The Method of Activating Blood and Dredging Collaterals for Reducing Chemotherapy-Induced Peripheral Neuropathy: A Systematic Review and Meta-Analysis

Table 1

Characteristics of the included studies of the systematic review.

First author	Year	Sample size; (drop-out)	Mean age (year); (median/range)	Cancer; Types	Common treatment; (regimen)	Interventions; (regimen, participants)	Comparators; (regimen, participants)	Main Outcomes
Herbal medicine for hand and foot baths or fumigation or compress or gel
Chen, Mou; [18]	2015	79 (0)	50.12±10.21	Gastric and colorectal; cancer	FOLFOX 4	Hand and foot bath of Huoxue Tongluo decoction(30 min, tid for 2wks, n=42)	No additional Tx. (n=37)	(1)  Incidence rate; (NCI-CTC; sensory neuropathy); (2)QoL (KPS); (3)Adverse events
Li, Cai; [19]	2017	65 (0)	I:53; C:56	colorectal; cancer	XELOX (d1-14, 3wks/cycle for 2 cycles)	Hand and foot bath, fumigation of Wenjing Huoxue formula(15 min, qd for 6 wk, n=34)	No additional Tx. (n=31)	(1)Incidence rate; (Levi‘s grade); (2)QoL (KPS); (3)Adverse events
Lou; [20]	2014	102(1)	I:59.84±9.30 C:57.94±10.55	Various types of cancer	Oxaliplatin based CTx.	Hand and foot bath of Wenjing Tongluo formula(20 min, bid for 7 days, n=67)	placbo(20 min, bid for 7 days, n=34)	(1)Clinical improvement (NCI-CTC; sensory neuropathy,); (2)NRS (pain); (3)NCCN (pain); (4) Adverse events
Qin; [21]	2012	68 (0)	I:57.2±8.6 C:59.5±7.9	Various types of cancer	(1)Oxaliplatin/paclitaxel based CTx.; (2)AD pro injection (80ml qd); (3) Thymopentin(1 mg qd); (for 14 days)	Hand and foot bath of Network Vessel-freeing Formula(30 min, qd for 14 days, n=34)	Cobamamide for intramuscular injection(1mg qd for 14 days, n=34)	(1)Clinical effectiveness (Nimodipine trichotomy); (2)Incidence rate (researcher’s own criteria); (3)Adverse events
Shen; [22]	2015	60 (0)	I:59.67±12.72 C:56.57±11.32	Various types of cancer	(1)Oxaliplatin based CTx.; (2)Mecobalamin for intramuscular injection (0.5 mg tiw); (3)AD pro injection (50ml qd); (4)Thymopentin for subcutaneous injection(1.6 mg biw); (for 14 days)	Hand and foot bath of modified Huangqi-Guizhi Wuwu decoction(30 min, qd for 14 days, n=30)	No additional Tx. (n=30)	(1)Clinical improvement (NCI-CTC; sensory neuropathy,); (2)Clinical symptom (GPCR-NCM); (3)Adverse events
Tang; [23]	2014	128(23)	I:59.46±11.51 C:61.16±9.47	Gastric and colorectal; cancer	Oxaliplatin based CTx (for 6-8 cycles)	Hand and foot bath of Yangxue Wenjing Tongluo decoction (; during CTx, 20 min, bid, n=54)	No additional Tx. (n=51)	(1)Incidence rate; (WHO grade); (2)Clinical symptom (TCSS); (3) Adverse events
Yi, Li; [24]	2017	100 (0)	Not mentioned	colorectal; cancer	Oxaliplatin based CTx.(21 d/cycle for 6 cycles)	Hand and foot bath of Tongluo Zhibi decoction (during CTx, 30 min, qd for 6 cycles, n=50)	Warm water for Hand and foot bath (during CTx, 30 min, qd for 6 cycles, n=50)	(1)Incidence rate; (Levi‘s grade); (2)QoL (KPS); (3) Adverse events
