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Keywords:

  • Chinese medicinal herb;
  • effect;
  • injection of brucea javanica oil emulsion;
  • lung cancer;
  • safety

Abstract

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

Objective: Injection of brucea javanica oil emulsion (IBJOE), one of Chinese patent drugs has been widely used for lung cancer (LC) in China, and is known to provide some favorable outcomes, in particular when it combined with conventional treatment. However, little available best evidence is known about its effect and safety. This paper aims to evaluate the effectiveness and safety of IBJOE plus chemoradiotherapy to alleviate symptoms of LC patients.

Methods: A complete literature searching was conducted in databases including Chinese Biomedical Literature Database, China Academic Journals Full-text Database, Chinese Scientific Journals Database, the Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE to identify randomized controlled trials (RCTs) of IBJOE with chemoradiotherapy versus chemoradiotherapy alone for LC patients regardless of blinding, duration of treatment or duration of follow-up. All searching dates were from the beginning to December 2011. Quality of the included studies was assessed using the method by Cochrane Reviewer Handbook, and data analysis was performed using RevMan 5.10 software developed by The Cochrane Collaboration.

Results: The searching yielded over 1371 relevant citations, most of which did not meet the inclusion criteria. Finally, only 21 RCTs involving 1619 patients were included, and all the studies were of poor quality. Pooled analyses were performed to reveal that compared with chemoradiotherapy alone, IBJOE plus chemoradiotherapy had a better complete response rate (relative risk (RR) = 1.42; 95% CI 1.05 to 1.92; P = 0.02) and improved quality of life (RR = 1.83; 95% CI 1.63 to 2.07; P < 0.00001) measured by Karnofsky Performance Status scale. In addition, there was a significant difference on the outcome of long-term survival rate, level of immune function, and some incidences of adverse effects.

Conclusions: IBJOE plus chemoradiotherapy may have positive effects on LC patients in response rate, improvement of quality of life, and reducing incidences of some adverse effects compared with chemoradiotherapy alone. However, the results need to be viewed with caution because of low quality of the included studies.


Background

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

Lung cancer (LC) is a leading cause of cancer death all over the world (1), it was also one of the most commonly diagnosed cancers since 1985 for both men and women (2). In United Kingdom, one in seven new cancer cases were LC in 2004 (3). And in United States, 172,570 new cancer patients were diagnosed and 163,510 resulted in death in 2005 (1). Besides, the incidence and mortality are increasing rapidly in Southern and Eastern European countries in recent years (2). In China, LC is killing 283,031 people each year since 2003(4). LC has remained a global health problem all over the world because of its high prevalence and low diagnosis (3). In addition, the long-term survival rate is so lower that it has been a heavy burden to individuals, their families and society (5).

The most updated internationally accepted staging of therapeutic interventions by ascribing an accurate prognosis for cancer is the tumor, node, metastasis staging system which was applied to stage for LC (3). For early-stage cases, surgical resection remains the primary option (6-8), whereas for patients with locally advanced cancer, chemotherapy or radiotherapy can clearly improve the quality of life and prolong the survival time (9). However, there are some limitations on chemoradiotherapy because of its toxicity and morbidity including bone marrow suppression, digestive toxic reaction, phlebitis and anaphylactic shock, which have serious influence on the completion of treatment regimens, so chemoradiotherapy treatment remain difficult to administer (10).

Traditional Chinese medicine (TCM) is one of alterative treatment options for modern therapies currently and has been practiced worldwide. Among the components of TCM, herbs agents possess complex biological activities. For instance, herbs preparations might resolve toxin, eliminate pathological dampness, disperse the blood clots, invigorate the blood circulation, etc. (11). Some studies suggested that TCM plus chemoradiotherapy may be an excellent alternative for cancer patients to relieve toxicity and side effects reduced by chemoradiotherapy, and improve the immune function and quality of life (12-14). Injection of brucea javanica oil emulsion (IBJOE, as one of medicinal preparations, produced by Shenyang Yaoda Pharmaceutical Co., Ltd, Shenyang, China) is a botanically sourced, molecularly target agent that is prepared as a microemulsion for LC patients. The active substance is extracted from herb brucea javanica (Fructus Bruceae), which is often used in combination with chemotherapy to alleviate toxic reactions and enhance the effect of chemotherapy (14). In 1985, phase III clinical trials were completed and IBJOE was officially launched in China after final approval from the Ministry of Health of the People's Republic of China.

