Difference between revisions of "Esophageal cancer"

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=Neoadjuvant chemoradiation=
 
=Neoadjuvant chemoradiation=
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==Capecitabine & Paclitaxel {{#subobject:17bbec|Regimen=1}}==
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==Capecitabine, Carboplatin, Paclitaxel, RT {{#subobject:79bb5a|Regimen=1}}==
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===Regimen {{#subobject:f22688|Variant=1}}===
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Level of Evidence:
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border-style:solid;">Pilot, <20 patients reported</span>
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''The primary reference did not specify whether patients were intended to proceed to surgery.''
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*[[Carboplatin (Paraplatin)]] AUC 1.5 IV on days 2, 9, 16, 23, 30
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*[[Paclitaxel (Taxol)]] 45 mg/m2 IV over 1 hour on days 2, 9, 16, 23, 30
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*[[Capecitabine (Xeloda)]] 600 mg/m2 PO BID, starting on day 1 and finishing the evening of the last day of radiation therapy
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*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
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'''6-week course'''
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===References===
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# 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. [http://www.sciencedirect.com/science/article/pii/S0360301606033621 link to original article] '''contains verified protocol''' [http://www.ncbi.nlm.nih.gov/pubmed/17197129 PubMed]
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==Capecitabine, Paclitaxel, RT {{#subobject:17bbec|Regimen=1}}==
 
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*[[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  
 
*[[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 on days 1, 8, 15, 22, 29
 
*[[Paclitaxel (Taxol)]] 45 to 50 mg/m2 IV on days 1, 8, 15, 22, 29
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*Concurrent radiation therapy not defined
  
 
'''5-week course'''
 
'''5-week course'''

Revision as of 19:48, 21 December 2015

Use of this site is subject to you reading and agreeing with the terms set forth in the disclaimer.

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 version 2.2011, and their inclusion here reflects the overlap between treatments of esophageal and gastric cancer.

56 regimens on this page
74 variants on this page


Neoadjuvant chemoradiation

Capecitabine, Carboplatin, Paclitaxel, RT

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Regimen

Level of Evidence: Pilot, <20 patients reported

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

  • Carboplatin (Paraplatin) AUC 1.5 IV 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. 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, Paclitaxel, RT

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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.

  • 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 on days 1, 8, 15, 22, 29
  • Concurrent radiation therapy not defined

5-week course

Carboplatin, Fluorouracil, RT

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Regimen

Level of Evidence: Non-randomized

  • 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 50.4-56.8 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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Regimen

Study Evidence Comparator
van Meerten et al. 2006 Phase II
van Hagen et al. 2012 (CROSS) Phase III Surgery alone
  • 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 (Platinol) & Capecitabine (Xeloda)

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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.

  • 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

Cisplatin (Platinol) & Docetaxel (Taxotere)

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Regimen

Level of Evidence: Phase II

21-day cycles x 2 cycles, THEN

  • Cisplatin (Platinol) 25 mg/m2 IV on days 1, 8, 15, 22, 29
  • Docetaxel (Taxotere) 20 mg/m2 IV 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.
  • Surgery planned to be done 3-8 weeks after finishing chemoradiation

5-week course

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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Regimen #1

Study Evidence Comparator
Tepper et al. 2008 (CALGB 9781) Phase III Surgery alone
  • 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 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
Bedenne et al. 2007 (FFCD 9102) Phase III Cisplatin, Fluorouracil, RT (no surgery)

Study did not show a benefit of surgery after 2 cycles of chemoradiation as compared to additional chemoradiation.

  • 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 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 hydration:

  • 1 liter NS IV over 2 hours before and after cisplatin

21-day cycle x 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 (Platinol) & Fluorouracil (5-FU) -> Paclitaxel (Taxol), Fluorouracil (5-FU), RT

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Regimen

Level of Evidence: Phase II

28-day cycles x 2 cycles, THEN

  • Paclitaxel (Taxol) 45 mg/m2 IV on days 1, 8, 15, 22, 29
  • Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion on days 1 to 5, 8-12, 15-19, 22-26, 29-33
  • 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 (Platinol) & Irinotecan (Camptosar)

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Regimen #1, Ilson et al. 2011

