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Comparison 1 All Immunotherapy Studies, Outcome 1 Remission.
Figures and Tables -
Analysis 1.1

Comparison 1 All Immunotherapy Studies, Outcome 1 Remission.

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Comparison 1 All Immunotherapy Studies, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 1.2

Comparison 1 All Immunotherapy Studies, Outcome 2 Deaths at One Year.

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Study

Arm 1

Arm 2

Arm 3

Aass 2005

17.3

13.2

Atzpodien 2001

24

13

Atzpodien 2004

>25.0

>27.0

16

Boccardo 1998

17.7

28.3

13.2

Creagan 1991

8.8

8.0

DeMulder 1995

7.8

9.9

Dexeus 1989

8.8

9.1

Donskov(i) 2005

18.3

11.4

Donskov(ii) 2005

13.2

12.9

Figlin 1999

12.8

11.5

Flanigan 2001

11.1

8.1

Fossa 1992

12.6

10.4

Gleave 1998

12.2

15.7

Henriksson 1998

11.8

13.3

Jayson 1998

12.5

14.6

Kriegmair 1995

15.9

10.0

Law 1995

13

11

Lummen 1996

13

13

McDermott 2005

13.0

17.1

Mickisch 2001

17

7

Motzer 2000

15

15

MRCRCC 2000

9

6.8

Naglieri 1998

18

26

Negrier 1998

13

26

17

Negrier 2000

13

13

Negrier 2005

15.2

15.3

16.8

Negrier 2005 (D)

15.8

14.9

Neidhart 1991

9.6

9.0

Osband 1990

>15

8.6

Porzsolt 1988

6.7

7.2

Pyrhonen 1999

15.6

8.7

Rosenberg 1993

20.7

16.4

Sagaster 1995

8

9

Steineck 1990

7.5

6.6

Tsavaris 2000

5.8

6.0

Witte 1995

8.0

8.4

Yang 2003(i)

20

21

Yang 2003(ii)

20

20

20

Figures and Tables -
Analysis 1.3

Comparison 1 All Immunotherapy Studies, Outcome 3 Median Survival (months).

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Study

Arm #

IL2 MU/m2/day

Interleukin‐2 Detail

Interferon‐alfa

Other Protocol Rx

Aass 2005

1,2

s.c. 3‐9 MU daily

13CRA

Aass 2005

Atzpodien 2001

1

5‐20

s.c. 10 MU/m2 b.i.d. d3‐5 w1+4; 5 MU/m2 d1+3+5 w2+3

s.c. 5 MU/m2 d1 w1+4, d1,3,5 w2+3; 10 MU/m2 d1,3,5 w5‐8

5‐fluorouracil

Atzpodien 2001

Atzpodien 2004

1,2

5‐20

s.c. 10 MU/m2 b.i.d. d3‐5 w1+4; 5 MU/m2 d1+3+5 w2+3

s.c. 5 MU/m2 d1 w1+4, d1,3,5 w2+3; 10 MU/m2 d1,3,5 w5‐8

5FU (arms 1&2); 13CRA (arm 1)

Atzpodien 2004

3

s.c. 5 MU/m2 d1 w1, 10 MU/m2 d1,3,5 w2‐8

vinblastine

Boccardo 1998

1,3

i.m. 6 MU/m2 t.i.w.

Boccardo 1998

2,3

18

c.i.v.i 18 MU/m2 /24hr d1‐4 w1,3,7,9,13,17,21,25

Brinkmann 2001

1

4.5‐9

s.c. 9 MU/m2 d3‐5 w1+4; 4.5 MU/m2 d1+3+5 w2+3

s.c. 4.5 MU/m2 d1 w1+4, d1,3,5 w2+3; 9 MU/m2 d1,3,5 w5‐8

Brinkmann 2001

Buzogany 2001

1,2

s.c. 10 MU t.i.w. x12w

vinblastine (arm 1)

Buzogany 2001

Creagan 1991

1,2

i.m. 20 MU/m2 t.i.w.

ASA (arm 1)

Creagan 1991

DeMulder 1995

1,2

s.c. 10 MU/m2 b.i.w.

