Comparative efficacy and safety of Chinese medicine injections as an adjunctive therapy for cervical cancer in Chinese patients: a network meta-analysis

Figures & data

Figure 1. The fYlow diagram of study selection.

Table 1. The main characteristics of the included randomized controlled trials.

Study	Country	Sample size		Age		Stage (FIGO)	Interventions		Duration (days)	Outcomes
		Control	Experimental	Control	Experimental		Control	Experimental		Efficacy	Safety
Cao and Wen (2005)	China	53	57	31–72	35–74	II-IV	RT	RT + KA	40	CER, KPS	LRR
Liu (2009)	China	42	42	28–65	30–70	Ia-IIa	RT	RT + KA	30	CER, KPS	–
Hu and Lei (2011)	China	34	73	45–75	45–75	IIb-IV	RT	RT + AD	42	CER, KPS	LRR
Lu et al. (2011)	China	33	33	58.1 ± 9.5	60.4 ± 11.6	II-III	RT	RT + FFKS	63	CER, KPS	–
Wang et al. (2011)	China	23	23	43–75	35–72	–	RT	RT + FFKS	28	CER, KPS	–
Yin et al. (2011)	China	43	46	30-–75	32–78	IIb-IIIb	RT	RT + FFKS	28	CER, KPS	LRR, GRR
Wu et al. (2013)	China	32	28	33–72	29–71	Ib-IIa	RT	RT + YDZ	28	CER	–
Deng and Cai (2014)	China	34	34	33–66	33–66	IIb-IIIb	RT	RT + YDZ	21	CER	LRR
Deng and Chen (2014)	China	34	34	33-66	33-66	IIb-IIIb	RT	RT + YDZ	21	CER	–
Chen et al. (2014)	China	34	34	33–66	33–66	IIb-IIIb	RT	RT + YDZ	21	CER	–
Deng et al. (2015a)	China	34	34	33–66	33–66	IIb-IIIb	RT	RT + YDZ	21	–	LRR
Deng et al. (2015b)	China	35	35	33–65	32–64	IIb-IIIb	RT	RT + FFKS	21	CER	–
Liu et al. (2015)	China	40	40	60–71	60–73	I-IIb	RT	RT + YDZ	84	KPS	–
Yan et al. (2018)	China	30	30	41–68	33–65	IIb-IIIb	RT	RT + FFKS	42	CER, KPS	LRR
Li et al. (2018)	China	40	40	–	–	IIa-IV	RT	RT + YDZ	28	KPS	–
Tian et al. (2019)	China	75	75	22–50	22–50	IIb-IIIb	RT	RT + KLT	35	CER, KPS	LRR, GRR
Li and Xi (2020)	China	39	39	60–70	60–70	I-IIb	RT	RT + YDZ	21	CER, KPS	–
Zhou et al. (2011)	China	28	28	35–66	35–66	IIb-IV	RT + DDP	RT + DDP + AD	28	CER, KPS	LRR, GRR
Li et al. (2014)	China	40	40	25–70	25–70	IIb-IVa	RT + DDP	RT + DDP + KA	30	CER, KPS	GRR
Zhong et al. (2014)	China	34	34	31–59	33–62	III-IV	RT + DDP	RT + DDP + KA	42	CER, KPS	LRR, GRR
Xiong and Zhou (2016)	China	64	64	31–71	27–72	IIb-IV	RT + DDP	RT + DDP + FFKS	42	CER	–
Qin et al. (2016)	China	30	30	40–76	42–77	IIb-IIIb	RT + DDP	RT + DDP + FFKS	28	CER, KPS	LRR
