Abstract 10P
Background
Oxaliplatin-induced peripheral neuropathy (OIPN) is a challenging side effect for colorectal cancer (CRC) patients that often resists treatment and affects quality of life (QOL). Lentinula edodes mycelia (L.E.M.) has demonstrated potential for OIPN management in preclinical studies.
Methods
This randomized, placebo-controlled trial assessed the safety and efficacy of L.E.M. in CRC patients with persistent OIPN (visual analog scale [VAS] ≥4). Participants received placebo, low-dose (300 mg b.i.d.), or high-dose (900 mg b.i.d.) of L.E.M. for 12 weeks. Eligibility included radically resected CRC patients with residual OIPN for at least 3 months after postoperative oxaliplatin-based chemotherapy. Primary endpoint was reduction of VAS numbness scores in low-dose vs. placebo at 12 weeks post-treatment. Secondary endpoints included reduction of VAS numbness and pain scores in low-, high-dose vs. placebo at 12 weeks post-treatment, and safety. Adverse events (AE) and QOL were assessed based on CTCAE Ver. 4 and FACT-GOG/NTX.
Results
Of the 45 enrolled patients, 44 were eligible and constituted the full analysis set and safety analysis set. Patients were randomly assigned to the placebo (n=15), low-dose (n=15), and high-dose (n=14), respectively. The median adherence was 98.8% (range, 67.0 to 100%). For the reduction of VAS numbness scores at 12 weeks, no significant difference was detected in the low-dose vs. placebo (−1.2 [95% confidence interval {CI}; −3.5 to 1.0] vs. −1.1 [95% CI; −2.7 to 5.7]). Although not significant, however, the high-dose vs. placebo showed a beneficial change both in VAS numbness and pain scores (−1.2 [95% CI; −3.5 to 1.0], vs. −2.9 [95% CI; −5.3 to −0.5]; −0.2 [95% CI; −2.6 to 2.2] vs. −0.6 [95% CI; −3.5 to 2.3]). Similarly, the high-dose showed an improvement of An6（”I have trouble walking”）score at 12 weeks in FACT-GOG/NTX questionnaire (−0.1 [95% CI; −1.2 to 1.0], −0.4 [95% CI; −1.6 to 0.8], −1.0 [95% CI; −2.0 to 0.0]). No grade 3 or higher AE was observed.
Conclusions
The high-dose group showed a clinically meaningful improvement in VAS numbness and pain scores as well as QOL, warranting further investigation.
Clinical trial identification
jRCTs051210085; Release date: September 16, 2021.
Legal entity responsible for the study
Kobayashi Pharmaceutical Co., Ltd.
Funding
Kobayashi Pharmaceutical Co., Ltd.
Disclosure
H. Satake: Financial Interests, Personal, Invited Speaker: Bayer Co., Ltd., Bristol Myers Squibb Co., Ltd., Chugai Pharmaceutical Co., Ltd., Daiichi Sankyo Co., Ltd., Eli Lilly Japan Co., Ltd., Merck Bio Pharma Co., Ltd., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd., Sanofi Co., Ltd., Taiho Pharmaceutical Co., Ltd., Takeda Co., Ltd., Yakult Honsha Co., Ltd., Novartis Pharma; Financial Interests, Institutional, Research Grant: Ono Pharmaceutical Co. Ltd., Daiichi Sankyo, Taiho Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., Sanofi; Financial Interests, Institutional, Invited Speaker: Asahi Kasei; Non-Financial Interests, Member: ASCO, JSMO. T. Kudo: Financial Interests, Personal, Invited Speaker: Merck Biopharma Co., Ltd., Taiho Pharmaceutical Co., Ltd., Bristol Myers Squibb K.K., MSD Co., Ltd., Ono Pharmaceutical Co., Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co., Ltd.; Financial Interests, Institutional, Invited Speaker: Astellas Pharma Inc., Novartis Pharma K.K., Amgen inc., Ono Pharmaceutical Co., Ltd., MSD Co., Ltd., AstraZeneca K.K., Incyte Biosciences Japan G.K.; Financial Interests, Institutional, Research Grant: Pfizer Inc. M. Gotoh: Financial Interests, Personal, Invited Speaker, speaker: Ono Pharmaceutical Co., Ltd., MSD K.K.; Financial Interests, Institutional, Funding: Chugai Pharma, Taiho Pharmaceutical, Nippon Kayaku. T. Takagi: Financial Interests, Personal, Other, Advisor as a Statistician: Kobayashi Pharmaceutical Co. Ltd.; Non-Financial Interests, Other, Chief of TERMS Independent Evaluation Committee: Fujimoto Pharmaceutical Co. Ltd. H. Kawakami: Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb Co. Ltd., Ono Pharmaceutical Co. Ltd., Daiichi Sankyo Co. Ltd., Bayer Yakuhin Ltd., Eli Lilly Japan K.K., MSD K.K., Chugai Pharmaceutical Co. Ltd., Merck Biopharma Co., Ltd., Takeda Pharmaceutical Co. Ltd., Yakult Pharmaceutical Industry, Teijin Pharma Ltd., Taiho Pharmaceutical Co. Ltd.; Financial Interests, Personal, Advisory Board: Daiichi Sankyo Co. Ltd., Astellas; Financial Interests, Personal, Other, Lecture: GSK, Otsuka Pharmaceutical Co., Ltd.; Financial Interests, Institutional, Research Grant, Investigator-Initiated Trial: Bristol Myers Squibb Co. Ltd.; Financial Interests, Institutional, Research Grant: Taiho Pharmaceutical Co. Ltd., Eisai Co., Ltd., Kobayashi Pharmaceutical Co. Ltd., Parexel International Corp., Pra Healthsciences, EPS Corporation., Kissei Pharmaceutical Co., Ltd., EPS International Co., Ltd., MSD K.K., Ono Pharmaceutical Co., Ltd., PPD-SNBL K.K, SymBio Pharmaceuticals Limited, IQVIA Services Japan K.K., Syneos Health Clinical K.K., Nippon Kayaku Co., Ltd., EP-CRSU Co., Ltd., Mebix, Inc., Bristol Myers Squibb K.K., Janssen Pharmaceutical K.K., Eisai Co., Ltd., AstraZeneca K.K., Mochida Pharmaceutical Co., Ltd., Covance Japan Inc., Japan Clinical Research Operations, Chugai Pharmaceutical Co., Ltd., Takeda Pharmaceutical Co., Ltd., GSK K.K., Sanofi K.K., Nippon Boehringer Ingelheim Co., Ltd., Sysmex Corporation, Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., SRL, Inc., Daiichi Sankyo Co., Ltd., Amgen Inc., Medical Research Support, Eli Lilly Japan K.K. All other authors have declared no conflicts of interest.