Table 1 General Characteristics of Included Randomized Clinical Trials

From: A systematic review and meta-analysis of traditional insect Chinese medicines combined chemotherapy for non-surgical hepatocellular carcinoma therapy

 

Experimental group

Control group

Sex(M/F)

Age

Disease stage

Child-Pugh scores

KPS score

Treatment group

Control group

  

Huang W.K.30 2013

41

41

44/26

48.54 ± 4.16 years old

II, III

—

>60

Cinobufotalin injection + TACE (OXA, EPI)

TACE (OXA, EPI,)

3 weeks

1. Clinical effectiveness

2. Life quality

3. Blood routine examination

Cao Y.31 2014

68

68

78/58

E:55.2 ± 7.4 years old

—

A and B

>50

Compound cantharis capsule + FAP (5-FU, EPI, DDP)

FAP (5-FU, EPI, DDP)

10 days

1. Clinical effectiveness

 

2. Life quality

C:57.8 ± 6.9 years old

3. Complication

 

4. Economic evaluation

Zeng C.S.32 2012

30

30

19-Nov

E:51.65 ± 6.92 years old

II, III

A and B

—

Jinlong capsule + TACE (THP, DDP, 5-FU)

TACE (THP, DDP, 5-FU)

60 days

1. Clinical effectiveness

 

2. AFP

C:53.20 ± 9.24 years old

3. Liver function

 

4. Complication

 

5. Life quality

Deng Z.Y.33 2015

25

24

29/20

E:48.65 ± 16.12 years old

—

—

—

Cinobufotalin injection + TACE (THP, DDP)

TACE (THP, DDP)

4 weeks

1. AFP

 

2. Clinical effectiveness

C:48.30 ± 16.24 years old

3. TCM symptoms scores + KPS

  

4. Complication

Dong M.E.34 2014

60

60

76/44

E:median age 55 years

—

—

—

Cinobufotalin injection + TACE (GEM, DDP, 5-FU, CF)

TACE (GEM, DDP, 5-FU, CF)

4 weeks

1. Clinical effectiveness

C:median age 53 years

2. Complication

Feng X.M.35 2012

38

32

44/26

E:52.6 ± 11.7 years old

II III

—

>60

Cinobufotalin injection + FOLFOX4 (OXA, 5-FU, CF)

FOLFOX4 (OXA, 5-FU, CF)

3 rounds (2 days per round)

1. Clinical effectiveness

C:53.2 ± 11.4 years old

2. Life quality

 

3. Blood routine examination

Fu Z.L.36 2010

78

78

119/37

E:median age 58 years

—

—

>60

Cinobufotalin injection + TACE (5-FU, DDP, MMC)

TACE (5-FU, DDP. MMC)

3 months

1. Clinical effectiveness

C:median age 56 years

2. Life quality

 

3. Complication

He S.L.37 2012

26

25

37/14

58.8 years old

—

A and B

—

Cinobufotalin injection + TACE (OXA, 5-FU, THP)

TACE (OXA, 5-FU, THP)

2 weeks

1. Clinical effectiveness

2. MST and TTP

3. VEGF, HIF-1α and AFP

4. KPS

5. Complication

Ji J.F.38 2015

25

22

36/11

62.3 years old

—

—

—

Cinobufotalin injection + TACE (DDP, 5-FU, DOX)

TACE (DDP, 5-FU, DOX)

4–5 weeks

1. Clinical effectiveness

2. Survival at 6/12/24 months

3. Life quality

4. Comparison of WBC,TBIL and ALT

5. Immunological function

Jia C.H.39 2008

30

30

44/16

E:54.2 ± 6.4 years old

I, II, III

A, B and C

>60

Jinlong capsule + TACE (MMC)

TACE (MMC)

3 months

1. Clinical effectiveness

C:51.5 ± 7.0 years old

2. Immunological function. 3. Life quality

Jiang C.Y.40 2013

30

33

36/27

E:median age:57 years

II, III

—

 ≥ 60

Jinlong capsule + TACE (5-FU, THP)

TACE (5-FU, THP)

2 rounds (8 days per round)

1. Clinical effectiveness

C:median age:53 years

2. CBR

 

3. Complication

Ke J.41 2011

38

40

69/9

E:58.32 ± 11.59 years old

—

A and B

>60

Cinobufotalin injection + TACE (5-FU, DDP, DOX)

TACE (5-FU, DDP, DOX)

3 rounds (20 days per round)

