European Journal of Integrative Medicine 7 (2015) 577–585

Contents lists available at ScienceDirect

European Journal of Integrative Medicine

journal homepage: www.elsevier.com/eujim

Review article

Traditional herbal medicine as an adjuvant treatment for non-small

-cell lung cancer: A systematic review and meta-analysis
Jung-Woo Leea , Woojin Kima , Byung-Il Mina,b , Sun Kyung Baekc , Seung-Hun Chod,*
a
Department of East-West Medicine, Graduate School, Kyung Hee University, Seoul 130-701, South Korea
b
Department of Physiology, College of Medicine, Kyung Hee University, Seoul 130-701, South Korea
c
Department of Internal Medicine, Kyung Hee University Hospital, Seoul 130-701, South Korea
d
Hospital of Korean Medicine, Kyung Hee University Medical Center, #1 Heogi-Dong, Dongdaemun-Gu, Seoul 130-701, South Korea

A R T I C L E I N F O A B S T R A C T

Article history: Introduction: Non-small-cell lung cancer (NSCLC) is one of the most common cancers and the leading
Received 9 February 2015 cause of cancer-related deaths. In East Asia, traditional herbal medicine (THM) is commonly used in
Received in revised form 16 August 2015 clinical settings for the treatment of cancer. Therefore, the aim of the present review was to
Accepted 16 August 2015
systematically assess the efficacy of THM with varied components for the treatment of NSCLC.
Methods: This study identified randomized controlled trials (RCTs) that evaluated the effectiveness of
Keywords: combined THM and chemotherapy (CTx) in searches of English, Chinese, Japanese, and Korean language
Traditional herbal medicine
databases.
Non-small-cell lung cancer
Chemotherapy
Results: This meta-analysis systematically reviewed 27 RCTs involving 2382 patients and found that THM
Systematic review improved the quality of life (QoL) significantly for patients with NSCLC. Improvement in QoL was seen in
Meta-analysis 19 studies using the Karnofsky Performance Status score, three studies using the Eastern Cooperative
Oncology Group scale, three studies using the Functional Assessment of Cancer Therapy-Lung scale, and
six studies using the European Organization for Research and Treatment of Cancer.
Conclusions: The pooled results of this systematic review and meta-analysis suggest that THM
significantly improved the QoL for patients with NSCLC.
ã 2015 Elsevier GmbH. All rights reserved.

Contents

1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
2. Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
2.1. Search strategy . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
2.2. Study selection . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
2.3. Quality assessment . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 578
2.4. Statistical analysis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
3. Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
3.1. Study description . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 582
3.2. Descriptions of THM . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
3.3. Outcomes . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
3.4. THM+ CTx versus CTx . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
3.4.1. KPS scale (19 RCTs): [8–26] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
3.4.2. ECOG performance status (three RCTs): [26–28] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
3.4.3. FACT-L scale (three RCTs): [29–31] . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
3.4.4. EORTC (six RCTs): [23,25,26,32–34]. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
4. Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 583
5. Conclusions . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584
Conflict of interest . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584

* Corresponding author. Fax: +82 2 958 9186.

E-mail address: chosh@khmc.or.kr (S.-H. Cho).

http://dx.doi.org/10.1016/j.eujim.2015.08.005
1876-3820/ ã 2015 Elsevier GmbH. All rights reserved.

Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
578 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585
Acknowledgement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 584
1. Introduction
Lung cancer is classified as either non-small-cell lung cancer
(NSCLC) or small-cell lung cancer (SCLC) according to its tissue
form; therefore, a lung cancer diagnosis depends on the evaluation
of biopsy specimens to determine whether NSCLC or SCLC is
present [1]. NSCLC may be further categorized as squamous cell
carcinoma, adenocarcinoma, or large cell carcinoma [2]. In the
United States in 2007, 86% of patients with lung cancer died within
5 years of their diagnosis [3]; as of 2008, lung cancer was the single
most common cause of cancer-related deaths worldwide [4].
Despite improvements in conventional cancer treatments, the
5-year survival rate for NSCLC patients is approximately 15%,
which is one of the lowest rates among cancers [4]. Surgical
resection can be an effective therapy if the lung cancer is diagnosed
at an early stage, but most patients are already in its advanced
stages at the time of their initial diagnosis [3]. However, it is often
difficult to diagnose lung cancer in its early stages because its
symptoms, including coughing, hemoptysis, dyspnea, and pleuro-
dynia, typically manifest after the cancer has progressed [3]. Since
chemotherapy (CTx) is toxic, many patients have difficulty
completing the recommended number of cycles due to the
development of adverse effects such as neutropenia, anemia,
nausea, and fatigue [5]. In comparison, complementary adjuvant
therapies such as traditional herbal medicine (THM) or acupunc-
ture may effectively alleviate the side effects of conventional
cancer treatments. Thus, the present systematic review and meta-
analysis evaluated THM as an adjuvant treatment during CTx in
terms of the quality of life (QoL) of patients with NSCLC.
A literature search revealed that Chen et al. conducted a
systematic review of the effects of adjuvant THM during CTx in
patients with NSCLC in 2010 [6]; however, our systematic review
incorporated several improvements. For example, because THM is
commonly used in China, Japan, and South Korea, the present
review identified randomized controlled trials (RCTs) using not
only English and Chinese language databases but also Japanese and
Korean language databases; Chen et al. [6] retrieved studies only
from English and Chinese language databases. Additionally, the
present review improves upon the work of Chen et al. [6] by
including 16 additional RCTs, augmenting the outcome measures,
and adding a meta-analysis graph, which was produced using
Review Manager 5.1.
2. Methods
2.1. Search strategy
The following sources were used to search for RCTs that were
published up to February 2014: English language databases,
including the Allied and Complementary Medicine Database
(AMED), MEDLINE, EMBASE, CINAHL, the Cochrane Central
Register of Controlled Trials, and PsycINFO; Chinese language
databases, including the Century Journal Project, China Proceed-
ings Conference Full Text DB, China Academic Journal, and China
Doctor/Master Dissertation Full Text DB; the Japanese language
database Japan Science and Technology Information Aggregator
Electronic; and Korean language medical databases, including
KoreaMed, Korea Institute of Science Technology Information and
Research Information Service System, Korean Studies Information
Service System, National Assembly Library, and DBpia. In addition,
clinical trial databases were searched, including the National
Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
Center for Complementary and Alternative Medicine (NCCAM) at
the National Institutes of Health (http://nccam.nih.gov/), Current
Controlled Trials (http://www.controlledtrial.com), and the Com-
plementary and Alternative Medicine Specialist Library at the
National Health Service National Library for Health (http://www.
library.nhs.uk/cam/). The reference lists of the identified articles
were examined for additional appropriate publications, and a
number of experts in the field were asked for information
concerning any other trials. Finally, a manual search was
conducted for relevant conference proceedings, symposia, and
journals, and all identified publications were cross-referenced.
The keywords used in the search for RCTs were as follows:
(‘Bronchogenic Carcinoma’ OR ‘Non-Small-Cell Lung Carcinoma’
OR ‘Non-Small Cell Lung’ OR ‘Non-Small-Cell Lung’ OR ‘Non-Small-
Cell Lung’ OR ‘Non-small-Cell Lung’ OR ‘NSCLC’) AND (‘Neoplasms’
OR ‘Neoplasms*’ OR ‘Cancer*’ OR ‘Tumor*’ OR ‘Tumour*’ OR
‘Carcinoma’ OR ‘Carcinoma*’ OR ‘Adenocarcinoma’ OR ‘Adenocar-
cinoma*’ OR ‘adenomatous’ OR ‘Lymphoma’ OR ‘lymphom*’ OR
‘lymphedema*’ OR ‘Sarcoma’ OR ‘Sarcoma*’ OR ‘Antineoplastic
agents’ OR ‘antineoplas*’ OR ‘adenom*’ OR ‘adenopath*’) AND
(‘randomized controlled trial’ OR ‘controlled clinical trial’ OR
‘random*’ OR ‘placebo’ OR ‘drug therapy’ OR ‘trial’ OR ‘groups’).
Because the databases searched for the present review possessed
their own subject headings; each database was searched indepen-
dently.
2.2. Study selection
In this meta-analysis, only RCTs were selected. The experimen-
tal group included only studies using THM in combination with
conventional cancer therapy, while the control group consisted of
patients receiving only conventional therapy. The CTx regimens
included bronchial arterial infusion chemotherapy (BAIC); cyclo-
phosphamide, Adriamycin1, and cisplatin (CAP); cyclophospha-
mide, vincristine, and 5-fluorouracil (COF); docetaxel and cisplatin
(DP); gemcitabine and paclitaxel (GP); methyl-CCNU, vincristine,
and 5-fluorouracil (MOF); mitomycin, vinblastine, and cisplatin
(MVP); cisplatin and vinorelbine (NP); paclitaxel and cisplatin
(TP); and vinorelbine and cisplatin (VP) (Table 1).
The primary outcome in the present study was evidence of QoL
improvement based on the scores of four different scales
(Karnofsky Performance Status (KPS), Eastern Cooperative Oncol-
ogy Group (ECOG), Functional Assessment of Cancer Therapy-Lung
(FACT-L), and European Organization for Research and Treatment
of Cancer (EORTC)). The secondary outcome included adverse
effects of integrative THM treatment. Quasi-randomized and non-
randomized trials were excluded from the present meta-analysis.
Additionally, animal or in vivo studies and studies in which THM
was applied using methods other than oral administration were
excluded (Fig. 1).
2.3. Quality assessment
Each report identified using the abovementioned search
strategy was evaluated by one of the present reviewers according
to the inclusion criteria. When there was uncertainty about the
eligibility of a study, a second reviewer evaluated the report and a
judgment was reached through discussion and consensus follow-
ing independent evaluations of that study. A quality assessment
was performed following the descriptions of the categories in the
“Assessing Risk of Bias” chapter from the Cochrane Handbook for
 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585 579

Table 1
A summary of the randomized controlled trials of botanical drugs for non-small cell lung cancer.

Study Sample size Method Protocol Duration of Main outcome measures Quality
of the study assessmenta
diagnosis
Jie and He 60 (30 THM plus CTx; Cytology/ 1. Panax ginseng C. A. Mey.-based THM (Chinese 9 weeks 1. Short term effective rate U-U-N-N-Y-
[10] 30CTx) histology herbal medicine no.2) plus NP regimen Y-Y
Dropout: 1 2. NP regimen 2. Increase in QoL (KPS)
3. Decrease in natural killer cell
count
4. Anaemia
5.Thrombocytopenia

Liu [13] 60 (30 THM plus CTx; Cytology/ 1. Panax quinquefolium L.-based THM (Fuzheng At least 1. Short term curative effect U-U-N-N-Y-
30CTx) histology Guben decoction) plus NP regimen 2 months Y-Y
2. NP regimen 2. Increase in QoL (KPS)

Yang and 40 (20 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2-3 months 1. Short term effective rate U-U-N-N-Y-
Wang 20CTx) histology THM (KeLiu pills) plus GP regimen Y-Y
[21] 2. GP regimen 2. Increase in QoL (KPS)
3. Nausea
4. Vomiting
5. Diarrhea

Feng et al. 60 (30 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 3 weeks for 1. Short term effective rate U-U-N-N-Y-
[9] histology THM (Feiliuping II) plus CTx CTx, Y-Y
30CTx) 2. CTx (regimen not specified) 3 months for 2. Increase in QoL (KPS)
THM
3. Increase in QoL
(weight stability)

