Esophageal Cancer Treatment Protocols

Updated: Mar 31, 2018
  • Author: Mohammad Muhsin Chisti, MD, FACP; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
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Overview

Overview

Treatment protocols for esophageal cancer are provided below, including recommendations for surgical resection and regimens for the following [1] :

  • Neoadjuvant chemoradiotherapy
  • Perioperative chemotherapy
  • Definitive chemoradiotherapy
  • Postoperative chemoradiotherapy
  • Metastatic disease

Tumors shallow to the muscularis propria of the esophagus (Tis or T1) may be treated with endoscopic resection methods: endoscopic mucosal resection (EMR) and the newer, more extensive technique, endoscopic submucosal dissection (ESD), which is preferred for deeper tumors. For early and some locoregional cancers, surgery is the primary treatment. Esophagectomy may be performed using either the standard open approach or a minimally invasive procedure. 

For chemotherapy, two-drug cytotoxic regimens that include a platinum agent are generally preferred for first-line therapy. Second-line and subsequent therapy may involve single agents (eg, with taxanes) or molecular therapy such as ramucirumab to target vascular endothelial growth factor (VEGF) receptor or trastuzumab for metastatic adenocarcinoma that overexpresses human epidermal growth factor receptor 2 (HER2 ). [1]

Radiation therapy is often given with chemotherapy. External beam radiation therapy (EBRT) is used.

A study by Fogh et al of induction chemoradiotherapy followed by surgery, a strategy that is widely used in treating esophageal cancer, found that perioperative morbidity and mortality with this approach was not significantly different in patients aged 70 years or older compared with younger patients. Consequently, these authors suggest using this strategy in elderly patients. [2]

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General Recommendations Based on Stage

The following recommendations are based on tumor/node/metastasis (TNM)–based stages. Stage I, II, and III esophageal cancers are all potentially resectable.

Stage 0 - Stage 1

For Tis-T1a, N0, M0 disease, treatment options are as follows:

  • Endoscopic resection
  • Ablation
  • Endoscopic resection followed by ablation
  • Esophagectomy

For T1b, N0, M0 disease, treatment options are as follows:

  • Endoscopic resection followed by ablation
  • Esophagectomy

Stage II

For T2/T3, N0, M0 disease, treatment options are as follows:

  • Esophagectomy
  • Definitive chemoradiation therapy
  • Neoadjuvant chemoradiotherapy followed by esophagectomy 

Stage III

For T3, N1, M0 to T1-3, N2, M0 disease, chemoradiotherapy with or without esophagectomy is recommended

Stage IV

For T4, N0-2, M0-1 disease, treatment options are as follows:

  • Chemoradiation
  • Chemotherapy
  • Supportive care as indicated
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Neoadjuvant Chemoradiotherapy, Resectable Disease

Neoadjuvant chemoradiotherapy appears to be associated with better survival than local therapy or surgery alone. [3]  Regimens are listed below according to National Comprehensive Cancer Network (NCCN) categories of evidence: Category 1 recommendations are based on high-level evidence, while category 2A recommendations are based on lower-level evidence.  With both categories, there is uniform NCCN consensus that the intervention is appropriate.

Category 1 regimens

See the list below:

  • Paclitaxel 50 mg/m 2 IV over 60 minutes on Days 1, 8, 15, 22, and 29 plus carboplatin, area under the curve (AUC) 2  IV ( see the Carboplatin AUC Dose Calculation [Calvert formula]calculator) on Days 1, 8, 15, 22, and 29 of a 5-week cycle [4, 5]
  • Cisplatin 100 mg/m 2 IV on Day 1 plus 5-fluorouracil (5-FU) 800 mg/m 2/day continuous IV infusion on Days 1 to 5 of a 28-day cycle for two or three cycles [6, 7]   or
  • Cisplatin 60 mg/m 2 IV over 60 minutes on day 1 (given before first dose of capecitabine) plus capecitabine 1000 mg/m 2 PO BID on Days 1 to 14 of a 21-day cycle [8, 9]
  • Oxaliplatin 85 mg/m 2 IV over 2 hours on Day 1 plus   leucovorin 200 mg/m 2 IV over 2 hours on Day 1 plus 5-FU 400 mg/m 2 IV bolus, then 600 mg/m 2/day IV over 22 hours on Days 1 and 2 of a 14-day cycle for three cycles [10]