Level of Evidence: Phase II

21-day cycles x 2 cycles, THEN

  • Cisplatin (Platinol) 30 mg/m2 IV over 30 minutes on days 1 & 8; given before irinotecan
  • Irinotecan (Camptosar) 65 mg/m2 IV over 30 minutes 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
  • Surgery performed 4-8 weeks after chemoradiation

21-day cycles x 2 cycles

Supportive medications:

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

Regimen #2, Rivera et al. 2009

Level of Evidence: Phase II

21-day cycles x 2 cycles, THEN

  • Cisplatin (Platinol) 30 mg/m2 IV on days 1, 8, 15, 22
  • Irinotecan (Camptosar) 65 mg/m2 IV 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.
  • Surgery done 5-8 weeks after finishing chemoradiation

5-week course

Regimen #3, Yoon et al. 2011

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

  • Cisplatin (Platinol) 30 mg/m2 IV on days 1, 8, 22, 29
  • Irinotecan (Camptosar) 65 mg/m2 IV 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, THEN

  • Surgery done at least 28 days after finishing chemoradiation, then begin adjuvant chemotherapy at least 28 days after surgical resection:
  • Cisplatin (Platinol) 30 mg/m2 IV on days 1 & 8
  • Irinotecan (Camptosar) 65 mg/m2 IV on days 1 & 8

21-day cycles x 3 cycles

Regimen #4, Sharma et al. 2009

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

References

  1. 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. Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer (Regimen #2, Rivera et al. 2009, clinicaltrials.gov)
  3. 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
  4. 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. doi: 10.1002/cncr.26591. link to original article contains verified protocol PubMed
  5. 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 (Platinol) & Paclitaxel (Taxol)

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Regimen #1, Urba et al. 2003

Level of Evidence: Phase II

  • Cisplatin (Platinol) 75 mg/m2 IV over 2 hours on day 1
  • Paclitaxel (Taxol) 60 mg/m2 IV over 3 hours on days 1, 8, 15, 22
  • Concurrent radiation therapy, 1.5 Gy fractions given twice per day on days 1 to 5, 8-12, 15-19, with at least 6 hours between fractions, for a total dose of 45 Gy
  • 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

4-week course of therapy

Supportive medications:

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

Regimen #2, Yoon et al. 2011

Level of Evidence: Phase II

  • Cisplatin (Platinol) 30 mg/m2 IV 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, THEN

  • Surgery done at least 28 days after finishing chemoradiation, then begin adjuvant chemotherapy at least 28 days after surgical resection:
  • Cisplatin (Platinol) 75 mg/m2 IV on day 1
  • Paclitaxel (Taxol) 175 mg/m2 IV on day 1

21-day cycles x 3 cycles

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. Radiation Therapy and Chemotherapy Before and After Surgery in Treating Patients With Esophageal Cancer (Regimen #2, Yoon et al. 2011, clinicaltrials.gov)
  3. 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 (Taxotere) & Capecitabine (Xeloda)

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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.

5-week course

Docetaxel (Taxotere) & Fluorouracil (5-FU)

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Regimen #1, Hihara et al. 2007

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

5-week course

References

  1. 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

Oxaliplatin (Eloxatin) & Capecitabine (Xeloda)

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Regimen

5-week course

References

  1. 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

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

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Regimen

Level of Evidence: Phase II

  • Oxaliplatin (Eloxatin) 40 mg/m2 IV over 2 hours on days 1, 8, 15, 22, 29
  • Docetaxel (Taxotere) 20 mg/m2 IV over 30 minutes on days 1, 8, 15, 22, 29
  • Capecitabine (Xeloda) 1000 mg/m2 PO BID on days 1 to 7, 15-21, 29-35
  • 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.
  • Endoscopy, CT scan, and--if available--endoscopic ultrasound for restaging 2-4 weeks after finishing chemoradiation
  • Surgical resection for appropriate candidates during weeks 9-12

5-week course of therapy

Supportive medications:

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

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

Oxaliplatin (Eloxatin) & Fluorouracil (5-FU)

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Regimen #1, Lorenzen et al. 2008

Level of Evidence: Phase II

  • Oxaliplatin (Eloxatin) 45 mg/m2 IV over 2 hours on days 1, 8, 15, 22, 29
  • Fluorouracil (5-FU) 225 mg/m2/day IV continuous infusion over days 1-33
  • Concurrent radiation therapy, 1.8 Gy fractions x 25 fractions given 5 days per week, for a total dose of 45 Gy
  • Surgery 4-6 weeks after finishing chemoradiation

35-day course

Regimen #2, Khushalani et al. 2002

Level of Evidence: 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.

