_cancer#CX.2C_XP|CX]]
-|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)
+*[[Paclitaxel (Taxol)]] 175 mg/m<sup>2</sup> IV once on day 1
-*[[Cetuximab (Erbitux)]] as follows:
-**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1
-**Subsequently: 250 mg/m<sup>2</sup> IV once per week
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+'''21-day cycles'''
-===References===
+===Regimen #2 {{#subobject:ffaa05|Variant=1}}===
-# Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594786 PubMed]
-==CX & Trastuzumab {{#subobject:7cbb79|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
-===Regimen {{#subobject:27adc6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
+|[https://www.ncbi.nlm.nih.gov/pubmed/11079171 Ilson et al. 2000]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[Esophageal_cancer#CX.2C_XP|CX]]
-|style="background-color:#00cd00"|Superior OS
 |-
 |}
-''Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
+''Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the paclitaxel dose as 135 mg/m<sup>2</sup>. No primary reference could be found for the 135 mg/m<sup>2</sup> dosage. The protocol reported here was amended to change the original dose of 250 mg/m<sup>2</sup> to 200 mg/m<sup>2</sup> based on toxicity and treatment-related deaths.''
 ====Chemotherapy====
-*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV once on day 2, '''given after paclitaxel'''
-*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
+*[[Paclitaxel (Taxol)]] 200 mg/m<sup>2</sup> IV over 24 hours once on day 1
-*[[Trastuzumab (Herceptin)]] as follows:
-**Cycle 1: 8 mg/kg IV once on day 1
-**Subsequent cycles: 6 mg/kg IV once on day 1
-'''21-day cycles, given until progression of disease or unacceptable toxicity'''
+====Supportive medications====
+*"Granulocyte colony stimulating factor support"
-===References===
+'''21-day cycles'''
-# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-==Docetaxel (Taxotere) {{#subobject:421f5e|Regimen=1}}==
+===Regimen #3 {{#subobject:a5b523|Variant=1}}===
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:b279a5|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://link.springer.com/article/10.1007/s12032-007-0028-6 Albertsson et al. 2007]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063082 Petrasch et al. 1998]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
-Note: In addition to the original reference, the NCCN, Esophageal Cancer version 2.2011, also lists docetaxel 75 mg/m<sup>2</sup> as an alternate dosage.
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Cisplatin (Platinol)]] 50 mg/m<sup>2</sup> IV over 60 minutes once on day 1, '''given second'''
+*[[Paclitaxel (Taxol)]] 90 mg/m<sup>2</sup> IV over 3 hours once on day 1, '''given first'''
-'''21-day cycles'''
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Cimetidine (Tagamet)]] 300 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Clemastine (Tavist)]] 2 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*[[Ondansetron (Zofran)]] 8 mg IV 30 minutes prior to [[Paclitaxel (Taxol)]]
+*"Adequate pre- and posthydration" for [[Cisplatin (Platinol)]]
+'''14-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. [http://link.springer.com/article/10.1007/s12032-007-0028-6 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17917090 PubMed]
+# 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. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2063082 link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/9716036 PubMed]
-# Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [http://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
+# 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. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11079171 PubMed]
+# Zhang X, Shen L, Li J, Li Y, Li J, Jin M. A phase II trial of paclitaxel and cisplatin in patients with advanced squamous-cell carcinoma of the esophagus. Am J Clin Oncol. 2008 Feb;31(1):29 to 33. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2008&issue=02000&article=00005&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18376224 PubMed]
-==DCF; TCF {{#subobject:efbdc5|Regimen=1}}==
+==CX; XP {{#subobject:c58325|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
-<br>TCF: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>XP: '''<u>X</u>'''eloda (Capecitabine), '''<u>P</u>'''latinol (Cisplatin)
-===Regimen #1 {{#subobject:5aba07|Variant=1}}===
+===Regimen {{#subobject:130681|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 1,988: / Line 1,999: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/23/24/5660.long Ajani et al. 2005]
+|[http://annonc.oxfordjournals.org/content/20/4/666.long Kang et al. 2009]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#00cd00"|Phase III
-|[[#DC.2C_TC|DC]]
+|[[Esophageal_cancer#CF.3B_FP|CF]]
-|style="background-color:#00cd00"|Seems to have superior ORR
+|style="background-color:#eeee00"|Non-inferior PFS
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
+|style="background-color:#00cd00"|Phase III
+|[[#CX_.26_Trastuzumab|CX & Trastuzumab]]
+|style="background-color:#ff0000"|Inferior OS
 |-
-|[http://jco.ascopubs.org/content/24/31/4991.long Van Cutsem et al. 2006 (V325 Study Group)]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract Lordick et al. 2013 (EXPAND)]
 |style="background-color:#00cd00"|Phase III
-|[[#CF.2C_FP|CF]]
+|[[#CX_.26_Cetuximab|CX & Cetuximab]]
-|style="background-color:#00cd00"|Seems to have superior OS
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
+''Patients in '''ToGA''' had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
-''Note: In contrast to the original references, the NCCN, Esophageal Cancer version 2.2011, lists each cycle as lasting 28 days.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
-*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
+**Lordick et al. 2013 gave [[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)
 ====Supportive medications====
-*(varied depending on reference):
+*per Kang et al. 2009:
-*[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (6 total doses)
+*"Hyperhydration" for [[Cisplatin (Platinol)]]
-*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
-*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
-*"Hydration [was] administered in a standard manner"
 '''21-day cycles, given until progression of disease or unacceptable toxicity'''
-===Regimen #2 {{#subobject:baa015|Variant=1}}===
+===References===
+# Kang YK, Kang WK, Shin DB, Chen J, Xiong J, Wang J, Lichinitser M, Guan Z, Khasanov R, Zheng L, Philco-Salas M, Suarez T, Santamaria J, Forster G, McCloud PI. Capecitabine/cisplatin versus 5-fluorouracil/cisplatin as first-line therapy in patients with advanced gastric cancer: a randomised phase III noninferiority trial. Ann Oncol. 2009 Apr;20(4):666-73. Epub 2009 Jan 19. [http://annonc.oxfordjournals.org/content/20/4/666.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19153121 PubMed]
+# Moehler M, Kanzler S, Geissler M, Raedle J, Ebert MP, Daum S, Flieger D, Seufferlein T, Galle PR, Hoehler T; Arbeitsgemeinschaft Internistische Onkologie, Germany. A randomized multicenter phase II study comparing capecitabine with irinotecan or cisplatin in metastatic adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2010 Jan;21(1):71-7. Epub 2009 Jul 15. [https://academic.oup.com/annonc/article-lookup/doi/10.1093/annonc/mdp269 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/19605504 PubMed]
+# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
+# Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594786 PubMed]
+==CX-C {{#subobject:318959|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+CX-C: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine), '''<u>C</u>'''etuximab
+===Regimen {{#subobject:afe6a1|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 2,022: / Line 2,046: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract Lordick et al. 2013 (EXPAND)]
-|rowspan=2 style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#00cd00"|Phase III
-|[[#ECF_2|ECF]]
+|[[Esophageal_cancer#CX.2C_XP|CX]]
-|style="background-color:#d3d3d3"|Not reported
+|style="background-color:#eeee00"|Seems not superior
-|-
-|[[#DC.2C_TC|TC]]
-|style="background-color:#00cd00"|Might have superior ORR
 |-
 |}
-''Note: the protocol was amended to change the original dose of 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID from the evening of day 1 to the morning of day 15 (28 doses per cycle)
-*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 14
+*[[Cetuximab (Erbitux)]] as follows:
+**Cycle 1: 400 mg/m<sup>2</sup> IV once on day 1
+**Subsequently: 250 mg/m<sup>2</sup> IV once per week
-====Supportive medications====
+'''21-day cycles, given until progression of disease or unacceptable toxicity'''
-*3 liters per day "hyperhydration"
-*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO BID x 4 days after [[Docetaxel (Taxotere)]]
-*5-HT3 antagonist for emesis prophylaxis
-*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-'''21-day cycle for up to 8 cycles'''
 ===References===
-# Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
+# Lordick F, Kang YK, Chung HC, Salman P, Oh SC, Bodoky G, Kurteva G, Volovat C, Moiseyenko VM, Gorbunova V, Park JO, Sawaki A, Celik I, Götte H, Melezínková H, Moehler M; Arbeitsgemeinschaft Internistische Onkologie (AIO) and EXPAND Investigators. Capecitabine and cisplatin with or without cetuximab for patients with previously untreated advanced gastric cancer (EXPAND): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):490-9. Epub 2013 Apr 15. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70102-5/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594786 PubMed]
-# Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
-# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
-==mDCF {{#subobject:70e20f|Regimen=1}}==
+==CX & Trastuzumab {{#subobject:7cbb79|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-mDCF: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+CX: '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
-===Regimen #1 {{#subobject:323b13|Variant=1}}===
+===Regimen {{#subobject:27adc6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://meetinglibrary.asco.org/content/1882-72 Ozal et al. 2010]
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext Bang et al. 2010 (ToGA)]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[Esophageal_cancer#CX.2C_XP|CX]]
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
+''Patients had overexpression of HER2 protein by immunohistochemistry or gene amplification by fluorescence in-situ hybridisation.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 80 mg/m<sup>2</sup> IV once on day 1
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
+*[[Capecitabine (Xeloda)]] 1000 mg/m<sup>2</sup> PO BID on days 1 to 14
-*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4
+*[[Trastuzumab (Herceptin)]] as follows:
+**Cycle 1: 8 mg/kg IV once on day 1
+**Subsequent cycles: 6 mg/kg IV once on day 1
+'''21-day cycles, given until progression of disease or unacceptable toxicity'''
-'''21-day cycles'''
+===References===
+# Bang YJ, Van Cutsem E, Feyereislova A, Chung HC, Shen L, Sawaki A, Lordick F, Ohtsu A, Omuro Y, Satoh T, Aprile G, Kulikov E, Hill J, Lehle M, Rüschoff J, Kang YK; ToGA Trial Investigators. Trastuzumab in combination with chemotherapy versus chemotherapy alone for treatment of HER2-positive advanced gastric or gastro-oesophageal junction cancer (ToGA): a phase 3, open-label, randomised controlled trial. Lancet. 2010 Aug 28;376(9742):687-97. Epub 2010 Aug 19. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2810%2961121-X/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20728210 PubMed]
-===Regimen #2 {{#subobject:372f9c|Variant=1}}===
+==Docetaxel (Taxotere) {{#subobject:421f5e|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen #1 {{#subobject:044193|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/29/7/868.long Shah et al. 2010]
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext Ford et al. 2013 (COUGAR-2)]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#Placebo|Active symptom control]]
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
-''Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 1 hour on days 1, 15, 29
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once per day on days 3, 17, 31
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1, 15, 29, then 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 & 2, 15 & 16, 29 & 30
-====Supportive medications====
+'''21-day cycle for up to 6 cycles'''
-*"Standard premedication and delayed emesis regimens"
-'''42-day cycles, given until progression of disease or unacceptable toxicity'''
+===Regimen #2 {{#subobject:b279a5|Variant=1}}===
-===References===
-# '''Abstract:''' G. Ozal, M. Dogan, H. Akbulut, B. Yalcin, G. Utkan, Y. Urun, F. Icli. The safety and efficacy of modified-dose docetaxel, cisplatin, and 5-fluorouracil (mDCF) combination in the front-line treatment of advanced gastric cancer. 2010 Gastrointestinal Cancers Symposium abstract 113. [http://meetinglibrary.asco.org/content/1882-72 link to abstract]
-# Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
