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Table 7 Randomized trials of preoperative chemoradiation (CRT) and surgery versus surgery alone.

From: Neoadjuvant or adjuvant therapy for resectable esophageal cancer: a systematic review and meta-analysis

Study, year [Reference] Participants Number of patients Interventions Median Survival (Months) Survival Rate (%) Adverse Effects (Number of Patients)
      1 yr 2 yr 3 yr 4 yr 5 yr  
Nygaard* et al. 1992 [24] 103 patients Jan 1983–Jan 1988 Scandinavia, multi centre squamous cell, < 75 years of age, Karnofsky score > 50, T1, T2, Nx, M0 > 21 cm from incisors 53 cisplatin 20 mg/m2 × 5 days × 2 cycles; bleomycin 5 mg/m2 × 5 days × 2 cycles + 35 Gy sequential radiotherapy + esophagectomy 7 39 23 17 - - leaks,2; respiratory, 10
   versus versus versus versus versus
   50 esophagectomy (laparotomy and right thoracotomy) 7 34 13 9 - - respiratory, 5; leaks, 2; postoperative deaths, 5.
      No difference in survival (p = 0.30).  
Le Prise et al. 1994 [42] 86 patients (stopped early after 104/150 patients entered) Jan 1988–April 1991 France, single centre squamous cell, < 70 years of age, < 15% weight loss excluded poor performance, metastases, tracheoesophageal fistula 41 cisplatin 100 mg/m2 × 1 day × 2 cycles 5-fluorouracil 600 mg/m2 × 4 days × 2 cycles + 20 Gy concurrent RT + esophagectomy 11 47 27 19 - - Neurological, 1; hematological, 7; renal, 2; tracheo-esophageal fistulae, 3; infections, 4; effusions, 2; deaths, 3; pulmonary embolism, 1; respiratory failure, 1.
   versus versus versus versus versus
   45 esophagectomy 11 47 33 14 - - tracheoesophageal fistulae, 5; infections, 7; effusions, 3; deaths, 3.
      No difference in survival (p = 0.56 at one year).  
Apinop et al. 1994 [43] 69 patients Thailand, single centre Jan 1986–Dec 1992 squamous cell carcinoma Mid to distal 1/3 esophagus, operable 35 cisplatin 100 mg/m2 × 1 day × 2 cycles 5-fluorouracil 1000 mg/m2 × 8 days × 2 cycles + 40 Gy concurrent radiotherapy + esophagectomy 9.7 49 30 26 24 24 leaks, 1; toxic deaths, 2; respiratory, 2; esophageal perforation, 1; cardiovascular, 2; electrolytes, 2
   versus versus versus versus versus
   34 esophagectomy (right thoracotomy) 7.4 39 23 20 19 10 leaks, 2; respiratory, 2; cardiovascular, 1
      No overall survival difference (p = 0.40 for median survival). Responders had improved survival (p = 0.001).  
Walsh et al. 1996 [44] 113 patients (closed early after 113/190 patients) May 1990–Sept 1995 Ireland, single centre adenocarcinoma < 76 years of age excluded poor performance, metastases, other cancers, previous chemotherapy or radiotherapy 58 cisplatin 75 mg/m2 × 1 day × 2 cycles; 5-fluorouracil 15 mg/kg × 5 days × 2 cycles + 40 Gy concurrent RT + esophagectomy 16 52 37 32 - - gastrointestinal, 4; hematologic, 2; cardiac, 15; toxic deaths, 1; respiratory, 28; leaks, 2; recurrent laryngeal nerve palsy, 1; chylothorax, 1
   versus versus versus versus versus
   55 esophagectomy (transhiatal, or Lewis-Tanner, or abdominal and left thoracotomy) 11 44 26 6 - - leaks, 2; recurrent laryngeal nerve palsy, 1; chylothorax, 1; respiratory, 32; cardiac, 13
      Preoperative chemoradiation + surgery prolongs survival compared with surgery alone (p = 0.01). Inferior results in surgery alone arm.  
Bosset et al. 1994 [45] 282 patients Jan 1989–June 1995 France, multi centre squamous cell < 70 years of age < 15% weight loss < WHO status 2 resectable Exclude tracheal fistula, T3N1, T4N0, T4N1 143 cisplatin 80 mg/m2 × 3 days × 2 cycles + 37 Gy concurrent radiotherapy + esophagectomy 18.6 69 48 39 35 33 vomiting, 37; neutropenia, 3; toxic deaths, 1; postoperative deaths, 17; respiratory failure, 6; sepsis,7
   versus versus versus versus versus
   139 esophagectomy (right thoracotomy + cervical anastomosis) 18.6 67 43 37 34 32 sepsis, 2; postoperative deaths, 5 Note: Trial stopped early 282/320 due to increased mortality in CRT group.
      No difference in overall survival (p = 0.78).  
Urba et al. 2001 [46] 100 patients 1989–1994 Michigan, single centre 25% squamous cell 75% adenocarcinoma 50 cisplatin 20 mg/m2 × 5 days × 2 cycles vinblastine 1 mg/m2 × 4 days × 2 cycles 5-fluorouracil 300 mg/m2 × 21 days + 45 Gy concurrent radiotherapy +esophagectomy 17.6 72 42 30 25 20 grade 3/4 granulocytopenia, 38; grade 3/4 thrombocytopenia, 15; neutropenic fever, 19; red blood cell transfusion, 8; feeding tube, 31; perioperative deaths, 1
   versus versus versus versus versus
   50 esophagectomy (transhiatal with cervical anastomosis) 16.9 58 38 16 14 10 perioperative deaths, 2; anastomotic leaks, 7 versus 5
      No difference in overall survival (p = 0.15).  
Burmeister et al. 2002 [51] 256 randomized 128† Cisplatin 80 mg/m2 d1 + 5-FU 800 mg/m2 d2-5 + RT 35 Gy in 15 fractions 22 NR NR NR NR NR  
   versus versus versus versus Treatment related mortality 4.6%
   128† Surgery alone 19 NR NR NR NR NR  
Lee J-L et al. 2003 [53] [abstract] 102 March 1999 – May 2002 Stage II/III resectable esophageal SCC 52 Cisplatin 60 mg/m2 IV d1, 5FU 1,000 mg/m2 IV d2-5, cisplatin 60 mg/m2 IV d22 + RT 45.6 Gy, 1.2 Gy bid d1-28 + surgery 3–4 weeks post RT 28.2 NR NR NR NR NR NR
   versus versus versus versus versus
   50 Surgery alone 27.3 NR NR NR NR NR NR
     p = 0.67 p = NS  
  1. Note: NR, not reported; NS, not significant.
  2. *Patients randomized to four groups; data shown are for chemotherapy + radiotherapy + surgery versus surgery alone.
  3. † number of patients randomized into each treatment arm estimated from total number of patients.