  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on days 1, 15, 29
  • Fluorouracil (5-FU) 180 mg/m2/day IV continuous infusion over days 8-42
  • Concurrent radiation therapy, 1.8 Gy fractions x 20-22 fractions, for an initial total dose of 36-39.6 Gy, started on day 8
    • Followed by off-cord conformal oblique fields, 5.4-9 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 1-2 cycles of oxaliplatin and 5-FU within 2 weeks.

6-week cycle x 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 original article contains verified protocol PubMed

Perioperative chemotherapy

ECF

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ECF: Epirubicin, Cisplatin, Fluorouracil

Regimen, Sumpter et al. 2005 & Cunningham et al. 2006 (MAGIC)

Level of Evidence: Phase III

21-day cycles x 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.

Supportive medications:

References

  1. Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer. 2005 Jun 6;92(11):1976-83. 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

ECX

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ECX: Epirubicin, Cisplatin, Xeloda

Regimen

Level of Evidence: Phase III

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. 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. No follow-up report for this trial or its additional participants could be found.

21-day cycles x up to 8 cycles; for perioperative use per NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used

Supportive medications:

  • Dexamethasone (Decadron) 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
  • "5HT3 antagonist" prior to chemotherapy
  • Metoclopramide (Reglan) 10 mg PO TID x 3 days after day 1 chemotherapy
  • "Standard hydration" for cisplatin
  • Warfarin (Coumadin) 1 mg PO daily as thrombosis prophylaxis, started on day -1

References

  1. Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer. 2005 Jun 6;92(11):1976-83. link to original article contains verified protocol PubMed

EOF

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EOF: Epirubicin, Oxaliplatin, Fluorouracil

Regimen

Level of Evidence: Phase III

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. 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. No follow-up report for this trial or its additional participants could be found.

21-day cycles x up to 8 cycles; for perioperative use per NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used

Supportive medications:

  • Dexamethasone (Decadron) 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
  • "5HT3 antagonist" prior to chemotherapy
  • Metoclopramide (Reglan) 10 mg PO TID x 3 days after day 1 chemotherapy
  • Warfarin (Coumadin) 1 mg PO daily as thrombosis prophylaxis, started on day -1

References

  1. Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer. 2005 Jun 6;92(11):1976-83. link to original article contains verified protocol PubMed

EOX

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EOX: Epirubicin, Oxaliplatin, Xeloda

Regimen

Level of Evidence: Phase III

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. 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. No follow-up report for this trial or its additional participants could be found.

21-day cycles x up to 8 cycles; for perioperative use per NCCN, 3 cycles preoperatively and 3 cycles postoperatively would be used

Supportive medications:

  • Dexamethasone (Decadron) 8 mg IV prior to day 1 chemotherapy and 4 mg PO TID x 2 days thereafter
  • "5HT3 antagonist" prior to chemotherapy
  • Metoclopramide (Reglan) 10 mg PO TID x 3 days after day 1 chemotherapy
  • Warfarin (Coumadin) 1 mg PO daily as thrombosis prophylaxis, started on day -1

References

  1. Sumpter K, Harper-Wynne C, Cunningham D, Rao S, Tebbutt N, Norman AR, Ward C, Iveson T, Nicolson M, Hickish T, Hill M, Oates J. Report of two protocol planned interim analyses in a randomised multicentre phase III study comparing capecitabine with fluorouracil and oxaliplatin with cisplatin in patients with advanced oesophagogastric cancer receiving ECF. Br J Cancer. 2005 Jun 6;92(11):1976-83. link to original article contains verified protocol PubMed

Adjuvant chemoradiation

Fluorouracil (5-FU), Folinic acid (Leucovorin), RT

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Regimen #1, Macdonald et al. 2001

Level of Evidence: Phase III

Cycles 1, 3, 4:

28-day cycles x 3 total cycles, interrupted by cycle 2 as described below

Cycle 2:

  • Fluorouracil (5-FU) 400mg/m2 IV bolus on days 1 to 4 and the last 3 days of radiation therapy
  • Folinic acid (Leucovorin) 20 mg/m2 IV bolus 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 x 1 cycle, to be followed by cycle 3 as described above

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.

