Esophageal squamous cell carcinoma
Page editor | Section editor | ||
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Ryan Nguyen, DO University of Illinois at Chicago Chicago, IL |
Neeta K. Venepalli, MD, MBA University of Illinois at Chicago Chicago, IL |
Note: these are regimens tested in histology-specific populations, please see the main esophageal cancer page for other regimens.
45 regimens on this page
66 variants on this page
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Neoadjuvant induction therapy
Cisplatin & Etoposide (EP)
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Boonstra et al. 2011 | 1989-1996 | Phase III (E-esc) | Surgery alone | Seems to have superior OS |
Patients: 100% squamous cell histology
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV over 4 hours once on day 1
- Etoposide (Vepesid) 100 mg/m2/day IV over 2 hours once per day on days 1 & 2, then 200 mg/m2 PO once per day on days 3 & 5
21-day cycle for 2 to 4 cycles
Subsequent treatment
References
- Boonstra JJ, Kok TC, Wijnhoven BP, van Heijl M, van Berge Henegouwen MI, Ten Kate FJ, Siersema PD, Dinjens WN, van Lanschot JJ, Tilanus HW, van der Gaast A. Chemotherapy followed by surgery versus surgery alone in patients with resectable oesophageal squamous cell carcinoma: long-term results of a randomized controlled trial. BMC Cancer. 2011 May 19;11:181. link to original article contains verified protocol link to PMC article PubMed
Definitive therapy
Fluorouracil, Paclitaxel, RT
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Chen et al. 2019 (ESO-Shanghai1) | 2012-2015 | Phase III (E-switch-ic) | Cisplatin, Flourouracil, RT | Did not meet primary endpoint of OS36 |
Inclusion criteria: Esophageal SCC, stage IIA-IVA (AJCC 6th edition), ECOG 0-2, previously untreated. The total dose of 5-FU for this portion of the protocol is unclear in the manuscript; dosing here is as clarified by the authors.
Chemotherapy
- Fluorouracil (5-FU) 75 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 300 mg/m2)
- Paclitaxel (Taxol) 50 mg/m2 IV once on day 1
7-day cycle for 5 cycles
Radiotherapy
- Concurrent radiation therapy, 1.8 Gy fractions x 34 fractions, for a total dose of 61.2 Gy
7-week course
Subsequent treatment
References
- ESO-Shanghai1: Chen Y, Ye J, Zhu Z, Zhao W, Zhou J, Wu C, Tang H, Fan M, Li L, Lin Q, Xia Y, Li Y, Li J, Jia H, Lu S, Zhang Z, Zhao K. Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. J Clin Oncol. 2019 Jul 10;37(20):1695-1703. Epub 2019 Mar 28. link to original article PubMed NCT01591135
Consolidation after definitive therapy
Fluorouracil & Paclitaxel
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Chen et al. 2019 (ESO-Shanghai1) | 2012-2015 | Phase III (E-switch-ic) | Cisplatin & Flourouracil | Did not meet primary endpoint of OS36 |
Inclusion criteria: Esophageal SCC, stage IIA-IVA (AJCC 6th edition), ECOG 0-2, previously untreated
Preceding treatment
Chemotherapy
- Fluorouracil (5-FU) 600 mg/m2/day IV continuous infusion over 72 hours, started on day 1 (total dose per cycle: 1800 mg/m2)
- Paclitaxel (Taxol) 175 mg/m2 IV once on day 1
28-day cycle for 2 cycles
References
- ESO-Shanghai1: Chen Y, Ye J, Zhu Z, Zhao W, Zhou J, Wu C, Tang H, Fan M, Li L, Lin Q, Xia Y, Li Y, Li J, Jia H, Lu S, Zhang Z, Zhao K. Comparing Paclitaxel Plus Fluorouracil Versus Cisplatin Plus Fluorouracil in Chemoradiotherapy for Locally Advanced Esophageal Squamous Cell Cancer: A Randomized, Multicenter, Phase III Clinical Trial. J Clin Oncol. 2019 Jul 10;37(20):1695-1703. Epub 2019 Mar 28. link to original article contains verified protocol PubMed NCT01591135
Metastatic or locally advanced disease, first-line
Cisplatin & Docetaxel
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DC: Docetaxel, Cisplatin
TC: Taxotere (Docetaxel), Cisplatin
Regimen
Study | Evidence |
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Kim et al. 2009 | Phase II |
Patients: 100% squamous cell histology. 5% with ECOG PS of 2.