Zhang; [25]	2015	64 (0)	Not mentioned	Gastric and colorectal; cancer	FOLFOX 4	Hand and foot bath of Tongjing, Huoxue formula (during CTx, 1000ml, 30 min, qd for 7 d, n=32)	Warm water for Hand and foot bath (during CTx, 1000ml, 30 min, qd for 7 d, n=32)	(1)Clinical improvement (Levi‘s grade, NCI-CTC); (2)QoL (KPS)
Feng; [26]	2014	120 (0)	I:53.18±13.61 C:51.95±11.37	Various types of cancer	(1)Cisplatin based CTx.; (2)Glutathione (1500mg/m^2,d1-7)	Herbal Compress (for 7 d, n=60)	No additional Tx. (n=60)	(1)Incidence rate; (WHO grade); (2)Duration time; (3)Herbal related adverse events
Xu, Zhang; [27]	2018	67 (0)	I:57.89±11.54 C:54.71±12.24	Various types of cancer	Not mentioned.	(1)Xiaotan Tongluo Gel for external use(1 mL/cm2,14 d/cycle for 2 cycles, n=36); (2)Mecobalamin tablets (0.5 mg tid)	(1)Placebo Gel for external use(1 mL/cm2,; 14 d/cycle for 2 cycles, n=31); (2)Mecobalamin tablets (0.5 mg tid)	(1)Clinical improvement (NCI-CTC; sensory neuropathy,); (2)Clinical symptom (GPCR-NCM); (3) NCV; (1)SNCV: median nerve/fibular nerve; (2)MNCV: median nerve/; fibular nerve
Herbal medicine for intravenous infusion
Chen, Huang; [28]	2018	58 (0)	I:42-78; C:43-78	Gastric and colorectal; cancer	(1)FOLFOX4(2wks/cycle for 4 cycles); (2)Methycobal Injection for Intramuscular injection (0.5 mg qd during CTx)	Astragalus injection for intravenous infusion(30ml qd during CTx, n=29)	No additional Tx. (n=29)	(1)  Incidence rate; (WHO grade); (2) QoL (KPS); (3) NCV; (1)SNCV: median nerve/peroneus communis nerve; (2)MNCV: median nerve/ Peroneus communis nerve
Cheng; [29]	2014	36 (0)	I:46; C:49	Various types of cancer	Oxaliplatin based CTx. (130mg/m^2,d1,21d/cycle for 4 cycles)	Tanshinone IIA Sodium Sulfonate Injection for intravenous infusion (80mg qd for d1-3,n=18)	(1)Tropisetron (5mg/d); (2)dxm (5mg/d); During CTx; (n=18)	(1)Incidence rate; (Levi‘s grade); (2)SNCV/MNCV; (3)SOD/MDA
Cui; [30]	2009	40 (0)	I:60; C:63	Gastric and colorectal; cancer	Oxaliplatin based CTx.(130mg/m^2,d1, for 1 cycle)	Astragalus injection for intravenous infusion(30ml qd for d1-7, n=20)	No additional Tx. (n=20)	(1)Incidence rate; (Levi‘s grade); (2)NGF
Herbal medicine for oral dosage form
Li, Sun; [31]	2017	56 (0)	I: 58.89±8.75C: 57.71±9.31	Various types of cancer	n.c.	Granulas of Chinese Medicine of modified Huangqi-Guizhi Wuwu and Shentong Zhuyu(10g, bid for 1month, n=28)	Placebo(10g, bid for 1 month, n=28)	(1)Clinical improvement (NCI-CTC, sensory neuropathy,); (2)NRS (numbness); (3)ECOG PS (EORTC QLQ-C30); (4) Adverse events
Liu,; Zhou; [32]	2011	90 (5)	I:61.47±9.05 C:60.43±9.48	Various types of cancer	Oxaliplatin based CTx.(130mg/m^2,d1, every 21 days/cycle, for 2 cycles)	Wangqi Guizhi Wuwu decoction(100ml, bid for 42 days, during CTx, n=28)	Mecobalamin (0.5 mg tid for 42 days, n=29)	(1) Clinical improvement (Levi‘s grade); (2)NCV; (1)SNCV: median nerve/fibular nerve; (2)MNCV: median nerve/; fibular nerve; (3)Effective rate