Category 2A regimens

See the list below:

  • Cisplatin 50 mg/m 2 IV over 60 minutes once per day on Days 1 and 8 plus etoposide 80 mg/m 2 IV over 60 minutes once per day on Days 3 to 5; chemoradiotherapy to start 2 weeks after the last day of chemotherapy for 12 weeks [3]   or
  • Oxaliplatin 45 mg/m 2 IV over 2 hours once per day on Days 1, 8, 15, 22, and 29 for 5 weeks plus 5-FU 225 mg/m 2/day IV continuous infusion over Days 1 to 33 [11]   or
  • Oxaliplatin 85 mg/m 2 IV over 2 hours once per day on Days 1, 15, and 29 plus  5-FU 180 mg/m 2/day continuous IV infusion over Days 8 to 42 [12]   or
  • Oxaliplatin 85 mg/m 2 IV once per day on Days 1, 15, and 29 plus capecitabine 625 mg/m 2 PO BID on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33 for 5 weeks [13]   or
  • Paclitaxel 50 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus cisplatin 30 mg/m 2 IV on Days 1, 8, 15, 22, and 29 (ie, weekly for 5 weeks) [14, 15]   or
  • Docetaxel 20 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus cisplatin 25 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 for one cycle [16]   or
  • Paclitaxel 60 mg/m 2 IV over 3 hours on Days 1, 8, 15, and 22 plus cisplatin 75 mg/m 2 IV over 2 hours on Day 1 for one cycle [17]   or
  • Carboplatin AUC 6 IV once per day on Days 1 and 22 plus 5-FU 200 mg/m 2/day IV continuous infusion on Days 1 to 42 [18]   or
  • Irinotecan 65 mg/m 2 IV on Days 1, 8, 22, and 29 plus cisplatin 30 mg/m 2 IV once per day on Days 1, 8, 22, and 29 [14, 19, 20]   or
  • Paclitaxel 45 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus 5-FU 300 mg/m 2 IV continuous infusion  on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [21, 22]   or
  • Paclitaxel 45-50 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus capecitabine 625-825 mg/m 2 PO BID on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [9, 21, 23]   or
  • Docetaxel 20 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus 5-FU 200-300 mg/m 2/day continuous IV infusion on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [24, 25]   or
  • Docetaxel 20 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus capecitabine 625-825 mg/m 2 PO BID on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [23, 25]   or
  • Oxaliplatin 40 mg/m 2 IV on Days 1, 8, 15, 22, and 29 plus docetaxel 20 mg/m 2 IV over 30 min on Days 1, 8, 15, 22, and 29 plus capecitabine 1000 mg/m 2 PO BID on Days 1 to 7, 15 to 21, and 29 to 35 for one cycle [25]
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Perioperative Chemotherapy, Resectable Disease

Perioperative chemotherapy with regimens such as ECF (epirubicin, cisplatin, and 5-FU) has led to significant improvement in overall survival in patients with operable lower esophageal adenocarcinomas. Treatment recommendations include three cycles preoperatively and three cycles postoperatively of ECF, only for adenocarcinoma of the distal esophagus or gastroesophageal junction. 