-==mDCF & Bevacizumab {{#subobject:30ea9e|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-mDCF: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:5485f9|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://jco.ascopubs.org/content/29/7/868.long Shah et al. 2010]
+|[http://link.springer.com/article/10.1007/s12032-007-0028-6 Albertsson et al. 2007]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 1 hour on days 1, 15, 29
+*[[Docetaxel (Taxotere)]] 100 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once per day on days 3, 17, 31
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1, 15, 29, then 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 2, 15 to 16, 29 to 30
-*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1, 15, 29
-====Supportive medications====
+'''21-day cycles'''
-*"Standard premedication and delayed emesis regimens"
-'''42-day cycles, given until progression of disease or unacceptable toxicity'''
 ===References===
-# Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
+# 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. [http://link.springer.com/article/10.1007/s12032-007-0028-6 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17917090 PubMed]
+# Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [http://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
+# Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24332238 PubMed]
-==Docetaxel, Carboplatin, Fluorouracil {{#subobject:f4e05b|Regimen=1}}==
+==DCF; TCF {{#subobject:efbdc5|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:e0e534|Variant=1}}===
+DCF: '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+<br>TCF: '''<u>T</u>'''axotere (Docetaxel), '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+===Regimen #1 {{#subobject:5aba07|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.asco.org/ASCOv2/Meetings/Abstracts?vmview=abst_detail_view&confID=53&abstractID=10199 Elkerm et al. 2008]
+|[http://jco.ascopubs.org/content/23/24/5660.long Ajani et al. 2005]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Randomized Phase II
+|[[#DC.3B_TC|DC]]
+|style="background-color:#00cd00"|Seems to have superior ORR
+|-
+|[http://jco.ascopubs.org/content/24/31/4991.long Van Cutsem et al. 2006 (V325 Study Group)]
+|style="background-color:#00cd00"|Phase III
+|[[#CF.3B_FP|CF]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
+''Note: In contrast to the original references, the NCCN, Esophageal Cancer version 2.2011, lists each cycle as lasting 28 days.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 2
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 1 to 3 hours once on day 1
-*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 3
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
 ====Supportive medications====
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 4 to 9
+*(varied depending on reference):
+*[[Dexamethasone (Decadron)]] 8 mg PO the night before chemotherapy, the morning of day 1, 1 hour before chemotherapy, the night of day 1, the morning of day 2, and the evening of day 2 (6 total doses)
+*[[Dexamethasone (Decadron)]] 20 mg IV before [[Cisplatin (Platinol)]] and 8 hours after [[Cisplatin (Platinol)]]
+*[[Ondansetron (Zofran)]] 8 mg IV before [[Cisplatin (Platinol)]], 4 hours after [[Cisplatin (Platinol)]], and 8 hours after [[Cisplatin (Platinol)]]
+*"Hydration [was] administered in a standard manner"
-'''21-day cycles'''
+'''21-day cycles, given until progression of disease or unacceptable toxicity'''
-===References===
+===Regimen #2 {{#subobject:baa015|Variant=1}}===
-# '''Abstract:''' Y. M. Elkerm, A. Elsaid, S. AL-Batran, C. Pauligk. Final results of a phase II trial of docetaxel-carboplatin-FU in locally advanced gastric carcinoma. 2008 Gastrointestinal Cancers Symposium abstract 38. [http://www.asco.org/ASCOv2/Meetings/Abstracts?vmview=abst_detail_view&confID=53&abstractID=10199 link to abstract]
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
-==Docetaxel & Irinotecan {{#subobject:96e013|Regimen=1}}==
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-{| class="wikitable" style="float:right; margin-left: 5px;"
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[[#top|back to top]]
+|rowspan=2|[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
-|}
+|rowspan=2 style="background-color:#00cd00"|Randomized Phase II
-===Regimen {{#subobject:38cdd0|Variant=1}}===
+|[[#ECF_2|ECF]]
-{| border="1" style="text-align:center;" !align="left"
+|style="background-color:#d3d3d3"|Not reported
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://annonc.oxfordjournals.org/content/20/7/1242.long Burtness et al. 2009]
+|[[#DC.3B_TC|TC]]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Might have superior ORR
 |-
 |}
+''Note: the protocol was amended to change the original dose of 85 mg/m<sup>2</sup> to 75 mg/m<sup>2</sup> based on high incidence of febrile neutropenia.''
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 1 hour on days 1 & 8, '''given first'''
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV over 1 hour once on day 1
-*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given second'''
+*[[Cisplatin (Platinol)]] 75 mg/m<sup>2</sup> IV over 4 hours once on day 1
+*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 14
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours before [[Docetaxel (Taxotere)]], then 10 mg IV within 1 hour before chemotherapy
+*3 liters per day "hyperhydration"
+*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours & 6 hours before [[Docetaxel (Taxotere)]], then 8 mg PO BID x 4 days after [[Docetaxel (Taxotere)]]
+*5-HT3 antagonist for emesis prophylaxis
+*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-'''21-day cycles'''
+'''21-day cycle for up to 8 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. [http://annonc.oxfordjournals.org/content/20/7/1242.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19429872 PubMed]
+# Ajani JA, Fodor MB, Tjulandin SA, Moiseyenko VM, Chao Y, Cabral Filho S, Majlis A, Assadourian S, Van Cutsem E. Phase II multi-institutional randomized trial of docetaxel plus cisplatin with or without fluorouracil in patients with untreated, advanced gastric, or gastroesophageal adenocarcinoma. J Clin Oncol. 2005 Aug 20;23(24):5660-7. [http://jco.ascopubs.org/content/23/24/5660.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16110025 PubMed]
+# Van Cutsem E, Moiseyenko VM, Tjulandin S, Majlis A, Constenla M, Boni C, Rodrigues A, Fodor M, Chao Y, Voznyi E, Risse ML, Ajani JA; V325 Study Group. Phase III study of docetaxel and cisplatin plus fluorouracil compared with cisplatin and fluorouracil as first-line therapy for advanced gastric cancer: a report of the V325 Study Group. J Clin Oncol. 2006 Nov 1;24(31):4991-7. [http://jco.ascopubs.org/content/24/31/4991.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17075117 PubMed]
+# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
-==DOF {{#subobject:6e7c57|Regimen=1}}==
+==mDCF {{#subobject:70e20f|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-DOF: '''<u>D</u>'''ocetaxel, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
+mDCF: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:2e0f55|Variant=1}}===
+===Regimen #1 {{#subobject:323b13|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=63&abstractID=10246 Shankaran et al. 2009]
+|[http://meetinglibrary.asco.org/content/1882-72 Ozal et al. 2010]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once on day 1
-*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 46 hours on days 1 to 2 (total dose: 2400 mg/m<sup>2</sup>)
+*[[Fluorouracil (5-FU)]] 750 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 4
-'''14-day cycles'''
+'''21-day cycles'''
-===References===
+===Regimen #2 {{#subobject:372f9c|Variant=1}}===
-# '''Abstract:''' V. Shankaran, M. F. Mulcahy, H. S. Hochster, T. Ryan, H. Choi, A. B. Benson. Docetaxel, oxaliplatin, and 5-fluorouracil for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinomas: Preliminary results of a phase II study. 2009 Gastrointestinal Cancers Symposium abstract 47. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=63&abstractID=10246 link to abstract]
-==ECF {{#subobject:6325cb|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:e5ede0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/5/7/609.long Findlay et al. 1994]
+|[http://jco.ascopubs.org/content/29/7/868.long Shah et al. 2010]
 |style="background-color:#eeee00"|Phase II
-|style="background-color:#d3d3d3"|
-|style="background-color:#d3d3d3"|
 |-
-|[http://jco.ascopubs.org/content/20/8/1996.long Ross et al. 2002]
+|}
-|style="background-color:#00cd00"|Phase III
+''Note: In contrast to the primary reference, the NCCN, Esophageal Cancer version 2.2011 listed this regimen without bevacizumab. Please see below for the original mDCF regimen that included bevacizumab.''
-|[[#MCF|MCF]]
+====Chemotherapy====
-|style="background-color:#eeee00"|Seems to have noninferior OS
+*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 1 hour on days 1, 15, 29
-|-
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once per day on days 3, 17, 31
-|[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
-|style="background-color:#00cd00"|Randomized Phase II
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1, 15, 29, then 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 & 2, 15 & 16, 29 & 30
-|[[#DC.2C_TC|TC]]<br> [[#DCF.2C_TCF|TCF]]
-|style="background-color:#d3d3d3"|Not reported
-|-
-|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
-|rowspan=3 style="background-color:#00cd00"|Phase III
-|[[#ECX_2|ECX]]
-|style="background-color:#eeee00"|Non-inferior OS
-|-
-|[[#EOF_2|EOF]]
-|style="background-color:#eeee00"|Non-inferior OS
-|-
-|[[#EOX.2C_EOC|EOX]]
-|style="background-color:#ff0000"|Seems to have inferior OS
-|-
-|}
-====Chemotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion
 ====Supportive medications====
-*(varied depending on reference):
+*"Standard premedication and delayed emesis regimens"
-*3 liters per day "hyperhydration"
-*5-HT3 antagonist for emesis prophylaxis
-*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
-*Ross et al. 2002 & Cunningham et al. 2008 used [[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-'''21-day cycle for up to 8 cycles'''
+'''42-day cycles, given until progression of disease or unacceptable toxicity'''
 ===References===
-# Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, et al. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. [http://annonc.oxfordjournals.org/content/5/7/609.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7993836 PubMed]
+# '''Abstract:''' G. Ozal, M. Dogan, H. Akbulut, B. Yalcin, G. Utkan, Y. Urun, F. Icli. The safety and efficacy of modified-dose docetaxel, cisplatin, and 5-fluorouracil (mDCF) combination in the front-line treatment of advanced gastric cancer. 2010 Gastrointestinal Cancers Symposium abstract 113. [http://meetinglibrary.asco.org/content/1882-72 link to abstract]
-# 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. [http://jco.ascopubs.org/content/20/8/1996.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11956258 PubMed]
+# Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
-# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
-==ECX {{#subobject:bb95b5|Regimen=1}}==
+==mDCF & Bevacizumab {{#subobject:30ea9e|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
+mDCF: '''<u>m</u>'''odified '''<u>D</u>'''ocetaxel, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
-===Regimen {{#subobject:e965c5|Variant=1}}===
+===Regimen {{#subobject:5485f9|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+|[http://jco.ascopubs.org/content/29/7/868.long Shah et al. 2010]
-|rowspan=2 style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#ECF_2|ECF]]
-|style="background-color:#eeee00"|Non-inferior OS
-|[[#EOF_2|EOF]]<br> [[#EOX.2C_EOC|EOX]]
-|style="background-color:#eeee00"|Non-inferior OS
 |-
 |}
 ====Chemotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Docetaxel (Taxotere)]] 40 mg/m<sup>2</sup> IV over 1 hour on days 1, 15, 29
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
+*[[Cisplatin (Platinol)]] 40 mg/m<sup>2</sup> IV over 1 to 3 hours once per day on days 3, 17, 31
-*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO BID on days 1 to 21
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV once per day on days 1, 15, 29
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus once per day on days 1, 15, 29, then 1000 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 2, 15 to 16, 29 to 30
+*[[Bevacizumab (Avastin)]] 10 mg/kg IV once per day on days 1, 15, 29
 ====Supportive medications====
-*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
+*"Standard premedication and delayed emesis regimens"
-'''21-day cycle for up to 8 cycles'''
+'''42-day cycles, given until progression of disease or unacceptable toxicity'''
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
+# Shah MA, Jhawer M, Ilson DH, Lefkowitz RA, Robinson E, Capanu M, Kelsen DP. Phase II study of modified docetaxel, cisplatin, and fluorouracil with bevacizumab in patients with metastatic gastroesophageal adenocarcinoma. J Clin Oncol. 2011 Mar 1;29(7):868-74. Epub 2010 Dec 28. [http://jco.ascopubs.org/content/29/7/868.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21189380 PubMed]