Herb brucea javanica is widely used as adjuvant TCM injection when combining with chemoradiotherapy for LC. The mechanisms of its pharmaceutical action contains following aspects: (1) decrease the number of G2/M phase cells, suppress the proliferation of cancer cells and induce the apoptosis of cancer cells; (2) involve in immune regulation; (3) increase the sensitivity of cancer cells to chemotherapeutic agents; (4) has some anti-thrombotic effects and without any adverse effects (AEs; 12,13,15,16) . Some earlier studies have suggested that IBJOE may be effective for the treatment of LC patients in improving immune function and quality of life as well as reducing toxic reactions (17). However, other studies found that there also existed some severe side effects of IBJOE (18). The available updated evidence is not consistent, and is lack of strict scientific and systematic appraisal. Therefore, a systematic review assessing evidence of the effect and safety of IBJOE for LC patients is necessary.

Materials and methods

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

Inclusion and exclusion criteria

The following criteria were used to determine which studies were included or excluded in the research.

Study design

Design of all studies should be randomized controlled trials (RCTs); blinding, language, published or unpublished, duration of treatment, and duration of follow-up were not considered.

Patients

Patients suffered from LC that was confirmed cytologically or pathologically, regardless of underlying malignancy types, the stage of disease, and nonsmall cell lung cancer or small cell lung cancer. Those with severe complications including dyspnea, shock and respiratory failure, or other type of cancer, however, were excluded.

Interventions

The IBJOE group received IBJOE plus chemoradiotherapy or placebo, and the control group only received chemoradiotherapy or placebo alone. The conventional treatments including chemotherapy plus platinum-based regimen or not, radiotherapy combined platinum-based regimen or not; chemotherapy plus radiotherapy regimen; immunotherapy was identical in both groups. And we conducted subgroup analysis according to different regimens. Studies that evaluated the effects of different dosage forms or nonintravenous administration ways of IBJOE were excluded.

Outcomes measures

The primary outcomes covered response rate and quality of life improvement rate, whereas one-year survival rate, some immune function outcomes (levels of CD3+, CD4+, CD8+), and incidences of different AEs were deemed as secondary outcome measures.

The response rate was evaluated using response evaluation criteria in solid tumors by the World Health Organization (WHO; 19). The response rate was classified as complete response rate (CR), partial response rate (PR), no change (NC) and progress disease (PD). In brief, CR refers to absolute absorption of the lesion revealed by tomography or bronchoscopy; PR refers to lesion that decreases by ≥ 50% but ≤ 99%; and overall response rate is defined as CR + PR (20). In addition, the other response evaluation criterion we applied was Chinese Response Evaluation Criteria in Tumor, which were adapted based on the WHO criteria by the Department of Medicine Administration of Ministry of Health of the People's Republic of China. There was no major change between the two criteria on the definition of CR and PR. Quality of life improvement rate was evaluated by the Karnofsky Performance Status (KPS) score increased before and after treatment (20). We only extracted the data of patients whose KPS score improved by no less than 10 points (the minimal clinically significant difference) after treatment. Another scale used to evaluate cancer patients’ quality of life of was the clinical outcome study 36-item short-form health survey (SF-36), which was used to compare the score of cancer patients’ quality of life before and after treatment (21). All data of AEs were extracted and classified according to WHO grading criteria for acute and subacute toxicity of anti-cancer drug (22) such as leucopenia, gastrointestinal reaction, shock, and death, etc.

Literature collection and selection

A comprehensive literature searching was conducted to identify studies that evaluated the IBJOE adjuvant chemoradiotherapy versus chemoradiotherapy alone for LC. We searched the Cochrane Controlled Trials Register (December 2011), MEDLINE (1950 to December 2011), EMBASE (1966 to December 2011), SCI (1995 to December 2011), SCI (1995 to December 2011), Chinese Biomedical Literature Database, China Academic Journals Full-Text Database and Chinese Scientific Journals Database in latest version and together with reference lists of the retrieved papers. The searching term combination for electronic databases was Medical Subject Headings (MeSHs), text words, and word variants of “brucea javaniva.” Search strategies were adjusted and ran according to the characteristics of different databases regardless of publication status.

