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This paper is part ofNMJ's Oncology Special Edition 2017. Read the newspaper or download the full edition here.
Relation
Chay WY, Tham CK, Toh HC, et al. Use of Coriolus versicolor (Yunzhi) as therapy in patients with advanced hepatocellular carcinoma with poor liver function or who are not suitable for standard therapy.J Aging Complement Med. 2017;23(8):648-652.
Objective
To evaluate the impact ofCoriolus versicolor(CV) on disease progression, survival, quality of life and blood markers in people with advanced hepatocellular carcinoma.
Draft
Randomized controlled trial
Participant
Fifteen individuals (14 men, 1 woman) of Asian descent aged 48 to 74 years with advanced hepatocellular carcinoma (HCC) were randomized in a 2:1 ratio to receive CV (n=9) or placebo (n=6). Participants were eligible if they had unresectable HCC and liver cirrhosis (Child-Pugh class C) or HCC with liver cirrhosis (Child-Pugh class A or B) and had failed or were ineligible 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
Mean TTP, PFS and OS and QoL; TTP, PFS and OS were analyzed by Kaplan-Meier and the hazard ratio (HR) was determined by Cox regression analysis.
Quality of life was measured using the Functional Assessment of Cancer Treatment questionnaire for people 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 insights
The median treatment duration was 12.1 weeks for the CV group and 5.9 weeks for the placebo group. Seventy percent of participants discontinued treatment because of progressive disease or death, and no difference in treatment tolerability was found between groups.
Disease-related outcomes
There were no statistically significant differences in median TTP, PFS or OS when treatment was compared to placebo:
- Mittlere TTP (Monate): 2,5 (95 % Konfidenzintervall [CI]: 1,4–5,3) vs. 4,2 (95 % KI: 0,4–4,2), mit einer HR von 0,7 (95 % KI: 0,16–3,05, P=0,63).
- Medianes PFS (Monate): 2,5 (95 % KI: 1,4–5,3) vs. 1,1 (95 % KI: 0,4–4,2), mit einer HR von 0,42 (95 % KI: 0,13–1,34), P=0,144)
- Medianes OS (Monate): 6,5 (95 % KI: 3,3–24,1) vs. 2,2 (95 % KI: 0,8–23,3) mit einer HR von 0,35 (95 % KI: 0,10–1,25), P=0,105)
- Gesamtansprechraten: 11,1 % (95 % KI: 0,3–48,2) vs. 16,7 % (95 % KI: 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), or
No other values on the EORTC or FACT-Hep were statistically significantly different.
Blood analysis
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. Liver cancer is the sixth most common malignancy and the second most common cause of cancer-related death worldwide.1Although the incidence of HCC is highest in Asia and Africa, rates in North America and Europe have increased over the past three decades.1Over 50% of patients are considered advanced at the time of diagnosis,2and in the United States, 5-year relative survival for liver cancer is only 17%.3In addition to survival, quality of life is an important aspect for individuals with HCC, as sleep disturbances, depression, fatigue, malnutrition, anorexia, and pain are commonly reported symptoms.3Given the high mortality rate associated with HCC and poor quality of life, exploration of adjunctive treatments is warranted.
The study provided evidence that CV may improve appetite and pain scores and this should be further evaluated in a larger population.
Mushroom extracts inclCoriolus versicolorare often used in integrative oncology as an adjunct to conventional treatment.4 Coriolus versicolor(also known as turkey tail,Trameten versicolorand Yun-Zhi) contains polysaccharides, particularly polysaccharopeptide crestin (PSK) and polysaccharopeptide (PSP), which are largely responsible for its medicinal benefits.5As a source of fungal polysaccharides, supplementaryCoriolus versicolorExtracts are primarily used for their immune-modulating properties.6 Coriolus versicoloris most commonly administered as a PSK standardized extract and has been studied for its effect in various cancer types, including lung, gastric, breast and colorectal cancers, showing benefit on various outcomes including OS, immune function, performance status and tumor-related symptoms.6.7
This current paper is the first to assess the impact ofCoriolus versicolorin people with advanced HCC. However, due to the small sample size and general lack of statistically significant results, little conclusive information can be gleaned from this paper. The study provided evidence that CV may improve appetite and pain scores and this should be further evaluated in a larger population. Given the statistically insignificant improvements in OS, PFS and QoL outcomes, the paper generates hypotheses for future research. A larger study with sufficient power to detect clinically meaningful changes is warranted.
Given the supporting evidenceCoriolus versicolorwith other cancers and the proven safety profile of this fungus, it is not unreasonable for clinicians to consider it for patients with HCC. However, there is another mushroom extract that has shown superior results specifically for HCC.
Active Hexose Correlated Compound (AHCC) is a mushroom extract from theBasidiomycotaDivision of fungi that has been studied in HCC with promising results. A prospective cohort study of 269 patients evaluated time to disease recurrence and OS in individuals with advanced HCC after liver resection. One hundred thirteen patients received 3 g of AHCC daily; 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 administered 6 g of AHCC daily to 34 patients with unresectable advanced HCC who received supportive care alone and compared them to 10 placebo controls.9Median 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 probably the better mushroom extract to consider for individuals with HCC. This paper onCoriolus versicoloris hypothesis generating, and larger studies are warranted to determine whetherCoriolusmay improve quality of life and survival in individuals with HCC.
restrictions
The major 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, no statistical comparisons were presented, so significance is unclear. The treatment arm had a larger number of participants with prior liver resection, chemotherapy, and radiation therapy. This may impact the observed differences between study arms.
Finally, the paper's methodology was incomplete in some areas, making the study difficult to replicate and threatening the external and internal validity of the results. For example, the study setting and patient selection were not well described, treatment details including standardization and extraction method were not mentioned, and there was no description of placebo or blinding, which could introduce bias.