-==EOF {{#subobject:a6390c|Regimen=1}}==
+==Docetaxel, Carboplatin, Fluorouracil {{#subobject:f4e05b|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:e0e534|Variant=1}}===
-===Regimen {{#subobject:abf19f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+|[http://www.asco.org/ASCOv2/Meetings/Abstracts?vmview=abst_detail_view&confID=53&abstractID=10199 Elkerm et al. 2008]
-|rowspan=2 style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#ECF_2|ECF]]<br> [[#ECX_2|ECX]]
-|style="background-color:#eeee00"|Non-inferior OS
-|-
-|[[#EOX.2C_EOC|EOX]]
-|style="background-color:#eeee00"|Non-inferior OS
 |-
 |}
 ====Chemotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Docetaxel (Taxotere)]] 75 mg/m<sup>2</sup> IV once on day 1
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Carboplatin (Paraplatin)]] AUC 6 IV once on day 2
-*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
+*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 3
 ====Supportive medications====
-*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
+*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day on days 4 to 9
-'''21-day cycle for up to 8 cycles'''
+'''21-day cycles'''
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
+# '''Abstract:''' Y. M. Elkerm, A. Elsaid, S. AL-Batran, C. Pauligk. Final results of a phase II trial of docetaxel-carboplatin-FU in locally advanced gastric carcinoma. 2008 Gastrointestinal Cancers Symposium abstract 38. [http://www.asco.org/ASCOv2/Meetings/Abstracts?vmview=abst_detail_view&confID=53&abstractID=10199 link to abstract]
-==EOX; EOC {{#subobject:438182|Regimen=1}}==
+==Docetaxel & Irinotecan {{#subobject:96e013|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
+===Regimen {{#subobject:38cdd0|Variant=1}}===
-<br>EOC: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>C</u>'''apecitabine
-===Regimen #1 {{#subobject:339609|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ Waddell et al. 2013 (REAL3)]
+|[http://annonc.oxfordjournals.org/content/20/7/1242.long Burtness et al. 2009]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|mEOC+P
-|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
 ====Chemotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
+*[[Docetaxel (Taxotere)]] 35 mg/m<sup>2</sup> IV over 1 hour on days 1 & 8, '''given first'''
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
+*[[Irinotecan (Camptosar)]] 50 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1 & 8, '''given second'''
-*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup>/day PO (it is assumed this daily dose was divided into two doses per day) on days 1 to 21
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 8 mg PO given 12 hours before [[Docetaxel (Taxotere)]], then 10 mg IV within 1 hour before chemotherapy
+'''21-day cycles'''
-'''21-day cycle for up to 8 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. [http://annonc.oxfordjournals.org/content/20/7/1242.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19429872 PubMed]
-===Regimen #2 {{#subobject:3e4f2b|Variant=1}}===
+==DOF {{#subobject:6e7c57|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+DOF: '''<u>D</u>'''ocetaxel, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:2e0f55|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+|[http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=63&abstractID=10246 Shankaran et al. 2009]
-|rowspan=3 style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#ECF_2|ECF]]
-|style="background-color:#00cd00"|Seems to have superior OS
 |-
-|[[#ECX_2|ECX]]
+|}
-|style="background-color:#eeee00"|Non-inferior OS
+====Chemotherapy====
-|-
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV once on day 1
-|[[#EOF_2|EOF]]
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV once on day 1
-|style="background-color:#eeee00"|Non-inferior OS
+*[[Fluorouracil (5-FU)]] 1200 mg/m<sup>2</sup>/day IV continuous infusion over 46 hours on days 1 to 2 (total dose: 2400 mg/m<sup>2</sup>)
-|-
-|}
-====Chemotherapy====
-*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO BID on days 1 to 21
-====Supportive medications====
+'''14-day cycles'''
-*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-'''21-day cycle for up to 8 cycles'''
 ===References===
-# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed] content property of [http://hemonc.org HemOnc.org]
+# '''Abstract:''' V. Shankaran, M. F. Mulcahy, H. S. Hochster, T. Ryan, H. Choi, A. B. Benson. Docetaxel, oxaliplatin, and 5-fluorouracil for the treatment of metastatic or unresectable gastric or gastroesophageal junction (GEJ) adenocarcinomas: Preliminary results of a phase II study. 2009 Gastrointestinal Cancers Symposium abstract 47. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=63&abstractID=10246 link to abstract]
-# Waddell T, Chau I, Cunningham D, Gonzalez D, Frances A, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. Epub 2013 Apr 15. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594787 PubMed]
-==Erlotinib (Tarceva) {{#subobject:5efb4d|Regimen=1}}==
+==ECF {{#subobject:6325cb|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:eaf7de|Variant=1}}===
+ECF: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:e5ede0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/24/30/4922.long Dragovich et al. 2006 (SWOG 0127)]
+|[http://annonc.oxfordjournals.org/content/5/7/609.long Findlay et al. 1994]
 |style="background-color:#eeee00"|Phase II
+|style="background-color:#d3d3d3"|
+|style="background-color:#d3d3d3"|
 |-
-|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.25602/full Ilson et al. 2010]
+|[http://jco.ascopubs.org/content/20/8/1996.long Ross et al. 2002]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|[[#MCF|MCF]]
+|style="background-color:#eeee00"|Seems to have noninferior OS
+|-
+|[http://jco.ascopubs.org/content/25/22/3217.long Roth et al. 2007]
+|style="background-color:#00cd00"|Randomized Phase II
+|[[#DC.3B_TC|TC]]<br> [[#DCF.3B_TCF|TCF]]
+|style="background-color:#d3d3d3"|Not reported
+|-
+|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+|rowspan=3 style="background-color:#00cd00"|Phase III
+|[[#ECX_2|ECX]]
+|style="background-color:#eeee00"|Non-inferior OS
+|-
+|[[#EOF_2|EOF]]
+|style="background-color:#eeee00"|Non-inferior OS
+|-
+|[[#EOX.2C_EOC|EOX]]
+|style="background-color:#ff0000"|Seems to have inferior OS
 |-
 |}
 ====Chemotherapy====
-*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28, at least 1 hour before a meal, or 2 hours after a meal
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion
+====Supportive medications====
+*(varied depending on reference):
+*3 liters per day "hyperhydration"
+*5-HT3 antagonist for emesis prophylaxis
+*Growth factor support allowed, such as with [[Filgrastim (Neupogen)]]
+*Ross et al. 2002 & Cunningham et al. 2008 used [[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-'''28-day cycles'''
+'''21-day cycle for up to 8 cycles'''
 ===References===
-# Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. [http://jco.ascopubs.org/content/24/30/4922.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17050876 PubMed]
+# Findlay M, Cunningham D, Norman A, Mansi J, Nicolson M, Hickish T, Nicolson V, Nash A, Sacks N, Ford H, et al. A phase II study in advanced gastro-esophageal cancer using epirubicin and cisplatin in combination with continuous infusion 5-fluorouracil (ECF). Ann Oncol. 1994 Sep;5(7):609-16. [http://annonc.oxfordjournals.org/content/5/7/609.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7993836 PubMed]
-# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25602/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21425140 PubMed]
+# Ross P, Nicolson M, Cunningham D, Valle J, Seymour M, Harper P, Price T, Anderson H, Iveson T, Hickish T, Lofts F, Norman A. Prospective randomized trial comparing mitomycin, cisplatin, and protracted venous-infusion fluorouracil (PVI 5-FU) With epirubicin, cisplatin, and PVI 5-FU in advanced esophagogastric cancer. J Clin Oncol. 2002 Apr 15;20(8):1996-2004. [http://jco.ascopubs.org/content/20/8/1996.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11956258 PubMed]
+# Roth AD, Fazio N, Stupp R, Falk S, Bernhard J, Saletti P, Köberle D, Borner MM, Rufibach K, Maibach R, Wernli M, Leslie M, Glynne-Jones R, Widmer L, Seymour M, de Braud F; Swiss Group for Clinical Cancer Research. Docetaxel, cisplatin, and fluorouracil; docetaxel and cisplatin; and epirubicin, cisplatin, and fluorouracil as systemic treatment for advanced gastric carcinoma: a randomized phase II trial of the Swiss Group for Clinical Cancer Research. J Clin Oncol. 2007 Aug 1;25(22):3217-23. [http://jco.ascopubs.org/content/25/22/3217.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17664469 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
-==Etoposide (Vepesid) {{#subobject:344c29|Regimen=1}}==
+==ECX {{#subobject:bb95b5|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:bdcf31|Variant=1}}===
+ECX: '''<u>E</u>'''pirubicin, '''<u>C</u>'''isplatin, '''<u>X</u>'''eloda (Capecitabine)
-''Note: The references cited by the NCCN, Esophageal Cancer version 2.2011, did not contain this regimen. Etoposide 120 mg/m<sup>2</sup> was used as part of ELF (Etoposide (Vepesid), Folinic acid (Leucovorin), Fluorouracil (5-FU)) regimens in [http://jco.ascopubs.org/content/18/14/2648.long Vanhoefer U et al. 2000] ([https://www.ncbi.nlm.nih.gov/pubmed/10894863 PubMed]) and [http://annonc.oxfordjournals.org/content/5/1/90.long Taal BG et al. 1994] ([https://www.ncbi.nlm.nih.gov/pubmed/8172800 PubMed]). No primary reference could be found for this monotherapy regimen.''
+===Regimen {{#subobject:e965c5|Variant=1}}===
-====Chemotherapy====
-*[[Etoposide (Vepesid)]] 90 to 120 mg/m<sup>2</sup> IV once per day on days 1 to 3
-'''28-day cycles'''
-==Fluorouracil (5-FU) {{#subobject:588907|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-===Regimen {{#subobject:3289d8|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 2,444: / Line 2,443: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|rowspan=2|[http://jco.ascopubs.org/content/21/1/54.long Ohtsu et al. 2003 (JCOG9205)]
+|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
 |rowspan=2 style="background-color:#00cd00"|Phase III
-|[[#CF.2C_FP|FP]]
+|[[#ECF_2|ECF]]
-|style="background-color:#ff0000"|Inferior PFS
+|style="background-color:#eeee00"|Non-inferior OS
 |-
-|[[#UFTM|UFTM]]
+|[[#EOF_2|EOF]]<br> [[#EOX.2C_EOC|EOX]]
-|style="background-color:#eeee00"|Seems not superior
+|style="background-color:#eeee00"|Non-inferior OS
 |-
 |}
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV over 4 hours once on day 1
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO BID on days 1 to 21
+====Supportive medications====
+*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-'''28-day cycles'''
+'''21-day cycle for up to 8 cycles'''
 ===References===
-# Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
+# Iveson T, Donehower RC, Davidenko I, Tjulandin S, Deptala A, Harrison M, Nirni S, Lakshmaiah K, Thomas A, Jiang Y, Zhu M, Tang R, Anderson A, Dubey S, Oliner KS, Loh E. Rilotumumab in combination with epirubicin, cisplatin, and capecitabine as first-line treatment for gastric or oesophagogastric junction adenocarcinoma: an open-label, dose de-escalation phase 1b study and a double-blind, randomised phase 2 study. Lancet Oncol. 2014 Aug;15(9):1007-18. Epub 2014 Jun 22. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(14)70023-3/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/24965569 PubMed]
+# Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. [http://ascopubs.org/doi/abs/10.1200/JCO.2013.54.1011 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25287828 PubMed]
-==Fluorouracil & Folinic acid (LV5FU2) {{#subobject:5aad1e|Regimen=1}}==
+==EOF {{#subobject:a6390c|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:2d601|Variant=1}}===
+EOF: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:abf19f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=2|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[#ECF_2|ECF]]<br> [[#ECX_2|ECX]]
+|style="background-color:#eeee00"|Non-inferior OS
 |-
-|[http://jco.ascopubs.org/content/22/21/4319.long Bouché et al. 2004 (FFCD 9803)]
+|[[#EOX.2C_EOC|EOX]]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#eeee00"|Non-inferior OS
-|[[#CLF.2C_FLP|LV5FU2 & Cisplatin]]<br> [[#FOLFIRI|LV5FU2 & Irinotecan]]
 |-
 |}
-''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.''
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion over 22 hours on days 1 to 2
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 200 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 21
+====Supportive medications====
+*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-'''14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity'''
+'''21-day cycle for up to 8 cycles'''
 ===References===
-# Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed]
-==Fluorouracil, Folinic acid, Mitomycin {{#subobject:a4ca9d|Regimen=1}}==