28-day cycles x 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

FP -> Capecitabine (Xeloda) & RT -> FP

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FP: Fluorouracil, Platinol

Regimen

Level of Evidence: 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 625-825 mg/m2 PO BID on days 1 to 5 or 1-7 while radiation is being given. FP starts 3 weeks after surgery. Cycles 1, 3, 4, 5:

21-day cycles x 4 total cycles (1 cycle prior to radiation and 3 cycles after chemoradiation, with cycle 2 starting 4 weeks after radiation is finished)

Cycle 2, chemoradiation:

  • 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, to begin immediately after cycle 1

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

Regimen

Level of Evidence: 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 200-250 mg/m2/day IV continuous infusion on days 1 to 5 or 1-7 while radiation is being given. Cycles 1, 3, 4:

21-day cycles x 3 total cycles (1 cycle prior to radiation and 2 cycles after radiation, with cycle 2 starting 1 month after radiation is finished)

Cycle 2, chemoradiation:

  • 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, to begin immediately after cycle 1, to be followed by cycles 3-5 as described above

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)

Carboplatin (Paraplatin) & Paclitaxel (Taxol)

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See Carboplatin (Paraplatin) & Paclitaxel (Taxol), except patients did not undergo surgery.

Cisplatin (Platinol) & Capecitabine (Xeloda)

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Regimen

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 only part:

21-day cycles

Chemoradiation part:

  • 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. 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

Cisplatin (Platinol) & Docetaxel (Taxotere)

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Regimen #1, Li et al. 2009

Level of Evidence: Phase II

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

1 cycle of chemoradiation

Supportive medications:

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

Regimen #2, Day et al. 2011

Note: The NCCN, Esophageal Cancer version 2.2011, suggests a wider dose range of 20-30 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.

  • Cisplatin (Platinol) 30 mg/m2 IV on days 1, 8, 15, 22, 29
  • Docetaxel (Taxotere) 30 mg/m2 IV 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.

5-week course

Supportive medications:

  • "Steroid and anti-emetic pre-medication"

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. Day FL, Leong T, Ngan S, Thomas R, Jefford M, Zalcberg JR, Rischin D, McKendick J, Milner AD, Di Iulio J, Matera A, Michael M. Phase I trial of docetaxel, cisplatin and concurrent radical radiotherapy in locally advanced oesophageal cancer. Br J Cancer. 2011 Jan 18;104(2):265-71. Epub 2010 Dec 14. link to original article contains verified protocol PubMed

Cisplatin, Fluorouracil, RT

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Regimen #1, Herskovic et al. 1992 (RTOG 85-01); al-Sarraf et al. 1997

Level of Evidence: Phase III

  • Cisplatin (Platinol) 75 mg/m2 IV 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 1-4, 29-32, 50-53, 71-74)
  • 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

Regimen #2, Minsky et al. 2002 (RTOG 94-05)

Level of Evidence: Phase III

  • Cisplatin (Platinol) 75 mg/m2 IV over 30 minutes 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 cycles x 2 cycles, THEN

28-day cycles x 2 cycles

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: 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. 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
  3. 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
  4. 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
  5. 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 original article contains verified protocol PubMed

Cisplatin (Platinol) & Irinotecan (Camptosar)

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

Cisplatin (Platinol) & Paclitaxel (Taxol)

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

Docetaxel (Taxotere) & Capecitabine (Xeloda)

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See Docetaxel (Taxotere) & Capecitabine (Xeloda).