1. Clinical effectiveness

C:57.09 ± 11.77 years old

2. Life quality

 

3. Comparison of WBC, TBIL, ALT and AFP

 

4. Survival at 6/12 months

 

5. Complication

Kou C.Y.42 2011

31

31

40/22

E:40.5 years old

—

—

>60

Cinobufotalin injection + TACE (HCPT, DDP, DOX)

TACE (HCPT, DDP, DOX)

4 weeks

1. Clinical effectiveness

C:41 years old

2. QoL scores

 

3. Complication

 

4. Survival at 12/24/36 months

Li B.43 2013

74

73

97/50

Median age:56.4 years

—

—

>60

Jinlong capsule + TACE (5-FU, EPI, DDP, MMC, CF)

TACE (5-FU, EPI, DDP, MMC, CF)

2 rounds (28 days per round)

1. Clinical effectiveness

2. Life quality

3. Comparison of Child-pugh, Classification and WBC

Li j.44 2013

43

62

76/29

E:45.2 ± 4.8 years old

—

A, B and C

—

Aidi injection + TACE (5-FU, THP, DDP, MMC)

TACE (5-FU, THP, DDP, MMC)

10 days

1. Life quality

C:45.7 ± 6.4 years old

2. Survival at 6/12/24/36 months

 

3. AFP

 

4. TACE times

Li Q.45 2008

50

46

84/12

50.2 years old

I, II, III

A and B

 ≥ 60

Cinobufotalin injection + TACE (5-FU, HCPT, DOX, MMC)

TACE (5-FU, HCPT, DOX, MMC)

4 weeks

1. Clinical effectiveness

2. Life quality

3. Survival at 6/12/24 months

4. Comparison of WBC, TBIL and ALT

5. Immunological function

Li Q.M.46 2003

20

18

28-Oct

29–65 years old

II, III

—

 ≥ 60

Qining injection + TACE (HCPT, 5-FU, MMC)

TACE (HCPT, 5-FU, MMC)

7 days

1. Clinical effectiveness

2. Complication

Li W.H.47 2006

19

19

28-Oct

45 years old

—

—

—

Cinobufotalin injection + TACE (5-FU, DDP, MMC)

TACE (5-FU, DDP, MMC)

2 rounds

1. Life quality

2. Clinical effectiveness

3. Comparison of WBC and AFP

4. Survival at 12/24 months and median survival time

5. Complication

Liang B.L.48 2010

20

20

30-Oct

E:59 ± 6 years old

—

—

 ≥ 50

Sodium Cantharidinate and vitamin B6 + TACE (MMC, 5-FU, EPI)

TACE (MMC, 5-FU, EPI)

4weeks

Comparison of liver function and blood routine examination

C:55 ± 8 years old

Liang C.X.49 2015

30

30

34/26

E:median age 53 years

—

A and B

>80

Sodium Cantharidinate and Vitamin B6 + TACE (5-FU, DDP, OXA, EPI)

TACE (5-FU, DDP, OXA, EPI)

3–4 rounds (15 days per round)

1. Clinical effectiveness

C:median age 52 years

2. Comparison of WBC and AFP

 

3. QoL scores

Liang.T.J.50 2005

116

108

187/37

E:52.1 ± 9.7 years old

—

A, B and C

—

Jinlong capsule + TACE (EPI, MMC, CBP)

TACE (EPI, MMC, CBP)

 ≥ 3 years

1. Survival at 6/12/24/36 months

C:50.4 ± 8.5 years old

2. Clinical effectiveness

 

3. QoL scores

Liang Y.51 2008

48

48

72/24

Median age:44.5 years

—

A, B and C

 ≥ 70

Cinobufotalin injection + TACE (EPI, DDP, 5-FU) and IFN

TACE (EPI, DDP, 5-FU) and IFN

2 rounds (4 weeks)

1. Clinical effectiveness

2. Live quality

3. Comparison of 6/12/18 months

4. Complication

Liu X.H.52 2009

42

42

70/14

48.5 years old

—

—

—

Cinobufotalin injection + TACE (5-FU, DDP, EPI)

TACE (5-FU, DDP, EPI)

2–3 rounds (4 weeks per round)

1. Clinical effectiveness

2. Survival at 12/24/36 months

3. Comparison of immune function and liver function

4. Complication

Liu Y.Q.53 2010

38

44

72/10

E:54.21 ± 10.32 years old

—

A and B

>60

Cinobufotalin injection + TACE (THP, DDP, MMC)

TACE (THP, DDP, MMC)