Li and Wu (2018)	China	30	30	30–60	28–59	IIa-IIIb	RT + DDP	RT + DDP + KLT	25	CER	–
Wang (2021)	China	49	49	71–84	70–85	III-IV	RT + DDP	RT + DDP + KLT	84	CER, KPS	LRR, GRR
Ge et al. (2022)	China	49	49	53–72	48–76	II-IV	RT + DDP	RT + DDP + AD	56-82	CER	GRR
Chen and Liu (2012)	China	36	42	31–61	35–59	IIIa-IV	RT + DP	RT + DP + KA	28	CER, KPS	LRR, GRR
Chen and Zhang (2012)	China	34	42	33–61	31–60	III-IV	RT + DP	RT + DP + RSDT	84	CER, KPS	LRR, GRR
Chen (2013)	China	30	30	36–61	32–64	III-IV	RT + DP	RT + DP + FFKS	84	CER, KPS	LRR, GRR
Li et al. (2015)	China	50	50	20–60	20–60	IIb-IVb	RT + DP	RT + DP + KLT	28	CER	–
Mu (2016)	China	100	100	57.1 ± 2.3	55.6 ± 2.5	IIIa-IV	RT + DP	RT + DP + FFKS	54	CER, KPS	LRR, GRR
Jiang et al. (2016)	China	40	40	42–67	40–65	IIIa-IV	RT + DP	RT + DP + FFKS	84	CER, KPS	LRR, GRR
Ma et al. (2018)	China	33	32	40–65	40–65	Ib-IIa	RT + DP	RT + DP + SQFZ	63	–	LRR, GRR
Wang et al. (2018)	China	51	51	30–65	32–63	Ia-IIb	RT + DP	RT + DP + KA	42	CER	GRR
Zhang (2019)	China	50	50	21–60	20–60	–	RT + DP	RT + DP + KLT	196	CER	–
Liu et al. (2020)	China	45	45	40–65	41–63	IIb-IIIb	RT + DP	RT + DP + FFKS	84	CER, KPS	GRR
Song et al. (2020)	China	50	50	35–70	35–70	IIb-IIIb	RT + DP	RT + DP + KA	56	CER	GRR
Wen et al. (2012)	China	32	33	>30	>30	IIb-IVa	RT + TP	RT + TP + SM	15	CER, KPS	LRR, GRR
Huang et al. (2014)	China	33	35	30–64	30–64	IIb-IV	RT + TP	RT + TP + SQFZ	21	CER, KPS	LRR, GRR
Li et al. (2016)	China	55	55	30–60	28–59	Ib-IIb	RT + TP	RT + TP + HQ	10	CER	–
Gao et al. (2017)	China	100	100	40–69	41–70	–	RT + TP	RT + TP + SM	21-35	CER	–
Li (2017)	China	32	32	31–64	31–65	III-IV	RT + TP	RT + TP + FFKS	28	CER	LRR, GRR
Zhang (2017)	China	60	60	31–75	30–74	IIb-IV	RT + TP	RT + TP + KA	56	CER	LRR, GRR
Shao (2018)	China	20	20	42–67	40–68	IIIa-IV	RT + TP	RT + TP + FFKS	63	CER	LRR, GRR
Cao (2019)	China	60	60	38–68	41–72	–	RT + TP	RT + TP + FFKS	30	CER	LRR, GRR
Dong et al. (2020)	China	37	37	35–66	35–65	IIIa-IV	RT + TP	RT + TP + FFKS	63	CER	GRR
Li et al. (2020)	China	65	65	42–52	44–54	Ib2-IIb	RT + TP	RT + TP + HQ	42	CER	LRR, GRR
Peng and Li (2022)	China	48	48	51.2 ± 3.4	49.9 ± 3.5	IIb-IIIb	RT + TP	RT + TP + YDZ	21	CER	LRR, GRR

