Impact Factor 4.137 | CiteScore 4.28
More on impact ›

Systematic Review ARTICLE

Front. Oncol., 16 August 2019 | https://doi.org/10.3389/fonc.2019.00730

Efficacy and Safety of Chinese Herbal Medicine on Ovarian Cancer After Reduction Surgery and Adjuvant Chemotherapy: A Systematic Review and Meta-Analysis

Rongyun Wang1, Qiuhua Sun1, Fang Wang2, Yuan Liu3, Xiang Li4, Tianhui Chen5, Xiaoke Wu4, Huijuan Tang5, Mengyun Zhou5, Shuzhi Zhang5, Yun Xiao5, Weijia Huang6, Chi Chiu Wang7,8 and Lu Li7,8,9*
  • 1School of Nursing, Zhejiang Chinese Medical University, Hangzhou, China
  • 2School of Medicine, Shanghai Jiaotong University, Shanghai, China
  • 3The First School of Clinical Medicine, Lanzhou University, Lanzhou, China
  • 4Department of Obstetrics and Gynecology, First Affiliated Hospital, Heilongjiang University of Chinese Medicine, Harbin, China
  • 5Group of Molecular Epidemiology and Cancer Precision Prevention, Zhejiang Academy of Medical Sciences, Hangzhou, China
  • 6School of Medicine, Second Affiliated Hospital, Zhejiang University, Hangzhou, China
  • 7College of Basic Medical Sciences, Zhejiang Chinese Medical University, Hangzhou, China
  • 8Department of Obstetrics and Gynaecology, The Chinese University of Hong Kong, Sha Tin, Hong Kong
  • 9Institute of Chinese Medicine, The Chinese University of Hong Kong, Sha Tin, Hong Kong

Background: Ovarian cancer (OvC) is a malignant tumor which invades ovarian epithelium and interstitium. Reduction surgery combined with adjuvant chemotherapy is standard treatment for OvC patients, but the adverse effects due to chemotherapy still remains a major problem. While Chinese herbal medicine (CHM) therapy has a unique therapeutic effect to reduce side effects of chemotherapy by boosting immune system, the evidence of CHM in the treatment of OvC patients are limited.

Objective: We conducted a systematic review to evaluate the efficacy and safety of CHM in the treatment of OvC after reduction surgery and adjuvant chemotherapy.

Method: Chinese National Knowledge Infrastructure (CNKI) and PubMed up to Dec 31st 2018 were searched to identify relevant studies. Only randomized controlled trials (RCTs) were included, and there was no limitation on language of the publication. Data were extracted from all included studies and meta-analysis was performed with Review Manager 5.3. Study quality was assessed and pooled risk ratios (RR) or mean difference (MD) with 95% CIs were used to evaluate the efficacy and safety of CHM.

Results: A total of 18 RCTs involving 975 participants were included. There was no placebo, no treatment and CHM alone. Compared with Western Medicine (WM) alone, Chinese herbal Medicine combined with WM (CHM-WM) significantly improved TCM syndromes and symptoms, KPS scores, CD4 counts, CA125 levels, and 3-years survival rate (P < 0.05). Incidences of gastrointestinal reactions, marrow depression, urinary system symptoms were significantly lower in CHM-WM group than in WM group (P < 0.01). There was no significant difference in CD3 counts, CD8 counts, quality of life, liver function, and peripheral neuropathy between the two groups (P > 0.05).

Conclusion: The systematic review indicated that CHM combined with WM is effective and safe as a treatment for OvC patients after reduction surgery and adjuvant chemotherapy. However, more high-quality and large-scale RCTs are needed to confirm the efficacy and safety of CHM intervention.

Ovarian Cancer (OvC) is a gynecological malignancy with high prevalence in women aged 50–70. It accounts for about 20% of all female reproductive cancers (1). Although the morbidity in OvC is lower than that in cervical and endometrial cancers, OvC has the highest mortality amongst the three, which is the leading cause of cancer-associated death in women (2). Owing to lack of typical symptoms and early detection methods, diagnosis is often belated. Fewer than one-half of patients can survive beyond 5 years after diagnosis (3). Over 60–70% of patients are diagnosed at advanced stage. In terminal stage, patients always suffer from severe abdominal pain and distension due to peritoneal metastasis.