Two reviewers (Nie YL, Liu KX) independently selected the articles initially based on title, keyword and abstract. Studies that did not meet the inclusion criteria were discarded during the initial review. When uncertainty existed, we retrieved and assessed the full-text article. Any disagreement was resolved through discussion or consulting a third author (Li J or Zhang MM) to reach consensus. When published data were insufficient, we contacted authors.

Validity assessment

Two authors (Nie YL, Liu KX) independently assessed quality of all the included studies according to Cochrane Handbook for Systematic Reviews of Interventions (23). Following characteristics were assessed by the reviewers: (1) Was the allocation sequence adequately generated? (2) Was allocation adequately concealed? (3) Was knowledge of the allocated interventions adequately prevented during the study? (4) Were incomplete outcome data adequately addressed? (5) Were reports of the study free of suggestion of selective outcome reporting? (6) Was the study apparently free of other problems that could put it at a high risk of bias? Each item rated “Yes” (Y) indicated a low risk of bias, “Unclear” (U) indicated either lack of information or uncertainty over the potential for bias, and “No” (N) indicated a high risk of bias. Disagreements were resolved through discussion with Li J and Zhang MM. Studies with more “Yes” were regarded as having a lower risk of bias (Table 1).

Table 1.  Characteristics and methodological assessment of included studies on IBJOE for LC
ReferenceNo. of patient trial/controlInterventionOutcomeQuality assessment
Trial groupControl groupRB§AIS**O††
  1. Intervention 1CE regimen: cis-diaminodichloroplatinum + Etoposide; 2EP regimen: Etoposide+ cis-platinum; 3Seldinger regimen: Fuorouracil + cis-platinum, mitomycin C/ adriamycin; 4NP regimen: Navelbine + cis-platin (non-small cell lung cancer); 5IVP regimen: Ifosfamide+ Etoposide/cis-platinum (small cell lung cancer); 6GP regimen: Gemcitabine + cis-platin; 7IP regimen: carboplatin + Docetaxel; 8TP regimen: paclitaxel + cis-platin; 9DP regimen: docetaxel + cis-platinum

  2. Outcome inline image complete response rate (World Health Organization); inline image quality-of-life (Karnofsky Performance Status); inline image adverse effects; inline image immune function; inline image quality-of –life improvement rate (short form-36); inline image complete response rate (Chinese criteria formulated by health ministry of China); inline image one-year survival rate.

  3. Quality assessment R: random; B§: blinding; A: allocation concealment; I: incomplete data; S**: selective outcome reporting; O††: other bias; Y: yes; N: no; U: unclear

He 2004 (26)30/30IBJOE + CECE1 inline image UUUYYU
Xing 2004 (27)]39/30IBJOE + EPEP2 inline image UUUNYU
Yuan 2005 (28)42/40IBJOE + SeldingerSeldinger3 inline image UUUYYU
Du 2006 (29)56/57IBJOE + NPNP4 inline image UUUNYU
Wang 2006 (30)20/20IBJOE + IVP/ NPIVP5/NP4 inline image UUUYYU
Chen 2007 (31)30/30IBJOE + NPNP4 inline image UUUYYU
Tian 2007 (32)58/57IBJOE + GPGP6 inline image YUUYYU
Wang 2007(33)20/20IBJOE + GPGP6 inline image YUUYYU
Mai 2008(34)35/30IBJOE +IPIP7 inline image UUUYYU
Sun 2008 (35)30/30IBJOE + NP,GPNP4/ GP6 inline image UUUYYU
Wu 2008 (36)32/28IBJOE + NPNP4 inline image UUUYYU
Deng 2009 (37)53/50IBJOE + SeldingerSeldinger3 inline image UUUYYU
Dong 2009 (38)34/34IBJOE + NPNP4 inline image UUUYYU
Fu 2009 (39)31 /30IBJOE + TPTP8 inline image YUUYYU
Ye 2009 (40)80/80IBJOE +γ-knife therapyγ-knife therapy inline image UUUYYU
Li 2009 (41)20/16IBJOE + NPNP4 inline image UUUYYU
Bo 2010 (42)98/50IBJOE + Seldinger + GPSeldinger3+ GP6 inline image YUUYYU
Chen 2010 (43)45/41IBJOE + GPGP6 inline image UUUYYU
Cui 2010 (44)25/25IBJOE + DPDP9 inline image UUUYYU
Liu 2010 (45)33/32IBJOE +TPTP8 inline image UUUYYU
Yao 2010 (46)40/38IBJOE + DPDP9 inline image UUUYYU

Data extraction

Two reviewers (Nie YL and LKX) independently extracted information using a piloted data extraction form, which included target population (sample size, age, sex, and tumor cell type), diagnosis methods, interventions, outcome measures, and quality assessment items.