Docetaxel (Taxotere) & Fluorouracil (5-FU)

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

FOLFOX 4

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FOLFOX: FOLinic acid, Fluorouracil, OXaliplatin

Regimen

Level of Evidence: Randomized Phase II, >20 per arm

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

  • Fluorouracil (5-FU) 400 mg/m2 IV bolus, then 600 mg/m2/day IV over 22 hours on days 1 & 2; given after Oxaliplatin (Eloxatin) and Folinic acid (Leucovorin)
  • Folinic acid (Leucovorin) 200 mg/m2 IV over 2 hours on day 1
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours 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 cycles x 3 cycles, THEN

14-day cycles x 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 original article contains verified protocol PubMed

Oxaliplatin (Eloxatin) & Capecitabine (Xeloda)

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See Oxaliplatin (Eloxatin) & Capecitabine (Xeloda).

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

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

Oxaliplatin (Eloxatin) & Fluorouracil (5-FU)

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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.

Paclitaxel (Taxol) & Capecitabine (Xeloda)

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See Paclitaxel (Taxol) & Capecitabine (Xeloda).

Radiation alone

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Regimen

Level of Evidence: Phase III

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
  2. 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

Surgery alone

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Regimen

Level of Evidence: Phase III

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. doi: 10.1056/NEJMoa1112088. link to original article contains verified protocol link to appendix with details about administration PubMed

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

Best supportive care

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Regimen

Study Evidence Comparator
Thuss-Patience et al. 2011 Phase III Irinotecan

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

Capecitabine (Xeloda)

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Regimen

Level of Evidence: 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.

21-day cycles x 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

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.

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

Level of Evidence: Phase II

  • Cetuximab (Erbitux) 400 mg/m2 IV over 120 minutes on cycle 1 day 1, then 250 mg/m2 IV over 60 minutes on days on cycle 1 days 8, 15, 22; then in cycles 2 and on, Cetuximab (Erbitux) is 250 mg/m2 IV on days 1, 8, 15, 22

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

Supportive medications:

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

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 original article contains verified protocol PubMed

DC, TC

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

Regimen #1

Study Evidence Comparator
Roth et al. 2007 Randomized Phase II ECF
TCF
  • Docetaxel (Taxotere) 75 mg/m2 IV over 1 hour once on day 1; the protocol was amended to change the original dose of 85 mg/m2 to 75 mg/m2 based on high incidence of febrile neutropenia
  • Cisplatin (Platinol) 75 mg/m2 IV over 4 hours once on day 1

21-day cycle x up to 8 cycles

Supportive medications:

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

Regimen #2

Study Evidence Comparator
Ajani et al. 2005 Randomized Phase II DCF

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

Supportive medications:

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

Regimen #3, Kim et al. 2010

Level of Evidence: Phase II

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

Supportive medications:

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

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, Van Cutsem et al. 2006 & Dank et al. 2008

Level of Evidence: Phase III

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

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

  • "Hyperhydration" for 2-3 days with each infusion
  • Ondansetron IV for antiemetic prophylaxis
  • Dexamethasone IV for antiemetic prophylaxis, then PO for 2-3 days
  • Metoclopramide for antiemetic prophylaxis
  • Filgrastim (Neupogen) daily SC, starting on day 4, to be continued until ANC > 1 x 10^9/L for grade 3-4 neutropenia, febrile neutropenia, or neutropenic infection
  • Atropine prn cholinergic symptoms
  • Loperamide prn delayed diarrhea

Regimen #2, Lorenzen et al. 2009

Level of Evidence: Randomized Phase II, >20 per arm

29-day cycles x up to 6 cycles

Regimen #3, Kang et al. 2009

Level of Evidence: Phase III

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

Supportive medications:

  • "Hyperhydration" for cisplatin

Regimen #4

Study Evidence Comparator
Ohtsu et al. 2003 (JCOG9205) Phase III Fluorouracil
UFTM

28-day cycle x 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 & Cetuximab

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CF: Cisplatin, Fluorouracil

Regimen

Study Evidence Comparator
Lorenzen et al. 2009 Randomized Phase II CF
  • 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

29-day cycle x up to 6 cycles

Supportive medications:

  • "Standard antiemetic prophylaxis and pre- and post- cisplatin hydration"

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
Bang et al. 2010 (ToGA) Phase III CF

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 (Platinol), Fluorouracil (5-FU), Doxorubicin liposomal (Doxil)

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Regimen

Level of Evidence: Randomized Phase II, >20 per arm

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 (Platinol) & Irinotecan (Camptosar) (CI)

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CI: Cisplatin, Irinotecan

Regimen #1, Ilson et al. 1999

Level of Evidence: Phase II

6-week cycles x 1-3 cycles, or until disease progression or unacceptable toxicity.

