Nutritional status and quality of life with or without Ninjin'yoeito during first-line chemotherapy for metastatic colorectal cancer: an exploratory, open-label randomized phase II trial

Purpose Cancer-associated malnutrition during chemotherapy may impair treatment tolerance and quality of life (QoL). Ninjin'yoeito (NYT), a Japanese Kampo medicine, is used to treat anorexia, fatigue, and general malaise. We evaluated NYT during first-line chemotherapy for metastatic colorectal cancer (mCRC). Methods This exploratory, open-label, multicenter, randomized phase II trial compared NYT plus CAPOX and bevacizumab with CAPOX and bevacizumab alone in patients with unresectable mCRC. Co-primary endpoints were longitudinal changes in Controlling Nutritional Status (CONUT) scores and grade ≥ 3 nonhematological adverse events. Secondary endpoints included body mass index (BMI), QoL, and progression-free survival (PFS). Results Enrollment was terminated early because of slow accrual. Of 78 randomized patients, 74 were included in the full analysis set (NYT, n = 39; non-NYT, n = 35). Neither co-primary endpoint differed significantly between groups: CONUT score changes (least-squares mean difference [LSMD], − 0.05; 95% confidence interval [CI], − 0.53 to 0.42; P = 0.822) and grade ≥ 3 nonhematological adverse events (25.6% vs 20.0%; P = 0.593). Exploratory analysis showed better BMI maintenance with NYT (LSMD, 0.66 kg/m²; 95% CI, 0.19–1.13; P = 0.007). Appetite loss was lower with NYT and remained significant in sensitivity analysis, whereas insomnia scores were higher. PFS did not differ significantly between groups (HR, 1.21; 95% CI, 0.44–3.33; log-rank P = 0.713). Conclusions NYT did not significantly affect either co-primary endpoint. Exploratory findings suggested better BMI maintenance and reduced appetite loss, whereas insomnia scores were higher. These findings are hypothesis-generating and require confirmation in adequately powered trials. Clinical trial registration This trial was registered in the Japan Registry of Clinical Trials (ID jRCTs041190071) on October 2, 2019.