FIGO: Federation of International of Gynecologists and Obstetricians; RT: radiotherapy; DDP, cisplatin chemotherapy; DP: docetaxel plus cisplatin chemotherapy; TP: paclitaxel plus cisplatin chemotherapy; AD: Aidi; HQ, Huangqi; FFKS: Fufangkushen; KA: Kangai; KLT: Kanglaite; RSDT: Renshenduotang; SQFZ: Shenqifuzheng; SM: Shenmai; YDZ: Yadanzi; CER: clinical efficacy rate; KPS: Karnofsky performance scale rate; LRR: leukocyte reduction rate; GRR: gastrointestinal reaction rate; -, not reported.

Figure 2. Risk of bias graph of included randomized controlled trials.

Figure 3. Network plot for the efficacy (CER) of CMIs combined with RT or CCRT for cervical cancer.

Table 2. Network meta-analysis for the efficacy of CMIs combined with RT or CCRT for cervical cancer.

	KPS
CER	RT	2.51 (0.42, 15.07)	3.35 (1.00, 11.26)	9.49 (1.76, 51.17)	–	1.74 (0.54, 5.63)
	2.12 (1.23, 3.65)	RT + AD	1.33 (0.15, 11.58)	3.77 (0.32, 44.12)	–	0.69 (0.08, 5.89)
	1.91 (1.11, 3.29)	0.90 (0.42, 1.95)	RT + FFKS	2.83 (0.36, 22.55)	–	0.52 (0.10, 2.81)
	2.40 (1.20, 4.82)	1.14 (0.47, 2.75)	1.26 (0.52, 3.04)	RT + KA	–	0.18 (0.02, 1.41)
	4.75 (1.67, 13.52)	2.25 (0.69, 7.31)	2.48 (0.76, 8.07)	1.98 (0.56, 6.94)	RT + KLT	–
	1.70 (0.88, 3.28)	0.80 (0.34, 1.89)	0.89 (0.38, 2.09)	0.71 (0.27, 1.84)	0.36 (0.10, 1.23)	RT + YDZ
	RT + DDP	3.00 (0.28, 32.67)	7.00 (0.49, 99.70)	2.82 (0.51, 15.62)	3.45 (0.28, 42.52)
	1.72 (0.68, 4.33)	RT + DDP + AD	2.33 (0.07, 83.01)	0.94 (0.05, 17.75)	1.15 (0.04, 36.79)
	1.47 (0.62, 3.52)	0.86 (0.24, 3.06)	RT + DDP + FFKS	0.40 (0.02, 9.50)	0.49 (0.01, 19.07)
	3.06 (1.38, 6.75)	1.78 (0.53, 6.03)	2.07 (0.46, 6.73)	RT + DDP + KA	1.22 (0.06, 25.53)
	2.49 (1.21, 5.12)	1.45 (0.45, 4.69)	1.69 (0.54, 5.23)	0.81 (0.28, 2.38)	RT + DDP + KLT
	RT + DP	3.63 (2.10, 6.27)	20.50 (2.51, 167.62)	–	1.29 (0.37, 4.42)
	2.12 (1.44, 3.13)	RT + DP + FFKS	5.65 (0.64, 49.57)	–	0.35 (0.09, 1.37)
	2.54 (1.44, 4.48)	1.20 (0.60, 2.38)	RT + DP + KA	–	0.06 (0.01, 0.72)-
	5.76 (2.23, 14.84)	2.71 (0.97, 7.56)	2.27 (0.75, 6.85)	RT + DP + KLT
	2.15 (0.86, 5.42)	1.02 (0.37, 2.77)	0.85 (0.29, 2.51)	0.37 (0.10, 1.40)	RT + DP + RSDT
	RT + TP	–	–	–	3.38 (0.13, 89.57)	2.96 (0.48, 18.21)	–
	3.98 (1.66, 9.56)	RT + TP + FFKS	–	–	–	–	–
	0.95 (0.33, 2.72)	0.24 (0.06, 0.94)	RT + TP + HQ	–	–	–	–
	4.64 (0.96, 22.54)	1.17 (0.19, 7.11)	4.90 (0.73, 32.74)	RT + TP + KA	–	–	–
	6.96 (2.18, 22.25)	1.75 (0.41, 7.51)	7.35 (1.53, 35.28)	1.50 (0.21, 10.66)	RT + TP + SM	0.87 (0.13, 5.86)	–
	2.96 (0.58, 15.09)	0.74 (0.12, 4.73)	3.13 (0.45, 21.75)	0.64 (0.07, 6.17)	0.43 (0.06, 3.14)	RT + TP + SQFZ	–
	2.74 (0.55, 13.77)	0.69 (0.11, 4.33)	2.89 (0.42, 19.89)	0.59 (0.06, 5.65)	0.39 (0.05, 2.88)	0.93 (0.09, 9.17)	RT + TP + YDZ