The National Comprehensive Cancer Network (NCCN) Guidelines recommend removal of the ovary and fallopian tubes as an initial treatment for OvC to patients with FIGO stage I and/or low-grade invasive carcinoma, and debulking surgery for patients with FIGO stage II-IV (4). Adjuvant treatments are necessary to minimize recurrence of OvC, which may include radical surgery (such as hysterectomy, unilateral salpingo-oophorectomy, etc.), radiotherapy (such as high-energy x-rays, etc.), chemotherapy (such as carboplatin plus paclitaxel regimen, cisplatin plus cyclophosphamide regimen, etc.), hormone therapy (such as tamoxifen, letrozole, etc.), tumor-targeted therapy (such as monoclonal antibody therapy, bevacizumab, etc.), and/or Chinese herbal medicine (CHM) (such as Bushenxiaozheng decoction, Lichongshensui decoction, etc.). Most postoperative patients suffer from constitutional debility and other surgery-related complications. While chemotherapy kills both tumor cells and normal cells, leading to many adverse effects, such as marrow depression, gastrointestinal reactions (nausea, vomiting), neurotoxicity, so on. In recent years, a growing number of clinical studies showed CHM could alleviate chemotherapy-related side effects and improves human immunity, which can be a supporting therapy of the adjuvant treatment for OvC (5).

Objective

The systematic review aimed to assess the efficacy and safety of CHM for ovarian cancer after reduction surgery and adjuvant chemotherapy.

Materials and Methods

Inclusion and Exclusion Criteria

Inclusion Criteria

(1) Patients were confirmed with diagnosis of OvC at FIGO stage II-IV by surgery and pathology;

(2) The tumors were primary, and the patients included should not have any other untreated malignant tumors simultaneously;

(3) OvC patients carried out reduction surgery and adjuvant platinum-based chemotherapy;

(4) No contraindications to chemotherapy, including bone marrow depression, fever, liver and renal dysfunction, blood picture, and electrocardiogram abnormalities;

(5) Study intervention started with comparable baseline;

(6) Life expectancy was longer than 6 months for observation;

(7) No serious diseases in major organs and systems;

(8) Patients participated in the trial voluntarily.

Exclusion Criteria

(1) Not meeting the diagnostic criteria;

(2) Allergic to drugs;

(3) Nursing women;

(4) With mental diseases not easy or refuse to cooperate;

Shedding cases, such as subjects with poor compliance, were asked to quit the study, etc.

Types of Research

Only randomized controlled trials (RCTs) were included.

Interventions and Comparison

(1) CHM vs. placebo;

(2) CHM vs. no treatment;

(3) CHM vs. WM;

(4) CHM combined with WM vs. WM alone; and

(5) CHM vs. other interventions (bed rest, nutritional support, etc.).

Literature Search

Database

We performed a comprehensive search from CNKI and PubMed databases for all the potentially eligible trials of CHM for OvC. All databases were searched from 31st January, 1966 to Dec 31st, 2018.

Search Strategy

Keywords for the search included “Chinese Medicine,” “Chinese Herbal Medicine,” “Traditional Chinese Medicine,” and “Ovarian Cancer.” For the CNKI database, the key words were searched in Chinese characters and Pinyin. There was no limitation on the languages.

Data Extraction

Based on a pre-designed and standardized data collection form, two authors (WRY & LL) reviewed the titles and abstracts of all the clinical studies independently for study inclusion. Subsequently, two authors read the full texts for study inclusion. Any non-conformity would be solved by discussion with the third author (CTH) to make a consensus. The following information was extracted from the included studies: first author, year, sample size, study design, baseline information, randomization, therapeutic outcomes, and adverse effects.

Quality Assessment

Assessment of methodological quality was conducted in accordance with Cochrane Reviewers' Handbook 5.0, including the randomization method, allocation concealment, description of inclusion criteria, evaluation on the curative effect with blinding, description of withdrawal and loss of follow-up, baseline consistency, and whether the intention-to-treatment (ITT) analysis was performed.

Data Synthesis and Analysis

We processed and analyzed the data using the Review Manager software (Revman 5.3, provided by the Cochrane Collaboration). Random-effects models were used to calculate pooled effects. Fixed-effect models were used for combining data where it was reasonable to assume that studies were estimating the same underlying treatment effect: i.e., where trials were examining the same intervention, and the trials' populations and methods were judged sufficiently similar. Dichotomous data were presented as pooled Risk Ratio (RR) with 95% confidence intervals (95% CIs), while continuous data were presented as Mean Difference (MD) with 95% CIs. We performed forest plot and funnel plot analysis to test heterogeneity, and assess reporting biases. P < 0.05 was considered statistically significant.

Heterogeneity was assessed through the I2 statistic, which estimates the fraction of variance that is due to heterogeneity and by Q test. The level of significance for the Q test was defined as P < 0.10.