Statistical analysis

Data analysis was carried out using Excel 2003, STATA 10.0 and RevMan 5.10. The pooled results were calculated using a fixed-effect model to combine data where there was no significant heterogeneity among trials. For dichotomous data, we presented the results as relative risks (RRs), whereas for continuous variables, mean differences (MDs) were calculated, both with 95% confidence intervals (CIs)(24). Z-test was used for the overall effect of RRs and MDs, and P ≤ 0.05 was considered to be statistically significant. Heterogeneity among studies was evaluated using chi-square test and I2 statistics. I2≥ 50% was considered significant heterogeneity and P ≤ 0.1 indicated statistical heterogeneity among studies. If heterogeneity was statistically significant, we explored the source of the heterogeneity and used a random effect model for meta-analysis when necessary.

Results

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

Description of studies

Electronic search resulted in over 1371 relevant citations. We did not obtain the full texts of two studies (24, 25) which clearly did not meet the inclusion criteria. Finally, 21 RCTs (26–46) involving 1619 patients were included according to the criteria, all of which were conducted in China. We identified studies based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA; Fig. 1; 47).

image

Figure 1. Flowchart of literature selection.

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Participants

Patients included were cytologically or pathologically diagnosed as LC. Baseline data (including age, sex, severity of disease) of most studies were comparable except six studies (29, 33, 36, 39, 40, 41). Duration of the studies ranged from 30 to 160 days. Characteristics and PICO (participants, intervention, comparison, and outcome) of the included studies were tabulated in Table 1.

Interventions

All included trials compared injection of IBJOE plus conventional treatment with conventional treatment alone. There were 12 kinds of different chemoradiotherapy regimens in conventional treatment in all and no studies using placebo as an intervention in our study. NP (vinorebine (NVB) + cisplatin (DDP)) regimen was applied in five studies (29, 31, 36, 38, 41); GP (gemcitabine + cisplatin) regimen was applied in three studies (32, 34, 43); Seldinger regimen (Seldinger technique) was applied in two studies (28, 37); and each of the other regimens was used in individual study (Table 1).

Outcome measures

Data on complete response rate (CR) was available in 16 studies (26, 27, 29, 32–35, 38–40, 42–46), and data on quality of life and improvement rate were available in 17 studies (26–28, 31, 33–45). Adverse events were reported in most studies except three (32, 41, 45): a total of six studies compared adverse events with the incidences of grade III to IV leucopenia (27, 28, 34, 39, 43, 44); six studies(29, 37, 38, 42, 43, 46) compared adverse information with the incidences of severe myelosupperssion and nine studies (27, 30, 33–, 37, 42–44) with the incidences of gastrointestinal reactions; data on one-year survival rate was available in three studies (29, 37, 42); and immune function compared with the levels of CD3+, CD4+, CD8+ and the ratios of CD4+/CD8+ in eight studies (28–32, 34, 38, 46; Table 1).

Methodological quality

Table 1 also showed the quality of the included studies. None of individual study satisfied all the items of validity assessment, so the overall quality was not high.

All included studies mentioned “random,” or “randomized” or “randomization,” however, only four studies described methods of randomization in detail (32, 33, 39, 43). No details of allocation concealment and blinding were reported. Two studies reported the loss of follow-up (27, 29), but no intention-to-treat analysis was conducted, and no explanation was given. There was no selective outcome reporting bias in all studies. The sample size varied from 40 to 160 patients. A total of six studies (29, 33, 36, 39–41) did not compare the baseline conditions between two groups, so some other source of bias may be presented.