+==EOX; EOC {{#subobject:438182|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:672a28|Variant=1}}===
+EOX: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>X</u>'''eloda (Capecitabine)
+<br>EOC: '''<u>E</u>'''pirubicin, '''<u>O</u>'''xaliplatin, '''<u>C</u>'''apecitabine
+===Regimen #1 {{#subobject:339609|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.karger.com/Article/Abstract/64319 Hofheinz et al. 2002]
+|[https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ Waddell et al. 2013 (REAL3)]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Phase III
+|mEOC+P
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36; '''given after folinic acid'''
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36; '''given before fluorouracil'''
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV once on day 1
-*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 22
+*[[Capecitabine (Xeloda)]] 1250 mg/m<sup>2</sup>/day PO (it is assumed this daily dose was divided into two doses per day) on days 1 to 21
-'''56-day cycle for 2 cycles'''
+'''21-day cycle for up to 8 cycles'''
-===References===
+===Regimen #2 {{#subobject:3e4f2b|Variant=1}}===
-# Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer. A phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12119460 PubMed]
-==FLOT {{#subobject:b427b1|Regimen=1}}==
-{| class="wikitable" style="float:right; margin-left: 5px;"
-|-
-|[[#top|back to top]]
-|}
-FLOT: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin, '''<u>T</u>'''axotere (Docetaxel)
-===Regimen {{#subobject:bb5eb6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|rowspan=3|[http://www.nejm.org/doi/full/10.1056/NEJMoa073149 Cunningham et al. 2008 (REAL-2)]
+|rowspan=3 style="background-color:#00cd00"|Phase III
+|[[#ECF_2|ECF]]
+|style="background-color:#00cd00"|Seems to have superior OS
 |-
-|[http://annonc.oxfordjournals.org/content/19/11/1882.long Al-Batran et al. 2008]
+|[[#ECX_2|ECX]]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#eeee00"|Non-inferior OS
 |-
-|}
+|[[#EOF_2|EOF]]
-====Chemotherapy====
+|style="background-color:#eeee00"|Non-inferior OS
-*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous 24-hour infusion on day 1, '''given last'''
+|-
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
+|}
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
+====Chemotherapy====
-*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
+*[[Epirubicin (Ellence)]] 50 mg/m<sup>2</sup> IV bolus once on day 1
+*[[Oxaliplatin (Eloxatin)]] 130 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Capecitabine (Xeloda)]] 625 mg/m<sup>2</sup> PO BID on days 1 to 21
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 8 mg PO once per day on days 0 to 3 of every cycle
+*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
-'''14-day cycle for up to 8 (or more) cycles'''
+'''21-day cycle for up to 8 cycles'''
 ===References===
-# Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. [http://annonc.oxfordjournals.org/content/19/11/1882.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18669868 PubMed]
+# 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. [http://www.nejm.org/doi/full/10.1056/NEJMoa073149 link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18172173 PubMed] content property of [http://hemonc.org HemOnc.org]
+# Waddell T, Chau I, Cunningham D, Gonzalez D, Frances A, Okines C, Wotherspoon A, Saffery C, Middleton G, Wadsley J, Ferry D, Mansoor W, Crosby T, Coxon F, Smith D, Waters J, Iveson T, Falk S, Slater S, Peckitt C, Barbachano Y. Epirubicin, oxaliplatin, and capecitabine with or without panitumumab for patients with previously untreated advanced oesophagogastric cancer (REAL3): a randomised, open-label phase 3 trial. Lancet Oncol. 2013 May;14(6):481-9. Epub 2013 Apr 15. [https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3669518/ link to PMC article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/23594787 PubMed]
-==FOLFIRI {{#subobject:ba35aa|Regimen=1}}==
+==Erlotinib (Tarceva) {{#subobject:5efb4d|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
+===Regimen {{#subobject:eaf7de|Variant=1}}===
-<br>IF: '''<u>I</u>'''rinotecan & 5-'''<u>F</u>'''luorouracil
-===Regimen #1, "IF" {{#subobject:cec083|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/19/8/1450.long Dank et al. 2008]
+|[http://jco.ascopubs.org/content/24/30/4922.long Dragovich et al. 2006 (SWOG 0127)]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#CF.2C_FP|CF]]
+|-
-|style="background-color:#eeee00"|Seems not superior
+|[http://onlinelibrary.wiley.com/doi/10.1002/cncr.25602/full Ilson et al. 2010]
+|style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup>/day IV continuous 22-hour infusion on days 1, 8, 15, 22, 29, 36; '''given last'''
+*[[Erlotinib (Tarceva)]] 150 mg PO once per day on days 1 to 28, at least 1 hour before a meal, or 2 hours after a meal
-*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36; '''given second'''
-*[[Irinotecan (Camptosar)]] 80 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36; '''given first'''
-====Supportive medications====
+'''28-day cycles'''
-*[[Ondansetron (Zofran)]] for antiemetic prophylaxis
-*[[Dexamethasone (Decadron)]] for antiemetic prophylaxis
-*[[Filgrastim (Neupogen)]] SC once per day, starting on day 4, to be continued until ANC greater than 1 x 10<sup>9</sup>/L for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
-*[[Atropine (Atropen)]] prn cholinergic symptoms
-*[[Loperamide (Imodium)]] prn delayed diarrhea
-'''7-week cycles'''
+===References===
+# Dragovich T, McCoy S, Fenoglio-Preiser CM, Wang J, Benedetti JK, Baker AF, Hackett CB, Urba SG, Zaner KS, Blanke CD, Abbruzzese JL. Phase II trial of erlotinib in gastroesophageal junction and gastric adenocarcinomas: SWOG 0127. J Clin Oncol. 2006 Oct 20;24(30):4922-7. [http://jco.ascopubs.org/content/24/30/4922.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17050876 PubMed]
+# 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. [http://onlinelibrary.wiley.com/doi/10.1002/cncr.25602/full link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21425140 PubMed]
-===Regimen #2, LV5FU2 & Irinotecan {{#subobject:56018a|Variant=1}}===
+==Etoposide (Vepesid) {{#subobject:344c29|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:bdcf31|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
 |-
-|[http://jco.ascopubs.org/content/22/21/4319.long Bouché et al. 2004 (FFCD 9803)]
+|[https://link.springer.com/article/10.1007%2FBF00685952 Harstrick et al. 1992]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#eeee00"|Phase II
-|[[#Fluorouracil_.26_Folinic_acid_.28LV5FU2.29|LV5FU2]]<br> [[#CLF.2C_FLP|LV5FU2 & Cisplatin]]
 |-
 |}
+''Note: this is higher than the dose usually employed in modern settings.''
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Etoposide (Vepesid)]] 200 mg/m<sup>2</sup> (route not specified) once per day on days 1 to 3
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion over 22 hours on days 1 to 2
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+'''21-day cycles'''
-'''14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity''' (primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used)
+===References===
+# Harstrick A, Bokemeyer C, Preusser P, Köhne-Wömpner CH, Meyer HJ, Stahl M, Knipp H, Schmoll HJ, Wilke H. Phase II study of single-agent etoposide in patients with metastatic squamous-cell carcinoma of the esophagus. Cancer Chemother Pharmacol. 1992;29(4):321-2. [https://link.springer.com/article/10.1007%2FBF00685952 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/1537080 PubMed]
-===Regimen #3 {{#subobject:6526d0|Variant=1}}===
+==Fluorouracil (5-FU) {{#subobject:588907|Regimen=1}}==
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable" style="float:right; margin-left: 5px;"
-|'''Study'''
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:3289d8|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.em-consulte.com/article/280010/alertePM Samalin et al. 2010]
+|rowspan=2|[http://jco.ascopubs.org/content/21/1/54.long Ohtsu et al. 2003 (JCOG9205)]
-|style="background-color:#ff0000"|Retrospective
+|rowspan=2 style="background-color:#00cd00"|Phase III
+|[[#CF.3B_FP|FP]]
+|style="background-color:#ff0000"|Inferior PFS
+|-
+|[[#UFTM|UFTM]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
+*[[Fluorouracil (5-FU)]] 800 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 5
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 46 hours on days 1 to 2 (total dose per cycle: 2400 mg/m<sup>2</sup>)
-*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
-'''14-day cycles'''
+'''28-day cycles'''
 ===References===
-# Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
+# Ohtsu A, Shimada Y, Shirao K, Boku N, Hyodo I, Saito H, Yamamichi N, Miyata Y, Ikeda N, Yamamoto S, Fukuda H, Yoshida S; Japan Clinical Oncology Group Study (JCOG9205). Randomized phase III trial of fluorouracil alone versus fluorouracil plus cisplatin versus uracil and tegafur plus mitomycin in patients with unresectable, advanced gastric cancer: The Japan Clinical Oncology Group Study (JCOG9205). J Clin Oncol. 2003 Jan 1;21(1):54-9. [http://jco.ascopubs.org/content/21/1/54.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12506170 PubMed]
-# Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [http://annonc.oxfordjournals.org/content/19/8/1450.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18558665 PubMed]
-# Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. [http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2009&issue=03000&article=00002&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19125117 PubMed]
-# '''Retrospective:''' Samalin E, Afchain P, Thézenas S, Abbas F, Romano O, Guimbaud R, Bécouarn Y, Desseigne F, Edeline J, Mitry E, Bouché O, Adenis A, Aparicio T, Dorval E, Kramar A, Ychou M. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Gastroenterol Clin Biol. 2011 Jan;35(1):48-54. Epub 2010 Oct 28. [http://www.em-consulte.com/article/280010/alertePM link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21634054 PubMed]
-# '''Retrospective:''' Samalin E, Afchain P, Thézenas S, Abbas F, Romano O, Guimbaud R, Bécouarn Y, Desseigne F, Edeline J, Mitry E, Bouché O, Adenis A, Aparicio T, Dorval E, Kramar A, Ychou M. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Clin Res Hepatol Gastroenterol. 2011 Jan;35(1):48-54. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21634054 PubMed]
-==FOLFOX-C {{#subobject:e51095|Regimen=1}}==
+==Fluorouracil & Folinic acid (LV5FU2) {{#subobject:5aad1e|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-FOLFOX-C: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>C</u>'''etuximab
+===Regimen {{#subobject:2d601|Variant=1}}===
-===Regimen {{#subobject:2a9d10|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 2,627: / Line 2,651: @@
 |'''Comparator'''
 |-
-|[http://jco.ascopubs.org/content/34/23/2736.long Enziger et al. 2016 (CALGB 80403/ECOG E1206)]
+|[http://jco.ascopubs.org/content/22/21/4319.long Bouché et al. 2004 (FFCD 9803)]
 |style="background-color:#00cd00"|Randomized Phase II
-|ECF-C<br> IC-C
+|[[#CLF.3B_FLP|LV5FU2 & Cisplatin]]<br> [[#FOLFIRI|LV5FU2 & Irinotecan]]
 |-
 |}
+''Note: the primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used.''
 ====Chemotherapy====
-*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given after oxaliplatin and folinic acid''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion over 22 hours on days 1 to 2
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
-*[[Cetuximab (Erbitux)]] 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1 of the first cycle and then 250 mg/m<sup>2</sup> IV over 60 minutes once per week
-'''14-day cycles'''
+'''14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity'''
 ===References===
-<!--
+# Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
-# P. C. Enzinger, B. Burtness, D. Hollis, D. Niedzwiecki, D. Ilson, A. B. Benson, R. J. Mayer, R. M. Goldberg. CALGB 80403/ECOG 1206: A randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. 2010 ASCO Annual Meeting abstract 4006. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=44487 link to abstract] -->
-# 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. [http://jco.ascopubs.org/content/34/23/2736.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27382098 PubMed]
-==Gemcitabine, Fluorouracil, Folinic acid {{#subobject:876cd7|Regimen=1}}==
+==Fluorouracil, Folinic acid, Mitomycin {{#subobject:a4ca9d|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen {{#subobject:173a91|Variant=1}}===
+===Regimen {{#subobject:672a28|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.karger.com/Article/Abstract/87815 Morgan-Meadows et al. 2005]
+|[http://www.karger.com/Article/Abstract/64319 Hofheinz et al. 2002]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemotherapy====
-*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous infusion over 24 hours once per day on days 1, 8, 15, 22, 29, 36; '''given after folinic acid'''
-*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36; '''given before fluorouracil'''
-*[[Folinic acid (Leucovorin)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Mitomycin (Mutamycin)]] 10 mg/m<sup>2</sup> IV once per day on days 1 & 22
