Esophageal Cancer Treatment Protocols

Updated: Dec 30, 2015
  • Author: Terence D Rhodes, MD, PhD; Chief Editor: N Joseph Espat, MD, MS, FACS  more...
  • Print
Overview

Overview

Treatment protocols for esophageal cancer are provided below, including for neoadjuvant chemoradiotherapy, perioperative chemotherapy, definitive chemoradiotherapy, postoperative chemoradiotherapy, and metastatic disease. [1]

Category 1 and 2A regimens are indicated to guide selection of preferred regimens. Selections should be based on preferred regimens but may need to be modified, or other regimens may need to be selected for the specific clinical situations.

A study by Fogh et al examined the use of induction chemoradiotherapy followed by surgery a strategy that is widely used in treating esophageal cancer. The study compared the perioperative morbidity and mortality of patients aged 70 years or older with those of patients younger than 70 years who underwent chemoradiotherapy followed by esophagectomy. The study found no significant differences in mortality or morbidity in elderly patients. Thus, the authors suggest using this strategy in elderly patients. [2]

Next:

General Recommendations Based on Stage

Stage I, II, and III esophageal cancers are all potentially resectable.

Stage 0 to stage I

See the list below:

  • Surgery is primarily indicated for early stage esophageal cancer

Stage II

See the list below:

  • Surgery, definitive chemoradiation therapy, or neoadjuvant chemoradiotherapy followed by surgery are appropriate options

Stage III

See the list below:

  • Chemoradiotherapy with or without surgery is recommended

Stage IV

See the list below:

  • Chemotherapy, symptomatic treatment/supportive care as indicated
Previous
Next:

Neoadjuvant Chemoradiotherapy, Resectable Disease

Neoadjuvant chemoradiotherapy appears to be associated with better survival than local therapy or surgery alone. [1]

Category 1: recommendations based on high level of clinical evidence

See the list below:

  • Paclitaxel 50 mg/m 2 IV on day 1 plus  carboplatin AUC 2 IV on day 1; weekly for 5wk [3, 4] ( see the Carboplatin AUC Dose Calculation [Calvert formula] calculator) or
  • Cisplatin 75-100 mg/m 2 IV on days 1 and 29 plus  5-fluorouracil (5-FU) 750-1000 mg/m 2/day continuous IV infusion on days 1-4 and days 29-32; 35d cycle for 2-4 cycles [5, 6] or
  • Cisplatin 30 mg/m 2 IV on day 1 plus  capecitabine 800 mg/m 2 PO BID on days 1-5; weekly for 5wk [7, 8] or
  • Cisplatin 15 mg/m 2 IV daily on days 1-5 and days 22-26 plus  5-FU 800 mg/m 2/day continuous IV infusion on days 1-5 and days 22-26; 1 cycle [9]

Category 2A: recommendations based on lower level of clinical evidence

See the list below:

  • Oxaliplatin 45-50 mg/m 2 IV on day 1 weekly for 5wk plus  5-FU 225 mg/m 2 IV daily on days 1-42 [10] or
  • Oxaliplatin 85 mg/m 2 IV on days 1, 15, and 29 plus  5-FU 180 mg/m 2/day continuous IV infusion on days 1-33 [11] or
  • Oxaliplatin 85 mg/m 2 IV on days 1, 15, and 29 plus  capecitabine 625 mg/m 2 PO BID on days 1-5 for 5wk [12] 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 IVP on day 1 plus  5-FU 1200 mg/m 2 IV continuous infusion daily on days 1 and 2; every 14d for 3 cycles [13] or
  • Paclitaxel 50 mg/m 2 IV on day 1 plus  cisplatin 25-30 mg/m 2 IV on day 1; weekly for 5wk [14, 15] or
  • Docetaxel 20 mg/m 2 IV on days 1, 8, 15, 22, and 29 plus  cisplatin 25-30 mg/m 2 IV on days 1, 8, 15, 22, and 29; 1 cycle [16] or
  • Paclitaxel 60 mg/m 2 IV on days 1, 8, 15, and 22 plus  cisplatin 75 mg/m 2 IV on day 1; 1 cycle [17] or
  • Carboplatin AUC 6 IV on days 1 and 22 plus  5-FU 200 mg/m 2 IV daily on days 1-42 [18] or
  • Irinotecan 50-65 mg/m 2 IV on days 1, 8, and 22 (some studies suggest also on days 15 and 29) plus  cisplatin 25-30 mg/m 2 IV on days 1, 8, and 22 (some studies suggest also on days 15 and 29) [14, 19, 20] or
  • Paclitaxel 45-50 mg/m 2 IV on day 1 plus  5-FU 200-300 mg/m 2 IV daily on days 1-5; weekly for 5wk [21, 22] or
  • Paclitaxel 45-50 mg/m 2 IV on day 1 plus  capecitabine 625-825 mg/m 2 PO BID on days 1-5; weekly for 5wk [21, 23, 8] or
  • Docetaxel 20 mg/m 2 IV on day 1 plus  5-FU 200-300 mg/m 2/day continuous IV infusion on days 1-5; weekly for 5wk [24, 25] or
  • Docetaxel 20 mg/m 2 IV on day 1 plus  capecitabine 625-825 mg/m 2 PO twice daily on days 1-5; 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 on days 1, 8, 15, 22, and 29 plus  capecitabine 1000 mg/m 2 PO twice daily on days 1-7, 15-21, and 29-35; 1 cycle [25]
Previous
Next:

Perioperative Chemotherapy, Resectable Disease

Perioperative chemotherapy with drugs such as epirubicin, cisplatin, and 5-FU (ECF) have shown significant improvement in progression-free survival and overall survival in patients with operable lower esophageal adenocarcinomas. Treatment recommendations include 3 cycles preoperatively and 3 cycles postoperatively of ECF, only for adenocarcinoma of the distal esophagus or gastroesophageal junction (GE).

Category 1: recommendations based on high level of clinical evidence

See the list below:

  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV 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 on day 1 plus  oxaliplatin 130 mg/m 2 IV 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 [27] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID on days 1-21; every 21d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [27] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID on days 1-21; every 21d for cycles 1-3 preoperatively and cycles 4-6 postoperatively [27]
Previous
Next:

Unresectable Nonmetastatic Disease

Definitive chemoradiotherapy is used in patients with unresectable nonmetastatic disease.

Category 1: recommendations based on high level of clinical evidence

See the list below:

  • 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 2-4 cycles [28, 29] or
  • Cisplatin 30 mg/m 2 IV on day 1 plus  capecitabine 800 mg/m 2 PO BID on days 1-5; weekly for 5wk [7]

Category 2A: recommendations based on lower level of clinical evidence

See the list below:

  • Oxaliplatin 45-50 mg/m 2 IV on day 1 weekly for 5wk plus  5-FU 225 mg/m 2/day continuous IV infusion on days 1-42 [10] or
  • Oxaliplatin 85 mg/m 2 on days 1, 15, and 29 plus  5-FU 180 mg/m 2/day continuous IV infusion on days 1-33 [11] or
  • Oxaliplatin 85 mg/m 2 IV on days 1, 15, and 29 plus  capecitabine 625 mg/m 2 PO BID on days 1-5 weekly for 5wk [12] 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 IVP on day 1 plus  5-FU 1200 mg/m 2 continuous IV infusion daily on days 1 and 2; every 14d for 3 cycles [13] or
  • Paclitaxel 50 mg/m 2 IV on day 1 plus  cisplatin 25-30 mg/m 2 IV on day 1; weekly for 5wk [14] or
  • Docetaxel 20 mg/m 2 IV on days 1, 8, 15, 22, and 29 plus  cisplatin 25-30 mg/m 2 IV on days 1, 8, 15, 22, and 29; 1 cycle [16] or
  • Paclitaxel 60 mg/m 2 IV on days 1, 8, 15, and 22 plus  cisplatin 75 mg/m 2 IV on day 1; 1 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; 1 cycle [30] or
  • Paclitaxel 50 mg/m 2 IV on day 1 plus  carboplatin AUC 2 IV on day 1; weekly for 5wk [3] or
  • Irinotecan 50-65 mg/m 2 IV on days 1, 8, and 22 (some studies suggest also on days 15 and 29) plus  cisplatin 25-30 mg/m 2 IV on days 1, 8, and 22 (some studies suggest also on days 15 and 29) [14, 19, 20] or
  • Paclitaxel 45-50 mg/m 2 IV on day 1 plus  5-FU 200-300 mg/m 2 IV daily on days 1-5; weekly for 5wk [21, 22] or
  • Paclitaxel 45-50 mg/m 2 IV on day 1 plus  capecitabine 625-825 mg/m 2 PO BID on days 1-5; weekly for 5wk [21, 23] or
  • Docetaxel 20 mg/m 2 IV on day 1 plus  5-FU 200-300 mg/m 2/day continuous IV infusion on days 1-5; weekly for 5wk [24, 25] or
  • Docetaxel 20 mg/m 2 IV on day 1 plus  capecitabine 625-825 mg/m 2 PO BID on days 1-5; 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 on days 1, 8, 15, 22, and 29 plus  capecitabine 1000 mg/m 2 PO BID on days 1-7, 15-21, and 29-35; 1 cycle [25]
Previous
Next:

Postoperative Chemoradiotherapy, Adenocarcinomas

Surgery can be the initial treatment for patients with adenocarcinoma; however, it is advisable to treat these patients with postoperative chemoradiotherapy because of an increase in survival.

