Abstract

Background

Ganoderma lucidum is a natural medicine that is widely used and recommended by Asian physicians and naturopaths for its supporting effects on immune system. Laboratory research and a handful of preclinical trials have suggested that G. lucidum carries promising anticancer and immunomodulatory properties. The popularity of taking G. lucidum as an alternative medicine has been increasing in cancer patients. However, there is no systematic review that has been conducted to evaluate the actual benefits of G. lucidum in cancer treatment.

Objectives

To evaluate the clinical effects of G. lucidum on long‐term survival, tumour response, host immune functions and quality of life in cancer patients, as well as adverse events associated with its use.

Search methods

We searched an extensive set of databases including the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, NIH, AMED, CBM, CNKI, CMCC and VIP Information/Chinese Scientific Journals Database was searched for randomised controlled trials (RCTs) in October 2011. Other strategies used were scanning the references of articles retrieved, handsearching of the International Journal of Medicinal Mushrooms and contact with herbal medicine experts and manufacturers of G. lucidum. For this update we updated the searches in February 2016.

Selection criteria

To be eligible for being included in this review, studies had to be RCTs comparing the efficacy of G. lucidum medications to active or placebo control in patients with cancer that had been diagnosed by pathology. All types and stages of cancer were eligible for inclusion. Trials were not restricted on the basis of language.

Data collection and analysis

Five RCTs met the inclusion criteria and were included in this review. Two independent review authors assessed the methodological quality of individual trials. Common primary outcomes were tumour response evaluated according to the World Health Organization (WHO) criteria, immune function parameters such as natural killer (NK)‐cell activity and T‐lymphocyte co‐receptor subsets, and quality of life measured by the Karnofsky scale score. No trial had recorded long‐term survival rates. Associated adverse events were reported in one study. A meta‐analysis was performed to pool available data from the primary trials. Results were gauged using relative risks (RR) and standard mean differences (SMD) for dichotomous and continuous data respectively, with a 95% confidence interval (CI).

Main results

The methodological quality of primary studies was generally unsatisfying and the results were reported inadequately in many aspects. Additional information was not available from primary trialists. The meta‐analysis results showed that patients who had been given G. lucidum alongside with chemo/radiotherapy were more likely to respond positively compared to chemo/radiotherapy alone (RR 1.50; 95% CI 0.90 to 2.51, P = 0.02). G. lucidum treatment alone did not demonstrate the same regression rate as that seen in combined therapy. The results for host immune function indicators suggested that G. lucidum simultaneously increases the percentage of CD3, CD4 and CD8 by 3.91% (95% CI 1.92% to 5.90%, P < 0.01), 3.05% (95% CI 1.00% to 5.11%, P < 0.01) and 2.02% (95% CI 0.21% to 3.84%, P = 0.03), respectively. In addition, leukocyte, NK‐cell activity and CD4/CD8 ratio were marginally elevated. Four studies showed that patients in the G. lucidum group had relatively improved quality of life in comparison to controls. One study recorded minimal side effects, including nausea and insomnia. No significant haematological or hepatological toxicity was reported.

Authors' conclusions

Our review did not find sufficient evidence to justify the use of G. lucidum as a first‐line treatment for cancer. It remains uncertain whether G. lucidum helps prolong long‐term cancer survival. However, G. lucidum could be administered as an alternative adjunct to conventional treatment in consideration of its potential of enhancing tumour response and stimulating host immunity. G. lucidum was generally well tolerated by most participants with only a scattered number of minor adverse events. No major toxicity was observed across the studies. Although there were few reports of harmful effect of G. lucidum, the use of its extract should be judicious, especially after thorough consideration of cost‐benefit and patient preference. Future studies should put emphasis on the improvement in methodological quality and further clinical research on the effect of G. lucidum on cancer long‐term survival are needed. An update to this review will be performed every two years.

Author(s)

Xingzhong Jin, Julieta Ruiz Beguerie, Daniel Man‐yuen Sze, Godfrey CF Chan

Abstract

Plain language summary

G. lucidum (Reishi mushroom) for cancer treatment

There have been an increasing number of patients diagnosed with cancer each year. Certain malignancies have been a major cause of death in some populations. People who have been diagnosed with cancer want to do everything they can to combat the disease, manage its symptoms and cope with the side effects of radio/chemotherapy. Many turn to complementary and alternative medicine. G. lucidum extract is a medication that has been widely used by traditional Chinese medicine (TCM) practitioners for this regard. It is usually recommended as an immune system support supplement in cancer treatment. Latest laboratory research and preclinical trials of G. lucidum have shown promising results of its antitumour activity. However, clinical evidence of its efficacy is sparse and a systematic review is in need to provide collective information for health‐care consumers.