-'''28-day cycles'''
+'''56-day cycle for 2 cycles'''
 ===References===
-<!-- # Michelle Pipp, Daniel Mulkerin, Deb Warren, Wesley Hotchkis, Jordan Berlin, James P Thomas. A Phase II Trial of Gemcitabine and 5-Fluoruracil in Advanced Esophageal Cancer. 2001 ASCO Annual Meeting abstract 630. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10&abstractID=630 link to abstract] -->
+# Hofheinz RD, Hartung G, Samel S, Hochhaus A, Pichlmeier U, Post S, Hehlmann R, Queisser W. High-dose 5-fluorouracil / folinic acid in combination with three-weekly mitomycin C in the treatment of advanced gastric cancer. A phase II study. Onkologie. 2002 Jun;25(3):255-60. [http://www.karger.com/Article/Abstract/64319 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12119460 PubMed]
-# 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. [http://www.karger.com/Article/Abstract/87815 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16118509 PubMed]
-==Irinotecan (Camptosar) {{#subobject:6df2c0|Regimen=1}}==
+==FLOT {{#subobject:b427b1|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen #1, q3wk dosing {{#subobject:160f2f|Variant=1}}===
+FLOT: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin, '''<u>T</u>'''axotere (Docetaxel)
+===Regimen {{#subobject:bb5eb6|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract Thuss-Patience et al. 2011]
+|[http://annonc.oxfordjournals.org/content/19/11/1882.long Al-Batran et al. 2008]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#eeee00"|Phase II
-|[[#Best_supportive_care|Best supportive care]]
-|style="background-color:#00cd00"|Seems to have superior OS
 |-
 |}
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] as follows:
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous 24-hour infusion on day 1, '''given last'''
-**Cycle 1: 250 mg/m<sup>2</sup> (capped at BSA = 2 m<sup>2</sup>) IV over 30 minutes once on day 1
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
-**Cycles 2 to 10 (depending on toxicity): 350 mg/m<sup>2</sup> IV over 30 minutes once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
+*[[Docetaxel (Taxotere)]] 50 mg/m<sup>2</sup> IV over 1 to 2 hours once on day 1
 ====Supportive medications====
-*[[Atropine (Atropen)]] 0.25 mg SC before irinotecan as prophylaxis against cholinergic symptoms
+*[[Dexamethasone (Decadron)]] 8 mg PO once per day on days 0 to 3 of every cycle
-*"5-HT3 antagonists and dexamethasone"
+'''14-day cycle for up to 8 (or more) cycles'''
-'''21-day cycle for up to 10 cycles'''
+===References===
+# Al-Batran SE, Hartmann JT, Hofheinz R, Homann N, Rethwisch V, Probst S, Stoehlmacher J, Clemens MR, Mahlberg R, Fritz M, Seipelt G, Sievert M, Pauligk C, Atmaca A, Jäger E. Biweekly fluorouracil, leucovorin, oxaliplatin, and docetaxel (FLOT) for patients with metastatic adenocarcinoma of the stomach or esophagogastric junction: a phase II trial of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2008 Nov;19(11):1882-7. Epub 2008 Jul 31. [http://annonc.oxfordjournals.org/content/19/11/1882.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18669868 PubMed]
-===Regimen #2, alternate q3wk dosing {{#subobject:c410d|Variant=1}}===
+==FOLFIRI {{#subobject:ba35aa|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+FOLFIRI: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>IRI</u>'''notecan
+<br>IF: '''<u>I</u>'''rinotecan & 5-'''<u>F</u>'''luorouracil
+===Regimen #1, "IF" {{#subobject:cec083|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://annonc.oxfordjournals.org/content/24/6/1567.long Roy et al. 2013]
+|[http://annonc.oxfordjournals.org/content/19/8/1450.long Dank et al. 2008]
-|style="background-color:#00cd00"|Randomized Phase II
+|style="background-color:#00cd00"|Phase III
-|[[#Docetaxel_.28Taxotere.29|Docetaxel]]<br> Irinotecan liposome
+|[[#CF.3B_FP|CF]]
+|style="background-color:#eeee00"|Seems not superior
 |-
 |}
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
+*[[Fluorouracil (5-FU)]] 2000 mg/m<sup>2</sup>/day IV continuous 22-hour infusion on days 1, 8, 15, 22, 29, 36; '''given last'''
+*[[Folinic acid (Leucovorin)]] 500 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 8, 15, 22, 29, 36; '''given second'''
+*[[Irinotecan (Camptosar)]] 80 mg/m<sup>2</sup> IV over 30 minutes once per day on days 1, 8, 15, 22, 29, 36; '''given first'''
+====Supportive medications====
+*[[Ondansetron (Zofran)]] for antiemetic prophylaxis
+*[[Dexamethasone (Decadron)]] for antiemetic prophylaxis
+*[[Filgrastim (Neupogen)]] SC once per day, starting on day 4, to be continued until ANC greater than 1 x 10<sup>9</sup>/L for grade 3 to 4 neutropenia, febrile neutropenia, or neutropenic infection
+*[[Atropine (Atropen)]] prn cholinergic symptoms
+*[[Loperamide (Imodium)]] prn delayed diarrhea
-'''21-day cycles'''
+'''7-week cycles'''
-===Regimen #3, q2wk dosing {{#subobject:fa1ef9|Variant=1}}===
+===Regimen #2, LV5FU2 & Irinotecan {{#subobject:56018a|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |'''Comparator'''
-|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/30/13/1513.full Kang et al. 2012]
+|[http://jco.ascopubs.org/content/22/21/4319.long Bouché et al. 2004 (FFCD 9803)]
-|style="background-color:#00cd00"|Phase III
+|style="background-color:#00cd00"|Randomized Phase II
-|[[#Best_supportive_care|Best supportive care]]
+|[[#Fluorouracil_.26_Folinic_acid_.28LV5FU2.29|LV5FU2]]<br> [[#CLF.3B_FLP|LV5FU2 & Cisplatin]]
-|style="background-color:#00cd00"|Superior OS
 |-
 |}
-''Note: This regimen was listed by the NCCN, Esophageal Cancer version 2.2011 as 180 mg/m<sup>2</sup> dosing, but no primary reference could be found for esophageal cancer at this dose level. This regimen is a gastric cancer regimen.''
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 600 mg/m<sup>2</sup>/day IV continuous infusion over 22 hours on days 1 to 2
+*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1
-'''14-day cycles'''
+'''14-day cycle for at least 4 cycles or until progression of disease or unacceptable toxicity''' (primary reference said every cycle was 15 days, but also said that medications were given every 14 days, so the assumption was made that this more typical schedule was used)
-===Regimen #4, 4 weeks on, 2 weeks off dosing {{#subobject:9fb427|Variant=1}}===
+===Regimen #3 {{#subobject:6526d0|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://link.springer.de/link/service/journals/00384/contents/02/00464/ Mühr-Wilkenshoff et al. 2003]
+|[http://www.em-consulte.com/article/280010/alertePM Samalin et al. 2010]
-|style="background-color:#ff0000"|Phase II, <20 patients
+|style="background-color:#ff0000"|Retrospective
-|-
-|[http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 Enzinger et al. 2005]
-|style="background-color:#eeee00"|Phase II
 |-
 |}
-''Note: In contrast to the primary references, the NCCN, Esophageal Cancer version 2.2011, lists a dosing schedule of 125 mg/m<sup>2</sup> IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."''
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 60 minutes (Mühr-Wilkenshoff et al. 2003) or 90 minutes (Enzinger et al. 2005) once per day on days 1, 8, 15, 22
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1, '''given second'''
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 1200 mg/m<sup>2</sup>/day IV continuous infusion over 46 hours on days 1 to 2 (total dose per cycle: 2400 mg/m<sup>2</sup>)
+*[[Irinotecan (Camptosar)]] 180 mg/m<sup>2</sup> IV over 90 minutes once on day 1, '''given first'''
-'''6-week cycles'''
+'''14-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. [http://link.springer.de/link/service/journals/00384/contents/02/00464/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12774248 PubMed]
+# Bouché O, Raoul JL, Bonnetain F, Giovannini M, Etienne PL, Lledo G, Arsène D, Paitel JF, Guérin-Meyer V, Mitry E, Buecher B, Kaminsky MC, Seitz JF, Rougier P, Bedenne L, Milan C; Fédération Francophone de Cancérologie Digestive Group. Randomized multicenter phase II trial of a biweekly regimen of fluorouracil and leucovorin (LV5FU2), LV5FU2 plus cisplatin, or LV5FU2 plus irinotecan in patients with previously untreated metastatic gastric cancer: a Federation Francophone de Cancerologie Digestive Group Study--FFCD 9803. J Clin Oncol. 2004 Nov 1;22(21):4319-28. [http://jco.ascopubs.org/content/22/21/4319.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/15514373 PubMed]
-# Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16416165 PubMed]
+# Dank M, Zaluski J, Barone C, Valvere V, Yalcin S, Peschel C, Wenczl M, Goker E, Cisar L, Wang K, Bugat R. Randomized phase III study comparing irinotecan combined with 5-fluorouracil and folinic acid to cisplatin combined with 5-fluorouracil in chemotherapy naive patients with advanced adenocarcinoma of the stomach or esophagogastric junction. Ann Oncol. 2008 Aug;19(8):1450-7. Epub 2008 Jun 16. [http://annonc.oxfordjournals.org/content/19/8/1450.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18558665 PubMed]
-# Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
+# Wolff K, Wein A, Reulbach U, Männlein G, Brückl V, Meier C, Ostermeier N, Schwab SA, Horbach T, Hohenberger W, Hahn EG, Boxberger F. Weekly high-dose 5-fluorouracil as a 24-h infusion and sodium folinic acid (AIO regimen) plus irinotecan in patients with locally advanced nonresectable and metastatic adenocarcinoma or squamous cell carcinoma of the oesophagus: a phase II trial. Anticancer Drugs. 2009 Mar;20(3):165-73. [http://journals.lww.com/anti-cancerdrugs/pages/articleviewer.aspx?year=2009&issue=03000&article=00002&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/19125117 PubMed]
-# Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
+# '''Retrospective:''' Samalin E, Afchain P, Thézenas S, Abbas F, Romano O, Guimbaud R, Bécouarn Y, Desseigne F, Edeline J, Mitry E, Bouché O, Adenis A, Aparicio T, Dorval E, Kramar A, Ychou M. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Gastroenterol Clin Biol. 2011 Jan;35(1):48-54. Epub 2010 Oct 28. [http://www.em-consulte.com/article/280010/alertePM link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21634054 PubMed]
-# Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [http://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
+# '''Retrospective:''' Samalin E, Afchain P, Thézenas S, Abbas F, Romano O, Guimbaud R, Bécouarn Y, Desseigne F, Edeline J, Mitry E, Bouché O, Adenis A, Aparicio T, Dorval E, Kramar A, Ychou M. Efficacy of irinotecan in combination with 5-fluorouracil (FOLFIRI) for metastatic gastric or gastroesophageal junction adenocarcinomas (MGA) treatment. Clin Res Hepatol Gastroenterol. 2011 Jan;35(1):48-54. '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21634054 PubMed]
+# Guimbaud R, Louvet C, Ries P, Ychou M, Maillard E, André T, Gornet JM, Aparicio T, Nguyen S, Azzedine A, Etienne PL, Boucher E, Rebischung C, Hammel P, Rougier P, Bedenne L, Bouché O. Prospective, randomized, multicenter, phase III study of fluorouracil, leucovorin, and irinotecan versus epirubicin, cisplatin, and capecitabine in advanced gastric adenocarcinoma: a French intergroup (Fédération Francophone de Cancérologie Digestive, Fédération Nationale des Centres de Lutte Contre le Cancer, and Groupe Coopérateur Multidisciplinaire en Oncologie) study. J Clin Oncol. 2014 Nov 1;32(31):3520-6. Epub 2014 Oct 6. Erratum in: J Clin Oncol. 2015 Apr 20;33(12):1416. [http://ascopubs.org/doi/abs/10.1200/JCO.2013.54.1011 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25287828 PubMed]
-==Irinotecan & Mitomycin {{#subobject:dfc95f|Regimen=1}}==
+==FOLFOX-C {{#subobject:e51095|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen #1 {{#subobject:87100a|Variant=1}}===
+FOLFOX-C: '''<u>FOL</u>'''inic acid, '''<u>F</u>'''luorouracil, '''<u>OX</u>'''aliplatin, '''<u>C</u>'''etuximab
+===Regimen {{#subobject:2a9d10|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 2,770: / Line 2,807: @@
 |'''Comparator'''
 |-
-|[http://journals.lww.com/jto/Fulltext/2010/05000/Phase_II_Randomized_Study_of_Two_Regimens_of.20.aspx Lustberg et al. 2010]
+|[http://jco.ascopubs.org/content/34/23/2736.long Enziger et al. 2016 (CALGB 80403/ECOG E1206)]
 |style="background-color:#00cd00"|Randomized Phase II
-|Irinotecan & Mitomycin
+|ECF-C<br> IC-C
 |-
 |}
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 2 & 9
+*[[Fluorouracil (5-FU)]] 400 mg/m<sup>2</sup> IV bolus, then 2400 mg/m<sup>2</sup> IV continuous infusion over 46 to 48 hours, '''given after oxaliplatin and folinic acid''' (total dose per cycle: 2800 mg/m<sup>2</sup>)
-*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1
+*[[Folinic acid (Leucovorin)]] 400 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once on day 1
+*[[Cetuximab (Erbitux)]] 400 mg/m<sup>2</sup> IV over 120 minutes once on day 1 of the first cycle and then 250 mg/m<sup>2</sup> IV over 60 minutes once per week
-====Supportive medications====
+'''14-day cycles'''
-*[[Ondansetron (Zofran)]] or [[Granisetron (Kytril)]] and [[Dexamethasone (Decadron)]] premedication
-*[[Loperamide (Imodium)]] started with first episode of diarrhea
-*Erythropoietin for hemoglobin less than 10 g/dL permitted
-'''28-day cycle for up to 6 cycles'''