Results

Literature Search

480 clinical studies were identified in the literature search. After screening the titles and abstracts, 38 RCTs were selected initially according to the inclusion, and exclusion criteria. Subsequently, full texts of these studies were further reviewed, 20 studies were further excluded, and 18 studies were finally included for meta-analysis (623). Amongst these excluded studies, 14 studies applied wrong randomization (2437), 4 trials reported only recruit FIGO stage II-IV patients but mixed with FIGO stage I patients in their outcome reports (3841), 1 study used wrong intervention (42), and 1 study included non OvC patient (43). Besides, the subjects and study design of 2 trials (12, 18) were same, but the outcomes were different. We failed to get the responses and clarifications from the original authors. After discussion, we included all of these studies. Figure 1 summarizes the process of the study selection.

FIGURE 1
www.frontiersin.org

Figure 1. Study inclusion and exclusion.

Characteristics and Quality of the Studies

Table 1 shows a summary and quality assessment of all included studies. In total 18 studies with 975 patients were analyzed, whereas 488 patients were from study group (treated with combined CHM and WM), and the other 487 patients were from control group (treated with WM alone). There was no study group treated with CHM alone, and no placebo and no treatment in control group. CHM included Shenlingbaizhu decoction, Guizhifuling capsules, so on, where WM included Docetaxel, Cisplatin, so on. There were no significant differences in ages, BMI, clinical stages, pathological types, histological grade between the groups (P > 0.05). The baselines of patients' information between groups were similar, but blinding, allocation concealment and ITT were not reported in all studies.

TABLE 1
www.frontiersin.org

Table 1. Summary of characteristics of included studies.

Efficacy and Safety

Outcomes of efficacy and safety were separately analyzed as below and summarized as in Supplementary Table 1. Comparisons and meta-analysis were only available and performed between combined Chinese herbal Medicine and Western Medicine (CHM-WM) group and Western Medicine alone (WM) group.

Efficacy

Syndromes and symptoms

Ten trials (6, 7, 10, 11, 13, 1518, 21) evaluated the efficacy in the improvement of TCM syndromes and symptoms (such as poor appetite, fatigue, etc.) between the two groups. Meta-analysis showed that the symptoms were significantly improved in CHM-WM group when compared with WM group (RR = 0.29, 95% CI: 0.21–0.37, P < 0.00001, Figure 2A).

FIGURE 2
www.frontiersin.org

Figure 2. Meta-analysis on efficacy. (A–I) showed the comparisons and meta-analyses on efficacy between CHM-WM group and WM group. The I2 statistic described the percentage of total variation across studies that was due to heterogeneity rather than chance. CI indicated the confidence interval. Dichotomous data were presented as pooled Risk Ratio (RR) with 95% confidence intervals (95% CIs), while continuous data were presented as Mean Difference (MD) with 95% CIs.

Performance status (KPS scores)

Nine trials (6, 1016, 20) compared patients' performance status by KPS scores before and after the treatments. Meta-analysis showed that the KPS scores were significantly increased in CHM-WM group when compared with WM group (MD = 3.75, 95% CI: 0.85–6.65, P = 0.01, Figure 2B).

Tumor evaluation

Five trials (6, 8, 9, 15, 16) evaluated the tumor by Response Evaluation Criteria in Solid Tumors (RECIST) between two groups. Meta-analysis showed that the pathological change of tumor was significantly more stable in the CHM-WM group when compared with WM group (RR = 1.30, 95% CI: 1.01–1.67, P = 0.04, Figure 2C).

Immunologic function

Four trials (13, 1517) evaluated the immunologic function by CD3, CD4, and CD8 counts before and after the treatments. Meta-analysis showed that CD4 counts level were significantly higher in CHM-WM group when compared with WM group (MD = 4.16, 95% CI: 1.25–7.06, P = 0.005, Figure 2D). CD3 and CD8 counts were not significantly different between CHM-WM group and WM group (WM) (MD = 3.74 CI: −0.43–7.91, P = 0.08, Figure 2E, MD = −076 CI: −4.07–2.54, P = 0.65, Figure 2F).

CA125

Four trials (10, 12, 13, 16) evaluated CA125 before and after the treatments. Meta-analysis showed that CA125 was significantly lower in CHM-WM group when compared with WM group (MD = −7.76, 95% CI: −12.57 to −2.95, P = 0.002, Figure 2G).

Quality of life

Quality of life was reported in 3 trials (6, 10, 16). Meta-analysis showed that there was no significant difference in quality of life between CHM-WM group and WM group (MD = 2.55, 95% CI: 0.01–5.10, P = 0.05, Figure 2H).

