Yun Zhi

Seven parallel RCTs, 1569 participants, six from Japan and one from China; Coriolus was given as an extract, in practice PSK, in every included trial. The review found very low certainty evidence about adverse events, with no clear effect on withdrawal for adverse events (RR 1.03, 95% CI 0.45 to 2.34) and uncertain effects on neutropenia, oral mucositis, nausea, diarrhoea and fatigue. It found low certainty evidence of a small survival benefit at five years (RR 1.08, 95% CI 1.01 to 1.15, NNT 16). The authors caution that the chemotherapy regimens used do not reflect current preferred practice.

A meta-analysis of eight centrally randomised controlled trials totalling 8009 patients with curatively resected gastric cancer, comparing chemotherapy with chemotherapy plus PSK. The overall hazard ratio for survival was 0.88 (95% CI 0.79-0.98, p = 0.018) with no significant heterogeneity. This is the largest survival dataset for the drug and it is entirely for PSK extract given as postoperative adjuvant immunochemotherapy.

A meta-analysis of centrally randomised data from 1094 patients across three colorectal trials with at least five years of follow-up, analysed by intention to treat. Adding PSK to standard chemotherapy gave an overall survival risk ratio of 0.71 (95% CI 0.55-0.90, p = 0.006) and a disease-free survival risk ratio of 0.72 (95% CI 0.58-0.90, p = 0.003). Note that this same patient pool underlies the more conservative Cochrane estimate.

The landmark trial. 262 patients at 46 institutions in central Japan who had undergone curative gastrectomy were randomised to mitomycin plus oral fluorouracil with or without protein-bound polysaccharide, with a minimum five years of follow-up. PSK improved the 5-year disease-free rate (70.7% versus 59.4%, p = 0.047) and 5-year survival (73.0% versus 60.0%, p = 0.044), with only slight toxicity in both arms and no significant between-group difference in adverse effects.

A double-blind placebo-controlled trial of 28 days of PSP, not PSK, in 68 patients who had completed conventional treatment for advanced non-small cell lung cancer. The PSP arm showed significant improvement in leukocyte and neutrophil counts, serum IgG and IgM and percent body fat, and significantly fewer withdrawals for disease progression (5.9% versus 23.5%, p = 0.04). NSCLC-related symptoms did not improve and no adverse reactions were attributed to the trial medication. This is the principal human trial of the Chinese PSP preparation and it is small and short.

Twenty-three RCTs and 4246 cancer patients. Coriolus and Ganoderma products together were associated with lower mortality (HR 0.82, 95% CI 0.72-0.94) and higher total efficacy (RR 1.30, 95% CI 1.09-1.55) but not with disease control rate, and Coriolus products specifically showed no effect on relapse-free survival (HR 1.19, 95% CI 0.91-1.55). Immunologically, CD3 rose by 9.03% and CD4 by 9.2% with no change in CD8, CD4/CD8 or NK cells. Pooling two different fungi weakens the inference for Yun Zhi alone.

A network meta-analysis of 23 trials, 10684 patients and 13 intervention arms in gastrointestinal cancer, registered as PROSPERO CRD42017065193. PSK significantly increased 1 to 5 year overall survival and 1 to 7 year disease-free survival without increasing side effects, with the effect concentrated in colorectal and gastric cancer and in PSK combined with chemotherapy rather than PSK alone.

Thirty-one reports of 28 studies, of which six were randomised controlled trials, five non-randomised controlled trials and 17 preclinical; nine reports were in Japanese. Randomised trials showed benefits on immune parameters, haematological function, performance status, body weight and tumour-related symptoms such as fatigue and anorexia, with conflicting results on median survival. PSK was safely given with standard radiation and chemotherapy. The authors call for larger and more rigorous trials, which have not since appeared.

A randomised phase II trial in 186 patients after radical resection, comparing six months of UFT/LV against six or twelve months of UFT/LV plus 3 g/day PSK. Three-year disease-free survival was 72.5%, 82.2% and 74.2% respectively, with no significant differences; grade 3 or worse adverse events were 13.5%, 9.6% and 9.9%. Treatment completion was significantly worse in the twelve-month arm (70.4%). A contemporary trial that does not reproduce the large historical survival effect.

A population-based cohort study outside Japan, testing whether the PSK survival signal from Japanese randomised trials transfers to another Asian population receiving gastrectomy and adjuvant chemotherapy for gastric cancer. It reports prolonged overall survival with PSK. As observational data it cannot exclude confounding by indication, but it is the main non-Japanese evidence for the drug.

An English-language systematic review and meta-analysis pooling randomised trials of Yun Zhi preparations for cancer survival, published under the Yun Zhi name rather than the PSK trade name. It reports a survival advantage concentrated in breast, gastric and colorectal cancer. Its trial pool overlaps heavily with the Japanese PSK meta-analyses, so it should be read as a re-presentation of that evidence rather than independent confirmation.