A Systematic Review of Herbal Medicine for Chemotherapy Induced Peripheral Neuropathy

Table 1

Summary of the included randomised controlled trials of herbal medicines (preventive effect) for CIPN.

First author (year)	Sample size (dropouts): type of cancer	Treatment method			Main outcomes	Main results: (A) versus (B) (at end of treatment)	Effects estimate RR or MD (95% CI)
		Common treatment in both groups (regimen)	(A) Intervention group (regimen, participants)	(B) Control group (regimen, participants)
Herbal medicine for hand and foot baths or fumigation
Chen (2012)	120 (0): rectal cancer	FOLFOX (1 wk/cycle, ≥2 cycles)	Hand and foot baths of huoxue tongluo formula 20 min bid for 2 wk, )	Vitamin B12 (2 wk, )	(1) Incidence rate (NCI-CTC; sensory neuropathy)	(1) Grade 1/2/3/4; 14/4/3/0 versus 36/7/3/0 ()	(1) Incidence rate (≥grade 1); 0.46 (0.31, 0.66)
Jiang (2013)	70 (0): gastrointestinal cancer	FOLFOX (3 wk/cycle for 6 cycles)	Hand and foot baths of herbal formula; (bid for 2 wk, )	No additional Tx. ()	(1) Clinical improvement (researcher’s own criteria)	(1) CR/PR/NP; 26/6/2 versus 0/3/33 ()	(1) Effective rate; 11.29 (3.81, 33.48)
Jiang (2015)	150 (0): colorectal cancer	Oxaliplatin based CTx. (3 wk/cycle, ≥2 cycles)	Hand and foot baths of siteng yixian formula (40 min bid during CTx., )	No additional Tx. ()	(1) Incidence rate (Levi’s grade)	(1) Grade 0/1/2/3/4 (1 month after the end of treatment); 61/4/8/2/0 versus 33/7/22/13/0 ()	(1) Incidence rate (≥grade 1); 0.33 (0.20, 0.56)
Cai (2016)	50 (0): colorectal cancer	XELOX (3 wk/cycle for 2 cycles)	Hand and foot baths of wenjing huoxue formula (30 min qd during CTx., )	No additional Tx. ()	(1) Incidence rate (NCI-CTC; sensory neuropathy); (2) Adverse events; (3) CTx. related A/E	(1) Grade 0/1~2//3~4 19/5/1 versus 10/11/4 (); (2) No A/E; (3) NS	(1) Incidence rate (≥grade 1); 0.40 (0.19, 0.86)
Guo (2015)	71 (6): gastrointestinal cancer	Oxaliplatin based CTx.	Fumigation of herbal formula (20 min qd for 45 days, )	Warm water for hand and foot baths (20 min qd for )	(1) Incidence rate (NCI-CTC; sensory neuropathy); (2) QoL (KPS); (3) NCS; (4) Adverse events	(1) Grade 0/1/2/3/4; 0/16/14/2/0 versus 0/9/10/14/0 (); (2) versus (); (3) Significantly effective in NCS; (4) No A/E	(1) Incidence rate (≥grade 3); 0.15 (0.04, 0.60); (2) 3.43 (0.84, 6.02)
Pan (2012)	48 (0): ovarian cancer	PC	(1) Chaihu jia longgu muli decoction (oral administration, 100 ml tid for 4 wk); (2) Hand and foot baths of yiqi huayu formula (20 min bid for 4 wk, )	No additional Tx. ()	(1) Incidence rate (WHO grade)	(1) Grade 1/2/3/4; 6/4/0/0 versus 8/6/1/0 ()	(1) Incidence rate (≥grade 1); 0.56 (0.32, 0.99)