IFN‐gamma (arm 1)

DeMulder 1995

Dexeus 1989

1

i.m. 3 MU/m2 d1,15, 5 MU/m2 d2,16, 10 MU/m2 d3,17‐19 q7weeks

combination chemotherapy

Dexeus 1989

Donskov(i) 2005

1,2

10.5

s.c. 18 MU d1‐5, 8‐12, 15‐19 q5w

histamine dihydrochloride

Donskov(i) 2005

Donskov(ii) 2005

1,2

10.5

s.c. 18 MU d1‐5, 8‐12, 15‐19 q5w

histamine dihydrochloride

Donskov(ii) 2005

Edsmyr 1985

1

i.m. 3 MU daily

Edsmyr 1985

Figlin 1999

1,2

5

c.i.v.i. 5 MU/m2/24hr d1‐4 w1‐4

TIL (arm 1); placebo (arm 2)

Figlin 1999

Flanigan 2001

1,2

s.c. 5 MU/m2 t.i.w.

nephrectomy (arm 1)

Flanigan 2001

Foon 1988

1,3

s.c. 2 MU/m2 t.i.w.

Foon 1988

Fossa 1992

1,2

i.m. 18 MU t.i.w.

Fossa 1992

Fujita 1992

1

i.m. 3 MU 6d/week

Fujita 1992

2

i.m. 1 MU 6d/week

Henriksson 1998

1

4.8‐14.4

s.c. 4.8 MU/m2 q8h d1,22 + q12h d2,23 + 2.4 MU/m2 q12h d3‐5, 8‐12, 15‐19, 24‐26, 29‐33, 36‐40

s.c. 3 MU/m2 d3,5,24,26 + 6 MU/m2 d8,10,12,15,17,19,29,31,33,38,40

tamoxifen

Henriksson 1998

Jayson 1998

1

10.5

s.c. 18 MU d1‐5 w1‐3 q4w

s.c. 9 MU t.i.w. w1‐3 q4w

Jayson 1998

2

10.5

s.c. 18 MU d1‐5 w1‐3 q4w

Kinouchi 2004

1,2

5 MU 5d/week (route not stated)

cimetidine (arm 1)

Kinouchi 2004

Kirkwood 1985

1

i.m. 10 MU daily

Kirkwood 1985

2

i.m. 1 MU daily

Kriegmair 1995

1

s.c. 8 MU t.i.w.

Kriegmair 1995

Law 1995

1,2

3

c.i.v.i 3 MU/m2/24hr d1‐5 w1‐4

LAK cells (arm 1)

Law 1995

Lissoni 1993b

1

3.5

s.c. 3 MU b.i.d. 1‐5 x6w x2 cycles, then 6d/month

s.c. 5 MU/m2 t.i.w.

Lissoni 1993b

2

3.5

s.c. 3 MU b.i.d. 1‐5 x6w x2 cycles, then 6d/month

Lissoni 2000

1,2

6

s.c. 3 MU b.i.d. 1‐5 x4w

morphine; melatonin (arm 1)

Lissoni 2000

Lummen 1996

1

2.4‐14.4

s.c. 4.8 MU/m2 q8hx4 d1,22 + q12hx2 d2,23; 2.4 MU/m2 q12hx2 with each IFNa

s.c. 3 MU/m2 d3,5,24,26; 6 MU/m2 d8,10,12,15,17,19,29,31,33,36,38,40

Lummen 1996

McCabe 1991

1,2

19.5

i.v. 0.1 MU/kg t.i.d. d1‐5,11‐15

LAK (arm 1)

McCabe 1991

McDermott 2005

1

5‐15

s.c. 5 MU/m2 q8hx3 d1 then dailyx5 x4w, q6w

s.c. 5 MU/m2 t.i.w. x4w q6w

McDermott 2005

2

69

i.v. 0.6 MU/kg t.i.d. d1‐5,15‐19 q12w

Mickisch 2001

1,2

s.c. 5 MU/m2 t.i.w.

nephrectomy (arm 1)

Mickisch 2001

Motzer 2000

1,2

s.c. 3 MU d1‐7, 6 MU d8‐14, 9 MU d15‐

13CRA (arm 1)

Motzer 2000

Motzer 2001

2

s.c. 9 MU t.i.w.