Complete response

Data on complete response (CR) was available in 16 studies (26, 27, 29, 31–35, 38–45), which evaluated short-term effects. They were divided into 10 subgroups according to the different chemoradiotherapy regimens, and there was no statistical heterogeneity in all the studies on CR (P = 0.88; I2= 0%). Results of fixed-effect model meta-analysis showed that there was no significant difference on CR between the two groups (RR = 1.42; 95% CI 1.05 to 1.92; P = 0.02; Fig. 2).

image

Figure 2. Forest plot of complete response (CR).

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Quality of life improvement rate

Quality of life improvement rate (KPS scale) was also evaluated as a primary outcome in 17 studies (26–28, 32–45). There was no significant heterogeneity between the two groups in all studies (P = 0.05; I2= 40%). Figure 3 showed that quality of life improvement rate in the IBJOE group was higher than the control group (RR = 1.83; 95% CI 1.63 to 2.07; P < 0.00001). Similarly, two studies (29, 46) evaluated the improvement in quality of life with SF-36 scale and the results showed that the IBJOE group had a better quality of life than the control group (MD = 79.46; 95% CI 45.97 to 112.95; P < 0.00001; Table 2).

image

Figure 3. Forest plot of quality of life improvement (KPS).

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Table 2.  Meta-analysis of outcomes
Outcome measureRR95% CIP valueTotal no. of RCTsTotal no. of participants
  1. RCTs, randomized controlled trials; KPS, Karnofsky Performance Status; SF-36, short form 36; aMDs, mean differences; No, number; RR, relative risks; CI, confidence intervals.

  2. Some patients may experience phlebitis, muscular soreness, low-grade fever or occasional skin rashes, but no data was appeared in the original studies (30, 39). In addition, there was no significant in hepatic, renal, or heart dysfunction reported between the two groups (27, 34).

Quality of life (SF-36 scale)79.46a45.97 to 112.95a0.000012191
Grade III to IV leucopenia0.480.23 to 0.990.056413
Gastrointestinal reactions0.670.55 to 0.820.00019661
Severe myelosuppression0.50.26, 1.000.186596
One-year survival rate1.971.27 to 3.060.0033364
Level of CD+38.64a6.26 to 11.02a0.000018621
Level of CD+48.1a5.80 to 10.39a0.000018621
Level of CD8+0.81a–2.86 to 4.48a0.668621
Other outcomes

In general, the IBJOE group had better immune function than the control group in terms of levels of CD3+ and CD4+, one-year survival rate and reduction of incidences of grade III-IV leucopenia and gastrointestinal reaction except for incidences of severe bone marrow suppression and level of CD8+ (Table 2).

Publication bias

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

There were 17 out of 21 studies (26–28, 31, 33–45) used quality of life improvement evaluated effectiveness, so a total of 17 data were plotted a funnel using STATA 10.0 software and Egger's test (P = 0.005) to evaluate publication bias (Fig. 4).

image

Figure 4. Funnel plot, based on the studies with data on quality of life improvement (KPS).

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Discussion

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

LC remains a kind of highly lethal disease and chemoradiotherapy is effective but causes severe AEs in patients with LC. However, this systematic review utilized standardized methodology and described the potential for IBJOE plus chemoradiotherapy to improve quality of life and mitigate the toxicity for LC patients. A variety of TCM treatment may manage the short-term side effects reduced by chemotherapy with cancer patients (11), and IBJOE is such a TCM injection for patients with LC. A total of 21 trials were identified with low quality, and all studies compared IBJOE plus chemoradiotherapy with chemoradiotherapy alone.

Despite the heterogeneity of the trials, there is a consistency of conventional and TCM diagnosis and treatment principles that make it appropriate to evaluate their impact as an adjuvant therapy for patients with LC. The result of pooled analysis showed that IBJOE group had beneficial effects on several aspects including CR (RR = 1.18; 95% CI 1.05 to 1.32; P = 0.02), quality of life (for KPS scale: RR = 1.97; 95% CI 0.59 to 2.43; P < 0.00001; for SF-36 scale: MD = 79.46; 95% CI 45.97 to 112.95; P < 0.00001); one-year survival rate (RR = 1.97; 95% CI 1.27 to 3.06; P = 0.003) and levels of CD3+ (MD = 8.64; 95% CI 6.26 to 11.02; P < 0.00001) and CD4+ (MD = 8.10; 95% CI 5.80 to 10.39; P < 0.00001).

