Esophageal cancer

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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 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.

80 regimens on this page
100 variants on this page

Contents


Guidelines

CAP/ASCP/ASCO

ESMO

NCCN

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

  1. 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 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.

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

  1. 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: 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/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

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

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

  1. 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

5-week course

References

  1. 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: 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

  • 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

  1. 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

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

  1. 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
  2. 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

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

  1. 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

21-day cycle for 2 cycles

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

References

  1. 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
  2. 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 & Fluorouracil -> Fluorouracil, Paclitaxel, RT

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RT: Radiation Therapy

Regimen

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

Chemotherapy

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

  1. 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

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

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

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 (2 cycles per NCCN, Esophageal Cancer version 2.2011; abstract did not specify number of cycles)

References

  1. 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
  2. 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
  3. 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

Note: In contrast to the original reference, the NCCN, Esophageal Cancer version 2.2011, lists the dosage of preoperative irinotecan as 50 mg/m2.

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

  1. 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

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

  1. 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
  2. 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

7-week course

Regimen #2

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/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

  1. 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

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/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

  1. 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
  2. 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

Perioperative chemotherapy

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

Supportive medications

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

  1. 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

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

References

  1. 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 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.

Chemotherapy

Supportive medications

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 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.

Chemotherapy

Supportive medications

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

  1. 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
  2. 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
  3. 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
  4. 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

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

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

28-day cycle for 2 cycles

Regimen #2

Note: This regimen was listed by the NCCN, Esophageal Cancer version 2.2011, but the reference cited, André T et al. 2007 (PubMed), was for colon cancer, did not include radiation, and did not match this regimen. No primary reference could be found for this regimen.

Chemotherapy

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

References

  1. 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

21-day cycle for 3 cycles

References

  1. 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

21-day cycle for 3 cycles

References

  1. 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

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

21-day cycle for 3 cycles

References

  1. 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

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

21-day cycle for 2 cycles

References

  1. 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

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

  1. 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

4 cycles

References

  1. Crosby T, Hurt CN, Falk S, Gollins S, Mukherjee S, Staffurth J, Ray R, Bashir N, Bridgewater JA, Geh JI, Cunningham D, Blazeby J, Roy R, Maughan T, Griffiths G. Chemoradiotherapy with or without cetuximab in patients with oesophageal cancer (SCOPE1): a multicentre, phase 2/3 randomised trial. Lancet Oncol. 2013 Jun;14(7):627-37. 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

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

  1. 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
  2. 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

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

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

14-day cycle for 3 cycles

References

  1. 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
  2. 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

  1. 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)

Best supportive care

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Regimen

Study Evidence Comparator Efficacy
Thuss-Patience et al. 2011 Phase III Irinotecan Seems to have inferior OS

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

References

  1. 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
  2. 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

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

21-day cycle for up to 6 cycles

References

  1. 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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Regimen

Study Evidence
Leary et al. 2008 Phase II

Chemotherapy

Supportive medications

21-day cycle for up to 8 cycles

References

  1. 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

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

21-day cycles

References

  1. 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
  2. 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

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

References

  1. 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
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

Supportive medications

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

Supportive medications

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

Regimen #3

Study Evidence
Kim et al. 2009 Phase II

Chemotherapy

Supportive medications

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

References

  1. 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
  2. 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
  3. 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:

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

Supportive medications

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
UFTM Seems not superior

Chemotherapy

28-day cycle for up to 6 cycles

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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
  6. 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

29-day cycle for up to 6 cycles

References

  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. 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

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

References

  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. 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

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

References

  1. 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

21-day cycles

Regimen #2

Study Evidence
Ilson et al. 1999 Phase II

Chemotherapy

Supportive medications

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

References

  1. 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
  2. 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

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

Supportive medications

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

References

  1. 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
  2. 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

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

Supportive medications

  • "Granulocyte colony stimulating factor support"

21-day cycles

Regimen #3

Study Evidence
Petrasch et al. 1998 Phase II

Chemotherapy

Supportive medications

14-day cycles

References

  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. link to PMC article contains verified protocol PubMed
  2. 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
  3. 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

Supportive medications

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

References

  1. 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
  2. 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
  3. 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

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

References

  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. 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

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

References

  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. link to original article contains verified protocol PubMed

Docetaxel (Taxotere)

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Regimen

Study Evidence
Albertsson et al. 2007 Phase II

Note: In addition to the original reference, the NCCN, Esophageal Cancer version 2.2011, also lists docetaxel 75 mg/m2 as an alternate dosage.

Chemotherapy

21-day cycles

References

  1. 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
  2. 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

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

Supportive medications

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
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

Supportive medications

21-day cycle for up to 8 cycles

References

  1. 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
  2. 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
  3. 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

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

Supportive medications

  • "Standard premedication and delayed emesis regimens"

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

References

  1. 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
  2. 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

Supportive medications

  • "Standard premedication and delayed emesis regimens"

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

References

  1. 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

Supportive medications

21-day cycles

References

  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. link to abstract

Docetaxel & Irinotecan

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Regimen

Study Evidence
Burtness et al. 2009 Phase II

Chemotherapy

Supportive medications

21-day cycles

References

  1. 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

14-day cycles

References

  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. 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

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

  1. 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
  2. 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
  3. 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
  4. 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 EOF
EOX
Non-inferior OS

Chemotherapy

Supportive medications

21-day cycle for up to 8 cycles

References

  1. 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

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
EOX Non-inferior OS

Chemotherapy

Supportive medications

21-day cycle for up to 8 cycles

References

  1. 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

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

Supportive medications

21-day cycle for up to 8 cycles

References

  1. 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
  2. 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

  1. 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
  2. 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

Note: The references cited by the NCCN, Esophageal Cancer version 2.2011, did not contain this regimen. Etoposide 120 mg/m2 was used as part of ELF (Etoposide (Vepesid), Folinic acid (Leucovorin), Fluorouracil (5-FU)) regimens in Vanhoefer U et al. 2000 (PubMed) and Taal BG et al. 1994 (PubMed). No primary reference could be found for this monotherapy regimen.

Chemotherapy

28-day cycles

Fluorouracil (5-FU)

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Regimen

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

Chemotherapy

28-day cycles

References

  1. 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

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

References

  1. 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

56-day cycle for 2 cycles

References

  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. 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

Supportive medications

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

References

  1. 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

Supportive medications

7-week cycles

Regimen #2, LV5FU2 & Irinotecan

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

Chemotherapy

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

14-day cycles

References

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

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

  1. 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

28-day cycles

References

  1. 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

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

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

  1. 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
  2. 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
  3. 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
  4. 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
  5. 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

Supportive medications

28-day cycle for up to 6 cycles

Regimen #2

Study Evidence
Giuliani et al. 2005 Phase II

Chemotherapy

28-day cycles

Regimen #3

Study Evidence
Bamias et al. 2003 Phase II

Chemotherapy

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

References

  1. 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
  2. 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
  3. 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

Supportive medications

42-day cycle for up to 6 months

References

  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. link to original article contains verified protocol PubMed
  2. 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

Supportive medications

  • Antiemetic medications per "local protocols"

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

References

  1. 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

Supportive medications

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

21-day cycles

References

  1. 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
  2. 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

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
FP Seems not superior

Chemotherapy

References

  1. 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