Motzer 2001

MRCRCC 2000

1

s.c. 10 MU t.i.w. x12w

MRCRCC 2000

Muss 1987

1

i.v. 30 (‐50) MU/m2 d1‐5 q3w

Muss 1987

2

s.c. 2 (‐10) MU/m2 t.i.w.

Naglieri 1998

1

2.6‐5.3

s.c. 9 MU d1,2 then 4.5 MU d3‐5 week 1 + d1‐5 wk2‐6

s.c. 3 MU d1,3,5 x6w

Naglieri 1998

2

2.6‐5.3

s.c. 9 MU d1,2 then 4.5 MU d3‐5 week 1 + d1‐5 wk2‐6

4‐epirubicin

Negrier 1998

1

s.c. 18 MU/m2 t.i.w.

Negrier 1998

2,3

18

c.i.v.i. 18 MU/m2/24hr d1‐5 w1,3,7,9,13,17,21,25

arm3 only: s.c. 6 MU/m2 t.i.w. w1,3,7,9.13,17,21,25

Negrier 2000

1,2

5.3

s.c. 9 MU d1‐6 w1,3,5,7

s.c. 6 MU d1,3,5 w1,3,5,7

5FU (arm 1)

Negrier 2000

Negrier 2005

1,3

s.c. 9 MU t.i.w.

Negrier 2005

2,3

10.5

s.c. 18 MU 5d/week x4w

Negrier 2005 (D)

4

medroxyprogesterone

Negrier 2005 (D)

Neidhart 1991

1,2

i.m. 3‐5‐20‐20‐20 MU/m2 d1‐5 q2w

vinblastine (arm 1)

Neidhart 1991

Porzsolt 1988

1,2

s.c. 2MU d1‐5 x8‐12w, then once weekly

medroxyprogesterone (arm 1)

Porzsolt 1988

Pyrhonen 1999

1

s.c. 18 MU t.i.w.

vinblastine

Pyrhonen 1999

Quesada 1985

1

i.m. 20 MU daily

Quesada 1985

2

i.m. 2 MU daily

Radosavljevic 2000

1,2

6 MU t.i.w. (route not stated)

vinblastine; MPA (arm 1)

Radosavljevic 2000

Rosenberg 1993

1,2

83

i.v. 0.72 MU/kg q8h x4‐5d, x2 cycles

LAK cells (arm 1)

Rosenberg 1993

Sagaster 1995

1,2

s.c. 5 MU d1‐5

coumarin, cimetidine (arm 1)

Sagaster 1995

Scardino 1997

1

3.5‐7

s.c. 18 MU d1‐3 preop + 6 MU d1‐5 x6w postop

nephrectomy

Scardino 1997

2

3.5‐7

s.c. 6 MU d1‐5 x6w postop

nephrectomy

Steineck 1990

1

i.m. 10(‐20) MU/m2 t.i.w.

Steineck 1990

Tannir 2004

1

s.c. 5 MU daily

Tannir 2004

2

s.c. 0.5 MU b.i.d.

Tsavaris 2000

1

s.c. 5 MU t.i.w.

vinblastine

Tsavaris 2000

2

s.c. 15 MU t.i.w.

Weiss 1992

1

15

c.i.v.i. 1 mg (3‐5 MU)/m2/24hr x 4.5d, 1.25 mg/m2/24hr d11‐15

LAK cells

Weiss 1992

2

4‐5

i.v. 33 mcg/kg q8h x14 doses d1‐5,11‐15

LAK cells

Witte 1995

1,2

6

i.v. 6 MU/m2 t.i.w. x4w then 2 weeks out of 4

interferon‐beta (arm 1)

Witte 1995

Yang 1995

1

83

i.v. 0.72 MU/kg q8h x15(max) week 1, then PEG‐IL2 3(‐6) MU/kg weekly x3, q2months

Yang 1995

2

83

i.v. 0.72 MU/kg q8h x15(max) week x2, q2months

Yang 2003(i)

1

83

i.v. 0.72 MU/kg q8h x4‐5d, x2 cycles

Yang 2003(i)

2

8.3

i.v. 0.072 MU/kg q8h x4‐5d, x2 cycles

Yang 2003(ii)

3

5‐10

s.c. 0.25 MU/kg d1‐5, then 0.125 MU/kg x5d weeks 2‐6

Yang 2003(ii)

Figures and Tables -
Analysis 1.4

Comparison 1 All Immunotherapy Studies, Outcome 4 Interferon‐alfa and Interleukin‐2 Route, Doses & Schedules.

