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Traditional Medicine Research  2018, Vol. 3 Issue (1): 40-51    DOI: 10.12032/TMR201809063
Empirical Formula Research     
Gemcitabine and cisplatin combined with the Chinese herbal medicine compound Fuzhenggubenfang improve quality of life and progression-free survival in patients with advanced non-small cell lung cancer
Dong-Mei Jiang1, Feng-Wei Wang2,*(), Li-Juan Zhang3, Long Zhang2, Tai Zhang2, Wen-Hua Zhang2
1Medical College of Nankai University; No. 94, Weijin Road, Nankai District, Tianjin, China.
2The Second Department of Oncology, Tianjin People’s Hospital; No. 190, Jieyuan Road, Hongqiao District, Tianjin, China.
3Hebei Provincial People’s Hospital Oncology; No. 348, Heping West Road, Shijiazhuang, China.
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Highlights

Fuzhenggubenfang could be used as promising complementary medicine in chemotherapy for advanced NSCLC to improve quality of life and progression-free survival.

Editor’s Summary

Fuzhenggubenfang is the Chinese herbal medicine compound created on the basis of the addition and subtraction formula from Buzhongyiqi Soup, which was first recorded in Piweilun published in 1249 A.D. (Jin Dinasty of China).

Abstract

Objective: To assess the role of chemotherapy combined with the compound Chinese herbal medicine, Fuzhenggubenfang (FZGBF), for treating advanced non-small-cell lung cancer. Methods: A total of 84 eligible patients were enrolled from October 2013 to July 2016. Patients were randomized to receive either chemotherapy alone as the control group or chemotherapy combined with FZGBF as the experimental group. The primary endpoint of the study was quality of life (QOL) and progression-free survival (PFS). Secondary endpoints were tumor response rate, toxicity, dropout rate, and univariate and multivariate analyses of clinicopathologic factors for QOL and PFS. Results: There was a significant improvement in QOL, including better overall health (P < 0.001), physical function (P < 0.001), role function (P < 0.001), emotional function (P < 0.001), cognitive function (P < 0.001), and social function (P = 0.031). Less fatigue, nausea or vomiting, insomnia, appetite loss, constipation, and alopecia were noted (All P < 0.001) when FZGBF was combined with chemotherapy in comparison to chemotherapy alone. The experimental group had a better PFS compared with the control group (P = 0.032). There was no significant difference in tumor response rate. FZGBF significantly reduced chemotherapy-induced anemia (P < 0.001), neutropenia (P = 0.023), nausea and vomiting (P < 0.001). The use of Chinese herbal compounds had only mild side effects. In this study, factors influencing QOL were the use of the Chinese herbal compounds (P < 0.001), performance status score (P = 0.027), clinical staging of cancer (P = 0.009), and sex (P = 0.044). Use of traditional Chinese medicine (P = 0.043) and the number of previous chemotherapy sessions (P = 0.003) were the factors influencing PFS in this study. Conclusion: FZGBF could improve QOL, compliance to treatment, relieved chemotherapy-related toxicities of patients, and consequently improved PFS, which is a promising drug combination in complementary medicine for the treatment of advanced NSCLC.



Key wordsNon-small-cell lung cancer      Chinese herbal medicine      Randomized trial      Complementary medicine     
Published: 05 January 2018
Corresponding Authors: Wang Feng-Wei     E-mail: wfengwei2003@163.com
Cite this article:

Dong-Mei Jiang, Feng-Wei Wang, Li-Juan Zhang, Long Zhang, Tai Zhang, Wen-Hua Zhang. Gemcitabine and cisplatin combined with the Chinese herbal medicine compound Fuzhenggubenfang improve quality of life and progression-free survival in patients with advanced non-small cell lung cancer. Traditional Medicine Research, 2018, 3(1): 40-51. doi: 10.12032/TMR201809063

URL:

https://www.tmrjournals.com/tmr/EN/10.12032/TMR201809063     OR     https://www.tmrjournals.com/tmr/EN/Y2018/V3/I1/40