Supportive medications:

  • Dexamethasone (Decadron) 20 mg IV prior to chemotherapy
  • Granisetron 2 mg PO prior to chemotherapy
  • At least 500 mL D5NS IV over 30-60 minutes before cisplatin
  • Atropine used as pretreatment medication if there was diarrhea or abdominal cramps within 1 hour of irinotecan

Regimen #2, Ilson et al. 2004

Level of Evidence: 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.

21-day cycles

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. contains protocol PubMed

CLF, FLP

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

Regimen #1, Al-Batran et al. 2008

Level of Evidence: Phase III

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.

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

Supportive medications:

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

Regimen #2, Bouche et al. 2004 (FFCD 9803)

Level of Evidence: Randomized Phase II, >20 per arm

14-day cycles x 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 regular schedule was used)

Supportive medications:

  • 1 liter hydration over 3 hours before and after cisplatin
  • 5-HT3 antagonist IV before cisplatin
  • Methylprednisolone (Solu-Medrol) 120 mg IV 10 minutes before cisplatin
  • Oral antiemetics and corticosteroids from days 2-5

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 (Platinol) & Paclitaxel (Taxol)

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Regimen #1, Ilson et al. 2000

Level of Evidence: 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.

  • Cisplatin (Platinol) 75 mg/m2 IV on day 2, given after paclitaxel
  • Paclitaxel (Taxol) 200 mg/m2 IV over 24 hours on day 1; the protocol was amended to change the original dose of 250 mg/m2 to 200 mg/m2 based on toxicity and treatment-related deaths

21-day cycles

Supportive medications:

  • "Granulocyte colony stimulating factor support"

Regimen #2, Zhang et al. 2008

Level of Evidence: Phase II

21-day cycles

Regimen #3, Petrasch et al. 1998

Level of Evidence: Phase II

14-day cycles

Supportive medications:

  • Dexamethasone (Decadron) 20 mg IV 30 minutes prior to paclitaxel
  • Cimetidine (Tagamet) 300 mg IV 30 minutes prior to paclitaxel
  • Clemastine 2 mg IV 30 minutes prior to paclitaxel
  • Ondansetron 8 mg IV 30 minutes prior to paclitaxel
  • "Adequate pre- and posthydration" for cisplatin

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 original 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):29-33. 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
Kang et al. 2009 Phase III CF
Bang et al. 2010 (ToGA) Phase III CX & Trastuzumab
Lordick et al. 2013 (EXPAND) Phase III CX & Cetuximab

Supportive medications per Kang et al. 2009:

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. doi: 10.1016/S1470-2045(13)70102-5. Epub 2013 Apr 15. link to original article contains verified protocol PubMed

CX & Cetuximab

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CX: Cisplatin, Xeloda (Capecitabine)

Regimen

Study Evidence Comparator
Lordick et al. 2013 (EXPAND) Phase III CX

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
Bang et al. 2010 (ToGA) Phase III CX

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

Level of Evidence: 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.

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. contains protocol PubMed

DCF, TCF

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

Regimen #1

Study Evidence Comparator
Ajani et al. 2005 Randomized Phase II DC
Van Cutsem et al. 2006 (V325 Study Group) Phase III CF

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

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

Supportive medications (varied depending on reference):

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

Regimen #2

Study Evidence Comparator
Roth et al. 2007 Randomized Phase II ECF
TC
  • Docetaxel (Taxotere) 75 mg/m2 IV over 1 hour once on day 1; the protocol was amended to change the original dose of 85 mg/m2 to 75 mg/m2 based on high incidence of febrile neutropenia
  • Cisplatin (Platinol) 75 mg/m2 IV over 4 hours once on day 1
  • Fluorouracil (5-FU) 300 mg/m2/day IV continuous infusion on days 1 to 14

21-day cycle x up to 8 cycles

Supportive medications:

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

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, Ozal et al. 2010

21-day cycles

Regimen #2, Shah et al. 2011

Level of Evidence: 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.