Category 1: recommendations based on high level of clinical evidence

See the list below:

  • Leucovorin 20 mg/m 2 IVP on days 1-5 plus  5-FU 425 mg/m 2 IVP daily on days 1-5; every 28d, cycles 1, 4, and 5 given before and after radiation; plus  leucovorin 20 mg/m 2 IVP on days 1-3 (some studies suggest also on day 4) plus  5-FU 400 mg/m 2 IVP daily on days 1-3 (some studies suggest also on day 4); every 28d, cycles 2 and 3 given with radiation [31] or
  • Leucovorin 400 mg/m 2 IV on days 1, 2, 15, and 16 plus  5-FU 400 mg/m 2 IVP 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 as 1 cycle before 5 weeks of chemotherapy/radiation and 2 cycles after chemotherapy/radiation [32] or
  • 5-FU 200-250 mg/m 2/day continuous IV infusion on days 1-5 or days 1-7; weekly for 5wk with radiation [33] or
  • Capecitabine 625-825 mg/m 2 PO BID on days 1-5 or days 1-7; weekly for 5wk with radiation [34]
Previous
Next:

Recurrent or Metastatic Disease

First-line therapy

Category 1: recommendations based on high level of clinical evidence:

  • Docetaxel 75 mg/m 2 IV on day 1 plus  cisplatin 75 mg/m 2 IV on day 1 plus  5-FU 1000 mg/m 2/day continuous IV infusion on days 1-5; every 28d [35] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV on day 1 plus  5-FU 200 mg/m 2/day IV continuous infusion on days 1-21; every 21d [36, 37] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 on day 1 plus  5-FU 200 mg/m 2/day IV continuous infusion on days 1-21; every 21d [37] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  cisplatin 60 mg/m 2 IV on day 1 plus  capecitabine 625 mg/m 2 PO BID on days 1-21; every 21d [37] or
  • Epirubicin 50 mg/m 2 IV on day 1 plus  oxaliplatin 130 mg/m 2 IV on day 1 plus capecitabine 625 mg/m 2 PO BID on days 1-21; every 21d [37] 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 1-4; every 28d [38] or
  • Cisplatin 50 mg/m 2 IV on day 1 plus  leucovorin 200 mg/m 2 IV on day 1 plus  5-FU 2000 mg/m 2/day IV continuous infusion on day 1; every 14d [39, 40] or
  • Cisplatin 80 mg/m 2 IV on day 1 plus  capecitabine 1000 mg/m 2 PO twice daily on days 1-14; every 21d [38, 41]
  • For HER2-NEU overexpressing adenocarcinomas, trastuzumab 8 mg/m 2 IV loading dose on day 1 of cycle 1, then 6 mg/m 2 IV; every 21d with chemotherapy [38]

Category 2A: recommendations based on lower level of clinical evidence:

  • Docetaxel 40 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 on day 1 plus  5-FU 1000 mg/m 2/day continuous IV infusion on days 1 and 2 plus  cisplatin 40 mg/m 2 on day 3; every 14d [42] or
  • Docetaxel 50 mg/m 2 on day 1 plus  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 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 [44] 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 1-4; every 21d [45] 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 1-14; every 21d [46] 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 1-3; every 21d [47] 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 IVP on day 1 plus  5-FU 1200 mg/m 2/day continuous IV infusion on days 1 and 2; every 14d [48] 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 [39] 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 [49] or
  • Irinotecan 180 mg/m 2 IV on day 1 plus  leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IVP on day1 plus  5-FU 1200 mg/m 2/day IV continuous infusion on days 1 and 2; every 14d [40, 50] or
  • Irinotecan 80 mg/m 2 IV on day 1 plus  leucovorin 500 mg/m 2 IV combined with 5-FU 2000 mg/m 2/day IV continuous infusion on day 1; weekly for 6wk followed by 2wk off treatment [51] or
  • Paclitaxel 135 mg/m 2 IV on day 1 plus  cisplatin 75 mg/m 2 IV on day 2; every 21d [52] or
  • Paclitaxel 90 mg/m 2 IV on day 1 plus  cisplatin 50 mg/m 2 IV on day 1; every 14d [53] or
  • Paclitaxel 200 mg/m 2 IV on day 1 plus  carboplatin AUC 6 IV on day 1; every 21d [54] or
  • Docetaxel 70-85 mg/m 2 IV on day 1 plus  cisplatin 70-75 mg/m 2 IV on day 1; every 21d [46, 55, 56] or
  • Docetaxel 35 mg/m 2 IV on days 1 and 8 plus  irinotecan 50 mg/m 2 IV on days 1 and 8; every 21d [57] or
  • Leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IVP on day 1 plus  5-FU 1200 mg/m 2/day IV continuous infusion on days 1 and 2; every 14d [40] or
  • 5-FU 800 mg/m 2/day IV continuous infusion on days 1-5; every 28d [58] or
  • Capecitabine 1000 mg/m 2 PO BID on days 1-14; every 21d [59] or
  • Docetaxel 75-100 mg/m 2 IV on day 1; every 21d [60] or
  • Paclitaxel 135-175 mg/m 2 IV on day 1; every 21d [61] or
  • Paclitaxel 80 mg/m 2 IV on day 1; every week [62]

