Herbal Medicine

STUDY PURPOSE: To summarize the results from randomized, controlled trials (RCTs) of the effectiveness of Chinese herbal medicines (CHMs) for managing fatigue, paresthesias, chronic pain, anorexia, edema, and constipation

TYPE OF STUDY: Meta-analysis and systematic review

• FINAL NUMBER STUDIES INCLUDED = 14 
• TOTAL PATIENTS INCLUDED IN REVIEW = 878
• SAMPLE RANGE ACROSS STUDIES: 35–124 patients
• KEY SAMPLE CHARACTERISTICS: Various cancer sites

PHASE OF CARE: Multiple phases of care
 
APPLICATIONS: Elder care, palliative care

• Fatigue—four RCTs. In three RCTs, no difference existed between CHM and chemotherapy versus chemotherapy alone. In the other RCT, Fu Zheng decoction plus chemotherapy (ellence [epirubicin]/paclitaxel [taxol]) improved fatigue score compared to chemotherapy alone in breast cancer (MD: –18.62, 95% CI [–24.18, –13.16]).
• Pain—three RCTs. CHM plus conventional treatment decreased the pain score compared to conventional treatment alone (WMD: –0.9, 95% CI [–1.69, –0.11]).
• Constipation—seven RCTs. In six RCTs, CHM compared to conventional treatment had a similar effect. In the other RCT, Tong-Tai decoction plus chemotherapy compared to chemotherapy alone showed no difference.
• Anorexia—two RCTs. No difference existed with CHM plus conventional treatment.

Combining CHM with chemotherapy may improve fatigue in patients with breast cancer. Adding CHM to conventional treatment may improve pain control. CHM alone may improve constipation.

• Mostly low quality/high risk of bias studies
• High heterogeneity
• Trials conducted and published in China

Further research needs to be performed on CHM treating cancer- and cancer treatment-related symptoms.

PHASE OF CARE: Active antitumor treatment
 
APPLICATIONS: Palliative care

CHM used alone or in combination with chemotherapy or supportive care showed significant relief in CRF compared to placebo, chemotherapy, and supportive care based on single trials. CHM plus chemotherapy or supportive care was superior to chemotherapy or supportive care in improving quality of life. Data from one trial demonstrated that CHM exerted a greater beneficial effect on relieving anxiety but no difference in alleviating depression. Seven trials reported adverse events, and no severe adverse effects were found in CHM groups.

The work suggests that CHM may be effective and safe in the treatment of CRF. However, the current evidence is insufficient to draw a confirmatory conclusion due to the poor methodological quality of included trials.

Quality of methods:

• Lack of information about randomization
• No blinding of participants or providers
• Few adequate allocation concealment
• Short-term interventions (approximately four weeks)

It is necessary to conduct rigorously designed trials on potential CHM.

To review the evidence regarding the effects of Chinese herbal medicine on side effects of chemotherapy in women with breast cancer.

Databases searched were Cochrane Library, EMBASE, LILACS, SIGLE, and Chinese Biomedical Disk. Handsearching of key medical journals and references lists of retrieved articles was also performed.

Search keywords were Chinese medicine, plants, drugs, botanical, herbal medicine, and additional search terms related to herbal medicine as well as breast cancer treatments. A full listing of search terms was provided.

Studies were included if they included

• Women with breast cancer receiving chemotherapy as adjuvant or palliative treatment. 
• Single and compound herbal treatments. 
• Randomized clinical trials with chemotherapy-induced side effects.

Patients were excluded if they had other cancers as well as breast cancer (except for skin cancer).

In total, 88 references were retrieved. The authors allocated trials to quality categories described in the Cochrane Reviewers' Handbook and assessed quality according to criteria from Schultz (1995); studies were categorized as having a low, moderate, or high risk of bias.

• The final number of studies included was seven.  
• The sample range across studies was 48 to 120 patients (N = 541).
• All patients had breast cancer and were receiving chemotherapy. 
• All studies were performed on Chinese patients in a mix of settings.

Patients were undergoing multiple phases of care.

Trial duration ranged from 14 to 84 days. Treatments were varied with different herbal concoctions; most included radix ginseng along with other substances. The authors did not provide the findings for all outcomes of interest. A few studies measured quality of life, and several attempted to evaluate the effect on thrombocytopenia and white blood cell volumes and types. Some studies used inappropriate statistical methods. The quality of the included trials was poor.

The nature of the evidence in use of Chinese herbal medicine was not sufficient to draw any conclusions.