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

Supportive medications:

  • "Standard premedication and delayed emesis regimens"

References

  1. 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 (Avastin)

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mDCF: modified Docetaxel, Cisplatin, Fluorouracil

Regimen

Level of Evidence: Phase II

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

Supportive medications:

  • "Standard premedication and delayed emesis regimens"

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 (Taxotere), Carboplatin (Paraplatin), Fluorouracil (5-FU)

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Regimen

Level of Evidence: Phase II

21-day cycles

Supportive medications:

References

  1. 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 (Taxotere) & Irinotecan (Camptosar)

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Regimen

Level of Evidence: Phase II

21-day cycles

Supportive medications:

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

Level of Evidence: Phase II

14-day cycles

References

  1. 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

Level of Evidence: Phase III

21-day cycles x up to 8 cycles

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 daily for catheter thrombosis prophylaxis

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. 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. 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

Regimen

Level of Evidence: Phase III

21-day cycles x up to 8 cycles

Supportive medications:

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

Level of Evidence: Phase III

21-day cycles x up to 8 cycles

Supportive medications:

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
EOC: Epirubicin, Oxaliplatin, Capecitabine

Regimen #1, Cunningham et al. 2008 (REAL-2)

Level of Evidence: Phase III

21-day cycles x up to 8 cycles

Supportive medications:

Regimen #2, Waddell et al. 2013 (REAL3)

Level of Evidence: Phase III

21-day cycles x 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. doi: 10.1016/S1470-2045(13)70096-2. Epub 2013 Apr 15. link to original article contains verified protocol PubMed

Erlotinib (Tarceva)

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Regimen

Level of Evidence: Phase II

  • 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. doi: 10.1002/cncr.25602. 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.

28-day cycles

Fluorouracil (5-FU)

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Regimen

Study Evidence Comparator
Ohtsu et al. 2003 (JCOG9205) Phase III FP
UFTM

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 (5-FU) & Folinic acid (Leucovorin)

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Regimen

Level of Evidence: Randomized Phase II, >20 per arm

14-day cycles x 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 regular schedule was used)

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 (5-FU), Folinic acid (Leucovorin), Mitomycin (Mutamycin)

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Regimen

Level of Evidence: Phase II

56-day cycles x 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. contains protocol PubMed

FLOT

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FLOT: Fluorouracil, Leucovorin, Oxaliplatin, Taxotere

Regimen

Level of Evidence: Phase II

14-day cycles x up to 8 (or more) cycles

Supportive medications:

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

Regimen #1, Dank et al. 2008

Level of Evidence: Phase III

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

7-week cycles

Supportive medications:

  • Ondansetron for antiemetic prophylaxis
  • Dexamethasone for antiemetic prophylaxis
  • Filgrastim (Neupogen) daily SC, starting on day 4, to be continued until ANC > 1 x 10^9/L for grade 3-4 neutropenia, febrile neutropenia, or neutropenic infection
  • Atropine prn cholinergic symptoms
  • Loperamide prn delayed diarrhea

Regimen #2, Bouché et al. 2004 (FFCD 9803)

Level of Evidence: Randomized Phase II, >20 per arm

14-day cycles x 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 regular schedule was used)

Regimen #3, Samalin et al. 2010 & Samalin et al. 2011

Level of Evidence: Non-randomized

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. 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. 2010 Oct 28. [Epub ahead of print] link to original article contains verified protocol PubMed
  5. 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 (Cetuximab (Erbitux))

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

Regimen

Note: This regimen included Cetuximab (Erbitux), but the dosage was not listed in the abstract nor clinicaltrials.gov listing. The NCCN, Esophageal Cancer version 2.2011, listed this regimen without cetuximab.