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Study

Aass 2005

12 mo

Atzpodien 2001

3 cycles

Atzpodien 2004

3 cycles

Boccardo 1998

IL2 6 mo; IFN 12 mo

Creagan 1991

Disease progression

DeMulder 1995

12 months

Donskov(i) 2005

4 cycles

Donskov(ii) 2005

4 cycles

Figlin 1999

4 cycles

Flanigan 2001

Disease progression

Fossa 1992

Disease progression (12 mo for stable disease)

Gleave 1998

Disease progression

Henriksson 1998

40 weeks

Jayson 1998

3 cycles

Kriegmair 1995

Disease progression or no change for 3 mo

Law 1995

4 cycles

Lissoni 1993b

Disease progression

Lummen 1996

Disease progression

McDermott 2005

36 weeks

Mickisch 2001

12 months

Motzer 2000

Disease progression

MRCRCC 2000

12 weeks

Negrier 1998

Disease progression

Negrier 2000

investigator discretion after 2 cycles

Negrier 2005

6 months

Negrier 2005 (D)

6 months

Neidhart 1991

vinblastine 6 cycles; IFN 12 mo

Osband 1990

6 months

Porzsolt 1988

48 weeks

Pyrhonen 1999

12 mo (3 mo beyond CR)

Rosenberg 1993

3+ cycles

Sagaster 1995

Disease progression

Scardino 1997

6 weeks (postop)

Steineck 1990

Disease progression

Tsavaris 2000

12 weeks

Witte 1995

Disease progression (or CR 12 mo)

Yang 2003(i)

CR+1cycle (otherwise unclear)

Yang 2003(ii)

CR+1cycle (otherwise unclear)

Figures and Tables -
Analysis 1.5

Comparison 1 All Immunotherapy Studies, Outcome 5 Maximum Therapy Duration for Studies Reporting Survival.

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Study

Total Randomized

Survival Assessed

Arm 1: 1 yr OS

Arm 2: 1 yr OS

Arm 3: 1 yr OS

Arm 1: 1 yr Censored

Arm 2: 1 yr Censored

Arm 3: 1 yr Censored

Aass 2005

320

320

60%

54%

9

4

Atzpodien 2001

78

78

80%

51%

0

0

Atzpodien 2004

341

341

70%

76%

58%

5

1

1

Boccardo 1998

66

66

76%

70%

56%

0

1

0

Creagan 1991

179

176

38%

34%

10

10

DeMulder 1995

102

97

41%

41%

0

0

Donskov(i) 2005

63

63

76%

47%

0

0

Donskov(ii) 2005

41

41

52%

55%

0

0

Figlin 1999

160

160

55%

47%

0

0

Flanigan 2001

246

241

50%

37%

1

1

Fossa 1992

178

178

51%

44%

0

0

Gleave 1998

197

181

52%

52%

0

0

Henriksson 1998

128

128

49%

58%

12

12

Jayson 1998

60

60

58%

64%

2

3

Kriegmair 1995

89

76

60%

29%

6

7

Law 1995

71

71

52%

50%

0

0

Lissoni 1993b

30

30

73%

80%

0

0

Lummen 1996

60

60

55%

56%

0

1

McDermott 2005

193

192

53%

61%

0

0

Mickisch 2001

85

84

62%

37%

7

10

Motzer 2000

284

284

54%

54%

1

1

MRCRCC 2000

335

335

43%

32%

0

0

Negrier 1998

425

425

59%

56%

65%

0

0

0

Negrier 2000

131

131

52%

53%

0

0

Negrier 2005

369

369

62%

61%

63%

8

8

8

Negrier 2005 (D)