Containing herb Dosage Pharmacology
Huangqi (Astragalus propinquus) 15 g Activates NK and macrophage cells [11, 12]
Inhibits T-helper cell type 2 cytokines [13]
May increase cancer cell apoptosis [14]
Baizhu (Atractylodes macrocephala) 10 g Activates lymphocyte cells activity [15]
Modulates of the gut microbial distribution [16]
Chenpi (Citrus reticulata) 10 g Resists oxidant activity [17]
Chaihu (Bupleurum longiradiatum) 10 g Inhibits NF-κB activation [18]
Induces cancer cell apoptosis [19]
Dangshen (Codonopsis pilosula) 10 g Activates CD4 T cells [20]
Danggui (Angelica sinensis) 15 g Increases macrophage, lymphocyte and NK cell activity [21,22]
Promotes cancer cell apoptosis [23]
Danshen (Salvia miltiorrhiza) 10 g Protects cardiovascular system and resists inflammation [24]
Duzhong (Eucommia ulmoides) 10 g Protects glomerular cells [25]
Inhibits NF-κB transcription [26]
Nüzhenzi (Fructus Ligustri lucidi) 10 g Cultivates spirit and and protects liver and kidney [27]
Increases lymphocyte cell activity [28]
Inhibits Th1and Th2 cytokines [29]
Suanzaoren (Semen Zizyphi spinosae) 10 g Has hypnotic effect [30]
Maiya (Hordeum vulgare) 10 g Promotes digestion and absorption
Gancao (Glycyrrhiza uralensis) 6 g Compromises drug properties of above herbs
Table 1 The Chinese herbs of FZGBF containing and the pharmacology of CHM used
Characteristic Experimental group
(N = 42)
Control group
(N = 42)
P
Sex-number
Male
Female
27 (64.3%)
15 (35.7%)
30 (71.4%)
12 (28.6%)
0.641c
Age(year)
Mean
95% CI
59.33
(57.09, 61.57)
61.14
(58.48, 63.80)
0.298a
Previous chemotherapy cycles-time
Mean
1.76 2.19 0.652b
Pathological types-number
Adenocarcinoma
Squamous carcinoma
Adenosquamous carcinoma
Others
29 (69.0%)
12 (28.6%)
1 (2.4%)
0 (0%)
26 (61.9%)
13 (31.0%)
2 (4.8%)
1 (2.4%)
0.674c
ECOG PS score-number
0
1
2
2 (4.8%)
30 (71.4%)
10 (23.8%)
1 (2.4%)
29 (69.0%)
12 (28.6%)
0.530b
Clinical stage-number
III stage
IVstage
11(26.2%)
31(73.8%)
14 (33.3%)
28 (66.7%)
0.474b
Table 2 Baseline characteristics of patients
Item First cycle Second cycle Third cycle Fourth cycle
EG
(N=42)
CG
(N=41)
P EG
(N=39)
CG
(N=40)
P EG
(N=34)
CG
(N=30)
P EG
(N=28)
CG
(N=21)
P
Global health 46.825 46.816 0.995 53.704 44.097 < 0.001 54.248 43.889 < 0.001 56.746 44.180 < 0.001
Physical 62.698 56.436 0.004 70.775 55.192 < 0.001 69.385 54.593 < 0.001 67.722 56.011 < 0.001
Role 47.222 42.547 0.041 56.980 44.222 < 0.001 57.255 46.667 < 0.001 58.571 43.862 < 0.001
Emotional 76.191 73.848 0.092 84.972 75.208 < 0.001 83.660 76.852 < 0.001 87.103 75.794 < 0.001
Cognitive 87.831 82.249 0.004 92.735 81.181 < 0.001 93.301 80.278 < 0.001 93.452 79.894 < 0.001
Social 61.839 61.206 0.716 66.672 59.306 < 0.001 63.340 57.437 0.001 57.738 53.069 0.031
Fatigue 23.545 32.195 < 0.001 22.792 41.759 < 0.001 22.985 44.074 < 0.001 25.661 49.912 < 0.001
Nausea or vomiting 21.825 31.165 0.012 15.242 35.417 < 0.001 13.399 34.444 < 0.001 14.286 33.333 < 0.001
Pain 34.127 31.978 0.526 35.185 30.972 0.219 33.170 27.593 0.153 32.143 27.778 0.339
Insomnia 31.217 43.360 < 0.001 23.077 47.778 < 0.001 23.203 48.889 < 0.001 23.413 51.323 < 0.001
Appetite loss 36.773 52.575 < 0.001 30.484 63.889 < 0.001 31.373 64.074 < 0.001 29.762 62.434 < 0.001
Constipation 29.365 34.959 0.100 22.222 46.667 < 0.001 20.261 46.667 <0.001 19.841 51.323 < 0.001
Table 3 The average scale scores of every period chemothrapy for QOL
Figure 1 The survival curve

CG: Control group; EG: Experimental group.