  • Fluorouracil (5-FU) 500 mg/m2 IV bolus, then 1200 mg/m2/day IV continuous infusion on days 1 & 2; given after Oxaliplatin (Eloxatin) and Folinic acid (Leucovorin)
  • Folinic acid (Leucovorin) 500 mg/m2 IV over 2 hours on day 1, given second
  • Oxaliplatin (Eloxatin) 85 mg/m2 IV over 2 hours on day 1, given first
  • Cetuximab (Erbitux) dosage not described (but based on other applications may be 400 mg/m2 for the first dose, then 250 mg/m2 on subsequent doses) IV over 1-2 hours on days 1 & 8

14-day cycles

References

  1. Combination Chemotherapy and Cetuximab in Treating Patients With Metastatic Esophageal Cancer or Gastroesophageal Junction Cancer (ClinicalTrials.gov)
  2. P. C. Enzinger, B. Burtness, D. Hollis, D. Niedzwiecki, D. Ilson, A. B. Benson, R. J. Mayer, R. M. Goldberg. CALGB 80403/ECOG 1206: A randomized phase II study of three standard chemotherapy regimens (ECF, IC, FOLFOX) plus cetuximab in metastatic esophageal and GE junction cancer. 2010 ASCO Annual Meeting abstract 4006. link to abstract

Gemcitabine (Gemzar), Fluorouracil (5-FU), Folinic acid (Leucovorin)

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Regimen

Level of Evidence: Phase II

28-day cycles x up to 8 cycles

References

  1. Michelle Pipp, Daniel Mulkerin, Deb Warren, Wesley Hotchkis, Jordan Berlin, James P Thomas. A Phase II Trial of Gemcitabine and 5-Fluoruracil in Advanced Esophageal Cancer. 2001 ASCO Annual Meeting abstract 630. link to abstract

Irinotecan (Camptosar)

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Regimen #1, q3wk dosing

Study Evidence Comparator
Thuss-Patience et al. 2011 Phase III Best supportive care
  • 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

21-day cycle x up to 10 cycles

Supportive medications:

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

Regimen #2, 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 Irinotecan (Camptosar) 125 mg/m2 IV 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."

  • 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

Regimen #3, alternate q3wk dosing

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

21-day cycles

Regimen #4, q2wk dosing

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

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.

14-day 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 (Camptosar) & Capecitabine (Xeloda)

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Regimen

Level of Evidence: Phase II

21-day cycles x up to 8 cycles

Supportive medications:

  • Atropine 0.25 mg SC before irinotecan as prophylaxis against cholinergic symptoms
  • Loperamide (Imodium) 4 mg PO prn first unformed stool, then 2 mg PO Q2H x at least 12 hours, or for 12 hours after last liquid stool
  • Ciprofloxacin (Cipro) 250 mg PO BID prn diarrhea lasting longer than 24 hours despite Loperamide (Imodium)

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

Irinotecan (Camptosar) & Mitomycin (Mutamycin)

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Regimen #1, Giuliani et al. 2005

Level of Evidence: Phase II

28-day cycles

Regimen #2, Bamias et al. 2003

Level of Evidence: Phase II

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

Regimen #3, Lustberg et al. 2010

Level of Evidence: Phase II

28-day cycles x up to 6 cycles

Supportive medications:

  • "Ondansetron or granisetron and dexamethasone premedication"
  • Loperamide started with first episode of diarrhea
  • Erythropoietin for hemoglobin <10 g/dL permitted

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

Level of Evidence: Phase III

42-day cycles x up to 6 months

Supportive medications:

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

Level of Evidence: Phase III

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

Supportive medications:

  • Antiemetic medications per "local protocols"

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, Ajani et al. 1994

Level of Evidence: Phase II

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

  • 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

21-day cycles

Supportive medications:

  • Dexamethasone (Decadron) 20 mg PO 14 hours and 7 hours before paclitaxel
  • Cimetidine (Tagamet) 300 mg IV 60 minutes prior to paclitaxel
  • Diphenhydramine (Benadryl) 50 mg IV 60 minutes prior to paclitaxel
  • Filgrastim (Neupogen) 5 mcg/kg SC daily, starting 24 hours after the paclitaxel infusion finishes

Regimen #2, Ilson et al. 2007

Level of Evidence: Phase II

28-day cycles

Supportive medications:

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

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
Ohtsu et al. 2003 (JCOG9205) Phase III Fluorouracil
FP

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
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