Three-year survival rate

Three-year survival rate was reported in 2 trials (19, 22). Meta-analysis indicated that the 3-year survival rate in CHM-WM group was significantly higher than in WM group (RR = 1.29, 95% CI: 1.06–1.57, P = 0.01, Figure 2I).

Safety

Gastrointestinal reactions

Gastrointestinal reactions (including nausea or vomiting, diarrhea) were recorded in 7 trials (6, 7, 10, 11, 1416). Meta-analysis showed that the incidence of gastrointestinal reactions was significantly lower in CHM-WM group when compared with WM group (RR = 0.74, 95% CI: 0.56–0.93, P = 0.01, Figure 3A).

FIGURE 3
www.frontiersin.org

Figure 3. Meta-analysis on safety. (A–F) shown the comparisons and meta-analysis on safety between CHM-WM group and WM group. The I2 statistic described the percentage of total variation across studies that was due to heterogeneity rather than chance. CI indicated the confidence interval. Dichotomous data were presented as pooled Risk Ratio (RR) with 95% confidence intervals (95% CIs).

Bone marrow depression

Bone marrow depressions (parameters such as nausea or vomiting, diarrhea) were recorded in 10 trials (6, 7, 1013, 1518). Meta-analysis showed that the bone marrow depression in CHM-WM group was significantly lower than that in WM group (RR = 0.70, 95% CI: 0.62–0.79, P < 0.00001, Figure 3B).

Urinary system symptoms

Symptoms and markers in the urinary system including hematuria, proteinuria, urea nitrogen and creatinine, were recorded in 6 trials (6, 10, 12, 13, 18, 19). Meta-analysis results showed that incidence of urinary system symptoms in CHM-WM group was significantly lower than that in WM group (RR = 0.47, 95% CI: 0.32–0.70, P = 0.0002, Figure 3C).

Liver function

Liver function (parameters such as ALT) was recorded in 4 trials (6, 12, 15, 16). Meta-analysis indicated that there was no significant difference in liver function between two groups (RR = 0.72, 95% CI: 0.44–1.17, P = 0.18, Figure 3D).

Peripheral neuropathy

Peripheral neuropathy (such as loss of sensation, muscle weakness and atrophy, loss of tendon reflexes, and vasomotor symptoms) was recorded in 3 trials (9, 15, 16). Meta-analysis showed that there was no significant difference in peripheral neuropathy between two groups (RR = 1.11, 95% CI: 0.81–1.50, P = 0.52, Figure 3E).

Others

Additionally, one study (23) compared appetite score by daily intake between the two groups, and reported that the appetite score of the CHM-WM group (4.54 ± 1.22) was significantly higher than the score of the WM group (2.12 ± 1.23), (P < 0.05, Figure 4A). Another study (10) recorded the incidence rate of hair loss, infection and oral ulcer. It showed that the incidence rate of hair loss in CHM-WM group was significantly lower than that in WM group (P = 0.005, Figure 4B), but there was no significant difference in incidence rate of infection and oral ulcer between two groups (P > 0.05, Figures 4C,D).

FIGURE 4
www.frontiersin.org

Figure 4. Other results. (A–D) shown the comparisons and meta-analysis on the appetite score, hair loss, infection and oral ulcer between CHM-WM group and WM group. The I2 statistic described the percentage of total variation across studies that was due to heterogeneity rather than chance. CI indicated the confidence interval. Dichotomous data were presented as pooled Risk Ratio (RR) with 95% confidence intervals (95% CIs), while continuous data were presented as Mean Difference (MD) with 95% CIs.

Discussion

In this study, we reviewed the efficacy and safety of CHM in the treatment of OvC after reduction surgery and adjuvant chemotherapy. A total number of 18 trials involved 975 patients were included, 488 patients in CHM-WM group, and 487 patients in WM group. Meta-analysis indicated that using CHM combined with WM improves the efficacy and safety of treatment on OvC patients.

The meta-analysis showed that the improvements of TCM syndromes and symptoms, KPS Scores, CD4, CA125, and 3-years survival rate in CHM-WM group were significantly better than WM group. These results implied that, compared with WM alone treatment, CHM combined with WM treatment can improve the symptoms and quality of life, consolidating the curative effects and alleviating the pain of OvC patients. There are no special symptoms in the early stage of OvC, and the methods for screening and early detection of OvC are still lacking. Therefore, most of the OvC patients were diagnosed at late stage, resulting in a poor prognosis (44). Although the adjuvant platinum-based chemotherapy is a therapeutically effective treatment after tumor debulking reduction surgery, adverse effects of chemotherapy, and high tumor recurrence are still a major problems for OcV patients (45). The application of CHM is extensive and profound, and there are a solid theoretical foundation and rich clinical experience in the treatment of cancer with CHM. Although CHM cannot inhibit the growth of tumors, CHM plays an important role in reinforcing healthy Qi, regulating the disharmony of Yin-Yang, Qi-Blood, and Zang-Fu, enhancing the patients' resistance, etc. These could be reflected by the improvement of performance status, TCM syndromes, and symptoms in the clinical trials.