Peng; [33]	2015	96 (0)	I:57.2; C:55.7	Gastric and colorectal; cancer	(1)mFOLFOX6(2 wks/cycle for 4 cycles); (2)Calcium gluconate, magnesium sulfate for injection (before CTx, for 2 days)	Danggui Sini Decoction combined with Yanghe Decoction(150ml, ( bid for 8 wks, during CTx, n=48)	No additional Tx. (n=48)	(1)Incidence rate; (Levi‘s grade); (2) NCV; (1)SNCV: median nerve/fibular nerve; (2)MNCV: median nerve/; fibular nerve; (3)Hemodynamic parameters
Chen, Yi [34]	2016	70 (0)	I:63.9±7.9 C:64.0±8.1	colorectal; cancer	Oxaliplatin based CTx.(21 d/cycle for 4 cycles)	Tongluo Zhibi decoction(1wk before CTx- the end, n=35)	No additional Tx. (n=35)	(1)Incidence rate (researcher’s own criteria); (2)NGF; (3)SNCV/SNAPA
Shi; [35]	2010	56 (0)	I:62.8; C:62.1	Gastric and colorectal; cancer	FOLFOX 4 (for 4 cycles)	Wenjing Decoction; (bid for 2 months, during CTx, n=30)	No additional Tx. (n=26)	Incidence rate; (Levi‘s grade)
Xu; [36]	2016	76 (0)	I:45.3±5.8 C:44.9±5.5	Ovarian cancer	TP(21 d/cycle for 6 cycles)	Modified Wangqi Guizhi Wuwu decoction(150ml, qd for 2 wks, during CTx, n=38)	Mecobalamin tablets (0.5 mg tid for 2 wks, n=38)	(1)Incidence rate (NCI-CTC; sensory neuropathy,); (2) NCV; (1)SNCV: median nerve/fibular nerve; (2)MNCV: median nerve/; fibular nerve
Yu, Su; [37]	2014	50(1)	I:58.4±5.3 C:57.6±4.7	Various types of cancer	(1)TP(21 d/cycle for 6 cycles); (2)5-HT3 inhibitor	Jiawei Wangqi Guizhi Wuwu decoction (qd for 14 d/cycle, during CTx, for 6 cycles n=25)	Mecobalamin tablets (0.5 mg, tid for 14 d/cycle during CTx, for 6 cycles, n=24)	(1)Incidence rate; (WHO grade); (2) NCV; (1)SNCV: median nerve/fibular nerve; (2)MNCV: median nerve/; fibular nerve

FOLFOX: folinic acid, fluorouracil, and oxaliplatin, XELOX: capecitabine and oxaliplatin, TP: paclitaxel and cisplatin, n.c.: no common treatment, Tx.: treatment, CTx.: chemotherapy, d:day, min:minute, qd: once daily, bid: twice a day, tid: three times a day, biw: twice a week; tiw: three times a week,
GPCR-NCM: Guiding Principles for Clinical Research of New Chinese Medicines, TCSS:Toronto Clinical Scoring System, NCI-CTC: National Cancer Institute Common Toxicity Criteria for Adverse Events,
EORTC QLQ-C30: European Organization for Research and Treatment of Cancer Quality of Life Questionnaire-30,
ECOG PS: Eastern Cooperative Oncology Group performance status,
NCCN: National Comprehensive Cancer Network Guidelines for Adult Cancer, WHO: world health organization,
QoL: quality of life, KPS: Karnofsky Performance Scale, PNCV: peripheral nerve conduction velocity, NCV: nerve conduction velocity, MNCV: motor nerve conduction velocity, SNCV: sensory nerve conduction velocity, SNAPA: Sensory nerve action potential amplitude, NGF: nerve growth factor, SOD: superoxide dismutase, MDA: malondialdehyde, NRS: Numerical Rating Scale.