The following are NCCN category 1 regimens (ie, supported by high-level evidence):

  • Cisplatin 100 mg/m 2 IV on Day 1 plus 5-fluorouracil (5-FU) 800 mg/m 2/day continuous IV infusion on Days 1 to 5 of a 28-day cycle for two or three cycles [6]   or
  • Epirubicin 50 mg/m 2 IV bolus once on Day 1 plus cisplatin 60 mg/m 2 IV once on Day 1 plus 5-FU 200 mg/m 2/day continuous IV infusion daily on Days 1 to 21; every 21d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [26]   or
  • Epirubicin 50 mg/m 2 IV bolus once on Day 1 plus oxaliplatin 130 mg/m 2 IV over 2 hours once on Day 1 plus  5-FU 200 mg/m 2/day continuous IV infusion daily on Days 1-21; every 21d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [26]   or
  • Epirubicin 50 mg/m 2 IV once on Day 1 plus cisplatin 60 mg/m 2 IV once on Day 1 plus capecitabine 625 mg/m 2 PO BID on Days 1 to 21; every 21d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [26]   or
  • Epirubicin 50 mg/m 2 IV bolus once on day 1 plus  oxaliplatin 130 mg/m 2 IV over 2 hours on Day 1 plus capecitabine 500-625 mg/m 2 PO BID on Days 1 to 21; every 21d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [26]
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Unresectable Nonmetastatic Disease

Definitive chemoradiotherapy is used in patients with unresectable nonmetastatic esophageal cancer. The following are NCCN category 1 regimens (ie, supported by high-level evidence):

  • Cisplatin 75-100 mg/m 2 IV on Day 1 plus  5-FU 750-1000 mg/m 2/day continuous IV infusion on days 1-4; every 4wk for two to four cycles [27, 28]   or
  • Cisplatin 30 mg/m 2 IV on Day 1 plus capecitabine 800 mg/m 2 PO BID on Days1 to 5; weekly for 5wk [8]  
  • Oxaliplatin 85 mg/m 2 IV over 2 hours on Day 1 plus leucovorin 400 mg/m 2 IV over 2 hours on Day 1 plus  5-FU 400 mg/m 2 IV bolus on Day 1, then  5-FU 1200 mg/m 2 continuous IV infusion daily on Days 1 and 2; every 14d for three cycles [10]  
  • Paclitaxel 50 mg/m 2 IV over 60 minutes once per day on Days 1, 8, 15, 22, and 29 plus carboplatin AUC 2 IV on Days 1, 8, 15, 22, and 29; weekly for 5wk [4]

The following are NCCN category 2A regimens (ie, supported by a lower level of clinical evidence):

  • Oxaliplatin 45-50 mg/m 2 IV over 2 hours once per day on Days 1, 8, 15, 22, and 29 for 5 weeks plus  5-FU 225 mg/m 2/day continuous IV infusion on Days 1 to 42 [11]   or
  • Oxaliplatin 85 mg/m 2 IV over 2 hours once per day on Days 1, 15, and 29 plus  5-FU 180 mg/m 2/day continuous IV infusion on Days 1 to 33 [12]   or
  • Oxaliplatin 85 mg/m 2 IV once per day on Days 1, 15, and 29 plus capecitabine 625 mg/m 2 PO BID on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33 for 5wk [13]   or
  • Paclitaxel 50 mg/m 2 IV over 60 minutes on Days 1, 8, 15, 22, and 29 plus cisplatin 30 mg/m 2 IV once per day on Days 1, 8, 15, 22, 29; weekly for 5wk [14]   or
  • Docetaxel 20 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus cisplatin 25 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 for one cycle16  or
  • Paclitaxel 60 mg/m 2 IV over 3 hours once per day on Days 1, 8, 15, and 22 plus cisplatin 75 mg/m 2 IV over 2 hours on Day 1 for one cycle [17]   or
  • Docetaxel 60 mg/m 2 IV on Days 1 and 22 plus cisplatin 80 mg/m 2 IV on Days 1 and 22 for one cycle [29]   or
  • Irinotecan 65 mg/m 2 IV once per day on Days 1, 8, and 22 (some studies suggest also on Days 15 and 29) plus cisplatin 30 mg/m 2 IV on Days 1, 8, and 22 (some studies suggest also on days 15 and 29) [14, 19, 20]   or
  • Paclitaxel 45 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus 5-FU 300 mg/m 2 IV continuous infusion daily on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [21, 22]   or
  • Paclitaxel 45-50 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus capecitabine 625-825 mg/m 2 PO BID on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [21, 23]   or
  • Docetaxel 20 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus 5-FU 200-300 mg/m 2/day continuous IV infusion on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5wk [24, 25]   or
  • Docetaxel 20 mg/m 2 IV once per day on Days 1, 8, 15, 22, and 29 plus capecitabine 625-825 mg/m 2 PO BID on Days 1 to 5, 8 to 12, 15 to 19, 22 to 26, and 29 to 33; weekly for 5 wk [23, 25]   or
  • Oxaliplatin 40 mg/m 2 IV on Days 1, 8, 15, 22, and 29 plus docetaxel 20 mg/m 2 IV on days 1, 8, 15, 22, and 29 plus capecitabine 1000 mg/m 2 PO BID on Days 1 to 7, 15 to 21, and 29 to 35 for one cycle [25]
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Postoperative Chemoradiotherapy for Adenocarcinomas

