This paper is part of NMJ's 2017 Oncology Special Issue. Read the paper or download the full issue here.
Reference
Chay WY, Tham CK, Toh HC, et al. Coriolus versicolor (Yunzhi) use as therapy in advanced hepatocellular carcinoma patients with poor liver function or who are unfit for standard therapy. J Altern Complement Med. 2017;23(8):648-652.
Objective
To evaluate the impact of Coriolus versicolor (CV) on disease progression, survival, quality of life, and blood markers in individuals with advanced hepatocellular carcinoma.
Design
Randomized controlled trial
Participants
Fifteen individuals (14 men, 1 woman) of Asian ethnicity aged 48 to 74 with advanced hepatocellular carcinoma (HCC) were randomized 2:1 to receive CV (n=9) or placebo (n=6). Participants were eligible if they had inoperable HCC and liver cirrhosis (Child-Pugh class C) or HCC with liver cirrhosis (Child-Pugh class A or B) and had failed or were unfit for standard chemotherapy or radiotherapy.
Study Parameters Assessed
Median time to progression (TTP), response rates, toxicity, quality of life (QoL), progression-free survival (PFS), overall survival (OS), correlative analysis of blood markers
Primary Outcome Measures
Median TTP, PFS, and OS, and QoL; TTP, PFS, and OS were analyzed by Kaplan-Meier, and hazard ratio (HR) was determined by Cox regression analysis.
QoL was measured using the Functional Assessment of Cancer Treatment questionnaire for individuals with hepatobiliary cancer (FACT-Hep) and the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ-C30).
Intervention
Oral administration of 2.4 g CV daily until disease progression or unacceptable toxicity
Key Findings
Median treatment duration was 12.1 weeks for CV group and 5.9 weeks for placebo group. Seventy percent of participants terminated treatment due to progressive disease or death, and no difference in treatment tolerability between groups was found.
Disease-related outcomes
There were no statistically significant differences in median TTP, PFS, or OS when treatment was compared to placebo:
- Median TTP (months): 2.5 (95% confidence interval [CI]: 1.4-5.3) vs 4.2 (95% CI: 0.4-4.2), with an HR of 0.7 (95% CI: 0.16-3.05, P=0.63).
- Median PFS (months): 2.5 (95% CI: 1.4-5.3) vs 1.1 (95% CI: 0.4-4.2), with an HR of 0.42 (95% CI: 0.13-1.34, P=0.144)
- Median OS (months): 6.5 (95% CI: 3.3-24.1) vs 2.2 (95% CI: 0.8-23.3) with an HR of 0.35 (95% CI: 0.10-1.25, P=0.105)
- Overall response rates: 11.1% (95% CI: 0.3-48.2) vs 16.7% (95% CI: 0.4-64.1%)
Quality of life
On the EORTC QLQ-30, the CV group reported significantly lower pain and appetite loss scores compared to placebo, differences of −38.6 (95% CI: −65.5 to −11.8), and −39.7 (95% CI: −64.5 to −15.0), respectively.
No other scores on the EORTC or FACT-Hep were statistically significantly different.
Blood analyses
Interleukin (IL)-17F and monocyte chemoattractant protein (MCP)-1 were reduced, and prolactin and tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) R1 levels were increased in the CV group compared to placebo at the end of treatment. However, no statistical comparisons were reported.
Alpha-fetoprotein (AFP) levels were not different between groups.
Practice Implications
Hepatocellular carcinoma (HCC) accounts for more than 80% of primary liver tumors. Worldwide, liver cancer is the sixth most common malignancy and second largest cause of cancer-related mortality.1 Although the incidence of HCC is highest in Asia and Africa, rates in North America and Europe have risen in the past 3 decades.1 Over 50% of patients are considered advanced at time of diagnosis,2 and in the United States the 5-year relative survival of liver cancer is only 17%.3 In addition to survival, QoL is an important consideration for individuals with HCC as sleep disturbances, depression, fatigue, malnutrition, anorexia, and pain are commonly reported symptoms.3 Given the high mortality rate associated with HCC and poor quality of life, research into adjunctive treatments is warranted.
The study did provide evidence that CV may improve appetite and pain scores, and this should be further evaluated in a larger population.
Mushroom extracts including Coriolus versicolor are commonly used in integrative oncology as adjuncts to conventional treatment.4 Coriolus versicolor (also known as Turkey tail, Trametes versicolor, and Yun-Zhi) contains polysaccharides, specifically polysaccharopeptide Krestin (PSK) and polysaccharopeptide (PSP), which are largely responsible for its medicinal benefit.5 As a source of fungal polysaccharides, supplemental Coriolus versicolor extracts are used primarily for their immunomodulating properties.6 Coriolus versicolor is most commonly administered as an extract standardized to PSK and has been studied for effect in various cancers including lung, gastric, breast, and colorectal cancers, showing benefit for various outcomes including OS, immune function, performance status, and tumor-related symptoms.6,7
This current paper is the first to evaluate the impact of Coriolus versicolor on individuals with advanced HCC. However, little conclusive information can be gathered from this paper due to its small sample size and overall lack of statistically significant findings. The study did provide evidence that CV may improve appetite and pain scores, and this should be further evaluated in a larger population. The paper generates hypotheses for future research given the non-statistically significant improvements in OS, PFS, and QoL outcomes. A larger trial that is adequately powered to detect clinically meaningful changes is warranted.
Given the evidence supporting Coriolus versicolor in other cancer types and the demonstrated safety profile of this mushroom, it is not unreasonable for clinicians to consider it for patients with HCC. However, there is another mushroom extract that has demonstrated superior results specifically for HCC.
Active hexose correlated compound (AHCC) is a mushroom extract from the Basidiomycota division of fungi that has been studied in HCC with promising results. A prospective cohort study in 269 patients evaluated time to disease recurrence and OS in individuals with advanced HCC post-liver resection. One-hundred and thirteen patients received 3 g AHCC each day; compared to controls, the AHCC group had longer recurrence-free survival (HR: 0.639, P=0.0277), and improved OS (HR: 0.42, P=0.0009).8
A second, smaller prospective cohort study gave 6 g of AHCC daily to 34 patients with unresectable advanced HCC receiving supportive care only, and compared them to 10 placebo controls.9 Median survival was 3.5 months in the AHCC group vs 1.5 months in the control group (P=0.000). Furthermore, albumin and lymphocyte counts were statistically significantly improved in the AHCC group compared to controls.
Given current evidence, AHCC is likely the better mushroom extract to consider for individuals with HCC. The present paper on Coriolus versicolor is hypothesis-generating, and larger trials are warranted to determine if Coriolus may improve QoL and survival in individuals with HCC.
Limitations
The biggest limitation of the study is its small sample size; the study was not sufficiently powered to detect significant changes between groups.
Baseline characteristics were different between CV and placebo arms; however, statistical comparisons were not presented, so the significance is unclear. The treatment arm had greater numbers of participants with prior liver resection, chemotherapy, and radiotherapy. This may impact the differences observed between study arms.
Finally, the methodology of the paper was incomplete in some areas, making it difficult to recreate the study and jeopardizing the external and internal validity of the results. For example, trial setting and selection of patients was not well described, details of the treatment, including standardization and extraction method, were not mentioned, and there was no description of the placebo or blinding, which could introduce bias.