IBJOE plus chemoradiotherapy also reduced incidences of grade III to IV leucopenia (RR = 0.33; 95% CI 015 to 0.72; P = 0.05), and gastroenteric reaction (RR = 0.60; 95% CI 0.40 to 0.88; P = 0.0001). The results of quality of life were consistent using different evaluation scales (KPS and SF-36), which suggested that it was evident effect on improving the quality of life for LC patients.

The result of pooled analysis also indicated that in the IBJOE plus chemoradiotherapy group, there was no significantly improvement in the incidences of severe myelosuppression (RR = 0.50; 95% CI, 0.26 to 1.00; P = 0.05) and the level of CD8+ (MD = 0.81; 95% CI –2.86 to 4.48; P = 0.66). Although there was no significance on the level of CD8+ and the incidences of severe myelosuppression between the two groups, the pooled results of CD3+ and CD4+ favored the IBJOE combined chemoradiotherapy group, which indicated that the trial group may improve immune function to some extent. Therefore, it is possible that the sample size of single trial was too small to test validity.

All the studies identified were conducted in China, and their results were published in Chinese medical journals. None of trials had sample size determined by priority. None of them met 6 assessment items. Random sequence generation process was available in four studies (32, 33, 39, 42).

There was no selective reporting bias in the individual study. None of information of allocation concealment and blinding was reported, therefore, all of which demonstrated that there was a high risk of selective bias, detection bias and performance bias in this research and potentially affected the validity of results. Besides, publication bias cannot be fully excluded because the Egger's test result showed P value less than 0.05 (48). The chemoradiotherapy and primary tumor type were varied in 17 studies, so other source of bias may be presented. Therefore, the results of this review should be interpreted with caution.

Conclusion

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References

Despite most of individual included study being of low quality, this review raises the possibility that IBJOE plus chemoradiotherapy may have beneficial clinical and biological effects for LC patients on improving complete response rate, quality of life, immune function and decreasing incidence of some AEs. It also can significantly improve long-term survival rate and decrease the incidence of grade III-IV leucopenia for LC patients.