Li (2013)	126 (0): various types of cancer	(1) Oxaliplatin based CTx.; (2) Vitamin B12 (0.5 mg tid for 7 days)	(1) Buyang huanwu decoction (bid for 30 days); (2) Hand and foot baths of herbal formula (20 to 30 min qd 30 days )	No additional Tx. ()	(1) Incidence rate (researcher’s own criteria)	(1) Grade 1/2/3; 54/9/3 versus 27/24/9 ()	(1) Incidence rate (≥grade 2); 0.33 (0.19, 0.58)
Herbal medicine for intravenous infusion
Luo (2012)	90 (0): colorectal cancer	FOLFOX (4 wk/cycle for 6 cycles)	Astragali Radix for intravenous infusion (40 ml qd during CTx., )	(B1) (); No additional Tx.; (B2) () Glutathione IV infusion (1.8 g qd during CTx.)	(1) Incidence rate (Levi’s grade); (2) QoL (KPS); (3) CTx. related A/E	(1) Grade 1/2/3/4; 15/7/0/0 versus 10/12/3/4 versus 13/11/3/0; (2) versus versus; (3) Significant improvement for anaemia in (A) compared with (B)	(1) Incidence rate (≥grade 1); (A) versus (B1): 0.74 (0.59, 0.92); (A) versus (B2): 0.81 (0.64, 1.04); (2) (A) versus (B1): 7.68 (4.29, 11.07); (A) versus (B2): 1.70 (−1.66, 5.06)
Herbal medicine for oral dosage form
Nishioka (2011)	45 (0): advanced colon cancer	mFOLFOX 6 (2 wk/cycle for 20 cycles)	Goshajinkigan granules (7.5 g/day during CTx., )	No additional Tx. ()	(1) Incidence rate (DEB-NTC scale); (2) CTx. related A/E	(1) ≥Grade 3 (after 20 cycles); 33% versus 75% (); (2) NS	(1) No sufficient data
Abe (2013)	60 (0): breast cancer	Docetaxel based CTx.	Goshajinkigan granules (7.5 g/day during CTx., )	Vitamin B12 (1500 μg/day, )	(1) Incidence rate (DEB-NTC scale); (2) Incidence rate (NCI-CTC; sensory neuropathy); (3) Pain (VAS); (4) CTx. related A/E	(1) Grade 1/2/3; 2/5/6 versus 1/12/12 (); (2) Grade 1/2/3; 7/6/0 versus 11/12/1 (); (3) versus (); (4) NS	(1) Incidence rate (≥grade 1); 0.43 (0.27, 0.66); (2) Incidence rate (≥grade 1); 0.44 (0.28, 0.69); (3) −2.20 (−3.38, −1.02)
Kono (2013)	93 (4): colon cancer	mFOLFOX6 (2 wk/cycle)	Goshajinkigan granules (7.5 g/day for 26 wk, )	No additional Tx. ()	(1) Incidence rate (NCI-CTC; sensory neuropathy); (2) Clinical symptom (FACT/GOG-Ntx-12); (3) Adverse events	(1) Grade 2/3; 14/3 versus 17/6; (2) 7.0 versus 10.5 (); (3) No A/E	(1) Incidence rate (≥grade 3); 0.47 (0.12, 1.74)
Oki (2015)	186 (4): colon cancer	mFOLFOX6 (2 wk/cycle for 12 cycles)	Goshajinkigan granules (7.5 g/day during CTx., )	Placebo ()	(1) Incidence rate (NCI-CTC; sensory neuropathy); (2) CTx. related A/E	(1) Grade 0/1/2/3; 5/39/30/15 versus 6/58/19/10; (2) NS	(1) Incidence rate (≥grade 1); 1.01 (0.94, 1.09)
Zhu (2007)	120 (0): gastrointestinal cancer	FOLFOX (2 wk/cycle for 6 cycles)	Guilong tongluo decoction (during CTx., )	No additional Tx. ()	(1) Incidence rate (Levi’s grade); (2) QoL (KPS); (3) CTx. related A/E	(1) ≥Grade 1; 17 versus 27 (); (2) Improvement of KPS scale; 43/69 versus 25/51 (); (3) NS	(1) Incidence rate (≥grade 1); 0.47 (0.29, 0.76)