492

492

62%

59%

24

7

Neidhart 1991

165

165

41%

38%

0

0

Osband 1990

90

90

66%

47%

4

6

Porzsolt 1988

102

93

17%

25%

0

0

Pyrhonen 1999

160

160

56%

38%

0

0

Rosenberg 1993

97

97

63%

57%

0

0

Sagaster 1995

148

137

30%

32%

0

0

Scardino 1997

20

20

22%

18%

0

0

Steineck 1990

60

60

30%

27%

0

0

Tsavaris 2000

100

87

5%

11%

0

0

Witte 1995

84

75

39%

36%

0

0

Yang 2003(i)

117

117

69%

66%

0

0

Yang 2003(ii)

283

279

66%

66%

66%

0

0

0

Figures and Tables -
Analysis 1.6

Comparison 1 All Immunotherapy Studies, Outcome 6 Extracted Data Estimates for Studies Reporting 1‐Year Survival.

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Comparison 2 High Dose IL‐2 versus Control, Outcome 1 Remission.
Figures and Tables -
Analysis 2.1

Comparison 2 High Dose IL‐2 versus Control, Outcome 1 Remission.

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Comparison 2 High Dose IL‐2 versus Control, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 2.2

Comparison 2 High Dose IL‐2 versus Control, Outcome 2 Deaths at One Year.

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Comparison 3 High Dose IL‐2 +/‐ Enhancer, Outcome 1 Remission.
Figures and Tables -
Analysis 3.1

Comparison 3 High Dose IL‐2 +/‐ Enhancer, Outcome 1 Remission.

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Comparison 3 High Dose IL‐2 +/‐ Enhancer, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 3.2

Comparison 3 High Dose IL‐2 +/‐ Enhancer, Outcome 2 Deaths at One Year.

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Comparison 4 IFNa versus Control, Outcome 1 Remission.
Figures and Tables -
Analysis 4.1

Comparison 4 IFNa versus Control, Outcome 1 Remission.

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Comparison 4 IFNa versus Control, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 4.2

Comparison 4 IFNa versus Control, Outcome 2 Deaths at One Year.

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Comparison 5 Interferon Dose & Route Studies, Outcome 1 Remission.
Figures and Tables -
Analysis 5.1

Comparison 5 Interferon Dose & Route Studies, Outcome 1 Remission.

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Comparison 6 Interferon‐alpha Enhancement Studies, Outcome 1 Remission.
Figures and Tables -
Analysis 6.1

Comparison 6 Interferon‐alpha Enhancement Studies, Outcome 1 Remission.

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Comparison 6 Interferon‐alpha Enhancement Studies, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 6.2

Comparison 6 Interferon‐alpha Enhancement Studies, Outcome 2 Deaths at One Year.

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Comparison 7 Initial Nephrectomy Studies, Outcome 1 Remission.
Figures and Tables -
Analysis 7.1

Comparison 7 Initial Nephrectomy Studies, Outcome 1 Remission.

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Comparison 7 Initial Nephrectomy Studies, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 7.2

Comparison 7 Initial Nephrectomy Studies, Outcome 2 Deaths at One Year.

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Comparison 8 Hierarchy of Cytokine Therapies, Outcome 1 Remission.
Figures and Tables -
Analysis 8.1

Comparison 8 Hierarchy of Cytokine Therapies, Outcome 1 Remission.

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Comparison 8 Hierarchy of Cytokine Therapies, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 8.2

Comparison 8 Hierarchy of Cytokine Therapies, Outcome 2 Deaths at One Year.

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Comparison 9 Combination Immuno(chemo)therapy versus Control, Outcome 1 Remission.
Figures and Tables -
Analysis 9.1

Comparison 9 Combination Immuno(chemo)therapy versus Control, Outcome 1 Remission.

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Comparison 9 Combination Immuno(chemo)therapy versus Control, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 9.2

Comparison 9 Combination Immuno(chemo)therapy versus Control, Outcome 2 Deaths at One Year.

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Comparison 10 Other Immunotherapies, Outcome 1 Remission.
Figures and Tables -
Analysis 10.1

Comparison 10 Other Immunotherapies, Outcome 1 Remission.