Compared with WM group, the adverse effects including gastrointestinal reaction, marrow suppression, liver and kidney dysfunction and infection were significantly reduced in CHM-WM group. It implied that CHM combined with WM treatment could reduce the side effects caused either by the cancer itself or by the chemotherapy used in treating OvC. The toxic effects, medical complications and the poor quality of life are common, though surgery, radiotherapy, and chemotherapy have very good anti-cancer outcomes. Clinically, CHM combined with WM treatment not only provides higher clinical efficacy and longer survival time for patients, but also have therapeutically effects on alleviating and preventing the side effects of surgery, radiotherapy and chemotherapy. The mechanisms could be the formula was aimed at reducing the chemotherapy-induced side-effects, and some of the individual herbs included were also shown to have anti-oxidant and cytotoxic activities and they might also enhance cellular immunity

There are limitations in the study. Firstly, the methodology quality of the included RCTs was generally not high. Although all the studies claimed that randomization has been applied, only one study list the details of the randomized schemes and instructions. Six studies mentioned the application of “random number table” but without further details. The rest of studies only mentioned “randomization,” and we failed to get confirmation by contacting the original authors. Secondly, only one study reported blinding. We considered blinding was not carried out in most of the clinical studies due to clinical trial ethics on the treatment for cancer patients. Additionally, the included studies were mostly small sample sized. Thirdly, the CHM formula included studies which were different or not exactly the same. Based on TCM theory, personalized individual treatment plan should be applied according to the patient' s condition individually. So, our conclusion of this review is referring to the general concept of CHM, but not to individual CHM formula or individual herb.

Conclusion

In conclusion, the results showed that CHM significantly improved symptoms and enhanced curative effects. CHM also showed the unique superior chemotherapy tolerance in quality of patient's life and minimal toxic and adverse effects due to chemotherapy. So, our review and meta-analysis have provided evidence on the efficacy and safety of CHM for ovarian cancer after reduction surgery and adjuvant chemotherapy, but rigorously designed and large-scale RCTs are still needed in the future.

Data Availability

All datasets generated for this study are included in the manuscript and/or the Supplementary Files.

Author Contributions

LL contributed conception and design of the study. LL, YL, RW, and QS organized the databases. RW, QS, FW, YL, HT, and WH performed the statistical analysis and prepared the figures and tables. LL, RW, QS, and FW wrote the first draft of the manuscript. YL, XL, TC, XW, HT, MZ, SZ, and YX wrote the sections of the manuscript. CW modified the English of the manuscript. All authors contributed to manuscript revision, read, and approved the submitted version.

Funding

This work was supported by grants from Qianjiang Talents Fund of Zhejiang Province (Grant Number: QJD1602022 and QJD1602026), Joint Key Program of Zhejiang Province-Ministry of Health (Grant Number: WKJ-ZJ-1714), Zhejiang Provincial Natural Science Foundation of China (LY14H240001), Medical Health Science and Technology Project of Zhejiang Provincial Health Commission (2014KYA047, 2019KY360, and 2015KYA115), and National Natural Science Foundation of China (81303302).

Conflict of Interest Statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

The reviewer WL declared a shared affiliation, with no collaboration, with one of the authors, LL, to the handling editor at time of review.

Supplementary Material

The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fonc.2019.00730/full#supplementary-material

References

1. Yang YBJ, Li S, Chen R. Research and analysis on TCM therapy for ovarian cancer. J Liaoning Univ TCM. (2014) 5:121–4. doi: 10.13194/j.issn.1673-842x.2014.05.043

CrossRef Full Text | Google Scholar

2. Song ZY, Zhang G, Zhang HL. Ovarian cancer. Xinjiang J Trad Chin Med. (2012) 1:90–2. Available online at: http://www.cnki.com.cn/Article/CJFDTotal-XJZY201201049.htm

PubMed Abstract | Google Scholar

3. Torre LA, Trabert B, DeSantis CE, Miller KD, Samimi G, Runowicz CD, et al. Ovarian cancer statistics, 2018. CA Cancer J Clin. (2018) 68:284–96. doi: 10.3322/caac.21456

PubMed Abstract | CrossRef Full Text | Google Scholar

4. Lu HW, Xie LL, Lin ZQ. Interpretation of “Ovarian cancer, version 1. 2016, NCCN clinical practice guidelines in oncology.” Chin J Pract Gynecol Obst. (2016) 8:761–8.