Surgery can be the initial treatment of choice for patients with adenocarcinoma; however, it is advisable to treat these patients with postoperative chemoradiotherapy because of an evidence-based increase in survival. The following are NCCN category 1 regimens (ie, supported by high-level evidence):

  • Leucovorin (folinic acid) 20 mg/m 2 IV bolus once per day on Days 1 to 5 plus 5-FU 425 mg/m 2 IV bolus once per day on Days 1 to 5; every 28 d in cycles one, four, and five, given before and after radiation; plus leucovorin 20 mg/m 2 IV bolus once per day on Days 1 to 5 plus 5-FU 425 mg/m 2 IV bolus once per day on Days 1 to 5; every 28d in cycles two and three, given with radiation [30]  or
  • Leucovorin 400 mg/m 2 IV on Days 1, 2, 15, and 16 plus 5-FU 400 mg/m 2 IV bolus on Days 1, 2, 15, and 16 plus 5-FU 1200 mg/m 2/day continuous IV infusion on Days 1 and 2; 28-day cycle, one cycle before 5 weeks of chemotherapy/radiation and two cycles after chemotherapy/radiation [31]  or
  • 5-FU 200-250 mg/m 2/day continuous IV infusion on Days 1 to 5 or Days 1 to 7; weekly for 5wk with radiation [32]   or
  • Capecitabine 625-825 mg/m 2 PO BID on Days 1 to 5 or Days 1 to 7; weekly for 5wk with radiation [33]
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Systemic Therapy for Recurrent or Metastatic Disease

Trastuzumab should be added to first-line chemotherapy for metastatic adenocarcinomas that overexpress HER2. However,  it is not recommended for use with anthracyclines. [1]

The following are NCCN category 1 regimens (ie, supported by high-level evidence):

