Table 7

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

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


Note: NR, not reported; NS, not significant.

*Patients randomized to four groups; data shown are for chemotherapy + radiotherapy + surgery versus surgery alone.

† number of patients randomized into each treatment arm estimated from total number of patients.

Malthaner et al. BMC Medicine 2004 2:35   doi:10.1186/1741-7015-2-35

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