Google Scholar

5. Hao Y, Zhang X. TCM therapy for ovarian cancer research and analysis. J Pract Trad Chin Inter Med. (2011) 7:35–6. doi: 10.13729/j.issn.1671-7813.2011.07.014

CrossRef Full Text | Google Scholar

6. Chen M. Clinical research of warming the kidney and activating the blood methods combined with TP chemotherapy in the treatment of advanced ovarian cancer. Nanjing Univer Trad Chin Med. (2010). Available online at: http://cdmd.cnki.com.cn/article/cdmd-10315-2010245008.htm

Google Scholar

7. Chen LL. Clinical research of warming the kidney and activating the blood methods combined with TP chemotherapy in the treatment of advanced ovarian cancer. Nanjing Univer Trad Chin Med. (2012). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10393-1012510164.htm

Google Scholar

8. Cheng QA, Zhang QF. Effect of Xiaozheng decoction combined with chemotherapy for treating patients with middle and terminal stage ovarian cancer who resistant to taxanes. J N Chin Med. (2015) 2:181–2.

Google Scholar

9. Guo W. Clinical observation and nursing of endometrial and ovarian cancer treated by Chinese and Western Medicine. Henan Trad Chin Med. (2011) 06:689–91. doi: 10.1016/j.jtcme.2019.07.001

CrossRef Full Text | Google Scholar

10. Han FJ, Guo Y, Tian M, Sun R. Clinical observation of Bushenxiaozheng method on the quality of life of postoperative ovarian cancer patients. Acta Chin Med Pharmacol. (2016) 2:67–9. doi: 10.19664/j.cnki.1002-2392.2016.02.023

CrossRef Full Text | Google Scholar

11. Hao Y. The clinical research on the soothing effects of TCM flavored shenlingbaizhu prescription towards the chemotherapy of postoperative ovarian cancer. Liaoning Univer Trad Chin Med. (2011).

Google Scholar

12. Li JR. Effect of guizhi fuling capsule and earthworm combined with TC regimen on CA125 and quality of life of blood stasis type of ovarian cancer. Heilongjiang Univer Trad Chin Med. (2016). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10228-1016067436.htm

Google Scholar

13. Li Y. Effect of self-made yangzheng guiling decoction combined with TP on ovarian cancerand T cell immune function. Heilongjiang Univer Trad Chin Med. (2017). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10228-1017164775.htm

Google Scholar

14. Liu HR, Zhang SC, Wang RC, Feng WJ. Clinical observation on effect of Shaofu Zhuyu decoction on reducing toxicity and synergism of postoperative chemotherapy for advanced ovarian cancer. In: The Co-operation of Chinese and Western Medicine Tumor Academic Conference. Guangzhou. (2014).

Google Scholar

15. Ma L. Clinical study on YiQiJianPi and HuaYuJieDu method combined with TP regimen in the treatment of late-stage ovarian cance. Nanjing Univ Trad Chin Med. (2005). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10315-2006184268.htm

Google Scholar

16. Mei DY. Clinical study on YiQiJianPi and JieDuSanJie method combined with TP Regimen in the treatment of late-stage ovarian cancer. Nanjing Univ Trad Chin Med. (2014). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10315-1015628716.htm

Google Scholar

17. Qiu LN. Clinical and empirical study of Li Chong Sheng Sui Decoction interfere in ovarian cancer. Heilongjiang Univ Trad Chin Med. (2010). Available online at: http://cdmd.cnki.com.cn/article/cdmd-10228-1011037487.htm

Google Scholar

18. Zhao L. Observe the clinical effects: changes of hemodynamic indexes by the treatment of a combination of “Guizhi Fuling capsules” with lumbricus and TC chemotherapy to the ovarian cancer patients who belong to blood stasis type and have accepted surgery. Heilongjiang Univ Trad Chin Med. (2016). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10228-1016055411.htm

Google Scholar

19. Jia F. Analysis of effect of Traditional Chinese Medicine prescription combined with conventional Western Medicine treatment on advanced ovarian cancer. Strait Pharm J. (2017) 29:169–71. doi: 10.3969/j.issn.1006-3765.2017.02.093

CrossRef Full Text | Google Scholar

20. Yi LJ, Li SW, He DM. Clinical observation on ovarian cancer associated ascites treated by intraperitoneal infusion of modified Shenqi Baizhu powder combined with Interleukin-2. J Guangzhou Univ Trad Chin Med. (2017) 34:31–4. doi: 10.13359/j.cnki.gzxbtcm.2017.01.008

CrossRef Full Text | Google Scholar

21. Mao ZJ, Shen KP, Zhu LM, Zhu LM, Yao Q, Zheng JL. Effect of modified CHM formulae on the quality of life of ovarian cancer patients. Chin J Woman Child Health Res. (2017) S1:656–7.