Yi et al. 62 (32 THM plus CTx; Cytology/ 1. Solanum lyratum Thunb.-based THM (Baiyin 2 months 1. Short term effective rate U-U-N-N-Y-
[22] 30CTx) histology decoction) Y-Y
plus NP, MVP, or CAP regimen 2. Increase in QoL (KPS)
2. NP, MVP, or CAP regimen

Wang 93 (48 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 4–6 weeks 1. Short term effective rate U-U-N-N-
et al. 45CTx) histology THM (MOP) plus MVP regimen N-Y-Y
[18] 2. MVP regimen 2. Survival rate at one year
3. Survival rate at two years
4. Survival rate at three years
5. Increase in QoL (KPS)

Yan et al. 74 (37 THM plus CTx; 37CTx) Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 cycles of 1. Disease control rates U-U-N-N-Y-
[20] histology THM (Kangliu Zengxiao decoction) plus NP CTx Y-Y
regimen
2. NP regimen 2. CA50, CYFRA21-1, CEA
3. Improvement in clinical
symptoms
4. QoL (KPS)

Liu et al. 62 (31 THM plus CTx; 31CTx) Cytology/ 1. Ixeris denticulata (Houtt.) Stebb.-based THM Not 1. symptom response U-U-N-N-
[17] histology (Feitai Capsule) mentioned N-Y-Y
Dropout: 2 2. none 2. physical energy level
3. QoL (KPS)

Liu and 51 (17 THM plus CTx; 16CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 months 1. Short term effectiveness rate U-U-N-N-
Niu [14] 18 THM) histology THM (Yiqi Yangyin Jiedu decoction) plus MVP N-Y-Y
regimen
2. MVP regimen 2. Increase in QoL (KPS)
3. Astragalus membranaceus (Fisch.) Bge.-based
THM (Yiqi Yangyin Jiedu Fang)

Xu [19] 91 (32 THM plus CTx; 31CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 3–4 months 1. Short term effective rate U-U-N-N-
28 THM) histology THM (Feiyanning decoction) plus MVP or NP N-Y-Y
regimen
2. MVP or NP regimen 2. Increase in QoL (KPS)
3. Astragalus membranaceus (Fisch.) Bge.-based 3. Increase in QoL
THM (Feiyanning decoction)
(weight stability)

Li et al. 100 (33 THM plus CTx; Cytology/ 1. Trichosanthes kirilowii Mexim.-based THM 2 months 1. Short term effective rate U-U-N-N-
[11] 33CTx; 34 THM) histology (Qiankun capsule) plus CAP or MVP regimen N-Y-Y
2. CAP or MVP regimen 2. Increase in QoL (KPS)
3. Trichosanthes kirilowii Mexim.-based THM 3. Increase in QoL
(Qiankun capsules)
(weight stability)
4. Anaemia
5. Decrease in white blood cell

Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
580 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585

Table 1 (Continued)
Study Sample size Method Protocol Duration of Main outcome measures Quality
of the study assessmenta
diagnosis

Liu et al. 60 (20 THM plus CTx; 2O Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 cycles of 1. Qi-yin deficiency syndrome U-U-N-N-Y-
[16] CTx; 20 THM) histology THM (Yiqi Yangyin Jiedu decoction) plus NP or GP treatment Y-Y
regimen
2. NP or GP regimen 2. QoL (KPS)
3. Astragalus membranaceus (Fisch.) Bge.-based 3. Immune function
THM (Yiqi Yangyin Jiedu decoction)

Liu et al. 62 (30 THM plus CTx; Cytology/ 1. Individually tailored THM plus COF or MOF Not 1. Survival rate U-U-N-N-Y-
[15] 32CTx) histology regimen mentioned Y-Y
2. COF or MOF regimen 2. QoL (KPS)
3. Weight change
4. Immune function

Liu et al. 76 (39 THM plus CTx; 37CTx) Cytology/ 1. Individually tailored THM plus BAIC regimen Not 1. Short-term therapeutic effect U-U-N-N-Y-
[12] histology mentioned Y-Y
2. BAIC regimen 2.Long-term survival rate, 3.
Changes of clinical principal
symptoms
4.QoL (KPS)
5.Peripheral blood pictures

Zhang 85 (43 THM plus CTx; Cytology/ 1. Rehmannia glutinosa (Gaertn.)-based THM 42 days of 1. Hepatic function U-U-N-N-Y-
et al. 42CTx) histology (Yiguan decoction) plus NP regimen treatment Y-Y
[23] 2. NP regimen 2 .T-cell subgroup and NK cell
3. QoL (KPS, EORTC QLQ-C30,
EORTC LC13)

Fang et al. 160 (104 THM plus CTx; Cytology/ 1. Pinellia ternate (Thunb.) Breit.-based THM Not 1. Clinic effect U-U-N-N-Y-
[8] 56CTx) histology (Sansheng Huatan decoction) plus MVP regimen mentioned Y-Y
2. MVP regimen 2. QoL (KPS)
3. NK activities
4. Liver and kidney functions
5. Blood routine test

Zhang 70 (36 THM plus CTx; 34CTx) Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based Not 1. Immune function U-U-N-N-Y-
et al. histology THM (Buqihuoxue method) plus MVP regimen mentioned Y-Y
[28] 2. MVP regimen 2. Nausea/Vomit
3. Anorexia
4. QoL (ECOG)

Tian et al. 115 (58 THM plus CTx; Cytology/ 1. Brucea javanica (L.) Merr.-based THM (Fructus 2 cycles of 1. Cellular immune function U-U-N-N-Y-
[27] 57CTx) histology Bruceae oil emulsion) plus GP regimen CTx Y-Y
2. GP regimen 2. QoL (ECOG)