Group Total Events Censored Median PFS (month) P
N % Estimate σ 95% CI
Lower Upper
CG 42 35 7 16.7% 4.600 0.570 3.482 5.718 0.032
EG 41 25 16 39.0% 7.300 0.610 6.105 8.495
Total 83 60 23 27.7% 6.300 0.813 4.707 7.893
Table 4 Survival data
Arms CR PR SD PD RR P
EG 0 9 (32.1%) 16 (57.1%) 3 (10.7%) 9 (32.1%) 0.90
CG 0 7 (33.3%) 12 (57.1%) 2 (9.5%) 7 (33.3%)
Table 5 Tumor response
Adverse drug Reactions Control group (N = 40) Experimental group (N = 39) P
0 I II III IV 0 I II III IV
Hemoglobin 11 19 10 0 0 33 6 0 0 0 < 0.001
Leukocyte 3 8 20 9 0 8 14 12 5 0 0.013
Neutrophilic Granulocyte 3 8 20 9 0 7 15 11 6 0 0.023
Platelet 29 7 3 0 1 34 2 3 0 0 0.125
Nausea or vomitting 0 3 14 23 0 0 12 20 7 0 < 0.001
Aminopherase 36 3 1 0 0 37 0 1 1 0 0.461
Creatinine 40 0 0 0 0 39 0 0 0 0 1.00
Sensory Neuropathy 18 20 2 0 0 18 20 1 0 0 0.938
Table 6 Chemotherapy induced toxicities after two treatment cycles
Arms First cycle Second cycle Third cycle Fourth cycle P
EG 0.00% (0/42) 7.14% (3/42) 19.04% (8/42) 33.33% (14/42) 0.642
CG 2.38% (1/42) 4.76% (2/42) 28.57% (12/42) 50.00% (21/42)
Table 7 Dropout rate
Source Type III Sum of Squares df Mean Square F P
Corrected Moded 7623.375a 39 195.471 3.551 < 0.001
Intercept 17748.125 1 17748.125 322.379 < 0.001
Group 2085.912 1 2085.912 37.889 < 0.001
Sex 123.721 1 123.721 2.247 0.142
Age 1219.987 24 50.833 0.923 0.574
Pathological 45.302 2 22.651 0.411 0.665
PS 27.731 1 27.731 0.504 0.482
Stage 297.519 1 297.519 5.404 0.025
Prechemo 289.644 7 41.378 0.752 0.630
Error 2202.144 40 55.054
Total 192708.333 80
Corrected Total 9825.519 79
aR Squared = 0.776 (Adjusted R Squared = 0.557); PS, Performance statuses; ANOVA, analysis of variance.
Table 8 The results of ANOVA for QOL
Source Type III Sum of Squares df Mean Square F P
Corrected Moded 5960.864 4 1490.216 28.920 < 0.001
Intercept 118669.092 1 118669.092 2302.969 < 0.001
Group 5291.785 1 5291.785 102.696 < 0.001
PS 261.081 1 261.081 5.067 0.027
Table 9 The results of Multivariate analysis of variance for QOL
B SE Wald df P RR 95.0% CI to RR
Variable lower upper
Group -0.548 0.274 4.004 1 0.045 0.578 0.338 0.989
Prechemo 0.126 0.041 9.330 1 0.002 1.134 1.046 1.229
Sex 0.433 0.300 2.077 1 0.150 1.541 0.856 2.776
Age -0.015 0.019 0.616 1 0.433 0.985 0.949 1.023
Pathological 0.048 0.254 0.036 1 0.850 1.049 0.638 1.724
Ps 0.275 0.323 0.726 1 0.394 1.317 0.699 2.480
Stage 0.295 0.311 0.898 1 0.343 1.343 0.730 2.471
Table 10 The results of univariate Cox regression analysis of survival data
Variable B SE Wald df P RR 95.0% CI to RR
lower upper
Group -0.539 0.267 4.091 1 0.043 0.583 0.346 0.983
Prechemo 0.118 0.040 8.902 1 0.003 1.125 1.041 1.216
Table 11 The results of multi-factor Cox stepwise regression analysis for survival data
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