2–3 rounds (3weeks per round)

1. Lipiodol deposition after TACE

 

2. Clinical effectiveness

C:55.32 ± 11.62 years old

3. Comparison of TTP

 

4. Complication

Lu S.J.54 2014

30

30

33/17

E:46.5 years old

—

—

—

Cinobufotalin injection + THM and TACE (DDP, DOX, 5-FU)

TACE (DDP, DOX, 5-FU)

30 days

1. Clinical effectiveness

C:47.3 years old

2. Life quality

 

3. Survival at 6/12/24 months

 

4. Complication

Peng W.D.55 2011

40

40

43/37

E:45.0 ± 13.5 years old

II, III

—

 ≥ 50

Compound cantharis capsule + FAP (5-FU, EPI, DDP)

FAP (5-FU, EPI, DDP)

10 days

1. Clinical effectiveness

C:44.0 ± 13.9 years old

2. Life quality

 

3. Immunological function

Qu J.R.56 2012

40

40

64/16

E:median age 54 years

II, III

—

 ≥ 60

Secretio bufonis injection + TACE (CBP, 5-FU, MMC,DOX)

TACE (CBP, 5-FU, MMC, DOX)

28 days

1. Complication

C:median age 56 years

2. Comparison of liver function and blood routine examination

Shen J.J.57 2009

23

24

36/11

52.2 ± 7.4 years old

II, III

—

—

Cinobufotalin injection + TACE (5-FU, DDP, MMC)

TACE (5-FU, DDP, MMC)

4 weeks

1. Complication 2. Comparison of liver Function and AFP

3. Life quality

4. Solid tumor variation

Shen J.J.58 2015

18

18

23/13

E:57.5 years old

—

A and B

 ≥ 60

Cinobufotalin injection + TACE (Lobaplatin, DDP, MMC)

TACE (Lobaplatin, DDP, MMC)

2 weeks

1. Clinical effectiveness

C:54.7 years old

2. Comparison of HIF-1α and VEGF

Shu X.H.59 2004

29

29

48/10

Median age: 51 years

II, III

—

 ≥ 60

Cinobufotalin injection + 5-fluoro-uracil

5-fluorouracil

1–2 rounds (5 days per round)

1. Clinical effectiveness

2. The degree of pain relief

3. Life quality

4. Complication

Su Y.60 2013

33

30

53/10

E:53.2 ± 8.7 years old

II, III

—

>60

Cinobufotalin injection + TACE (5-FU, HCPT, DOX, MMC)

TACE (5-FU, HCPT, DOX, MMC)

4 weeks

1. Clinical effectiveness

C:52.7 ± 7.9 years old

2. Life quality

 

3. Complication

Sun Z.J.61 2002

118

118

197/39

51.4 years old

—

—

—

Cinobufotalin injection + TACE (EPI, MMC, CBP)

TACE (EPI, MMC, CBP)

2 rounds (4 weeks per round)

1. Clinical effectiveness

2. Survival at 12/24/36 months

3. Immunological function

4. Liver function and complication

Tang J.G.62 1999

46

42

67/21

E:49 years old

—

—

—

Cinobufotalin injection + FAM (5-FU, DOX, MMC)

FAM (5-FU, DOX, MMC)

1 month

1. Complication

C:48 years old

2. AFP

 

3. Life quality

Tian X.L.63 2006

36

36

53/19

E:53.4 ± 10.5 years old

—

—

 ≥ 70

Aiyishu injection + TACE (MMC, DOX, 5-FU, DDP)

TACE (MMC, DOX, 5-FU, DDP)

2–3 rounds (4–6 weeks per round)

1. Clinical effectiveness

C:52.5 ± 9.6 years old

2. QoL scores

 

3. Life quality

 

4. Survival at 6/12/18/24 months

Wang C.J.64 2001

30

30

—

48 years old

—

A,B and C

 ≥ 30

Cinobufotalin injection + TACE (DOX, CBP, MMC)

TACE (DOX, CBP, MMC)

—

1. Improvement of clinical symptom

2. Complication

3. Child-pugh level

4. Serum levels of hepatic fibrosis

5. AFP

6. Clinical effectiveness

7. Survival at 12/24/36 months

Wang L.J.65 2007

72

70

117/25

E:62.5 years old

II, III

A and B

 ≥ 50

Aidi injection + FAP (5-FU, EPI, DDP)

FAP (5-FU, EPI, DDP)

2 rounds (30 days per round)