Lin et al. 294 (103 THM plus CTx; Cytology/ 1. Individually tailored THM plus NP or VP regimen Not 1. QoL (FACT-L) U-U-N-N-Y-
[29] 92CTx; 99 THM) histology mentioned Y-Y
2. NP or VP regimen
3. Individually tailored THM

Sun et al. 40 (20 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 cycles of 1. QoL (FACT-L) U-U-N-N-Y-
[30] 20CTx) histology THM (Xiaoliu Baofei pill) plus NP regimen CTx Y-Y
2. NP regimen

You et al. 102 (61 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 treatment 1. QoL (FACT-L, EORTC QLQ- U-U-N-N-Y-
[31] 41CTx) histology THM (Feiji Recipe) plus NP regimen courses C43) Y-Y
2. NP regimen 2. Reduce adverse reaction of
CTx
3. Physical performance

Tian et al. 60 (20 THM plus CTx; 20CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based Not 1. QoL (EORTC QLQ-30) U-U-N-N-Y-
[32] 20 THM) histology THM (Feiji Recipe) plus NP or GP regimen mentioned Y-Y
2. NP or GP regimen 2. Prevention of functional
degeneration
3. Astragalus membranaceus (Fisch.) Bge.-based
THM (Feiji Recipe)

Shanet al. 91 (30 THM plus CTx; 30CTx; Cytology/ 1. Individually tailored THM plus CTx 2 cycles of 1. QoL (EORTC QLQ-LC43) U-U-N-N-
[33] 31 THM) histology CTx N-U-U-
2. CTx (regimen not specified)

Xu et al. 116 (63 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.- 4 cycles of 1. QoL (KPS) Y-Y-Y-Y-U-
[24] 53CTx) histology (Kangliuzengxiao, Feiyanning decoction) plus NP CTx Y-Y
regimen
Dropout: 5 2. NP regimen 2. Survival time

Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585 581

Table 1 (Continued)
Study Sample size Method Protocol Duration of Main outcome measures Quality
of the study assessmenta
diagnosis
3. Main clinical symptoms
4. Adverse reactions

Feng et al. 90 (30 THM plus CTx; 30CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 months 1. Tumor size U-U-N-N-Y-
[34] 30CRTx plus THM) histology THM plus DP regimen Y-Y
2. DP regimen 2. Tumor markers
3. I-125 implantation plus DP regimen plus 3. Clinical symptoms
Astragalus membranaceus (Fisch.) Bge.-based
THM
4. QoL (EORTC QLQ-C30, EORTC
LC

Yao [26] 118 (57 THM plus CTx; Cytology/ 1. Astragalus membranaceus (Fisch.) Bge.-based 2 treatment 1. QoL (EORTC QLQ-LC43, KPS, U-U-N-N-Y-
61CTx) histology THM (Feiji Recipe) plus NP or GP regimen courses ECOG) Y-Y
2. NP or GP regimen

Zhang 90 (30 THM plus CTx; 30CTx; Cytology/ 1. Coix lachryma-jobi var. ma-yeun (Roman.) Stapf 2 cycles of 1. QoL (KPS, EORTC QLQ-LC43) Y-U-N-N-Y-
et al. 30 intravenous THM plus histology –based THM (Bukangling) plus TP regimen CTx Y-Y
[25] CTx)
2. TP regimen
3. Coix lachryma-jobi var. ma-yeun (Roman.) Stapf-
based intravenous THM (Kanglaite) plus TP
regimen

BAIC, bronchial arterial infusion chemotherapy; CAP, cyclophosphamide, Adriamycin, cisplatin; COF, cyclophosphamide, 5-fluorouracil, vincristine; DP, docetaxel, cisplatin;
GP, gemcitabine, cisplatin; MOF, methyl-CCNU, vincristine, 5-fluorouracil; MVP, mitomycin, vinblastine, cisplatin; NP, vinorelbine, cisplatin; TP, paclitaxel, cisplatin; VP,
vinorelbine, cisplatin
a
Was the allocation sequence adequately generated? (b) Was allocation adequately concealed? (c) Was knowledge of the allocated interventions adequately prevented
during the study? (d) Was the blinding of outcome assessment adequate? (e) Were incomplete outcome data adequately addressed? (f) Were the results of the study free of
suggestion of selective outcome reporting? (g) Was the study apparently free of other problems that could put it at a risk of bias? Key: (Y) “Yes”; (U)”Unclear”; (N)”No”.

Fig. 1. Flow diagram showing the numbers of studies included and excluded from the systematic review and meta-analysis.
\

Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
582 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585

Systematic Reviews of Interventions [7]. The following questions
were assessed by the reviewers: (a) Was the allocation sequence
adequately generated? (b) Was allocation adequately concealed?
(c) Was knowledge of the allocated interventions adequately
prevented during the study? (d) Were procedures to ensure
blindness regarding outcome assessment adequate? (e) Were
incomplete outcome data adequately addressed? (f) Were the
results of the study free of selective outcome reporting? and (g)
Was the study apparently free of other problems that could put it at
a risk for bias?
The meta-analysis assessed the studies using the following
keys: “yes” (Y) indicated a low risk of bias, “unclear” (U) indicated
an unsure risk of bias, and “no” (N) indicated a high risk of bias.
2.4. Statistical analysis
All study data were summarized using basic statistics and
simple counts and means. The primary purpose of the analyses in
the present meta-analysis was to quantify and compare the effects
of conventional cancer therapy combined with THM (experimental
group) with those of conventional cancer therapy alone (control
group) in NSCLC patients using the findings of RCTs. All statistical
analyses were conducted using Review Manager 5.1 for Windows
(The Nordic Cochrane Center, Copenhagen, Denmark). Odds ratios
(ORs; 95% confidence intervals [CIs]) for QoL are presented
individually for each trial; an OR < 1 indicates a lower risk for
the experimental group than the control group, while an
OR > 1 indicates a greater risk for the experimental group than
the control group.
3. Results
3.1. Study description
The initial database searches identified 268 RCTs. Of these,
27 RCTs met our i nclusion criteria and were subjected to systematic
review; three studies were in English, and 24 were in Chinese.
Fifty-four studies that were clearly unrelated to the study topic
were initially excluded, and 166 more articles were excluded after
reviewing the abstracts. Fifteen studies were added after reviewing
the references. After more detailed evaluations of the articles,
32 additional studies were excluded; 14 did not meet our inclusion
criteria, and 18 were not RCTs. Fig. 1 presents the meta-analysis
flow diagram.