  • Docetaxel 75 mg/m 2 IV over 60 minutes once on Day 1 plus cisplatin 75 mg/m 2 IV over 1 to 3 hours once on Day 1 plus 5-FU 750 mg/m 2/day continuous IV infusion on Days 1 to 5; every 28d [34]   or
  • Epirubicin 50 mg/m 2 IV bolus once on Day 1 plus cisplatin 60 mg/m 2 IV over 4 hours once on Day 1 plus 5-FU 200 mg/m 2/day IV continuous infusion on Days 1 to 21; every 21d [35, 36]   or
  • Epirubicin 50 mg/m 2 IV bolus on Day 1 plus oxaliplatin 130 mg/m 2 IV over 2 hours on Day 1 plus 5-FU 200 mg/m 2/day IV continuous infusion on Days 1 to 21; every 21d [36]   or
  • Epirubicin 50 mg/m 2 IV bolus once on Day 1 plus cisplatin 60 mg/m 2 IV over 4 hours on Day 1 plus capecitabine 625 mg/m 2 PO BID on Days 1 to 21; every 21d [36]   or
  • Epirubicin 50 mg/m 2 IV once on Day 1 plus oxaliplatin 130 mg/m 2 IV once on Day 1 plus capecitabine 625 mg/m 2 PO BID on Days 1 to 21; every 21d [36]   or
  • Cisplatin 75-100 mg/m 2 IV on Day 1 plus 5-FU 750-1000 mg/m 2/day continuous IV infusion on Days 1 to 4; every 28d [37]   or
  • Cisplatin 50 mg/m 2 IV over 2 hours once on Day 1 plus leucovorin 200 mg/m 2 IV over 2 hours once on Day 1 plus 5-FU 400 mg/m 2 IV bolus, then 600 mg/m 2/day IV continuous infusion over 22 hours on Day 1; every 14d [38, 39]   or
  • Cisplatin 80 mg/m 2 IV over 2 hours once on Day 1 plus capecitabine 1000 mg/m 2 PO BID on Days 1 to 14; every 21d [37, 40] or
  • Capecitabine 850 mg/m PO BID on days 1 to 14 plus oxaliplatin 130 mg/m IV on Day 1 (CapeOx regimen); 21-day cycle for up to eight cycles [41]
  • For adenocarcinomas that overexpress HER2-NEU: Cisplatin 80 mg/m 2 IV on Day 1 plus 5-FU 800 mg/m 2/day continuous IV infusion on Days 1 to 5 plus trastuzumab 8 mg/m 2 IV loading dose on Day 1 of cycle one, then 6 mg/m 2 IV once on Day 1; every 21d with chemotherapy [37]  

The following are NCCN category 2A regimens (ie, supported by a lower level of clinical evidence):