Chemotherapy
- Cisplatin (Platinol) 70 mg/m2 IV over 60 minutes once on day 1
- Docetaxel (Taxotere) 70 mg/m2 IV over 60 minutes once on day 1, given 3 hours before cisplatin
Supportive medications
- Dexamethasone (Decadron) 8 mg PO twice per day x 1 day, starting 1 day before Docetaxel (Taxotere) administration
- At least 3 liters hydration (with mannitol, magnesium, and potassium chloride)
- "Antiemetic treatment"
21-day cycle for up to 6 cycles
References
- 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
Cisplatin & Fluorouracil (CF)
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CF: Cisplatin, Fluorouracil
FP: Fluorouracil, Platinol
Regimen variant #1, 80/4000, indefinite
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Moehler et al. 2019 (POWER) | 2012-2015 | Phase III (C) | CFP | Did not meet primary endpoint of OS |
Note: this was the dosing after a mid-protocol amendment.
Chemotherapy
- Cisplatin (Platinol) 80 mg/m2 IV once on day 1
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 96 hours, started on day 1 (total dose per cycle: 4000 mg/m2 )
28-day cycles
Regimen variant #2, 100/5000 x 6
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Lorenzen et al. 2009 | 2004-2006 | Randomized Phase II (C) | CF & Cetuximab | Did not meet primary endpoint of ORR |
Patients: 100% squamous cell histology. 87% with metastatic disease. No patients with ECOG PS greater than 1.
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on day 1, given second (total dose per cycle: 5000 mg/m2 )
Supportive medications
- "Standard antiemetic prophylaxis and pre- and post- Cisplatin (Platinol) hydration"
29-day cycle for up to 6 cycles
References
- Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. link to original article contains verified protocol PubMed
- POWER: Moehler M, Maderer A, Thuss-Patience PC, Brenner B, Meiler J, Ettrich TJ, Hofheinz RD, Al-Batran SE, Vogel A, Mueller L, Lutz MP, Lordick F, Alsina M, Borchert K, Greil R, Eisterer W, Schad A, Slotta-Huspenina J, Van Cutsem E, Lorenzen S. Cisplatin and 5-fluorouracil with or without epidermal growth factor receptor inhibition panitumumab for patients with non-resectable, advanced or metastatic oesophageal squamous cell cancer: a prospective, open-label, randomised phase III AIO/EORTC trial (POWER). Ann Oncol. 2020 Feb;31(2):228-235. Epub 2019 Dec 16. link to original article contains verified protocol PubMed NCT01627379
Cisplatin, Fluorouracil, Cetuximab
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CF-C: Cisplatin, Fluorouracil, Cetuximab
Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Lorenzen et al. 2009 | 2004-2006 | Randomized Phase II (E-esc) | CF | Did not meet primary endpoint of ORR |
Patients: 100% squamous cell histology. 87% with metastatic disease. No patients with ECOG PS greater than 1.
Chemotherapy
- Cisplatin (Platinol) 100 mg/m2 IV over 60 minutes once on day 1, given first
- Fluorouracil (5-FU) 1000 mg/m2/day IV continuous infusion over 120 hours, started on day 1 (total dose per cycle: 5000 mg/m2 )
Targeted therapy
- Cetuximab (Erbitux) as follows:
- Cycle 1: 400 mg/m2 IV over 2 hours once on day 1, then 250 mg/m2 IV over 60 minutes once per day on days 8, 15, 22
- Cycles 2 to 6: 250 mg/m2 IV once per day on days 1, 8, 15, 22
Supportive medications
- "Standard antiemetic prophylaxis and pre- and post- Cisplatin (Platinol) hydration"
29-day cycle for up to 6 cycles
References
- Lorenzen S, Schuster T, Porschen R, Al-Batran SE, Hofheinz R, Thuss-Patience P, Moehler M, Grabowski P, Arnold D, Greten T, Müller L, Röthling N, Peschel C, Langer R, Lordick F. Cetuximab plus cisplatin-5-fluorouracil versus cisplatin-5-fluorouracil alone in first-line metastatic squamous cell carcinoma of the esophagus: a randomized phase II study of the Arbeitsgemeinschaft Internistische Onkologie. Ann Oncol. 2009 Oct;20(10):1667-73. Epub 2009 Jun 23. link to original article contains verified protocol PubMed
Etoposide monotherapy
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Regimen
Study | Evidence |
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Harstrick et al. 1992 | Phase II |
Note: this is higher than the dose usually employed in modern settings.
Patients: metastatic 100% squamous cell carcinoma of the esophagus, with ECOG PS range 1-2.