The study included a small number of studies with relatively small samples and poor quality.

The evidence reviewed did not provide clear implications for the incorporation of findings into practice. Further well-designed research is needed.

To evaluate whether Bojungikki-tang has beneficial effects on fatigue and overall quality of life in patients with cancer.

Patients were randomized to the experimental group or the wait-list control group. The experimental group received Bojungikki-tang for two weeks. Bojungikki-tang was administered as granules containing a mixture of 10 medicinal plants given three times daily. Patients were randomized through computer generation. Patients were recruited through newspaper and hospital advertisements.

• The final sample included 36 patients (37.5% male).
• Mean age was 52.6 years. 
• Diagnoses included breast cancer (27.5%), stomach cancer (12.5%), lung cancer (12.5%), colon cancer (12.5%), and other (35%).

Unknown

The study was a randomized, controlled trial.

• Evaluation forms included the Visual Analogue Scale of Global Fatigue, which was used as the primary outcome variable.
• The secondary outcome was measured using the Functional Assessment of Cancer Therapy–General (FACT-G), the FACT-Fatigue (FACT-F), and the Trial Outcome Index–Fatigue (TOI-F).

The experimental group had statistically significant improvements in VAS-F scores, as well as FACT-G, FACT-F, and TOI-F (p < 0.05) at week 2.

The study had a possible effect from the study drug, although p-values were on the edge of significance. The benefit shown suggests additional study is required in a larger, placebo-controlled trial.

• The study had no placebo in place, and the treatment time was short.
• The plant mixture was not controlled for variability.
• One patient experienced an increase in BUN and creatinine above the reference ranges, and other adverse effects were reported (flatulence and dyspepsia); therefore, the potential for harm needs to be considered and the risks weighed versus potential benefits if additional study is to be performed with a larger population.
• Exclusion criteria for patients needs to be more rigorous and include consideration of antihypertensive medication and other drug interactions and baseline renal function.

Patients pursuing this treatment should be educated on the current need for additional research.

To observe functional and symptomatic changes related to quality of life in patients with advanced gastric cancer with administration of Jinlongshe granule (JLSG, a Chinese herbal medicine)

Patients were randomized into a JLSG group or a placebo group. All patients received Chinese medicinal herbs prescribed individually. The intervention arm additionally received JLSG, and the other arm received a placebo three times daily. Patients were followed biweekly in clinic visits. Study measures were obtained at enrollment and at 3, 6, 9, 12, and 15 months after treatment.

• N = 39  
• AGE: Mean and range not determinable
• MALES: 66.7%, FEMALES: 33.3%
• KEY DISEASE CHARACTERISTICS: All patients had advanced gastric cancer and most had liver metastasis.
• OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criteria included expected three-month survival.

• SITE: Single-site    
• SETTING TYPE: Outpatient    
• LOCATION: China

• PHASE OF CARE: End-of-life care
• APPLICATIONS: Palliative care 

Double-blind, placebo-controlled, randomized clinical trial

• European Organization for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire (QLQ–C30)

There were statistically significant group-by-time effects for multiple symptoms including cognitive function, fatigue, pain, dyspnea, insomnia, appetite loss, constipation, and and general quality of life (p < .05). For some symptoms, differences were due to increased symptoms in the placebo group. No information regarding any adverse effects is reported. The direction of change in symptom scores is not always clear in this manuscript.

This study has several limitations that make it difficult to assess the potential efficacy of JLSG for symptom management.

• Small sample (< 100)
• Unintended interventions or applicable interventions not described that would influence results
• Measurement validity/reliability questionable
• Findings not generalizable
• Subject withdrawals ≥ 10%  
• Other limitations/explanation: All patients received a variety of Chinese herbal medications that were not described and were not standardized; therefore, it is not possible to determine the actual effect of the JLSG. No other interventions aimed at symptoms are described. Repeated measures of the same instrument may produce testing effect.

This study provides minimal evidence in support of a specific Chinese herbal medicine in patients with advanced gastric cancer. Further well-designed studies are needed for clinically meaningful evaluation of efficacy.

To establish the safety and efficacy of traditional Chinese herbal medicine for the treatment of fatigue in patients with cancer who do not have anemia

Patients were recruited from those who visited a herbal medicine clinic. Patients were given a combination of 12 herbs, which they slowly cooked in 150 ml of water. This decoction was taken twice daily for six weeks. Study measures were obtained at baseline and after six weeks. Patients were evaluated by a traditional Chinese medicine doctor at the beginning and end of the study.