Google Scholar

22. Xu Y. Effect of Traditional Chinese Medicine combined with TP chemotherapy on quality of life of patients with advanced ovarian cancer. Chin J Med Guide. (2016) 18:1144–5. Available online at: http://www.cnki.com.cn/Article/CJFDTotal-DKYY201611034.htm

Google Scholar

23. Zhang LY. The Effect of Chinese Herbal application and acupoint massage on the loss of appetite in patients with ovarian cancer during chemotherapy. J Qilu Nurs. (2017) 23:77–8. doi: 10.3969/j.issn.1006-7256.2017.10.035

CrossRef Full Text | Google Scholar

24. Han SY, Zhu H, Jia CR, Wang XX. Clinical study on fuzhengyiliu decoction for reducing toxicity and enhancing efficacy and anti-tumor. J Emer Trad Chin Med. (2007) 16:285–7. doi: 10.3969/j.issn.1004-745X.2007.03.018

CrossRef Full Text | Google Scholar

25. Wang XP. Clinical experience of TCM combined with chemotherapy on advanced ovarian cancer. Asia-Pacific Trand Med. (2012) 8:84–5. doi: 10.3969/j.issn.1673-2197.2012.12.047

CrossRef Full Text | Google Scholar

26. Pan L, Gao H, Xin XR, Yin DF. Clinical observation on the prevention of peripheral neuropathy induced by paclitaxel chemotherapy by internal and external application of traditional Chinese medicine. Inner Mongolia J Trad Chin Med. (2012) 3:28. doi: 10.16040/j.cnki.cn15-1101.2012.03.204

CrossRef Full Text | Google Scholar

27. Zhao D, Deng J, Zhu YT, Shi DH. Systematic review of TCM combined with TP on advanced ovarian cancer. Strait Pharm J. (2015) 27:71–3. Available online at: http://www.cnki.com.cn/article/cjfdtotal-haix201501032.htm

Google Scholar

28. Chen JJ. The study of clinical efficacy evaluation and survival analysis of combined traditional Chinese and western medicine on advanced ovarian cancer. Zhejiang J Trad Chin Med. (2012) 47:751–2. doi: 10.3969/j.issn.0411-8421.2012.10.040

CrossRef Full Text | Google Scholar

29. Chen J, Zhang ZH, Zhou J, Cao SL, Chen GY. The study of Peripheral blood T lymphocyte subsets oh ovarian cancer. Chin J Pract Gynecol Obstet. (1993) 9:353–5. Available online at: http://www.cnki.com.cn/Article/CJFDTotal-ZGSF199306022.htm

Google Scholar

30. Zhang J, Cheng JX, Shan BE, Shi WC. The study of compound Chinese medicine on proliferation of peripheral blood mononuclear cells and TNF-α level on ovarian cancer patients. Clin Focus. (2005) 10:580–1. doi: 10.3969/j.issn.1004-583X.2005.10.029

CrossRef Full Text | Google Scholar

31. Pan TH, Fan QY. The study of surgery, chemotherapy and traditional Chinese medicine on primary ovarian cancer. J Anhui TCM College. (2004) 23:15–7. doi: 10.3969/j.issn.1000-2219.2004.04.007

CrossRef Full Text | Google Scholar

32. Chen J, Wang XH, Chen LS, Lin L, Chen LL. Clinical observation on 27 cases of ovarian cancer treated by nourishing and expelling pathogenic factors. Fujian J TCM. (2011) 42:14–6. doi: 10.13260/j.cnki.jfjtcm.010108

CrossRef Full Text | Google Scholar

33. Wang J, Sui LH, Lou G, Xu F. The study of element on ascites of ovarian cancer. Acta Chin Med Pharmacol. (1991) 1:35–6. doi: 10.19664/j.cnki.1002-2392.1999.01.031

CrossRef Full Text | Google Scholar

34. Wang BS, Liu XF, Wang LL, Li CY, Ding RL, Wang T, et al. The study of TCM on advanced ovarian cancer with refractory ascites. Chin J Inform Trad Chin Med. (2011) 8:78–9. doi: 10.3969/j.issn.1005-5304.2001.09.049

CrossRef Full Text | Google Scholar

35. Wang HC, Zhao YL. Clinical analysis of tuyuan decoction on ovarian cancer. J Liaoning Univ TCM. (2008) 8:110–1. doi: 10.13194/j.jlunivtcm.2008.08.112.wangkc.062

