Table 4 Randomized trials of preoperative chemotherapy (CT) and surgery versus surgery alone.

Nygaard* et al. 1992 [24]

106 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

56

cisplatin 20 mg/m² × 5 days × 2 cycles bleomycin 10 mg/m² × 5 days × 2 cycles + esophagectomy

7

31

6

3

-

-

respiratory, 3; leaks, 3; postoperative deaths, 6; hematologic, 1; alopecia, 1

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-value not reported).

Schlag 1992 [32]

46 patients dates not reported Germany, single centre squamous cell < 68 years of age Karnofsky > 70 Stage I, II, III

22

cisplatin 20 mg/m² × 5 days × 3 cycles 5-fluorouracil 1 g/m² × 5 days × 3 cycles + esophagectomy

7.5

20

-

-

-

-

vomiting, 11; alopecia, 10; fever, 2; bone marrow suppression, 5; renal, 2;

versus

versus

versus

versus

versus

24

esophagectomy (abdominothoracic or thoracoabdominocervical with gastric or colon interposition)

5

32

-

-

-

-

not reported

No difference in survival (p = 0.91).

Maipang et al. 1994 [33]

46 patients Aug 1988–Dec 1990 Thailand, single centre squamous cell < 75 years of age ECOG 1, 2. Stage I, II, III distal 2/3 esophagus

24

cisplatin 100 mg/m² × 1 day × 2 cycles vinblastine 3 mg/m² × 4 days × 2 cycles bleomycin 10 mg/m² × 5 days × 2 cycles + esophagectomy

17

58

31

31

-

-

hematologic, 15; vomiting, 15; alopecia, 14; hepatic, 3; lung, 1; urologic, 8; perioperative deaths, 4

versus

versus

versus

versus

versus

22

esophagectomy (laparotomy, right thoracotomy with gastric or colon interposition)

17

85

40

36

-

-

none reported

p = 0.186 Early survival better in surgery alone group.

Law et al. 1997 [34]

147 patients Dec 1989–Jan 1995 Hong Kong, single centre squamous cell exclude non regional nodes, tracheal involvement, metastases

74

cisplatin 100 mg/m² × 1 day × 2 cycles 5-fluorouracil 500 mg/m² × 5 days × 2 cycles + esophagectomy

16.8

60

44

38

28

28

Anemia, 47; neutropenia, 43; thrombocytopenia, 12; renal, 24; vomiting, 34; electrolytes, 21; leaks, 3; pulmonary, 10; respiratory failure, 14; perioperative deaths, 5

versus

versus

versus

versus

versus

73

esophagectomy (transhiatal or Lewis-Tanner)

13

50

31

14

14

-

pulmonary, 11; respiratory failure, 22; perioperative deaths, 6

p = 0.17 Responders to CT lived longer but non-responders had lower median survival than controls (p = 0.03). Lower local recurrence with CT.

Kok et al. 1997 [35] [abstract]

160 patients 1990–1996 Netherlands, multi-centered Squamous cell

74

cisplatin 80 mg/m² × 1 day × 2 cycles, etoposide 100 mg IV × 2 days + 200 mg/m² PO × 2 days × 2 cycles + esophagectomy Note: CT responders received an additional 2 cycles of CT prior to surgery while non-responders received only 2 cycles

18.5

toxic deaths, 1; alopecia, 67; renal, 10

versus

versus

versus

versus

74

esophagectomy (transhiatal).

11

none reported

Not reported but median survival favoured CT (p = 0.002).

MRC OE02 2002 [37]

802 patients Mar 1992 to June 1998 United Kingdom, multi-centered Resectable esophageal cancer 67% adenocarcinoma, 33% squamous or undifferentiated.

400

cisplatin 80 mg/m² × 1 day × 2 cycles 5-fluorouracil 1 g/m² × 4 days × 2 cycles + esophagectomy

16.8

59

43

35

28

26

postoperative complications, 41%; postoperative deaths, 10%

versus

versus

versus

versus

versus

402

esophagectomy

13.3

54

34

27

20

15

postoperative complications, 42%; postoperative deaths, 10%

Significant improvement in survival with chemotherapy HR = 0.79 (95% CI 0.67 to 0.93; p = 0.004)

Ancona et al. 2001 [48]

94

47

5-FU 1000 mg/m² CI d1-5 + Cisplatin 100 mg/m² d1

25

75

55

44

42

34

Gr. 3–4 neutropenia; 10 pts.

versus

versus

versus

versus

versus

47

Surgery alone

24

75

55

41

38

22

NR