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 |  |