Jin Xingzhong, Ruiz Beguerie Julieta, Sze Daniel Man-Yeun, Chan Godfrey C F
School of Public Health, University of Sydney, Sydney, Australia.
Cochrane Database Syst Rev. 2012 Jun 13(6):CD007731. doi: 10.1002/14651858.CD007731.pub2.
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.
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.
The authors ran 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.
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.
Five RCTs met the inclusion criteria and were included in this review. Two independent review authors were assigned to assess 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).
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.
灵芝是一种天然药物,因其对免疫系统的支持作用而被亚洲医生和自然疗法医生广泛使用和推荐。实验室研究和一些临床前试验表明,灵芝具有潜在的抗癌和免疫调节特性。在癌症患者中,将灵芝作为替代药物的使用越来越普遍。然而,尚未进行系统评价来评估灵芝在癌症治疗中的实际益处。
评估灵芝对癌症患者长期生存、肿瘤反应、宿主免疫功能和生活质量的临床效果,以及与其使用相关的不良事件。
作者在2011年10月检索了大量数据库,包括Cochrane对照试验中央登记库(CENTRAL)、MEDLINE、EMBASE、NIH、AMED、CBM、CNKI、CMCC和维普资讯/中文科技期刊数据库,以查找随机对照试验(RCT)。使用的其他策略包括扫描检索到的文章的参考文献、手工检索《国际药用蘑菇杂志》以及与草药专家和灵芝制造商联系。
为符合纳入本评价的条件,研究必须是将灵芝药物与活性对照或安慰剂对照在经病理诊断的癌症患者中的疗效进行比较的RCT。所有类型和阶段的癌症均符合纳入条件。试验不受语言限制。
五项RCT符合纳入标准并被纳入本评价。两名独立的评价作者被分配评估各个试验的方法学质量。常见的主要结局包括根据世界卫生组织(WHO)标准评估的肿瘤反应、免疫功能参数如自然杀伤(NK)细胞活性和T淋巴细胞共受体亚群,以及用卡诺夫斯基量表评分衡量的生活质量。没有试验记录长期生存率。一项研究报告了相关不良事件。进行了荟萃分析以汇总来自主要试验的可用数据。分别使用相对风险(RR)和标准化均数差(SMD)对二分法和连续数据进行结果评估,并给出95%置信区间(CI)。
主要研究的方法学质量总体上不令人满意,结果在许多方面报告不充分。主要试验研究者未提供额外信息。荟萃分析结果显示,与单纯化疗/放疗相比,同时接受灵芝与化疗/放疗的患者更有可能产生积极反应(RR 1.50;95% CI 0.90至2.51,P = 0.02)。单独使用灵芝治疗未显示出与联合治疗相同的缓解率。宿主免疫功能指标的结果表明,灵芝同时使CD3、CD4和CD8的百分比分别增加3.91%(95% CI 1.92%至5.90%,P < 0.01)、3.05%(95% CI 1.00%至5.11%,P < 0.01)和2.02%(95% CI 0.21%至3.84%,P = 0.03)。此外,白细胞、NK细胞活性和CD4/CD8比值略有升高。四项研究表明,与对照组相比,灵芝组患者生活质量相对改善。一项研究记录了轻微的副作用,包括恶心和失眠。未报告明显的血液学或肝脏毒性。
我们的评价未发现充分证据证明将灵芝作为癌症一线治疗的合理性。灵芝是否有助于延长癌症患者的长期生存仍不确定。然而,考虑到灵芝增强肿瘤反应和刺激宿主免疫的潜力,可将其作为传统治疗的替代辅助药物使用。大多数参与者对灵芝的耐受性普遍良好,仅有少数轻微不良事件。各项研究均未观察到重大毒性。尽管关于灵芝有害影响的报道很少,但使用其提取物应谨慎,尤其是在充分考虑成本效益和患者偏好之后。未来的研究应注重方法学质量的提高,并且需要进一步开展关于灵芝对癌症长期生存影响的临床研究。本评价将每两年更新一次。