A Placebo-controlled Study of the Doses and Efficacy of Lentinula edodes Mycelia for Oxaliplatin-induced Peripheral Neuropathy in Colorectal Cancer

Shogen Boku¹Hironaga Satake²Seiichiro Mitani³Kiyoshi Maeda⁴Toshihiro Kudo⁵Toshifumi Yamaguchi⁶Tatsuya TAKAGI⁷Hisato Kawakami^8*

• ¹Department of Clinical Oncology, Kansai Medical University Hospital, Osaka, Japan
• ²Department of Medical Oncology, Kochi Medical School, Kochi, Japan
• ³Department of Medical Oncology, Kindai University Faculty of Medicine, Osaka, Japan
• ⁴Department of Gastroenterological Surgery, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
• ⁵Department of Medical Oncology, Osaka International Cancer Institute, Osaka, Japan
• ⁶Cancer Chemotherapy Center, Osaka Medical and Pharmaceutical University, Osaka, Japan
• ⁷Graduate School of Pharmaceutical Sciences, Osaka University, Suita, Ōsaka, Japan
• ⁸Department of Clinical Oncology, Tohoku University Graduate School, Sendai, Japan

Preclinical studies have demonstrated the potential of Lentinula edodes mycelium (L.E.M.) extract for managing oxaliplatin-induced peripheral neuropathy (OIPN). The efficacy and optimal dosage of L.E.M. for OIPN remain uncertain. We evaluated the efficacy and safety as well as the optimal dosage of L.E.M. extract for OIPN in patients with colorectal cancer (CRC).Methods: After curative resection, we used a 1:1:1 ratio to randomly assign patients with CRC with persistent OIPN (defined by a visual analogue scale [VAS] numbness score ≥40 mm) to the low-dose (L.E.M. 300 mg twice daily [bid]), high-dose (L.E.M. 900 mg bid), and placebo groups. The primary endpoint of this double-blind, placebo-controlled phase 2 trial was the reduction in the VAS numbness score in the low-dose group compared with that in the placebo group at 12 weeks. Adverse events (AEs) and quality of life were evaluated.Results: Forty-five patients were randomly assigned to the placebo (n = 15), low-dose (n = 15), and high-dose (n = 15) groups. At 12 weeks, no significant difference in the reduction of the VAS numbness score was observed when the low-dose and placebo groups were compared (-12.20 [95% confidence interval {CI}; -34.54 to 10.14] vs. -10.69 [95% CI; -27.07 to 5.69]; p = 0.83); however, the high-dose group showed a favourable trend compared with the placebo group ; p = 0.06). Grade 3 or higher AEs related to the intervention were not observed.Discussion: High-dose L.E.M. extract resulted in a clinically meaningful improvement in VAS numbness scores without severe toxicity.Trial registration: This study was registered in the Japanese Clinical Trials Registry (jRCTs051210085).