  • Docetaxel 40 mg/m 2 IV over 60 minutes on Days 1, 15, and 29 plus leucovorin 400 mg/m 2 IV once on Days 1, 15, and 29 plus 5-FU 400 mg/m 2 IV once on Days 1, 15, and 29, then 5-FU 1000 mg/m 2/day continuous IV infusion on Days 1, 2, 15, 16, 29, and 30 plus cisplatin 40 mg/m 2 IV over 1 to 3 hours once on Days 3, 17, and 31 [42]   or
  • Docetaxel 50 mg/m 2 IV once on Day 1 plus oxaliplatin 85 mg/m 2 IV once on Day 1 plus leucovorin 200 mg/m 2 IV on Day 1 plus 5-FU 2600 mg/m 2/day continuous IV infusion on Day 1; every 14d [43]   or
  • Docetaxel 50 mg/m 2 on Day 1 plus  oxaliplatin 85 mg/m 2 IV on Day 1 plus 5-FU 1200 mg/m 2/day continuous IV infusion on Days 1 and 2; every 14d [43]   or
  • Docetaxel 60 mg/m 2 on Day 1 plus  cisplatin 60 mg/m 2 IV on Day 1 plus 5-FU 750 mg/m 2/day continuous IV infusion on Days 1 to 4; every 21d [44]   or
  • Docetaxel 85 mg/m 2 on Day 1 plus cisplatin 75-85 mg/m 2 IV on Day 1 plus 5-FU 300 mg/m 2/day continuous IV infusion on Days 1 to 14; every 21d [45]   or
  • Docetaxel 75 mg/m 2 on Day 1 plus carboplatin AUC 6 IV on Day 2 plus 5-FU 1200 mg/m 2/day continuous IV infusion on Days 1 to 3; every 21d [44]  (category 2B) or
  • Oxaliplatin 85 mg/m 2 IV on Day 1 plus leucovorin 400 mg/m 2 IV on Day 1 plus 5-FU 400 mg/m 2 IV push on Day 1 plus  5-FU 1200 mg/m 2/day continuous IV infusion on Days 1 and 2; every 14d [46]   or
  • Oxaliplatin 85 mg/m 2 IV on Day 1 plus leucovorin 200 mg/m 2 IV on Day 1 plus 5-FU 2600 mg/m 2/day IV continuous infusion on Day 1; every 14d [38]   or
  • Irinotecan 80 mg/m 2 IV on day 1 plus leucovorin 500 mg/m 2 IV on Day 1 plus 5-FU 2000 mg/m 2/day IV continuous infusion on Day 1; weekly for 6wk followed by 1wk off treatment [47]   or
  • Irinotecan 180 mg/m 2 IV over 90 minutes once per day on Day 1 plus leucovorin 400 mg/m 2 IV over 2 hours once on Day 1 plus 5-FU 400 mg/m 2 IV bolus on Day 1 then 5-FU 1200 mg/m 2/day IV continuous infusion over 46 hours on Days 1 and 2; every 14d [39, 48]   or
  • Irinotecan 80 mg/m 2 IV over 30 minutes once per day on Days 1, 8, 15, 22, 29, and 36 plus leucovorin 500 mg/m 2 IV over 2 hours once per day on Days 1, 8, 15, 22, 29, and 36 combined with 5-FU 2000 mg/m 2/day IV continuous 22-hour infusion on Days 1, 8, 15, 22, 29, and 36; weekly for 6wk followed by 2wk off treatment [49]   or
  • Paclitaxel 200 mg/m 2 IV over 24 hours on Day 1 plus cisplatin 75 mg/m 2 IV once on Day 2; every 21d [50]   or
  • Paclitaxel 90 mg/m 2 IV over 3 hours once on Day 1 plus cisplatin 50 mg/m 2 IV over 60 min once on Day 1; every 14d [51]   or
  • Paclitaxel 200 mg/m 2 IV over 3 hours on Day 1 plus carboplatin AUC 5 IV once on Day 1; every 21d [52]   or
  • Docetaxel 75 mg/m 2 (dose lowered from original level of 85 mg/m 2 because of high incidence of febrile neutropenia) IV over 60 minutes on Day 1 plus cisplatin 75 mg/m 2 IV over 4 hours once on Day 1; every 21d [45, 53, 54]   or
  • Docetaxel 35 mg/m 2 IV over 60 minutes on Days 1 and 8 plus irinotecan 50 mg/m 2 IV over 30 minutes once per day on Days 1 and 8; every 21d [55]   or
  • Leucovorin 200 mg/m 2 IV over 2 hours once on Day 1 plus 5-FU 400 mg/m 2 IV bolus on Day 1 then 5-FU 600 mg/m 2/day IV continuous infusion over 22 hours on Days 1 and 2; every 14d [39]   or
  • 5-FU 800 mg/m 2/day IV continuous infusion on Days 1 to 5; every 28d [56]   or
  • Capecitabine 1250 mg/m 2 PO BID on Days 1 to 14; every 21d [57]   or
  • Docetaxel 75 mg/m 2 IV over 60 minutes on Day 1; every 21d [58]   or
  • Paclitaxel 135-175 mg/m 2 IV over 24 hours on Day 1; every 21d [59]   or
  • Paclitaxel 80 mg/m 2 IV over 60 minutes on Days 1, 8, 15, and 22 [60]

Second-line therapy

Category 1 recommendations for second-line therapy based on high level of clinical evidence, are as follows:

  • For HER2-NEU overexpressing adenocarcinomas, trastuzumab 8 mg/m 2 IV loading dose on Day 1 of cycle one, then 6 mg/m 2 IV; every 21d with chemotherapy [37, 57]
  • Ramucirumab 8 mg/kg IV once per day on Days 1 and 15 plus paclitaxel 80 mg/m 2 IV once per day on Days 1, 8, and 15 of a 28-day cycle [58]  (category 1 for esophagogastric junction [EGJ] adenocarcinoma; category 2A for esophageal adenocarcinoma)  or
  • Ramucirumab (Cyramza) 8 mg/kg IV once every 2 weeks [61]  (category 1 for EGJ adenocarcinoma; category 2A for esophageal adenocarcinoma)  or
  • Docetaxel 75-100 mg/m 2 IV over 60 minutes on Day 1; every 21d [62]   or
  • Paclitaxel 135-175 mg/m 2 IV over 24 hours on Day 1; every 21d  [59]   or
  • Paclitaxel 80 mg/m 2 IV over 60 minutes on Days 1, 8, 15, and 22; every 28d [60]   or
  • Irinotecan 180 mg/m 2 IV over 90 minutes on Day 1 plus leucovorin 400 mg/m 2 IV over 2 hours on Day 1 plus 5-FU 400 mg/m 2 IV bolus on Day 1 then 5-FU 1200 mg/m 2/day IV continuous infusion over 46 hours on Days 1 and 2; every 14d [63]   or
  • Irinotecan 250-350 mg/m 2 IV on Day 1; every 21d [64]   or
  • Irinotecan 180 mg/m  2 IV on Day 1; every 14d [65, 66]   or
  • Irinotecan 125 mg/m  2 IV on days 1 and 8; every 21d [65, 66]