+===References===
+<!--
+# P. C. Enzinger, B. Burtness, D. Hollis, D. Niedzwiecki, D. Ilson, A. B. Benson, R. J. Mayer, R. M. Goldberg. CALGB 80403/ECOG 1206: A randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. 2010 ASCO Annual Meeting abstract 4006. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=74&abstractID=44487 link to abstract] -->
+# 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. [http://jco.ascopubs.org/content/34/23/2736.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/27382098 PubMed]
-===Regimen #2 {{#subobject:4a905|Variant=1}}===
+==Gemcitabine, Fluorouracil, Folinic acid {{#subobject:876cd7|Regimen=1}}==
-{| border="1" style="text-align:center;" !align="left"
+{| class="wikitable" style="float:right; margin-left: 5px;"
-|'''Study'''
-|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-|-
-|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2005&issue=12000&article=00009&type=abstract Giuliani et al. 2005]
-|style="background-color:#eeee00"|Phase II
 |-
+|[[#top|back to top]]
 |}
-====Chemotherapy====
+===Regimen {{#subobject:173a91|Variant=1}}===
-*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 15
-*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once on day 1
-'''28-day cycles'''
-===Regimen #3 {{#subobject:3213a7|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://www.jchemother.it/cgi-bin/digisuite.exe/product?ID=252&IDCategory=30 Bamias et al. 2003]
+|[http://www.karger.com/Article/Abstract/87815 Morgan-Meadows et al. 2005]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
 ====Chemotherapy====
-*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once on day 1
+*[[Gemcitabine (Gemzar)]] 1000 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-*[[Mitomycin (Mutamycin)]] 5 mg/m<sup>2</sup> IV once on day 1
+*[[Fluorouracil (5-FU)]] 600 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+*[[Folinic acid (Leucovorin)]] 25 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
-'''14-day cycles, given until progression of disease or unacceptable toxicity'''
+'''28-day cycles'''
 ===References===
-# Bamias A, Papamichael D, Syrigos K, Pavlidis N. Phase II study of irinotecan and mitomycin C in 5-fluorouracil-pretreated patients with advanced colorectal and gastric cancer. J Chemother. 2003 Jun;15(3):275-81. [http://www.jchemother.it/cgi-bin/digisuite.exe/product?ID=252&IDCategory=30 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12868555 PubMed]
+<!-- # Michelle Pipp, Daniel Mulkerin, Deb Warren, Wesley Hotchkis, Jordan Berlin, James P Thomas. A Phase II Trial of Gemcitabine and 5-Fluoruracil in Advanced Esophageal Cancer. 2001 ASCO Annual Meeting abstract 630. [http://www.asco.org/ascov2/Meetings/Abstracts?&vmview=abst_detail_view&confID=10&abstractID=630 link to abstract] -->
-# Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2005&issue=12000&article=00009&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16317268 PubMed]
+# 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. [http://www.karger.com/Article/Abstract/87815 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16118509 PubMed]
-# Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. [http://journals.lww.com/jto/Fulltext/2010/05000/Phase_II_Randomized_Study_of_Two_Regimens_of.20.aspx link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20354452 PubMed]
-==MCF {{#subobject:d3775b|Regimen=1}}==
+==Irinotecan (Camptosar) {{#subobject:6df2c0|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-MCF: '''<u>M</u>'''itomycin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+===Regimen #1, q3wk dosing {{#subobject:160f2f|Variant=1}}===
-===Regimen {{#subobject:47b99f|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 2,834: / Line 2,862: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/20/8/1996.long Ross et al. 2002]
+|[http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract Thuss-Patience et al. 2011]
 |style="background-color:#00cd00"|Phase III
-|[[#ECF_2|ECF]]
+|[[#Placebo|Best supportive care]]
-|style="background-color:#eeee00"|Seems to have noninferior OS
+|style="background-color:#00cd00"|Seems to have superior OS
-|-
-|[http://www.springerlink.com/content/n8477v3g21081103 Cascinu et al. 2010]
-|style="background-color:#00cd00"|Randomized Phase II
-|[[#Cisplatin.2C_Doxorubicin_liposomal.2C_Fluorouracil|Cisplatin, Doxorubicin liposomal, Fluorouracil]]
-|style="background-color:#00cd00"|Seems to have inferior OS
 |-
 |}
 ====Chemotherapy====
-*[[Mitomycin (Mutamycin)]] 7 mg/m<sup>2</sup> (maximum dose of 14 mg per cycle) IV once on day 1
+*[[Irinotecan (Camptosar)]] as follows:
-*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 22
+**Cycle 1: 250 mg/m<sup>2</sup> (capped at BSA = 2 m<sup>2</sup>) IV over 30 minutes once on day 1
-*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 42
+**Cycles 2 to 10 (depending on toxicity): 350 mg/m<sup>2</sup> IV over 30 minutes once on day 1
 ====Supportive medications====
-*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
+*[[Atropine (Atropen)]] 0.25 mg SC before irinotecan as prophylaxis against cholinergic symptoms
+*"5-HT3 antagonists and dexamethasone"
-'''42-day cycle for up to 6 months'''
+'''21-day cycle for up to 10 cycles'''
-===References===
+===Regimen #2, alternate q3wk dosing {{#subobject:c410d|Variant=1}}===
-# 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. [http://jco.ascopubs.org/content/20/8/1996.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11956258 PubMed]
+{| border="1" style="text-align:center;" !align="left"
-# 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. [http://www.springerlink.com/content/n8477v3g21081103/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20821330 PubMed]
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
-==OLF; FLO {{#subobject:98b4fa|Regimen=1}}==
+|'''Comparator'''
-{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[http://annonc.oxfordjournals.org/content/24/6/1567.long Roy et al. 2013]
+|style="background-color:#00cd00"|Randomized Phase II
+|[[#Docetaxel_.28Taxotere.29|Docetaxel]]<br> Irinotecan liposome
 |-
-|[[#top|back to top]]
 |}
-OLF: '''<u>O</u>'''xaliplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
+====Chemotherapy====
-<br>FLO: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin
+*[[Irinotecan (Camptosar)]] 300 mg/m<sup>2</sup> IV over 90 minutes once on day 1
-===Regimen {{#subobject:3d7273|Variant=1}}===
+'''21-day cycles'''
+===Regimen #3, q2wk dosing {{#subobject:fa1ef9|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
@@ Line 2,873: / Line 2,902: @@
 |[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
 |-
-|[http://jco.ascopubs.org/content/26/9/1435.long Al-Batran et al. 2008]
+|[http://jco.ascopubs.org/content/30/13/1513.full Kang et al. 2012]
 |style="background-color:#00cd00"|Phase III
-|[[#CLF.2C_FLP|FLP]]
+|[[#Best_supportive_care|Best supportive care]]
-|style="background-color:#00cd00"|Might have superior PFS
+|style="background-color:#00cd00"|Superior OS
 |-
 |}
+''Note: This regimen was listed by the NCCN, Esophageal Cancer version 2.2011 as 180 mg/m<sup>2</sup> dosing, but no primary reference could be found for esophageal cancer at this dose level. This regimen is a gastric cancer regimen.''
 ====Chemotherapy====
-*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once on day 1
-*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
-*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous 24-hour infusion on days 1, 15, 29, 43
-====Supportive medications====
+'''14-day cycles'''
-*Antiemetic medications per "local protocols"
-'''8-week cycles, given until progression of disease or unacceptable toxicity'''
+===Regimen #4, 4 weeks on, 2 weeks off dosing {{#subobject:9fb427|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://link.springer.de/link/service/journals/00384/contents/02/00464/ Mühr-Wilkenshoff et al. 2003]
+|style="background-color:#ff0000"|Phase II, <20 patients
+|-
+|[http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 Enzinger et al. 2005]
+|style="background-color:#eeee00"|Phase II
+|-
+|}
+''Note: In contrast to the primary references, the NCCN, Esophageal Cancer version 2.2011, lists a dosing schedule of 125 mg/m<sup>2</sup> IV once per day on days 1 & 8, with 21-day cycles. Enzinger et al. 2005 comment that "when irinotecan is used as a single-agent, a tri-weekly schedule may be preferable."''
+====Chemotherapy====
+*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV over 60 minutes (Mühr-Wilkenshoff et al. 2003) or 90 minutes (Enzinger et al. 2005) once per day on days 1, 8, 15, 22
+'''6-week cycles'''
 ===References===
-# Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
+# 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. [http://link.springer.de/link/service/journals/00384/contents/02/00464/ link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/12774248 PubMed]
+# Enzinger PC, Kulke MH, Clark JW, Ryan DP, Kim H, Earle CC, Vincitore MM, Michelini AL, Mayer RJ, Fuchs CS. A phase II trial of irinotecan in patients with previously untreated advanced esophageal and gastric adenocarcinoma. Dig Dis Sci. 2005 Dec;50(12):2218-23. [http://link.springer.com/article/10.1007%2Fs10620-005-3038-2 link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/16416165 PubMed]
+# Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
+# Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
+# Roy AC, Park SR, Cunningham D, Kang YK, Chao Y, Chen LT, Rees C, Lim HY, Tabernero J, Ramos FJ, Kujundzic M, Cardic MB, Yeh CG, de Gramont A. A randomized phase II study of PEP02 (MM-398), irinotecan or docetaxel as a second-line therapy in patients with locally advanced or metastatic gastric or gastro-oesophageal junction adenocarcinoma. Ann Oncol. 2013 Jun;24(6):1567-73. Epub 2013 Feb 13. [http://annonc.oxfordjournals.org/content/24/6/1567.long link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/23406728 PubMed]
-==Paclitaxel (Taxol) {{#subobject:ed008a|Regimen=1}}==
+==Irinotecan & Mitomycin {{#subobject:dfc95f|Regimen=1}}==
 {| class="wikitable" style="float:right; margin-left: 5px;"
 |-
 |[[#top|back to top]]
 |}
-===Regimen #1 {{#subobject:dd30a4|Variant=1}}===
+===Regimen #1 {{#subobject:87100a|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
 |-
-|[http://annonc.oxfordjournals.org/content/18/5/898.long Ilson et al. 2007]
+|[http://journals.lww.com/jto/Fulltext/2010/05000/Phase_II_Randomized_Study_of_Two_Regimens_of.20.aspx Lustberg et al. 2010]
-|style="background-color:#eeee00"|Phase II
+|style="background-color:#00cd00"|Randomized Phase II
+|Irinotecan & Mitomycin
 |-
 |}
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 1 hour on days 1, 8, 15, 22
+*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once per day on days 2 & 9
+*[[Mitomycin (Mutamycin)]] 6 mg/m<sup>2</sup> IV once on day 1
 ====Supportive medications====
-*[[Dexamethasone (Decadron)]] 20 mg IV 30 to 60 minutes before paclitaxel
+*[[Ondansetron (Zofran)]] or [[Granisetron (Kytril)]] and [[Dexamethasone (Decadron)]] premedication
-*[[Cimetidine (Tagamet)]] 300 mg IV 30 to 60 minutes prior to paclitaxel
+*[[Loperamide (Imodium)]] started with first episode of diarrhea
-*[[Diphenhydramine (Benadryl)]] 50 mg IV 30 to 60 minutes prior to paclitaxel
+*Erythropoietin for hemoglobin less than 10 g/dL permitted
-'''28-day cycles'''
+'''28-day cycle for up to 6 cycles'''
-===Regimen #2 {{#subobject:1d24a4|Variant=1}}===
+===Regimen #2 {{#subobject:4a905|Variant=1}}===
 {| border="1" style="text-align:center;" !align="left"
 |'''Study'''
 |[[Levels_of_Evidence#Evidence|'''Evidence''']]
 |-
-|[http://jnci.oxfordjournals.org/content/86/14/1086.long Ajani et al. 1994]
+|[http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2005&issue=12000&article=00009&type=abstract Giuliani et al. 2005]
 |style="background-color:#eeee00"|Phase II
 |-
 |}
-Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of paclitaxel as 135 to 175 mg/m<sup>2</sup>.
 ====Chemotherapy====
-*[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV over 24 hours on day 1; dosage adjusted based on toxicity down to 150 or 200 mg/m<sup>2</sup>, or up to 280 mg/m<sup>2</sup>
+*[[Irinotecan (Camptosar)]] 150 mg/m<sup>2</sup> IV once per day on days 1 & 15
+*[[Mitomycin (Mutamycin)]] 8 mg/m<sup>2</sup> IV once on day 1
-====Supportive medications====
+'''28-day cycles'''
-*[[Dexamethasone (Decadron)]] 20 mg PO 14 hours and 7 hours before paclitaxel
-*[[Cimetidine (Tagamet)]] 300 mg IV 60 minutes prior to paclitaxel
+===Regimen #3 {{#subobject:3213a7|Variant=1}}===
-*[[Diphenhydramine (Benadryl)]] 50 mg IV 60 minutes prior to paclitaxel
+{| border="1" style="text-align:center;" !align="left"
-*[[Filgrastim (Neupogen)]] 5 mcg/kg SC once per day, starting 24 hours after the paclitaxel infusion finishes
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://www.jchemother.it/cgi-bin/digisuite.exe/product?ID=252&IDCategory=30 Bamias et al. 2003]
+|style="background-color:#eeee00"|Phase II
+|-
+|}
+====Chemotherapy====
+*[[Irinotecan (Camptosar)]] 125 mg/m<sup>2</sup> IV once on day 1
+*[[Mitomycin (Mutamycin)]] 5 mg/m<sup>2</sup> IV once on day 1
-'''21-day cycles'''
+'''14-day cycles, given until progression of disease or unacceptable toxicity'''