Chemotherapy
- Etoposide (Vepesid) 200 mg/m2 (route not specified) once per day on days 1 to 3
21-day cycles
References
- Harstrick A, Bokemeyer C, Preusser P, Köhne-Wömpner CH, Meyer HJ, Stahl M, Knipp H, Schmoll HJ, Wilke H. Phase II study of single-agent etoposide in patients with metastatic squamous-cell carcinoma of the esophagus. Cancer Chemother Pharmacol. 1992;29(4):321-2. link to original article contains protocol PubMed
Metastatic or locally advanced disease, subsequent lines of therapy
Camrelizumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Huang et al. 2020 (ESCORT) | 2017-2018 | Phase III (E-switch-ooc) | 1. Docetaxel 2. Irinotecan |
Superior OS |
Immunotherapy
- Camrelizumab (AiRuiKa) 200 mg IV once on day 1
14-day cycles
References
- ESCORT: Huang J, Xu J, Chen Y, Zhang Y, Chen Z, Chen J, Niu Z, Fan Q, Lin L, Gu K, Liu Y, Ba Y, Miao Z, Jiang X, Chen J, Fu Z, Gan L, Wang J, Zhan X, Liu T, Li Z. Camrelizumab versus investigator's choice of chemotherapy as second-line therapy for advanced or metastatic oesophageal squamous cell carcinoma (ESCORT): a multicentre, randomised, open-label, phase 3 study. Lancet Oncol. 2020;21(6):832-842. link to original article contains protocol PubMed NCT03099382
Nivolumab monotherapy
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Regimen
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Kato et al. 2019 (ATTRACTION-3) | 2016-2017 | Phase III (E-RT-switch-ooc) | 1. Docetaxel 2. Paclitaxel |
Seems to have superior OS |
Inclusion Criteria: Unresectable advanced or recurrent esophageal SCC regardless of PDL1 expression, ECOG 0-1, refractory or intolerance to one prior 5-FU or platinum-based chemotherapy
Immunotherapy
- Nivolumab (Opdivo) 240 mg IV once on day 1
14-day cycles
References
- ATTRACTION-3: Kato K, Cho BC, Takahashi M, Okada M, Lin CY, Chin K, Kadowaki S, Ahn MJ, Hamamoto Y, Doki Y, Yen CC, Kubota Y, Kim SB, Hsu CH, Holtved E, Xynos I, Kodani M, Kitagawa Y. Nivolumab versus chemotherapy in patients with advanced oesophageal squamous cell carcinoma refractory or intolerant to previous chemotherapy (ATTRACTION-3): a multicentre, randomised, open-label, phase 3 trial. Lancet Oncol. 2019 Nov;20(11):1506-1517. Epub 2019 Sep 30. link to original article PubMed NCT02569242
Pembrolizumab monotherapy
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Regimen
FDA-recommended dose |
Study | Years of enrollment | Evidence | Comparator | Comparative Efficacy |
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Kojima et al. 2020 (KEYNOTE-181) | 2015-2017 | Phase III (E-RT-switch-ooc) | Investigator's choice of: 1. Docetaxel 2. Irinotecan 3. Paclitaxel |
Superior OS (*) |
Shah et al. 2019 (KEYNOTE-180) | 2016-2017 | Phase II (RT) |
Note: Efficacy in KEYNOTE-181 is for patients with squamous cell carcinoma or with PD-L1 combined positive score of at least 10; in all patients the experimental arm might have superior OS. Patients in KEYNOTE-180 had 100% squamous histology.
Biomarker eligibility criteria
- PD-L1 [Combined Positive Score (CPS) ≥10] as determined by an FDA-approved test
Immunotherapy
- Pembrolizumab (Keytruda) 200 mg IV once on day 1
21-day cycle for up to 35 cycles (2 years)
References
- KEYNOTE-180: Shah MA, Kojima T, Hochhauser D, Enzinger P, Raimbourg J, Hollebecque A, Lordick F, Kim SB, Tajika M, Kim HT, Lockhart AC, Arkenau HT, El-Hajbi F, Gupta M, Pfeiffer P, Liu Q, Lunceford J, Kang SP, Bhagia P, Kato K. Efficacy and Safety of Pembrolizumab for Heavily Pretreated Patients With Advanced, Metastatic Adenocarcinoma or Squamous Cell Carcinoma of the Esophagus: The Phase 2 KEYNOTE-180 Study. JAMA Oncol. 2019 Apr 1;5(4):546-550. link to original article PubMed
- KEYNOTE-181: Kojima T, Shah MA, Muro K, Francois E, Adenis A, Hsu CH, Doi T, Moriwaki T, Kim SB, Lee SH, Bennouna J, Kato K, Shen L, Enzinger P, Qin SK, Ferreira P, Chen J, Girotto G, de la Fouchardiere C, Senellart H, Al-Rajabi R, Lordick F, Wang R, Suryawanshi S, Bhagia P, Kang SP, Metges JP; KEYNOTE-181 Investigators. Randomized Phase III KEYNOTE-181 Study of Pembrolizumab Versus Chemotherapy in Advanced Esophageal Cancer. J Clin Oncol. 2020 Dec 10;38(35):4138-4148. Epub 2020 Oct 7. link to original article contains verified protocol PubMed NCT02564263