Fig. 2. Meta-analysis of the effects of THM on quality of life in non-small-cell lung cancer patients. EORTC: European Organization for Research and Treatment of Cancer; KPS:
Karnofsky Performance Status.

Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585
Of the included RCTs, 19 used the KPS scale, three used the ECOG
scale, three used the FACT-L scale, and six used the EORTC scale.
3.2. Descriptions of THM
Due to the lack of high-quality objective RCTs, the THM
treatments were employed with a cocktail combination of THM.
However, because Eastern medicine implements THM according to
the specific symptoms of an individual patient, the assessment of
each type of THM was difficult. Nonetheless, certain types of THM
were used more frequently than others. Astragalus membranaceus
(Fisch.) Bge. was included in 14 RCTs and was the most common
THM used among the trials. Despite the tradition of using different
THM cocktails for different patterns of symptoms, the most
commonly used type of THM is worthy of more detailed
investigation.
3.3. Outcomes
The primary outcome in the present study was evidence of QoL
improvement based on the scores of four different scales. Most of
the RCTs (n = 19) evaluated QoL using the KPS scale [8–26], while
three RCTs evaluated QoL using the ECOG performance status scale
[26–28]; both of these scales utilize dichotomous data. Three RCTs
evaluated QoL using the FACT-L scale [29–31] and six RCTs
evaluated QoL using the EORTC [23,25,26,32–34]; both of these
scales utilize continuous data. The secondary outcome included
adverse effects of treatment, and there was no study reporting it.
3.4. THM + CTx versus CTx
3.4.1. KPS scale (19 RCTs): [8–26]
The KPS evaluation from 19 RCTs revealed that 567 (78%)
patients in the treatment group (n = 725) and 330 (49%) patients in
the control group (n = 662) showed improvement in the QoL. This
result indicates that integrative THM therapy significantly
improved the KPS outcome (odds ratio: 3.90; 95% CI: 3.06–4.97;
p < 0.00001) (Fig. 2).
3.4.2. ECOG performance status (three RCTs): [26–28]
The ECOG results from three RCTs showed that 79 (85%)
patients in the treatment group (n = 93) and 28 (29%) in the control
group (n = 95) showed improved QoL. As there were only
188 patients, a meta-analysis was not conducted.
3.4.3. FACT-L scale (three RCTs): [29–31]
The FACT-L scale evaluation used four subscales: physical well-
being (PWB), emotional well-being (EWB), functional well-being
(FWB), and additional well-being (AWB).
The PWB from all three RCTs (337 patients) showed that the QoL
improved more in the integrative THM group than in the
conventional treatment group (p < 0.05), and the EWB from all
three RCTs (337 patients) showed statistically better results for the
integrative THM group than the conventional treatment group
(p < 0.05). Similarly, the FWB from all three RCTs (337 patients)
revealed that integrative THM was statistically more effective than
conventional treatment (p < 0.05), and the AWB from all three RCTs
(337 patients) also showed that integrative THM was statistically
more effective than the conventional treatment (p < 0.05). We did
not conduct a meta-analysis because of the statistical heterogene-
ity among trials.
3.4.4. EORTC (six RCTs): [23,25,26,32–34].
The EORTC analysis of six RCTs (423 patients) showed
significant improvement in global health. The pooled analysis
showed better improvement in the integrative THM than in the
Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
583
conventional treatment group (std. mean difference: 1.00; 95% CI:
0.79–1.20; p < 0.00001) (Fig. 2).
4. Discussion
This systematic review and meta-analysis evaluated 27 RCTs
assessing the efficacy of THM when co-administered with
conventional therapy in NSCLC patients. NSCLC is not only one
of the most common cancers worldwide but also the leading cause
of cancer-related death [4]. Conventional cancer treatments such
as CTx have a variety of limitations, including toxic effects that
diminish the QoL of cancer patients. Additionally, the side effects of
CTx, which include neutropenia, nausea, and fatigue, make it more
difficult for patients to maintain conventional CTx regimens [5].
Moreover, because most patients with advanced-stage lung cancer
are diagnosed at the age of 65 years or older, the performance of
CTx in elderly patients should be considered carefully [35,36]. In
fact, CTx in elderly patients is controversial among physicians
because this population has limited tolerance for such treatments
[37].
This review examined 27 RCTs that investigated the effects of
adjuvant THM during CTx on the QoL of patients with NSCLC. A
large amount of evidence has already demonstrated the beneficial
effects of THM for cancer patients. The findings of the present
systematic review and meta-analysis indicate that THM improved
QoL according to four QoL scales when administered in conjunc-
tion with CTx to patients with NSCLC.
The KPS scale is widely used because it is a simple instrument
with which to evaluate the QoL of a patient [38]; it assesses patient
behaviors in multiples of 10, from 0 (worst) to 100 (best) based on