References

  1. Top of page
  2. Abstract
  3. Background
  4. Materials and methods
  5. Results
  6. Publication bias
  7. Discussion
  8. Conclusion
  9. References
  • 1
    Maione P, Rossi A, Sacco PC, et al. Advances in chemotherapy in advanced non-small-cell lung cancer. Expert Opinion on Pharmacotherapy 2010; 11: 29973007.
  • 2
    Tyczynski JE, Bray F, Aareleid T, et al. Lung cancer mortality patterns in selected central, eastern and southern european countries. International Journal of Cancer 2004; 109: 598610.
  • 3
    Chen SS, Flower A, Ritchie A, et al. Oral Chinese herbal medicine (CHM) as an adjuvant treatment during chemotherapy for non-small cell lung cancer: a systematic review. Lung Cancer 2010; 68: 13745.
  • 4
    Jablons DM, Cheng SJ, Carolyn Clary-Macy RN. Hirsch FR1st international lung cancer conference in Beijing, October 27-30, 2002. Lung Cancer 2003; 41: 23744.
  • 5
    Carney DN, Hansen HH. Non-small cell lung cancer–stalemate or progress? The New England Journal of Medicine 2000; 343: 126162.
  • 6
    Hoffman PC, Mauer AM, Vokes EE. Lung cancer. Lancet 2000; 355: 47985.
  • 7
    Park BJ, Louie O, Altorki N. Staging and the surgical management of lung cancer. Radiologic Clinics of North America 2000; 38: 54561.
  • 8
    Rusch VW, Giroux DJ, Kraut MJ, et al. Induction chemoradiation and surgical resection for non-small cell lung carcinomas of the superior sulcus: initial results of Southwest Oncology Group Trial 9416 (Intergroup Trial 0160). TheJournal of Thoracic and Cardiovascular Surgergy 2001; 121: 47283.
  • 9
    Weick JK, Crowley J, Natale RB, et al. A randomized trial of five cisplatin-containing treatments in patients with metastatic non-small-cell lung cancer: a Southwest Oncology Group study. Journal of Clinical Oncology 1991; 9: 115762.
  • 10
    Rajeswaran A, Trojan A, Burnand B, Giannelli M. Efficacy and side effects of cisplatin- and carboplatin-based doublet chemotherapeutic regimens versus non-platinum-based doublet chemotherapeutic regimens as first line, treatment of metastatic non-small cell lung carcinoma: a systematic review of randomized controlled trials. Lung Cancer 2008; 59: 111.
  • 11
    Zhang M, Liu X, Li J, He L, Tripathy D. Chinese medicinal herbs to treat the side-effects of chemotherapy in breast cancer patients. Cochrane Database Systematic Reviews 2007: CD004921.
  • 12
    Fan ZZ, Gu XW. Brucea javanica oil to treat cancer. Chinese Traditional Patent Medicine 1989; (6): 26.
  • 13
    Wu SC, Sun DK, Chen WH, et al. Clinical pathological study of brucea javanica oil emulsion intravenous infused pre-operation patients with lung cancer. Shanghai Medical Journal 1991; 14(5): 27173.
  • 14
    Chen DC. Practical modern herb. Beijing : People's Medical Publishing House, 2000.
  • 15
    Guo CB, Ma DQ. The antineoplastic effects of unsaturated fatty acids. Chinese Journal of Clinical Nutrition 2000; 8(2): 13335.
  • 16
    Mertin J. Essential fatty acids and cell-mediated immunity. Progress in Lipid Research 1981; 20: 8516.
  • 17
    Guo Y, Wu J, Yang H, Cao C. Clinical study on the treatment of malignant pleural effusions by intracavitary application with DDP combined with fructus brucease emulsion. Journal of Oncology 2004; 10(2): 12930.
  • 18
    Huang CL, Zhu XX. Pharmacology and clinical manual about traditional Chinese medicine. Beijing : People's Medical Publishing House, 2006: 74446.
  • 19
    Park JO, Lee SI, Song SY, et al. Measuring response in solid tumors: comparison of RECIST and WHO response criteria. Japanese Journal of Clinical Oncology 2003; 33: 53337.
  • 20
    Department of Medical Administration of Ministry of health of the People's Republic of China Guideline of normal cancer diagnosis and treatment of common tumors in China, 9th branch main measurement indexes and statistical methods in normal cancer in China. Beijing , China : Beijing medical univerisity and China Uion Medicine University Press, 1991: 1115.
  • 21
    Ware JE, Jr., Sherbourne CD. The MOS 36-item short-form health survey (SF-36). I. Conceptual framework and item selection. Medical Care 1992; 30: 47383.
  • 22
    Miller AB, Hoogstraten B, Staquet M, Winlker A. Reporting result of cancer treatment. Cancer 1981; 20714.
  • 23
    Higgins JPT, Green S. Cochrane handbook for systematic reviews of interventions version 5.0.2 (updated September 2009).
  • 24
    Li SZ. Two cases sufferred from low back pain after brucea javanica intravenous infused. Journal of Yulin Medicine 1994; 21(2): 11415.
  • 25
    Mo SX. Effects of bruceolic oil emulsion combined with chemotherapy on immune function in patients with non-small lung cancer. Chinese Journal of Integrated Traditional and Western Medicine 2010; 19(9): 109899.
  • 26
    He X. Clinical obseration of brucea javanica oil emulsion combined chemotherapy on treating non-small cell lung cancer. Heilongjiang Journal of Traditional Chinese Medicine 2004; 10(6): 89.