RT: radiotherapy; CCRT: concurrent chemoradiotherapy; DDP: cisplatin chemotherapy; DP :docetaxel plus cisplatin chemotherapy; TP: paclitaxel plus cisplatin chemotherapy; AD: Aidi; HQ: Huangqi; FFKS: Fufangkushen; KA: Kangai; KLT, Kanglaite; RSDT: Renshenduotang; SQFZ: Shenqifuzheng; SM: Shenmai; YDZ: Yadanzi; CER: clinical efficacy rate; KPS: Karnofsky performance scale rate; LRR: leukocyte reduction rate; GRR: gastrointestinal reaction rate; -, not reported; The table data on the lower left of the gray bottom tables represents CER, and the upper right KPS; bold font data represents a significant difference.

Table 4. Rank of SUCRA for the efficacy and safety of CMIs combined with RT or CCRT for cervical cancer.

Therapy	efficacy		safety
	CER	KPS	LRR	GRR
RT	2.4	17.0	15.2	51.7
RT + AD	54.5	50.1	28.2	–
RT + FFKS	47.9	59.2	71.3	26.2
RT + KA	63.7	86.7	38.8	–
RT + KLT	92.1	–	51.7	72.1
RT + YDZ	39.4	37.1	94.8	–
RT + DDP	8.2	21.3	39.9	0.4
RT + DDP + AD	47.5	51.8	49.5	62.1
RT + DDP + FFKS	38.2	71.2	53.9	–
RT + DDP + KA	83.9	50.8	48.7	46.6
RT + DDP + KLT	72.2	54.8	58.1	90.9
RT + DP	1.3	11.5	29.2	4.3
RT + DP + FFKS	45.4	66.6	34.9	45.9
RT + DP + KA	59.7	97.6	53.6	88.0
RT + DP + KLT	95.7	–	78.5	46.9
RT + DP + RSDT	47.9	24.4	53.7	64.9
RT + TP	15.9	23.8	24.5	33.9
RT + TP + FFKS	64.1	–	12.9	49.6
RT + TP + HQ	16.9	–	68.8	41.9
RT + TP + KA	67.9	–	19.9	58.6
RT + TP + SM	80.7	63.3	78.0	55.8
RT + TP + SQFZ	53.7	62.9	82.1	57.7
RT + TP + YDZ	50.7	–	63.9	52.5

RT: radiotherapy; CCRT: concurrent chemoradiotherapy; DDP: cisplatin chemotherapy; DP: docetaxel plus cisplatin chemotherapy; TP: paclitaxel plus cisplatin chemotherapy; AD: Aidi; HQ: Huangqi; FFKS: Fufangkushen; KA: Kangai; KLT: Kanglaite; RSDT: Renshenduotang; SQFZ: Shenqifuzheng; SM: Shenmai; YDZ: Yadanzi; LRR: leukocyte reduction rate; GRR, gastrointestinal reaction rate; -, not reported.

Figure 4. Network plot for the efficacy (KPS) of CMIs combined with RT or CCRT for cervical cancer.

Figure 5. Network plot for the safety (LRR) of CMIs combined with RT or CCRT for cervical cancer.

Table 3. Network meta-analysis for the safety of CMIs combined with RT or CCRT for cervical cancer.