the performance of various activities. In a cross-sectional study of
57 disease-free patients with lung cancer (meaning that there were
no visible malignant tumors on computed tomography images),
the KPS scale was the best predictor of QoL [39]. The FACT-L is
comprised of 41 questions: 34 items relate to general health-
related QoL and seven items relate to lung cancer-specific
symptoms. This questionnaire has the disadvantage of not
emphasizing treatment-related symptoms, but it has high levels
of reliability and validity according to extensive psychometric
testing [40]. A change of two points on the seven-item symptom
scale is considered to indicate a clinically significant change in QoL
[41]. The EORTC, which includes 30 items to assess patient QoL, is
also widely used for measuring QoL in patients with cancer [42]. A
recent systematic review found it to be reliable in both clinical
practice and clinical trials [43].
The 27 RCTs assessed in this systematic review were conducted
on mainland China and all of the trials used THM decoctions.
Clinicians in Asian countries add THM according to the specific
combination of symptoms in an individual patient. THM decoc-
tions can have synergistic effects because the decoction can be
individualized [44]. Of the 27 RCTs, 14 used A. membranaceus
(Fisch.) Bge.-based THM decoctions, four used individually tailored
THM decoctions according to the patient’s symptoms, and the
remainder used THM decoctions based on Panax ginseng C. A. Mey.,
Panax quinquefolius L., Solanum lyratum Thunb., Rehmannia
glutinosa (Gaertn.), Pinellia ternata (Thunb.) Breit., Trichosanthes
kirilowii Maxim., Ixeris denticulata (Houtt.) Stebb., Brucea javanica
(L.) Merr., and Coix lacryma-jobi var. ma-yeun (Roman.) Stapf. The
included THM is summarized in Table 1.
This review identified a promising THM, A. membranaceus
(Fisch.) Bge., which was the most commonly used ingredient
among the THM decoctions. This is in accordance with previous
reports of THM treatments in NSCLC patients [6,45]. A. mem-
branaceus (Fisch.) Bge. is also known to have immunorestorative,
immunomodulatory, and antitumor effects both in vitro and in vivo
[46,47]. Another study concluded that A. membranaceus (Fisch.)
584 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585
Bge. has immunological effects via the stimulation of macrophage
and natural killer cell activity, but that it also inhibits the
production of T-helper cell type 2 cytokines [48].
This study has several limitations. First, the quality of each RCT
was not assessed completely. To assess the quality of the included
studies, we used the “risk-of-bias” tool of the Cochrane collabora-
tion [7]. As it is difficult to specify the subtle difference among the
items in the quality rating scale [49], we assessed each RCT
according to the seven critical domains: randomization, allocation
concealment, blindness of participants and personnel, blindness of
outcome assessment, reporting of incomplete outcome data,
selective-outcome reporting, and other biases. However, the
“risk-of-bias” tool may not be entirely objective [50]. Second, of
the 27 articles, only three were in English [24,32,34]. The
remaining 24 articles were in Chinese [8–23,25–31,33], making
it difficult for other researchers to follow up on this review.
This systematic review and meta-analysis is the first study to
evaluate QoL in patients with NSCLC undergoing concomitant and
integrative CTx and THM treatment. Because most patients with
NSCLC are diagnosed in advanced stages of the disease, CTx is the
primary treatment option. However, because CTx has toxic effects
that can result in toxicity-related death [51], the improvement of
QoL in these patients is essential. If the QoL for patients were to
improve, it is likely that the CTx dropout rate would decrease;
therefore, an integrative treatment would have cooperative effects
and improve patient outcomes. In this manner, THM may represent
a safe and economical complementary treatment modality for the
improvement of QoL in patients with NSCLC [5]. Furthermore, as a
complementary treatment method that can be added to existing
conventional treatments, including metoclopramide for nausea,
analgesics for pain, and oral solutions for mouth ulcers, THM could
be an effective alternative medicine for patients suffering from the
side effects of CTx.
5. Conclusions
The pooled results of this systematic review suggest that
integrative THM significantly improved the QoL of patients with
NSCLC according to four different scales. However, the limited
number and low quality of the included trials make it difficult to
provide a definitive conclusion regarding the efficacy of the
adjuvant treatments. The significant improvement in QoL identi-
fied by the present review indicates that there is an urgent need for
more rigorous clinical trials of higher quality investigating the
effects of THM in cancer patients. Future clinical trials should be
conducted according to internationally accepted procedures
because the scientific credibility of RCTs depends substantially
on the trial design.
Conflict of interest
There are no conflicts of interest to declare.
Acknowledgement
This work was supported by a grant from the Kyung Hee