1. Clinical effectiveness

C:64.1 years old

2. Life quality

 

3. Child-pugh level

 

4. AFP

Wang Q.C.66 2013

24

24

41/7

E:median age 55 years

—

A and B

—

THM (toad venom, Salvia miltiorrhiza, and matrine) + TACE (MMC, THP, OXA)

TACE(MMC, THP, OXA)

3 days

Comparison of T-lymphocyte subsets

C:median age 57.2 years

Wei Y.F.67 2015

48

44

61/31

58.6 ± 6.8 years old

—

A and B

 ≥ 70

Sodium cantharidinate and vitamin B6 + TACE (5-FU, EPI, MMC)

TACE (5-FU, EPI, MMC)

3 rounds (30 days per round)

1. Clinical effectiveness

2. Complication

3. Survival at 12/24/36 months

Wu H.M.68 200

36

44

69/11

E:52.4 ± 7.2 years old

II, III

—

—

Cinobufotalin injection + TACE (5-FU, MMC, DDP)

TACE (5-FU, MMC, DDP)

2 rounds (10 days per round)

1. Clinical effectiveness

 

2. AFP

C:50.5 ± 8.7 years old

3. Comparison of tumor metastasis

 

4. Survival at 3/6/12 months

 

5. Complication

Wu J.Y.69 2006

30

30

53/7

E:50 years old

III

—

—

Cinobufotalin injection + TACE (HCPT, THP)

TACE (HCPT, THP)

25 days

1. Clinical effectiveness

C:50 years old

2. Complication

Wu J.S.70 2015

15

15

26-Apr

44–68 years old

—

—

 ≥ 70

Sodium cantharidinate and vitamin B6 + TACE (5-FU, EPI, MMC)

TACE (5-FU, EPI, MMC)

3 rounds

1. Comparison of WBC, ALT and AST

2. Complication

Wu Z.M.71 2010

41

41

50/32

Median age 45 years old

—

—

—

Sodium cantharidinate and vitamin B6 + TACE (5-FU, EPI, DDP)

TACE (5-FU, EPI, DDP)

2 weeks

1. Clinical effectiveness

2. Comparison of liver function and AFP

3. Comparison of new vessel and portal vein tumor thrombosis

Xiao X.S.72 2011

25

25

35/15

E:65.4 years old

—

—

—

Cinobufotalin injection + TACE (MMC, 5-FU, DOX, DDP, HCPT)

TACE (MMC, 5-FU, DOX, DDP, HCPT)

2 rounds (15–20 days per round)

Clinical effectiveness

C:63.6 years old

Xie J.73 2015

50

50

89/11

E:58.09 ± 11.67 years old

—

A

—

Scorpion and earthworm + TACE (5-FU, MMC, EPI)

TACE (5-FU, MMC, EPI)

2 months

1. Numbers of TACE

C:58.32 ± 11.55 years old

2. AFP

 

3. Liver function

 

4. Lung metastasis

Xie Y.F.74 2003

31

31

49/13

Median age 53.5 years

I, II, III

—

>60

Jinlong capsule + TACE (5-FU, DDP, MMC)

TACE (5-FU, DDP, MMC)

21 days

1. Clinical effectiveness

2. Life quality

3. Comparison of WBC

4. Immunologic function

5. AFP

Xu Y.S.75 2011

64

64

84/44

50.25 years old

—

—

>60

Sodium norcantharidate (SNCTD) + TACE (DDP, 5-FU, DOX)

TACE (DDP, 5-FU, DOX)

1–3 rounds (15 days per round)

1. Clinical effectiveness

2. Survival at 12/24/36 months

3. KPS

4. Complication

Xue Q.76 2010

32

30

45/17

E:45.75 ± 11.40 years old

—

—

>60

Cinobufotalin injection + TACE (DDP, 5-FU, DOX)

TACE (DDP, 5-FU, DOX)

1–3 rounds (28 days per round)

1. Clinical effectiveness

C:45.45 ± 10.70 years old

2. Survival at 6/12/24/36 months

 

3. Comparison of clinical symptoms

 

4. KPS

 

5. Complication

Yang P.Y.77 2013

34

36

48/22

55.1 ± 8.2 years old

—

A and B

 ≥ 60

Jinlong capsule + TACE (EPI, 5-FU, DDP)

TACE (EPI, 5-FU, DDP)