  • 27
    Xing HY, Xue HN, Jiang K. Brucea javanica oil emulsion combined chemotherapy for 39 patients with non-small lung cancer-chemotherapy alone for 39 patients in comparision group. Liaoning Journal of Traditional Chinese Medicine 2004; 31(2): 12930.
  • 28
    Yuan GR, Lu LQ, Xue Q, et al. Clinical study on the treatment of local advanced non-small cell lung cancer by in vein injection of fructus bruceae emulsion combined with bronchus arterial infusion chemotherapy. Chinese Journal of Modern Applied Pharmacy 2005; 22(3): 25760.
  • 29
    Du M, Shi M. Observation of chemotherapy adjuvant injection of brucea javanica oil emulsion for advanced non-small lung cancer. Journal of Basic and Clinical Oncology 2006; 19(2), 15152.
  • 30
    Wang HY, Yu GM, Cui J, Zhou WJ. Effects of bruceolic oil emulsion combined with chemotherapy on immune function in patients with advanced lung cancer. Modern Journal of Integrated Traditional Chinese and Western Medicine 2006; 15(05) 58687.
  • 31
    Chen X, Cai B. Clinical obseration of brucea javanica oil emulsion plus chemotherapy on treating non-small cell lung cancer. Journal of Clinical Internal Medicine 2007; 24(08) 55657.
  • 32
    Tian HQ, Yu SY, Wang B, Liang GW, Huang XQ. Effect of fructus bruceae oil emulsion on cellular iImmune function and quality of life in patients with non-small cell lung cancer. Chinese Journal of Integrated Traditional and Western Medicine 2007; 27(2):15759.
  • 33
    Mai ZF. Observation on the effect of Javanica oil combined with chemotherapy on middle and late non-small cell lung cancer. China Tropical Medicine 2008; 8(11): 196566.
  • 34
    Wang YX, Shu QJ. Curative effect observation of brucea javanica oil emulsion combined with GP chemotherapy on treating advanced non-small cell lung cancer. Zhejiang Journal of Integrated Traditional Chinese and Western Medicine 2007; 17(9): 53536.
  • 35
    Sun XR. Bruceolic oil emulsion combined with chemotherapy for 30 patients with advanced non-small lung caner. Journal of Traditional Chinese Medicine 2008; 49(10): 921.
  • 36
    Wu YJ. Brucea javanica oil emulsion combined chemotherapy for 32 patients advanced non-small lung cancer. Modern Journal of Integrated Traditional Chinese and Western Medicine 2008; 17(14): 218081.
  • 37
    Deng XS, Xiao CJ. Clinical research of branchial artery infusion by oleum fructus bruceae on advanced stage non-small cell lung cancer. Modern Medical Journal 2009; 3(3), 29192.
  • 38
    Dong XL, Wang YJ, Zhou J, Xu J, Li JZ. Clinical study on the treatment of non-small cell lung cancer with NP chemotherapy regimen and brucea fruitwater in oil emulsion. Journal of Xi'an Jiaotong University (Medical Sciences) 2009; 30(2):24446.
  • 39
    Fu XJ, Fu SZ, Yang GH. Clinical obseration of brucea javanica oil emulsion combined chemotherapy on treating non-small cell lung cancer. Clinical Journal of Medical Officers 2009; 37(04): 63537.
  • 40
    Ye B, Dong G, Yu XH, Xiao ZP. Pharmacodynamics study of γ-ray stereotactic radiotherapy combined brucea javanica for old patients with non-small cell lung cancer. Contermporary Medicine 2009; 15 (21): 14041.
  • 41
    Li X, Wu H. Clinical obseration of brucea javanica oil emulsion combined chemotherapy injected for non-small cell lung cancer. Journal of Clinical Pulmonary Medicine 2010; 15(2): 26667.
  • 42
    Bo ZP, Deng XS. Effect of oleum fructus brucease injection via bronchial arterial infusion in treating advanced lung cancer. Chinese Journal of Integrated Traditional and Western Medicine 2010; 30(8): 83840.
  • 43
    Chen HL, Wang WP, Lan YP, Hong LH. Clinical obseration of brucea javanica oil emulsion combined GP regimen on treating non-small cell lung cancer. Journal of Practical Oncology 2010; 25(5): 58486.
  • 44
    Cui HZ, Niu Q, Guan JZ, Wang FY, Wang Y. The clinical observation of the patients with medium-term or advanced non-small cell lung cancer treated with Brucea Javanica Oil Injection combined with chemotherapy. Sichuan Medical Journal 2010; 31(5): 59091.
  • 45
    Liu ZW. Obseration of brucea javanica oil emulsion combined chemotherapy on treating non-small cell lung cancer. Massage and Rehabilitation Medicine 2010; 1(12): 41.
  • 46
    Yao YW, Hu MW, Wang HQ. Curative effect observation of brucea javanica oil emulsion combined with DP chemotherapy on treating advanced non-small cell lung cancer. Journal of Practical Oncology 2010; 25(1): 7476.
  • 47
    Moher D, Liberati A, Tetzlaff J, Altman DG. Preferred Reporting Items for Systematic Reviews and Meta-Analyses: The PRISMA Statement. PLoS Med , 2009; 6(7): e1000097. doi:10.1371/journal.pmed.1000097.
  • 48
    Egger M, Davey Smith G, Schneider M, Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ 1997; 315: 29634.