University in 2012 (KHU-20121742).
References
[1] C. Lu, A. Onn, A.A. Vaporciyan, Holland-Frei Cancer Medicine, 8th ed., People’s
Medical Publishing House, 2010.
[2] L. Horn, W. Pao, D.H. Johnson, Harrison’s Principles of Internal Medicine, 18th
ed., McGraw-Hill, 2012.
[3] L.G. Collins, C. Haines, R. Perkel, R.E. Enck, Lung cancer diagnosis and
management, Am. Acad. Fam. Phys. 75 (2007) 56–63.
Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
[4] J. Ferlay, H.R. Shin, F. Bray, D. Forman, C. Mathers, D.M. Parkin, Estimates of
worldwide burden of cancer in 2008: GLOBOCAN 2008, Int. J. Cancer 127
(2010) 2893–2917.
[5] Find Support and Treatment>>Treatments and Side Effects American Cancer
Society. (2013).
[6] S. Chen, A. Flower, A. Ritchie, J. Liu, A. Molassiotis, H. Yu, et al., Oral Chinese
herbal medicine (CHM) as an adjuvant treatment during chemotherapy for
non-small cell lung cancer: a systematic review, Lung Cancer 68 (2010)
137–145.
[7] J. Higgins, S. Green, Cochrane handbook for systematic reviews of
interventions, Cochrane Collab. (2008) .
[8] W.M. Fang, W.P. Wang, B.W. Yan, J.Y. Zhou, Treatment of non-small-cell lung
cancer with chemotherapy and Sansheng Huatan Decoction, J. Chin. Integr.
Med. 2 (2004) 103–105.
[9] L. Feng, B.J. Hua, B.K. Piao, Clinical study of Feiliuping II on quality of life of lung
cancer patients, Chin. J. Inf. TCM 13 (2006) 12–13.
[10] Y. Jie, W.G. He, Chinese herbal medicine 2nd combined with NP chemotherapy
in patients with advanced non-small cell lung cancer: clinical observation,
Cancer Res. Clin. 18 (2006) 701–703.
[11] G. Li, S.C. Zhang, L.J. Yang, Clinical study on Qiankun capsule in treating lung
cancer, Chin. J. Basic Med. Trad. Chin. Med. 10 (2004) 51–54.
[12] C.L. Liu, Y.D. Wang, X.J. Jin, Clinical observation on treatment of non-small cell
lung cancer with Chinese herbal medicine combined with bronchial arterial
infusion chemotherapy, Chin. J. Integr. Trad. West. Med. 21 (2001) 579–581.
[13] F. Liu, Clinical observation to non-small-cellular lung cancer treated with
Fuzheng Guben decoction and chemic-therapy, J. Zhejiang Univ. Trad. Chin.
Med. 31 (2007) 316–318.
[14] J.X. Liu, H.M. Niu, Effects of YiqiYangyin Jiedu Fang on serum vascular
endothelial growth factor and immunologic function in the patient of lung
cancer, J. Tradit. Chin. Med. 47 (2006) 190–192.
[15] J.X. Liu, Z.H. Xu, Z.M. Xhi, Prospective investigation on the treatment of
122 cases of late onset non-small cell lung cancer using Fuzhen method, Acta
Med. Sin. 2 (1987) 11–16.
[16] L.S. Liu, J.X. Liu, C.J. Li, Clinical effect of Yiqi Yangyin Jiedu decoction in treating
patients with advanced non-small cell lung cancer, Chin. J. Integr. Trad. West.
Med. 28 (2008) 352–355.
[17] Z.Z. Liu, Z.Y. Yu, X.N. Ouyang, X.H. Dai, X. Chen, Z.Q. Zhao, et al., Effects of Feitai
Capsule on quality of life in patients with advanced non-small-cell lung
cancer: a randomized controlled trial, J. Chin. Integr. Med. 7 (2009) 11–15.
[18] J.X. Wang, C.L. Zhu, Z.H. Gao, A clinical observation of the effect of
supplementing Qi and nourishing Yin prescription combined with MOP on the
stage III IV of the non-small cell lung cancer, J. Pract. Combination TCM West.
Med. 10 (1997) 1839–1840.
[19] Z.Y. Xu, Evidence-based medicine and treatment of lung cancer, J. Chin. Integr.
Med. 1 (2003) 151–154.
[20] G.Y. Yan, Z.Y. Xu, H.B. Deng, Z.Y. Wan, L. Zhang, J.Y. Zhu, Effects of chemotherapy
combined with Chinese herbal medicine Kangliu Zengxiao Decoction on
tumor markers of patients with advanced non-small-cell lung cancer: a
randomized, controlled trial, J. Chin. Integr. Med. 9 (2011) 525–530.
[21] C. Yang, R.P. Wang, Clinical observation on using KeLiu pills to treat late stage
non-small cell lung cancer, Chin. Arch. Trad. Chin. Med. 22 (2004) 2090–2091.
[22] L.H. Yi, F.D. Zhao, H.M. Wang, Clinical studies with advanced non-small cell
lung cancer of Baiying decoction combined with chemotherapy, Acta Acad.
Med. Jiangxi 45 (2005) 96–97.
[23] T. Zhang, S.L. Ma, J.H. Yeu, Clinical study on toxicity-attenuation effect of
Yiguan Decoction in treatment of non-small cell lung cancer with NP protocol
of chemotherapy, Chin. J. Integr. Trad. West. Med. 21 (2007) 396–399.
[24] Z.Y. Xu, C.J. Jin, C.C. Zhou, Z.Q. Wang, W.D. Zhou, H.B. Deng, et al., Treatment
of advanced non-small-cell lung cancer with Chinese herbal medicine by
stages combined with chemotherapy, J. Cancer Res. Clin. Oncol. 137 (2011)
1117–1122.
[25] J.L. Zhang, L. Yang, Q.H. Tan, Bukangling combined with chemotherapy
improves quality of life in patients with middle-advanced stage non-small cell
lung cancer, J. Pract. Oncol. 27 (2012) 182–184.
[26] Y. Yao, Effects of Feiji Decoction for soothing the liver combined with
psychotherapy on quality of life in primary lung cancer patients, Chin. J. Lung
Cancer 15 (2012) 27–33.
[27] H.Q. Tian, S.Y. Yu, B. Wang, Effect of Fructus Bruceae oil emulsion on cellular
immune function and quality of life in patients with non-small cell lung
cancer, Chin. J. Integr. Trad. West. Med. 27 (2007) 157–159.
[28] A.Q. Zhang, Z.D. Sun, S.Z. Bao, Clinical observation on the treatment of late
stage lung cancer using Bazhen soup to reduce adverse effects of