Our review identified and subsequently included five relevant randomised controlled trials. A total of 373 subjects were analysed. A meta‐analysis was performed to pool available data from individual trials. Our results found that patients with G. lucidum extract in their anticancer regimen were 1.27 times more likely to respond to chemotherapy or radiotherapy than those without. However, the data failed to demonstrate significant effect on tumour shrinkage when it was used alone. In addition, G. lucidum could stimulate host immune functions by considerably increasing CD3, CD4 and CD8 lymphocyte percentages. Nevertheless, natural killer (NK)‐cell activity, which has been suggested to be an indicator of self‐defence against tumour cell, was marginally elevated. Patients in the G. lucidum group were found to have a relatively better quality of life after treatment than those in the control group. A few cases of minor side effect associated with G. lucidum treatment including nausea and insomnia were reported.

There are limitations of the results from this systematic review. First, most included studies were small and there were concerns on the methodological quality of individual trials. Second, all participants in the individual trials were recruited from the Chinese population. Together, the robustness and applicability of the results were largely affected.

Author(s)

Xingzhong Jin, Julieta Ruiz Beguerie, Daniel Man‐yuen Sze, Godfrey CF Chan

Reviewer's Conclusions

Authors' conclusions 

Implications for practice 

The five studies included in this review do not provide clear and unbiased evidence to support the first‐line use of G. lucidum in treatment for cancer patients. There is lack of evidence to support the point that the use of G. lucidum in advanced cancer therapy improves long‐term survival. We do not recommend administration of G. lucidum preparations as a single treatment to patients with advanced cancer. However, the results of this review suggest that a better response may be expected when a G. lucidum preparation is incorporated as an adjuvant in conventional chemo/radiotherapy regimens. Regimens that incorporate G. lucidum are 1.25 times more likely to yield a better tumour response than those do not. Also, G. lucidum preparations can be administered in order to counter the immunosuppressive effect of chemo/radiotherapy, especially in terms of T‐lymphocyte depletion. Similar to other natural remedies, G. lucidum is well‐tolerated by cancer patients leading to better QoL and a relatively improved Karnofsky score. No severe toxicity has been observed according to current evidence. In short, current evidence does not support routine use of G. lucidum in all cancer patients. The decision of whether to use a G. lucidum preparation in an anticancer regimen should be made after careful consideration of cost‐benefit potential and patients' preferences. Given the results of this review and from a cultural perspective, it could beneficial to add G. lucidum to the regimen for patients who have a Chinese background.

Implications for research 

Currently, the evidence of using G. lucidum for cancer is sparse and the methodological quality of the trials is poor. As a result, we have only been able to draw a few definite conclusions from the evidence. The lack of standardisation in several aspects among included trials, for example uniformed preparation and administration of G. lucidum, and failure to include key information in the published reports, have jeopardised the reliability and validity of the original trials. Future studies should make efforts to address the following issues of trial design and reporting:

• Full details of the enrolment sequence generation and subsequent strategy for allocation concealment should be included in the published reports.
• True randomisation (e.g. shuffling envelopes or computer random numbers) should be adopted instead of simple or pseudo‐randomisation (e.g. hospital record number).
• Clinicians, patients and assessors should be blinded (e.g. use of a placebo) to prevent conscious or subconscious bias that may subsequently invalidate the results.
• An intention‐to‐treat (ITT) analysis should be applied to all future trials to avoid bias and false‐positive results. Complete information and reasons for participants who are enrolled and allocated to treatment groups but drop out of the assigned groups, should be provided.
• Standardisation of methods of data presentation and data analysis. Reporting of results should be improved according to standard guidelines (CONSORT 2010).

In this review, we have been able to clarify the beneficial effect from G. lucidum on tumour response, immune functions and QoL assessment. The findings are relatively general and vague. Future clinical trials should explore the clinical potential of G. lucidum in the following aspects:

• The effect of G. lucidum on one particular type of cancer should be further explored so as to differentiate the effectiveness of G. lucidum across different types of malignancy.
• The staging of cancer should be standardised and well documented in future trials so that the responsiveness of different stages of cancer to G. lucidum treatment can be compared in future reviews.
• Long‐term survival is an important end‐point assessment and should be investigated in any clinical trials of patients with cancer. It is of utmost importance to decide the clinical usefulness of an agent in cancer treatment.
• Data from demographic groups other than the Chinese population are needed to explore the clinical applicability of G. lucidum in the future.

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