Liu (2013)	120 (0): colorectal cancer	FOLFOX4 (2 wk/cycle for 6 cycles)	Guilong tongluo decoction (bid during CTx, )	Placebo ()	(1) Incidence rate (NCI-CTC; sensory neuropathy); (2) Adverse events	(1) Grade 0/1 to 2/3 to 4; 29/24/7 versus 18/23/19 (); (2) NS	(1) Incidence rate (≥grade 1); 0.74 (0.55, 0.99)
Sun (2008)	42 (0): gastric and rectal cancer	(1) FOLFOX (3 cycles); (2) Neurotropin (4 mg injection qd)	Yiqi huoxue decoction (4 wk, )	No additional Tx. ()	(1) Incidence rate (Levi’s grade)	(1) Grade 1/2/3/4; 2/1/0/0 versus 9/3/0/0 ()	(1) Incidence rate (≥grade 1); 0.25 (0.08, 0.75)
He (2010)	63 (1): gastrointestinal cancer	FOLFOX (3 wk/cycle for 6 cycles)	Yiqi wenjing tongluo decoction (during CTx., )	Glutathione IV infusion (1.8 g qd during CTx., )	(1) Incidence rate (Levi’s grade); (2) QoL (KPS); (3) CTx. related A/E	(1) Grade 1/2/3/4; 6/2/0/0 versus 10/5/1/0 (); (2) versus (); (3) NS	(1) Incidence rate (≥grade 1); 0.47 (0.24, 0.93); (2) 13.22 (9.99, 16.45)
Jia (2016)	80 (0): colorectal cancer	FOLFOX (2 wk/cycle for 8 cycles)	Shaoyao gouteng muer decoction (200 ml bid for 8 wk, )	No additional Tx. ()	(1) Incidence rate (NCI-CTC; sensory neuropathy); (2) QoL (KPS); (3) Adverse events	(1) Grade 0/1/2/3/4 (sum of 6 and 8 wk); 13/22/22/18/5 versus 4/13/14/35/14 (); (2) versus (); (3) No A/E	(1) Incidence rate (≥grade 1); 0.88 (0.79, 0.98); (2) 2.72 (−0.81, 6.25)
Xu (2016)	36 (0): gastrointestinal cancer	FOLFOX	Tanshinone II (80 mg qd during CTx., )	No additional Tx. ()	(1) Incidence rate (Levi’s grade); (2) NCS; (1) MNCV; (2) SNCV	(1) Grade 0/1/2/3; 13/4/1/0 versus 8/5/3/2 (); (2) versus (); (3) versus ()	(1) Incidence rate (≥grade 1); 0.50 (0.21, 1.17); (2) −8.30 (−10.72, −5.88); (3) −5.00 (−6.49, −3.51)

wk: week, FOLFOX: folinic acid, fluorouracil and oxaliplatin, bid: twice a day, NCI-CTC: National Cancer Institute Common Toxicity Criteria for Adverse Events, Tx.: treatment, CR: complete remission, PR: partial remission, NP: not perceptible, A/E: adverse events, NS: no significant differences between intervention and control groups, CTx.: chemotherapy, qd: once daily, XELOX: capecitabine and oxaliplatin, PC: paclitaxel and carboplatin, tid: three times a day, KPS: Karnofsky Performance Scale, IV: intravenous, DEB-NTC Scale: Neurotoxicity Criteria of Debiopharm, VAS: Visual Analogue Scale, FACT/GOG-Ntx: Functional Assessment of Cancer Therapy/Gynecological Oncology Group-Neurotoxicity, NCS: nerve conduction study, MNCV: motor nerve conduction velocity, SNCV: sensory nerve conduction velocity, and QoL: quality of life.