42 weeks

1. Clinical effectiveness

2. Comparison of ALT, TBIL and ALB

3. KPS scores

4. TCM clinical symptom

5. TH1 and TH2

6. Safety analysis

You S.Y.78 2006

25

25

32/18

E:49 ± 3 years old

—

—

—

Cinobufotalin injection + TACE (5-FU, DDP, EPI)

TACE (5-FU, DDP, EPI)

2 rounds

1. Clinical effectiveness

C:48 ± 9 years old

2. Survival at 12/24/36 months

 

3. Complication

Yu J.G.79 2013

30

30

29-Nov

E:49.7 years old

—

—

>60

Cinobufotalin injection + TACE (DDP, DOX, MMC, 5-FU)

TACE (DDP, DOX, MMC, 5-FU)

60 days

1. Clinical effectiveness

C:50.8 years old

2. Clinical symptom improvement

 

3. Comparison of blood routine examination, liver function and AFP

Yuan C.Y.80 2007

20

20

28-Dec

E:52.3 ± 3.5 years old

II, III

—

—

Cinobufotalin injection + TACE (5-FU, DDP, EPI)

TACE (5-FU, DDP, EPI)

2 rounds

1. Clinical effectiveness

C:53.2 ± 3.4 years old

2. AFP

 

3. Life quality

 

4. Immunological function

 

5. Complication

Zhang B.81 2007

51

49

76/24

E:54.3 years old

—

—

>80

Sodium cantharidinate and vitamin B6 + TACE (THP)

TACE (THP)

4 weeks

1. Clinical effectiveness

C:50.1 years old

2. Life quality

 

3. Clinical symptom improvement

 

4. Complication

Zhang C.Q.82 2005

116

108

187/37

E:52.1 ± 9.7 years old

—

A, B and C

—

Jinlong capsule + TACE (EPI, MMC, CBP)

TACE (EPI, MMC, CBP)

3 years

1. Survival at 6/12/24/36 months

C:50.4 ± 8.5 years old

2. Clinical effectiveness

 

3. QoL scores

Zhang M.J.83 2011

38

38

38/38

E:53.99 ± 2.43 years old

—

—

 ≥ 60

Sodium cantharidinate and vitamin B6 + TACE (MMC, DOX)

TACE (MMC, DOX)

4–6 weeks

1. Clinical effectiveness

C:55.02 ± 2.16 years old

2. Clinical symptom improvement and weight

 

3. Life quality

 

4. Immunological function

 

5. Complication

Zhang T.S.84 2011

32

32

53/11

E:52 years old

—

—

>60

Cinobufotalin injection + TACE (DOX, CBP, MMC)

TACE (DOX, CBP, MMC)

4–6 weeks

1. Clinical effectiveness

C:51 years old

2. AFP

 

3. Complication

 

4. Survival at 6/12/24/36 months

Zhou J.S.85 2006

21

22

34/9

60.08 years old

II, III

A, B and C

50–70

Cinobufotalin injection + TACE (5-FU, DDP, MMC)

TACE (5-FU, DDP, MMC)

4 rounds (4 weeks per round)

1. Clinical effectiveness

2. Liver function

3. Clinical symptom improvement

4. Life quality

5. Survival at 18/24 months

6. AFP and KPS

Zhu W.Q.86 2014

48

50

71/27

47.5 years old

—

—

—

Sodium cantharidinate and vitamin B6 + TACE (-)

TACE (-)

20 days

1. Complication

2. Liver function, Child-Pugh scores

3. Serum hepatic fibrosis markers

4. Clinical effectiveness

  1. Note: E: Experimental group; C: Control group; M: Male; F: Female; KPS: Karnofsky performance score; RCT: Randomized clinical trial; TACE: Transcatheter hepatic arterial chemoembolization; THM: Traditional herb medicine; AFP: Alpha-fetoprotein; Th1: Helper T cell type 1; Th2: Helper T cell type 2; HIF-1α: Hypoxia inducible factor-1α; MST: Median survival time; TTP: Time to progression; QoL: Quality of life; VEGF: Vascular endothelial growth factor; WBC: White blood cell; TBIL: Total bilirubin; ALT: Alanine aminotrnsferase; ALB: Albumin; MTTP: Median time to progression; CBR: Clinical beneficial rate; IFN: Interferon; OXA: Oxaliplatin; EPI: Epirubicin; 5-FU: 5-fluorouracil; THP: Pirarubicin; DDP: Cisplatin; CF: Calcium folinate; GEM: Gemcitabine; DOX: Doxorubicin; MMC: Mitomycin; HCPT: Hydroxycamptothecine; CBP: Carboplatin.
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