chemotherapy in 36 cases, Fujian J. Trad. Chin. Med. 36 (2005) 18–19.
[29] L.Z. Lin, D.H. Zhou, X.T. Zheng, Effect of traditional Chinese medicine in
improving quality of life of patients with non-small cell lung cancer in late
stage, Chin. J. Integr. Trad. West. Med. 26 (2006) 389–393.
[30] H.X. Sun, J. Qin, Y.Q. Zhou, Influence of Xiaoliu Baofei pill combined with
chemotherapy on quality of life of patients with advanced non-small cell lung
cancer, Chin. J. Integr. Trad. West. Med. 29 (2009) 23–25.
[31] J. You, Z.M. Shi, B.H. Han, Evaluation on effect of Feiji Recipe on quality of life of
patients with non-small cell lung cancer by adopting international
questionnaire of QOL, Chin. J. Integr. Trad. West. Med. 26 (2006) 33–37.
[32] J.H. Tian, L.S. Liu, Z.M. Shi, Z.Y. Zhou, a randomized controlled pilot trial of Feiji
Recipe on quality of life of non-small cell lung cancer patients, Am. J. Chin.
Med. 38 (2010) 15–25.
 J.-W. Lee et al. / European Journal of Integrative Medicine 7 (2015) 577–585
[33] M.J. Shan, B.H. Han, J. You, Assessment of therapeutic efficacy on treating
advanced non-small cell lung cancer in the aged by Chinese medicine adopting
the international questionnaire of quality of life, Chin. J. Integr. Trad. West.
Med. 31 (2011) 873–879.
[34] Y. Feng, Y.Y. Xiao, S.D. Li, M.X. Lin, Y. Zhang, H.M. Wang, et al., The treatment of
non-small cell lung cancer by interstitial i-125 seeds implantation combined
with chemotherapy and Chinese medicine, Chin. J. Integr. Med. 18 (2012) 663–
669.
[35] C. Gridelli, F. Perrone, S. Monfardini, Lung cancer in the elderly, Eur. J. Cancer 33
(1997) 2313–2314.
[36] E. Silverberg, J.A. Lubera, Cancer Statistics, CA Cancer J. Clin. 38 (1988) 5–22.
[37] C. Gridelli, Chemotherapy of non-small cell lung cancer in the elderly, Lung
Cancer 38 (2002) 67–70.
[38] D.A. Karnofsky, J.H. Burchenal, Evaluation of chemotherapeutic agents, The
clinical evaluation of chemotherapeutic agents in cancer, MacLeod CM, New
York, 1949.
[39] C.A.C. Schag, P.A. Ganz, D.S. Wing, M.S. Sim, J.J. Lee, Quality of life in adult
survivors of lung, colon and prostate cancer, Qual. Life Res. 3 (1994)
127–141.
[40] D.F. Cella, A.E. Bonomi, S.R. Lloyd, D.S. Tulsky, E. Kaplan, P. Bonomi, Reliability
and validity of the Functional Assessment of Cancer Therapy–Lung (FACT-L)
quality of life instrument, Lung Cancer 12 (1995) 199–220.
[41] D.F. Cella, D.T. Eton, D.L. Fairclough, P. Bonomi, A.E. Heyes, C. Silberman, et al.,
What is a clinically meaningful change on the Functional Assessment of Cancer
Therapy–Lung (FACT-L) questionnaire? Results from Eastern Cooperative
Oncology Group (ECOG) Study 5592, J. Clin. Epidemiol. 55 (2002) 285–295.
[42] N.K. Aaronson, S. Ahmedzai, B. Bergman, M. Mullinger, A. Cull, N.J. Duez, et al.,
The European Organization for Research and Treatment of Cancer QLQ-C30: a
quality-of-life instrument for use in international clinical trials in oncology, J.
Natl. Cancer Inst. 85 (1993) 365–376.
Downloaded for Valerie Duttlinger (valduttlinger@yahoo.com) at Universitas Tarumanagara from ClinicalKey.com by Elsevier on September 05, 2017.
For personal use only. No other uses without permission. Copyright ©2017. Elsevier Inc. All rights reserved.
585
[43] A.B. Smith, K. Cocks, M. Taylor, D. Parry, Most domains of the European
Organisation for Research and Treatment of Cancer Quality of Life
Questionnaire C30 are reliable, J. Clin. Epidemiol. 67 (2014) 952–957.
[44] D.M. Eisenberg, E.S. Harris, B.A. Littlefield, S. Cao, J.A. Craycroft, R. Scholten,
et al., Developing a library of authenticated traditional Chinese medicinal
(TCM) plants for systematic biological evaluation-rationale, methods and
preliminary results from a Sino-American collaboration, Fitoterapia 82 (2011)
17–33.
[45] S.G. Li, H.Y. Chen, C.S. Ou-Yang, X.X. Wang, Z.J. Yang, Y. Tong, et al., The efficacy
of Chinese herbal medicine as an adjunctive therapy for advanced non-small
cell lung cancer: a systematic review and meta-analysis, PLoS One 8 (2013) 1–
11.
[46] W.C. Cho, K.N. Leung, In vitro and in vivo anti-tumor effects of Astragalus
membranaceus, Cancer Lett. 252 (2007) 43–54.
[47] W.C. Cho, K.N. Leung, In vitro and in vivo immunomodulating and
immunorestorative effects of Astragalus membranaceus, J. Ethnopharmacol.
113 (2007) 132–141.
[48] M. McCulloch, C. See, X.J. Shu, M. Broffman, A. Kramer, W.Y. Fan, et al.,
Astragalus-based Chinese herbs and platinum-based chemotherapy for
advanced non-small-cell lung cancer: meta-analysis of randomized trials, J.
Clin. Oncol. 24 (2006) 419–430.
[49] D. Moher, A.R. Jadad, G. Nichol, M. Penman, P. Tugwell, S. Walsh, Assessing the
quality of randomized controlled trials: an annotated bibliography of scales
and checklists, Control. Clin. Trials 16 (1995) 62–73.
[50] E. Ernst, K.L. Resch, Reviewer bias: a blinded experimental study, J. Lab. Clin.
Med. 124 (1994) 178–182.
[51] F.A. Shepherd, J. Dancey, R. Ramlau, K. Mattson, R. Gralla, M. O’Rourke, et al.,
Prospective randomized trial of docetaxel versus best supportive care in
patients with non–small-cell lung cancer previously treated with platinum-
based chemotherapy, J. Clin. Oncol. 18 (2000) 2095–2103.