	GRR
LRR	RT	–	2.93 (0.29, 29.53)	–	0.33 (0.01, 17.66)	–
	0.63 (0.15, 2.62)	RT + AD	–	–	–	–
	0.10 (0.00, 0.48)	0.17 (0.02, 1.30)	RT + FFKS	–	0.11 (0.00, 4.27)	–
	0.42 (0.07, 2.62)	0.66 (0.06, 6.86)	3.98 (0.36, 44.13)	RT + KA	–	–
	0.14 (0.04, 1.56)	0.38 (0.04, 4.02)	2.32 (0.21, 25.83)	0.58 (0.04, 8.08)	RT + KLT	–
	0.01 (0.00, 0.21)	0.02 (0.00, 0.48)	0.14 (0.01, 3.06)	0.03 (0.00, 0.91)	0.06 (0.00, 1.58)	RT + YDZ
	RT + DDP	0.36 (0.19, 0.70)	–	0.46 (0.24, 0.89)	0.20 (0.07, 0.58)
	0.31 (0.00, 254)	RT + DDP + AD	–	–	–
	0.15 (0.00, 2.52e + 06)	0.49 (0.00, 24961)	RT + DDP + FFKS	1.27 (0.50, 3.21)	0.54 (0.15, 1.93)
	0.34 (0.00, 903)	1.07, (0.00, 4055)	2.19 (0.00, 1.21e + 07)	RT + DDP + KA	0.43 (0.12, 1.53)
	0.12 (0.00, 61.88)	0.37 (0.00, 269)	0.77 (0.00, 1.73e + 06)	0.35 (0.00, 2666)	RT + DDP + KLT
	RT + DP	0.48 (0.31, 0.75)	0.24 (0.14, 0.42)	0.49 (0.13, 1.78)	0.35 (0.12, 1.03)
	0.84 (0.19, 3.76)	RT + DP + FFKS	0.51 (0.25, 1.03)	1.02 (0.26, 4.00)	0.74 (0.23, 2.35)
	0.38 (0.03, 5.08)	0.46 (0.02, 8.98)	RT + DP + KA	2.01 (0.50, 8.11)	1.45 (0.44, 4.80)
	0.08 (0.00, 3.55)	0.10 (0.00, 5.59)	0.21 (0.00, 20.50)	RT + DP + KLT	0.72 (0.14, 3.88)
	0.38 (0.03, 5.13)	0.45 (0.02, 9.04)	0.98 (0.03, 38.59)	4.65 (0.05, 457.47)	RT + DP + RSDT
	RT + TP	0.54 (0.13, 2.26)	0.78 (0.06, 10.07)	0.36 (0.03, 4.71)	0.39 (0.03, 5.59)	0.38 (0.03, 5.41)	0.46 (0.03, 6.23)
	1.40 (0.53, 3.74)	RT + TP + FFKS	1.43 (0.08, 26.78)	0.66 (0.03, 12.50)	0.72 (0.04, 14.68)	0.70 (0.03, 14.21)	0.85 (0.04, 16.49)
	0.38 (0.16, 0.90)	0.27 (0.07, 1.00)	RT + TP + HQ	0.46 (0.01, 17.42)	0.50 (0.01, 20.19)	0.49 (0.01, 19.56)	0.60 (0.02, 22.91)
	1.14 (0.48, 2.71)	0.82 (0.22, 3.01)	3.00 (0.89, 10.16)	RT + TP + KA	1.09 (0.03, 44.12)	1.06 (0.03, 42.75)	1.29 (0.03, 50.07)
	0.29 (0.09, 0.91)	0.21 (0.05, 0.94)	0.77 (0.18, 3.20)	0.26 (0.06, 1.07)	RT + TP + SM	0.97 (0.02, 41.71)	1.19 (0.03, 48.88)
	0.26 (0.08, 0.80)	0.19 (0.04, 0.82)	0.68 (0.17, 2.81)	0.23 (0.06, 0.93)	0.89 (0.18, 4.41)	RT + TP + SQFZ	1.22 (0.03, 49.90)

RT: radiotherapy; CCRT: concurrent chemoradiotherapy; DDP: cisplatin chemotherapy; DP: docetaxel plus cisplatin chemotherapy; TP: paclitaxel plus cisplatin chemotherapy; AD: Aidi; HQ: Huangqi; FFKS, Fufangkushen; KA: Kangai; KLT: Kanglaite; RSDT: Renshenduotang; SQFZ: Shenqifuzheng; SM: Shenmai; YDZ: Yadanzi; GRR: gastrointestinal reaction rate; -, not reported; The table data on the lower left of the gray bottom tables represents LRR, and the upper right GRR; bold font data represents a significant difference.

Figure 6. Network plot for the safety (GRR) of CMIs combined with RT or CCRT for cervical cancer.

Figure 7. Publication bias (CER).

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Data availability statement

All data generated or analyzed during this study are included in this published article, further inquiries can be made with the corresponding author(s).