Evidence-Based Complementary and Alternative Medicine / 2018 / Article / Tab 1

Research Article

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 cancerTreatment methodMain outcomesMain 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 cancerFOLFOX (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 cancerFOLFOX (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 cancerOxaliplatin 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 cancerXELOX (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 cancerOxaliplatin 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 cancerPC(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 cancerFOLFOX (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 cancermFOLFOX 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 cancerDocetaxel 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 cancermFOLFOX6 (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 cancermFOLFOX6 (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 cancerFOLFOX (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 cancerFOLFOX4 (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 cancerFOLFOX (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 cancerFOLFOX (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 cancerFOLFOXTanshinone 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.

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