• N = 33
• MEDIAN AGE = 60 years (range = 41–81 years)
• MALES: 42%, FEMALES: 58%
• KEY DISEASE CHARACTERISTICS: Varied tumor types; off treatment for at least one month
• OTHER KEY SAMPLE CHARACTERISTICS: All had moderate to severe fatigue defined as a score of at least 4 on a 0–10 point scale; hemoglobin of at least 10 g/dl

• SITE: Single site  
• SETTING TYPE: Outpatient  
• LOCATION: China

• PHASE OF CARE: Transition phase after active treatment

Open-label phase I–II

• Single fatigue item scale from the Chinese version of the MD Anderson Symptom Inventory (MDASI)

Fatigue levels declined during the study (p = 0.024), and 64% of patients said they felt better within two weeks, and 33% felt better after three weeks. No adverse events were reported.

The findings of this study suggest that that a traditional Chinese herbal medicine formulation appears to be safe and may be helpful in the treatment of depression among patients with cancer.

• Small sample (< 100)
• Risk of bias (no control group)
• Risk of bias (no blinding)
• Risk of bias (no random assignment) 
• Other limitations/explanation: The approach described for the evaluation of potential side effects was according to traditional Chinese medicine practice, and its general validity is not clear.

This study was limited by design and sample size, so no firm conclusions about the safety and efficacy of traditional Chinese herbal medicine can be made.

To evaluate whether spore powder of Ganoderma lucidum (G. lucidum) has beneficial effects on fatigue and overall quality of life in patients with breast cancer undergoing endocrine therapy.

Patients in the experimental group received spore powder of G. lucidum 1,000 mg three times a day for four weeks (from Beijing Great Wall Pharmaceutical Factory, batch # B20050008). This is a traditional Chinese medicine that contains polysaccharides, alkaloids, enzymes, and proteins. The control group received placebo for four weeks. Outcomes were evaluated at baseline and the end of four weeks. 

• The total sample was comprised of 48 women, with 25 patients in the experiemental group and 23 in the control group.  
• Median age was 51.3 years (standard deviation [SD] = 9.8) in the experiemental group and 53.2 years (SD = 8.7) in the control group (p > 0.1).
• Patients were stage I to IIIA. 
• Multimodal treatment included surgery, radiation and/or chemotherapy, and endocrine therapy for all patients. 
• Duration of endocrine therapy varied from more than six months to up to five years. 
• No statistically significant differences existed between the groups.
• Patients received endocrine therapy for breast cancer.
   

The study was conducted at the Third Affiliated Hospital of Harbin Medical University in Harbin, China, from June 2009 to September 2010.

• Patients were undergoing the active treatment phase of care.
• The study has clinical applicability for patients undergoing endocrine therapy.
   

The study was a randomized, placebo-controlled trial.

• Functional Assessment of Cancer Therapy–Fatigue (FACT-F)
• Hospital Anxiety and Depression Scale (HADS)
• European Organisation for Research and Treatment of Cancer Core Quality of Life Questionnaire C30 (EORTC QLQ-C30)
• Biological Markers of Fatigue:  tumor necrosis factor (TNF) and interleukin-6 (IL-6)
• Safety and toxicity tests, such as a renal function test, liver function test, and the Common Toxicity Criteria version 2.0 scale
• Fatigue was measured with a single-item numeric rating scale with possible values from 0 (a great deal of fatigue) to 10 (no fatigue).
• Energy was measured with a single item, “How much energy have you had during the past 4 weeks?,” with possible values from 0 (no energy at all) to 10 (a great deal of energy).
   

No serious adverse effects occurred. No significant changes occurred in the renal and liver function tests. Fatigue scores were improved in the experimental group at four weeks (p < 0.01), but no significant improvement occurred in the control group. At four weeks, anxiety and depression scores had improved significantly from baseline in the experimental group. No significant improvement occurred over time in the control group.

The pilot suggested that spore powder G. lucidum may have beneficial effects on cancer-related fatigue and quality of life in patients with breast cancer undergoing endocrine therapy with no significant safety concerns.

• The study had a small sample size, with less than 100 patients.
• Nonspecific aspects of the intervention (social support) may influence the study. 
• Patients were healthy (e.g., no other comorbid conditions).
• No blinding was performed.
   

Additional research should be conducted in a larger randomized, controlled trial.