 ===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. [http://jnci.oxfordjournals.org/content/86/14/1086.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7912736 PubMed]
+# Bamias A, Papamichael D, Syrigos K, Pavlidis N. Phase II study of irinotecan and mitomycin C in 5-fluorouracil-pretreated patients with advanced colorectal and gastric cancer. J Chemother. 2003 Jun;15(3):275-81. [http://www.jchemother.it/cgi-bin/digisuite.exe/product?ID=252&IDCategory=30 link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/12868555 PubMed]
+# Giuliani F, Molica S, Maiello E, Battaglia C, Gebbia V, Di Bisceglie M, Vinciarelli G, Gebbia N, Colucci G; Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Irinotecan (CPT-11) and mitomycin-C (MMC) as second-line therapy in advanced gastric cancer: a phase II study of the Gruppo Oncologico dell' Italia Meridionale (prot. 2106). Am J Clin Oncol. 2005 Dec;28(6):581-5. [http://journals.lww.com/amjclinicaloncology/pages/articleviewer.aspx?year=2005&issue=12000&article=00009&type=abstract link to original article] '''contains protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/16317268 PubMed]
+# Lustberg MB, Bekaii-Saab T, Young D, Otterson G, Burak W, Abbas A, McCracken-Bussa B, Lustberg ME, Villalona-Calero MA. Phase II randomized study of two regimens of sequentially administered mitomycin C and irinotecan in patients with unresectable esophageal and gastroesophageal adenocarcinoma. J Thorac Oncol. 2010 May;5(5):713-8. [http://journals.lww.com/jto/Fulltext/2010/05000/Phase_II_Randomized_Study_of_Two_Regimens_of.20.aspx link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20354452 PubMed]
+==MCF {{#subobject:d3775b|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+MCF: '''<u>M</u>'''itomycin, '''<u>C</u>'''isplatin, '''<u>F</u>'''luorouracil
+===Regimen {{#subobject:47b99f|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://jco.ascopubs.org/content/20/8/1996.long Ross et al. 2002]
+|style="background-color:#00cd00"|Phase III
+|[[#ECF_2|ECF]]
+|style="background-color:#eeee00"|Seems to have noninferior OS
+|-
+|[http://www.springerlink.com/content/n8477v3g21081103 Cascinu et al. 2010]
+|style="background-color:#00cd00"|Randomized Phase II
+|[[#Cisplatin.2C_Doxorubicin_liposomal.2C_Fluorouracil|Cisplatin, Doxorubicin liposomal, Fluorouracil]]
+|style="background-color:#00cd00"|Seems to have inferior OS
+|-
+|}
+====Chemotherapy====
+*[[Mitomycin (Mutamycin)]] 7 mg/m<sup>2</sup> (maximum dose of 14 mg per cycle) IV once on day 1
+*[[Cisplatin (Platinol)]] 60 mg/m<sup>2</sup> IV once per day on days 1 & 22
+*[[Fluorouracil (5-FU)]] 300 mg/m<sup>2</sup>/day IV continuous infusion on days 1 to 42
+====Supportive medications====
+*[[Warfarin (Coumadin)]] 1 mg PO once per day for catheter thrombosis prophylaxis
+'''42-day cycle for up to 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. [http://jco.ascopubs.org/content/20/8/1996.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/11956258 PubMed]
+# 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. [http://www.springerlink.com/content/n8477v3g21081103/ link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/20821330 PubMed]
+==OLF; FLO {{#subobject:98b4fa|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+OLF: '''<u>O</u>'''xaliplatin, '''<u>L</u>'''eucovorin, '''<u>F</u>'''luorouracil
+<br>FLO: '''<u>F</u>'''luorouracil, '''<u>L</u>'''eucovorin, '''<u>O</u>'''xaliplatin
+===Regimen {{#subobject:3d7273|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://jco.ascopubs.org/content/26/9/1435.long Al-Batran et al. 2008]
+|style="background-color:#00cd00"|Phase III
+|[[#CLF.3B_FLP|FLP]]
+|style="background-color:#00cd00"|Might have superior PFS
+|-
+|}
+====Chemotherapy====
+*[[Oxaliplatin (Eloxatin)]] 85 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Folinic acid (Leucovorin)]] 200 mg/m<sup>2</sup> IV over 2 hours once per day on days 1, 15, 29, 43
+*[[Fluorouracil (5-FU)]] 2600 mg/m<sup>2</sup> IV continuous 24-hour infusion on days 1, 15, 29, 43
+====Supportive medications====
+*Antiemetic medications per "local protocols"
+'''8-week cycles, given until progression of disease or unacceptable toxicity'''
+===References===
+# Al-Batran SE, Hartmann JT, Probst S, Schmalenberg H, Hollerbach S, Hofheinz R, Rethwisch V, Seipelt G, Homann N, Wilhelm G, Schuch G, Stoehlmacher J, Derigs HG, Hegewisch-Becker S, Grossmann J, Pauligk C, Atmaca A, Bokemeyer C, Knuth A, Jäger E; Arbeitsgemeinschaft Internistische Onkologie. Phase III trial in metastatic gastroesophageal adenocarcinoma with fluorouracil, leucovorin plus either oxaliplatin or cisplatin: a study of the Arbeitsgemeinschaft Internistische Onkologie. J Clin Oncol. 2008 Mar 20;26(9):1435-42. [http://jco.ascopubs.org/content/26/9/1435.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/18349393 PubMed]
+==Paclitaxel (Taxol) {{#subobject:ed008a|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen #1 {{#subobject:dd30a4|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://annonc.oxfordjournals.org/content/18/5/898.long Ilson et al. 2007]
+|style="background-color:#eeee00"|Phase II
+|-
+|}
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV over 1 hour on days 1, 8, 15, 22
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg IV 30 to 60 minutes before paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV 30 to 60 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV 30 to 60 minutes prior to paclitaxel
+'''28-day cycles'''
+===Regimen #2 {{#subobject:1d24a4|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|-
+|[http://jnci.oxfordjournals.org/content/86/14/1086.long Ajani et al. 1994]
+|style="background-color:#eeee00"|Phase II
+|-
+|}
+Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of paclitaxel as 135 to 175 mg/m<sup>2</sup>.
+====Chemotherapy====
+*[[Paclitaxel (Taxol)]] 250 mg/m<sup>2</sup> IV over 24 hours on day 1; dosage adjusted based on toxicity down to 150 or 200 mg/m<sup>2</sup>, or up to 280 mg/m<sup>2</sup>
+====Supportive medications====
+*[[Dexamethasone (Decadron)]] 20 mg PO 14 hours and 7 hours before paclitaxel
+*[[Cimetidine (Tagamet)]] 300 mg IV 60 minutes prior to paclitaxel
+*[[Diphenhydramine (Benadryl)]] 50 mg IV 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'''
+===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. [http://jnci.oxfordjournals.org/content/86/14/1086.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/7912736 PubMed]
 # 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. [http://annonc.oxfordjournals.org/content/18/5/898.long link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/17351256 PubMed]
+# Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/25240821 PubMed]
+==Placebo==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|'''Comparator'''
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|-
+|[http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract Thuss-Patience et al. 2011]
+|style="background-color:#00cd00"|Phase III
+|[[#Irinotecan_.28Camptosar.29|Irinotecan]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext Fuchs et al. 2013 (REGARD)]
+|style="background-color:#00CD00"|Phase III
+|[[#Ramucirumab_.28Cyramza.29|Ramucirumab]]
+|style="background-color:#ff0000"|Seems to have inferior OS
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext Ford et al. 2013 (COUGAR-2)]
+|style="background-color:#00CD00"|Phase III
+|[[#Docetaxel_.28Taxotere.29|Docetaxel]]
+|style="background-color:#ff0000"|Inferior OS
+|-
+|}
+''Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."''
+''No active antineoplastic treatment. Used as a comparator arm and here for reference purposes only.''
+===References===
+# Thuss-Patience PC, Kretzschmar A, Bichev D, Deist T, Hinke A, Breithaupt K, Dogan Y, Gebauer B, Schumacher G, Reichardt P. Survival advantage for irinotecan versus best supportive care as second-line chemotherapy in gastric cancer--a randomised phase III study of the Arbeitsgemeinschaft Internistische Onkologie (AIO). Eur J Cancer. 2011 Oct;47(15):2306-14. [http://www.ejcancer.com/article/S0959-8049(11)00396-0/abstract link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/21742485 PubMed]
+# Kang JH, Lee SI, Lim do H, Park KW, Oh SY, Kwon HC, Hwang IG, Lee SC, Nam E, Shin DB, Lee J, Park JO, Park YS, Lim HY, Kang WK, Park SH. Salvage chemotherapy for pretreated gastric cancer: a randomized phase III trial comparing chemotherapy plus best supportive care with best supportive care alone. J Clin Oncol. 2012 May 1;30(13):1513-8. Epub 2012 Mar 12. Erratum in: J Clin Oncol. 2012 Aug 20;30(24):3035. [http://jco.ascopubs.org/content/30/13/1513.full link to original article] [https://www.ncbi.nlm.nih.gov/pubmed/22412140 PubMed]
+# Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24094768 PubMed]
+# Ford HE, Marshall A, Bridgewater JA, Janowitz T, Coxon FY, Wadsley J, Mansoor W, Fyfe D, Madhusudan S, Middleton GW, Swinson D, Falk S, Chau I, Cunningham D, Kareclas P, Cook N, Blazeby JM, Dunn JA; COUGAR-02 Investigators. Docetaxel versus active symptom control for refractory oesophagogastric adenocarcinoma (COUGAR-02): an open-label, phase 3 randomised controlled trial. Lancet Oncol. 2014 Jan;15(1):78-86. Epub 2013 Dec 10. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045(13)70549-7/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24332238 PubMed]
+==Ramucirumab (Cyramza) {{#subobject:425b15|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:813cff|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|Pt Population
+|-
+|[http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext Fuchs et al. 2013 (REGARD)]
+|style="background-color:#00CD00"|Phase III
+|3%
+|[[#Placebo|Placebo]]
+|3%
+|style="background-color:#00CD00"|Seems to have superior OS
+|Chemo exposed
+|-
+|}
+''Patients in REGARD previously had "disease progression within 4 months of the last dose of first-line platinum-containing or fluoropyrimidine-containing chemotherapy for metastatic disease, or within 6 months of the last dose of platinum-containing or fluoropyrimidine-containing adjuvant treatment."''
+====Chemotherapy====
+*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once every 2 weeks
+'''Given until progression of disease, unacceptable toxicity, or death'''
+===References===
+# Fuchs CS, Tomasek J, Yong CJ, Dumitru F, Passalacqua R, Goswami C, Safran H, dos Santos LV, Aprile G, Ferry DR, Melichar B, Tehfe M, Topuzov E, Zalcberg JR, Chau I, Campbell W, Sivanandan C, Pikiel J, Koshiji M, Hsu Y, Liepa AM, Gao L, Schwartz JD, Tabernero J; REGARD Trial Investigators. Ramucirumab monotherapy for previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (REGARD): an international, randomised, multicentre, placebo-controlled, phase 3 trial. Lancet. 2014 Jan 4;383(9911):31-9. Epub 2013 Oct 3. [http://www.thelancet.com/journals/lancet/article/PIIS0140-6736%2813%2961719-5/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/24094768 PubMed]
+==Ramucirumab & Paclitaxel {{#subobject:fdd93f|Regimen=1}}==
+{| class="wikitable" style="float:right; margin-left: 5px;"
+|-
+|[[#top|back to top]]
+|}
+===Regimen {{#subobject:f66446|Variant=1}}===
+{| border="1" style="text-align:center;" !align="left"
+|'''Study'''
+|[[Levels_of_Evidence#Evidence|'''Evidence''']]
+|[[Overall response rate|'''ORR''']]
+|'''Comparator'''
+|Comparator [[Overall response rate|'''ORR''']]
+|[[Levels_of_Evidence#Efficacy|'''Efficacy''']]
+|Pt Population
+|-
+|[http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext Wilke et al. 2014 (RAINBOW)]
+|style="background-color:#00CD00"|Phase III
+|28% (95% CI 23-33%)
+|[[#Paclitaxel_.28Taxol.29|Paclitaxel]]
+|16% (95% CI 13-20%)
+|style="background-color:#00CD00"|Seems to have superior OS
+|Chemo exposed
+|-
+|}
+''Eligibility criteria for patients in RAINBOW included: "documented objective radiological or clinical disease progression during or within 4 months of the last dose of first-line platinum and fluoropyrimidine doublet with or without anthracycline."''
+====Chemotherapy====
+*[[Ramucirumab (Cyramza)]] 8 mg/kg IV once per day on days 1 & 15
+*[[Paclitaxel (Taxol)]] 80 mg/m<sup>2</sup> IV once per day on days 1, 8, 15
+'''28-day cycles, given until progression of disease or unacceptable toxicity'''
+===References===
+# Wilke H, Muro K, Van Cutsem E, Oh SC, Bodoky G, Shimada Y, Hironaka S, Sugimoto N, Lipatov O, Kim TY, Cunningham D, Rougier P, Komatsu Y, Ajani J, Emig M, Carlesi R, Ferry D, Chandrawansa K, Schwartz JD, Ohtsu A; RAINBOW Study Group. Ramucirumab plus paclitaxel versus placebo plus paclitaxel in patients with previously treated advanced gastric or gastro-oesophageal junction adenocarcinoma (RAINBOW): a double-blind, randomised phase 3 trial. Lancet Oncol. 2014 Oct;15(11):1224-35. [http://www.thelancet.com/journals/lanonc/article/PIIS1470-2045%2814%2970420-6/fulltext link to original article] '''contains verified protocol''' [https://www.ncbi.nlm.nih.gov/pubmed/25240821 PubMed]
 ==UFTM {{#subobject:96e8bf|Regimen=1}}==
@@ Line 2,960: / Line 3,246: @@
 |style="background-color:#eeee00"|Seems not superior
 |-
-|[[#CF.2C_FP|FP]]
+|[[#CF.3B_FP|FP]]
 |style="background-color:#eeee00"|Seems not superior
 |-