CrossRef Full Text | Google Scholar

36. Zhang W, Wang MX, Guo YF, Tan XY. The study of matrine on perioperative period of ovarian cancer patients. Chin J Lab Diag. (2014) 18:1290–1. Available online at: http://www.cnki.com.cn/article/cjfdtotal-zszd201408030.htm

Google Scholar

37. Yu JF. Clinical study on ovarian tumour treated with fuzhengxiaoliu decoction combined with chemotherapy. Heilongjiang Univ Trad Chin Med. (2005). Available online at: http://cdmd.cnki.com.cn/article/cdmd-10228-2005120574.htm

Google Scholar

38. Cheng K. The clinical research on the treatment of ovarian tumor by Lichongshengsuiyin combined with chemotherapy. Heilongjiang Univ Trad Chin Med. (2010). Available online at: http://cdmd.cnki.com.cn/article/cdmd-10228-1011037600.htm

Google Scholar

39. Liu Y. Clinical study on oophoroma after treated with Fuzhengquyu decoction combined with chemotherapy. Heilongjiang Univ Trad Chin Med. (2008). Available online at: http://cdmd.cnki.com.cn/article/cdmd-10228-2008179650.htm

Google Scholar

40. Xia J. Efficacy analysis of LCSSY on attenuation of postoperative chemotherapy in patients with ovarian cancer. Heilongjiang Univ Trad Chin Med. (2017). Available online at: http://cdmd.cnki.com.cn/Article/CDMD-10228-1017145170.htm

Google Scholar

41. Chan KKL, Yao TJ, Jones B, Ma FK, Leung CY, Lau SK, et al. The use of Chinese herbal medicine to improve quality of life in women undergoing chemotherapy for ovarian cancer: a double-blind placebo-controlled randomized trial with immunological monitoring. Ann Oncol. (2011) 22:2241–9. doi: 10.1093/annonc/mdq749

PubMed Abstract | CrossRef Full Text | Google Scholar

42. Li Y, Zhang T, Guo YP, Liu L, Zhu JH, Zhao Y, et al. Effect of cantharidin sodium vitamin B6 combing with PT therapy on the lymphatic growth factor of ovarian cancer tissues. J Hainan Med Univ. (2015) 21:1701–4. doi: 10.13210/j.cnki.jhmu.20151021.003

CrossRef Full Text | Google Scholar

43. Piao BK, Wang YX, Xie GR, Mansmann U, Mathess H, Beuth J, et al. Impact of complementary mistletoe extract treatment on quality of life in breast, ovarian and non-small cell lung cancer patients. a prospective randomized controlled clinical trial. Anticancer Res. (2004) 24:303–10. doi: 10.1007/BF00725830

PubMed Abstract | CrossRef Full Text | Google Scholar

44. Shen WJ, Dai DQ. Advances of epigenetics in ovarian cancer. Chin J Cancer Prev Treat. (2010) 14:790–4. doi: 10.16073/j.cnki.cjcpt.2007.10.021

CrossRef Full Text | Google Scholar

45. Yang Y. Clinical study of docetaxel combined with platinum for the treatment of 58 cases recurrent ovarian carcinoma. Chin J Cancer Prev Treat. (2008) 15:1176–7. doi: 10.16073/j.cnki.cjcpt.2008.15.016

CrossRef Full Text | Google Scholar

Keywords: meta-analysis, ovarian cancer, Chinese herbal medicine, efficacy, safety

Citation: Wang R, Sun Q, Wang F, Liu Y, Li X, Chen T, Wu X, Tang H, Zhou M, Zhang S, Xiao Y, Huang W, Wang CC and Li L (2019) Efficacy and Safety of Chinese Herbal Medicine on Ovarian Cancer After Reduction Surgery and Adjuvant Chemotherapy: A Systematic Review and Meta-Analysis. Front. Oncol. 9:730. doi: 10.3389/fonc.2019.00730

Received: 22 February 2019; Accepted: 22 July 2019;
Published: 16 August 2019.

Edited by:

Chiara Riganti, Department of Oncology, School of Medicine, University of Turin, Italy

Reviewed by:

Luis Vitetta, University of Sydney, Australia
Weicheng Liang, The Chinese University of Hong Kong, China

Copyright © 2019 Wang, Sun, Wang, Liu, Li, Chen, Wu, Tang, Zhou, Zhang, Xiao, Huang, Wang and Li. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Lu Li, lucia.lu.lee@zcmu.edu.cn

These authors have contributed equally to this work