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Comparison 10 Other Immunotherapies, Outcome 2 Deaths at One Year.
Figures and Tables -
Analysis 10.2

Comparison 10 Other Immunotherapies, Outcome 2 Deaths at One Year.

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Comparison 1. All Immunotherapy Studies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

69

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

1.1 2‐arm Studies

53

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.2 3‐arm Studies (Comparison A)

6

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.3 3‐arm Studies (Comparison B)

6

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

1.4 3‐arm Studies (Comparison C)

4

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2 Deaths at One Year Show forest plot

43

Odds Ratio (M‐H, Random, 95% CI)

Totals not selected

2.1 2‐arm Studies

33

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.2 3‐arm Studies (Comparison A)

4

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.3 3‐arm Studies (Comparison B)

4

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

2.4 3‐arm Studies (Comparison C)

2

Odds Ratio (M‐H, Random, 95% CI)

0.0 [0.0, 0.0]

3 Median Survival (months) Show forest plot

Other data

No numeric data

4 Interferon‐alfa and Interleukin‐2 Route, Doses & Schedules Show forest plot

Other data

No numeric data

5 Maximum Therapy Duration for Studies Reporting Survival Show forest plot

Other data

No numeric data

6 Extracted Data Estimates for Studies Reporting 1‐Year Survival Show forest plot

Other data

No numeric data
Figures and Tables -
Comparison 1. All Immunotherapy Studies
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Comparison 2. High Dose IL‐2 versus Control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

4

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

1.1 IL2(hd) vs IL2(ld) iv

2

306

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.82 [1.00, 3.30]

1.2 IL2(hd) vs IL2(ld) sc

1

154

Peto Odds Ratio (Peto, Fixed, 95% CI)

2.67 [1.06, 6.71]

1.3 IL2(hd) vs IFNa+IL2(ld) sc

1

192

Peto Odds Ratio (Peto, Fixed, 95% CI)

2.70 [1.26, 5.82]

2 Deaths at One Year Show forest plot

4

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2.1 IL2(hd) vs IL2(ld) iv

2

305

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.95 [0.59, 1.53]

2.2 IL2(hd) vs IL2(ld) sc

1

187

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.00 [0.55, 1.83]

2.3 IL2(hd) vs IFNa+IL2(ld) sc

1

192

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.71 [0.40, 1.26]
Figures and Tables -
Comparison 2. High Dose IL‐2 versus Control
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Comparison 3. High Dose IL‐2 +/‐ Enhancer

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

1

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2 Deaths at One Year Show forest plot

1

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only
Figures and Tables -
Comparison 3. High Dose IL‐2 +/‐ Enhancer
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Comparison 4. IFNa versus Control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

8

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 IFNa versus Non‐immuno Control

4

644

Odds Ratio (M‐H, Random, 95% CI)

7.61 [3.02, 19.18]

1.2 IFNa vs Non‐Imm. (intermed.prognosis)

1

245

Odds Ratio (M‐H, Random, 95% CI)

1.71 [0.40, 7.32]

1.3 IFNa versus Low Dose IL‐2

3

576

Odds Ratio (M‐H, Random, 95% CI)

0.93 [0.47, 1.84]

2 Deaths at One Year Show forest plot

8

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 IFNa versus Non‐immuno Control

4

615

Odds Ratio (M‐H, Random, 95% CI)

0.56 [0.40, 0.77]

2.2 IFNa vs Non‐Imm. (intermed.prognosis)

1

230

Odds Ratio (M‐H, Random, 95% CI)

0.86 [0.51, 1.46]

2.3 IFNa versus Low Dose IL‐2

3

559

Odds Ratio (M‐H, Random, 95% CI)

0.93 [0.66, 1.31]
Figures and Tables -
Comparison 4. IFNa versus Control
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Comparison 5. Interferon Dose & Route Studies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

5

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 IFNa (same route)

4

199

Odds Ratio (M‐H, Random, 95% CI)

2.45 [0.92, 6.55]

1.2 IFNa (different route)

1

112

Odds Ratio (M‐H, Random, 95% CI)

0.62 [0.14, 2.74]
Figures and Tables -
Comparison 5. Interferon Dose & Route Studies
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Comparison 6. Interferon‐alpha Enhancement Studies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