Difference between revisions of "Esophageal cancer"

Revision as of 20:20, 7 July 2017

Guidelines

CAP/ASCP/ASCO

ESMO

NCCN

Neoadjuvant therapy

Capecitabine, Carboplatin, Paclitaxel, RT

Regimen

Chemoradiotherapy

References

Capecitabine, Cisplatin, RT

Regimen

Chemoradiotherapy

References

Capecitabine, Docetaxel, RT

Regimen

Chemoradiotherapy

References

Capecitabine, Docetaxel, Oxaliplatin, RT

Regimen

Chemoradiotherapy

Supportive medications

References

Capecitabine, Oxaliplatin, RT

Regimen

Chemoradiotherapy

References

Capecitabine, Paclitaxel, RT

Regimen

Chemoradiotherapy

Carboplatin, Fluorouracil, RT

Regimen

Chemoradiotherapy

References

Carboplatin, Paclitaxel, RT

Regimen

Chemoradiotherapy

Supportive medications

References

Cisplatin & Docetaxel -> Cisplatin, Docetaxel, RT

Regimen

Chemotherapy

Chemoradiotherapy

References

Cisplatin, Fluorouracil, RT

Regimen #1

Chemoradiotherapy

Regimen #2

Chemoradiotherapy

Supportive medications

References

Cisplatin & Etoposide

Regimen

Chemotherapy

References

Cisplatin & Fluorouracil

Regimen

Chemotherapy

References

Cisplatin & Fluorouracil -> Fluorouracil, Paclitaxel, RT

Regimen

Chemotherapy

Chemoradiotherapy

References

Cisplatin & Irinotecan -> Cisplatin, Irinotecan, RT

Regimen #1

Chemotherapy

Chemoradiotherapy

Supportive medications

Regimen #2

Chemotherapy

Chemoradiotherapy

Regimen #3

Chemoradiotherapy

References

Cisplatin, Irinotecan, RT

Regimen

Chemoradiotherapy

References