Category 2A recommendations for second-line therapy, based on lower level of clinical evidence, include the following:

  • Irinotecan 65 mg/m 2 IV once per day on Days 1 and 8 plus cisplatin 30 mg/m 2 IV on Days 1 and 8; every 21d [46, 67]   or
  • Irinotecan 250 mg/m 2 IV over 30 to 90 minutes once on Day 1 plus capecitabine 1000 mg/m 2 PO BID on Days 1 to 14; every 21d [68]   or
  • Docetaxel 35 mg/m 2 IV on Days 1 and 8 plus irinotecan 50 mg/m 2 on Days 1 and 8; every 21d [55]   or
  • Irinotecan 150 mg/m 2 IV once per day on Days 1 and 15 plus mitomycin 8 mg/m 2 IV once on Day 1; every 28d [69]   or
  • Irinotecan 125 mg/m 2 IV on ays 1 and 8 plus mitomycin 5 mg/m 2 IV on Day 1; every 28d [70]   or
  • Pembrolizumab 200 mg IV on Day 1; 21-day cycle [71]  (for second-line or subsequent therapy for high microsatellite instability (MSI-H)/deficient mismatch repair (dMMR) tumors; for third-line or subsequent therapy for programmed cell death ligand 1 (PD-L1)–positive esophageal and EGJ adenocarcinoma)
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Other Regimens to Consider

See the list below:

  • Gemcitabine 1000 mg/m 2 IV once on Dys 1, 8, and 15 plus leucovorin 25 mg/m 2 IV once on Days 1, 8, and 15 plus 5-FU 600 mg/m 2 IV on Days 1, 8, and 15; every 28d [72]   or
  • Pegylated liposomal doxorubicin 20 mg/m 2 IV once on Day 1 plus cisplatin 50 mg/m 2 IV once on Day 1 plus 5-FU 400 mg/m 2 IV bolus on Day 1 then 5-FU 600 mg/m 2/day continuous IV infusion on Days 1 and 2; every 14d [73]   or
  • Mitomycin 6 mg/m 2 IV once on Day 1 plus irinotecan 125 mg/m 2 IV on Days 2 and 9; every 28d [74]   or
  • Mitomycin 7 mg/m 2 (maximum 14 mg per cycle) IV once on Day 1 plus cisplatin 60 mg/m 2 IV once on  Days 1 and 22 plus 5-FU 300 mg/m 2/day continuous IV infusion on Days 1 to 42; every 6 wk [35]   or
  • Mitomycin 10 mg/m 2 IV once per day on Days 1 and 22 plus leucovorin 500 mg/m 2 IV over 2 hours once per day on Day 1 plus 5-FU 2600 mg/m 2/day continuous IV infusion over 24 hours on Days 1, 8, 15, 22, 29, and 36 for 8 wk cycle (6wk followed by 2wk off treatment) [75]   or
  • Etoposide 90-120 mg/m 2 on Days 1 to 3; every 28d [76, 77]   or
  • Erlotinib 150 mg PO daily on Days 1 to 28 [78, 79]   or
  • Cetuximab 400 mg/m 2 IV over 2 hours on Day 1 of week 1, then cetuximab 250 mg/m 2 IV over 60 minutes once per day on Days 8, 15, and 22; can be used as single agent or with chemotherapy [80]
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