12

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

1.1 IFNa +/‐ Hormone

2

183

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.98 [0.37, 2.62]

1.2 IFNa +/‐ Chemotherapy

3

455

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.36 [0.80, 2.32]

1.3 IFNa +/‐ IFNg

2

170

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.42 [0.13, 1.40]

1.4 IFNa +/‐ 13CRA

2

387

Peto Odds Ratio (Peto, Fixed, 95% CI)

2.28 [1.17, 4.45]

1.5 IFNa +/‐ Other Agents

3

395

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.96 [0.53, 1.73]

2 Deaths at One Year Show forest plot

8

Peto Odds Ratio (Peto, Fixed, 95% CI)

Subtotals only

2.1 IFNa +/‐ Hormone

1

63

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.58 [0.47, 5.30]

2.2 IFNa +/‐ Chemotherapy

2

343

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.81 [0.53, 1.25]

2.3 IFNa +/‐ IFNg

1

58

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.98 [0.34, 2.81]

2.4 IFNa +/‐ 13CRA

2

592

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.88 [0.63, 1.21]

2.5 IFNa +/‐ Other Agents

2

287

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.94 [0.58, 1.53]
Figures and Tables -
Comparison 6. Interferon‐alpha Enhancement Studies
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Comparison 7. Initial Nephrectomy Studies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

2

331

Peto Odds Ratio (Peto, Fixed, 95% CI)

1.45 [0.56, 3.75]

2 Deaths at One Year Show forest plot

2

306

Peto Odds Ratio (Peto, Fixed, 95% CI)

0.53 [0.34, 0.83]
Figures and Tables -
Comparison 7. Initial Nephrectomy Studies
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Comparison 8. Hierarchy of Cytokine Therapies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

9

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Single Agent Cytokine versus Control

5

1014

Odds Ratio (M‐H, Random, 95% CI)

4.82 [1.96, 11.85]

1.2 Combination Cytokine vs Single Agent

3

860

Odds Ratio (M‐H, Random, 95% CI)

2.17 [1.03, 4.57]

1.3 High Dose IL2 versus Combination Cytokine

1

192

Odds Ratio (M‐H, Random, 95% CI)

2.87 [1.25, 6.62]

2 Deaths at One Year Show forest plot

9

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Single Agent Cytokine versus Control

5

962

Odds Ratio (M‐H, Random, 95% CI)

0.63 [0.46, 0.86]

2.2 Combination Cytokine versus Single Agent

3

835

Odds Ratio (M‐H, Random, 95% CI)

0.99 [0.61, 1.62]

2.3 High Dose IL2 versus Combination Cytokine

1

192

Odds Ratio (M‐H, Random, 95% CI)

0.71 [0.40, 1.26]
Figures and Tables -
Comparison 8. Hierarchy of Cytokine Therapies
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Comparison 9. Combination Immuno(chemo)therapy versus Control

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

4

442

Odds Ratio (M‐H, Fixed, 95% CI)

12.06 [4.79, 30.34]

2 Deaths at One Year Show forest plot

3

243

Odds Ratio (M‐H, Fixed, 95% CI)

0.82 [0.50, 1.37]
Figures and Tables -
Comparison 9. Combination Immuno(chemo)therapy versus Control
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Comparison 10. Other Immunotherapies

Outcome or subgroup title

No. of studies

No. of participants

Statistical method

Effect size

1 Remission Show forest plot

2

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

1.1 Interferon Gamma

1

197

Odds Ratio (M‐H, Random, 95% CI)

0.66 [0.18, 2.41]

1.2 Autolymphocyte Therapy

1

90

Odds Ratio (M‐H, Random, 95% CI)

4.65 [0.93, 23.27]

2 Deaths at One Year Show forest plot

2

Odds Ratio (M‐H, Random, 95% CI)

Subtotals only

2.1 Interferon Gamma

1

150

Odds Ratio (M‐H, Random, 95% CI)

1.00 [0.53, 1.91]

2.2 Autolymphocyte Therapy

1

85

Odds Ratio (M‐H, Random, 95% CI)

0.48 [0.20, 1.16]
Figures and Tables -
Comparison 10. Other Immunotherapies
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