Second-line therapy

Category 1: recommendations based on high level of clinical evidence:

  • For HER2-NEU overexpressing adenocarcinomas, trastuzumab 8 mg/m 2 IV loading dose on day 1 of cycle 1, then  6 mg/m 2 IV; every 21d with chemotherapy [38]

Category 2A: recommendations based on lower level of clinical evidence:

  • Irinotecan 65 mg/m 2 IV on days 1 and 8 plus  cisplatin 25-30 mg/m 2 IV on days 1 and 8; every 21d [48, 63] or
  • Irinotecan 250 mg/m 2 IV on day 1 plus  capecitabine 1000 mg/m 2 PO BID on days 1-14; every 21d [64] or
  • Irinotecan 180 mg/m 2 IV on day 1 plus  leucovorin 400 mg/m 2 IV on day 1 plus  5-FU 400 mg/m 2 IVP on day 1 plus  5-FU 1200 mg/m 2/day IV continuous infusion on days 1 and 2; every 14d [65] 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 [57] or
  • Irinotecan 150 mg/m 2 IV on days 1 and 15 plus  mitomycin 8 mg/m 2 IV on day 1; every 28d [66] or
  • Irinotecan 125 mg/m 2 IV on days 1 and 8 plus  mitomycin 5 mg/m 2 IV on day 1; every 28d [67] or
  • Docetaxel 75-100 mg/m 2 IV on day 1; every 21d [60] or
  • Paclitaxel 135-175 mg/m 2 IV on day 1; every 21d [61] or
  • Paclitaxel 80 mg/m 2 IV on day 1 weekly; every 28d [62] or
  • Irinotecan 250-350 mg/m 2 IV on day 1; every 21d [68] or
  • Irinotecan 180 mg/m 2 IV on day 1; every 14d [69, 70] or
  • Irinotecan 125 mg/m 2 IV on days 1 and 8; every 21d [69, 70]
Previous
Next:

Other Regimens to Consider

See the list below:

  • Gemcitabine 1000 mg/m 2 IV on days 1, 8, and 15 plus  leucovorin 20 mg/m 2 on days 1, 8, and 15 plus  5-FU 500 mg/m 2 IV on days 1, 8, and 15; every 28d [71] or
  • Pegylated liposomal doxorubicin 20 mg/m 2 IV on day 1 plus  cisplatin 50 mg/m 2 on day 1 plus  5-FU 400 mg/m 2 IVP on day 1 plus  5-FU 600 mg/m 2/day continuous IV infusion on days 1 and 2; every 14d [72] or
  • Mitomycin 6 mg/m 2 IV on day 1 plus  irinotecan 125 mg/m 2 IV on days 2 and 9; every 28d [73] or
  • Mitomycin 7 mg/m 2 (maximum 14 mg) IV on day 1 plus  cisplatin 60 mg/m 2 on days 1 and 22 plus  5-FU 300 mg/m 2/day continuous IV infusion on days 1-42; every 6wk [36] or
  • Mitomycin 10 mg/m 2 IV on days 1 and 22 plus  leucovorin 500 mg/m 2 IV on day 1 plus  5-FU 2600 mg/m 2/day continuous IV infusion on day 1 weekly for 8 wk cycle (6wk followed by 2wk off treatment) [74] or
  • Etoposide 90-120 mg/m 2 on days 1-3; every 28d [75, 76] or
  • Erlotinib 150 mg PO daily [77, 78] or
  • Cetuximab 400 mg/m 2 IV on day 1 of week 1, then cetuximab 250 mg/m 2 IV on day 1 weekly beginning with week 2; can be used as single agent or with chemotherapy [79]
Previous