Department of Medical Oncology, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
Department of General and Gastroenterological Surgery, Kanazawa Medical University, 1-1 Daigaku, Uchinada, Ishikawa, 920-0293, Japan.
Int J Clin Oncol. 2020 Jun;25(6):1123-1129. doi: 10.1007/s10147-020-01648-3. Epub 2020 Mar 30.
Peripheral neuropathy (PN) is an intractable side effect of oxaliplatin, with no effective prophylaxis so far. Ninjin'yoeito (NYT), a Kampo medicine, is protective against oxaliplatin-induced neuronal cell injury in vitro and ameliorates oxaliplatin-induced PN in vivo. Thus, this randomized controlled trial was aimed at clarifying NYT's prophylactic effect for oxaliplatin-induced cumulative PN.
52 patients with colorectal cancers of pathological stage 3 received postoperative adjuvant chemotherapy with the CapeOX regimen: eight cycles of capecitabine (2400 mg/m) plus oxaliplatin (130 mg/m) at 3-week intervals. They were randomly assigned to NYT administration and non-administration groups. NYT (9.0 g/day) was administered from day 1 of cycle 1 in the NYT group. The NYT was administered orally daily throughout each cycle. The primary endpoint was the grade of cumulative PN at the end of eight cycles. The secondary endpoints included relative dose intensity (RDI) of oxaliplatin, recurrence-free survival (RFS), and overall survival (OS).
40 patients (n = 20 in both groups) completed 8 chemotherapy cycles. The incidence of grade 2 or greater cumulative PN at the 8th chemotherapy cycle was significantly lower in the NYT group (2/20, 10.0%) than in the control group (11/20, 55.0%, P < 0.01). RDI of oxaliplatin was significantly higher in the NYT group than in the control group (P = 0.02). RFS and OS were better in the NYT group than in the control group, but the difference was not significant.
NYT may reduce the incidence of oxaliplatin-induced cumulative PN and facilitate maintenance of the CapeOX dosing regimen.
周围神经病变（PN）是奥沙利铂的一种难治性副作用，目前尚无有效的预防措施。人参制剂（NYT）是一种汉方药，在体外具有预防奥沙利铂诱导的神经元细胞损伤的作用，并改善体内奥沙利铂诱导的 PN。因此，本随机对照试验旨在阐明 NYT 对奥沙利铂诱导的累积性 PN 的预防作用。
52 例病理分期为 3 期的结直肠癌患者接受 CapeOX 方案术后辅助化疗：8 个周期的卡培他滨（2400mg/m）加奥沙利铂（130mg/m），每 3 周 1 次。他们被随机分配到 NYT 给药组和非给药组。在 NYT 组中，从第 1 周期的第 1 天开始给予 NYT（9.0g/天）。在每个周期中，NYT 均每日口服给药。主要终点是 8 个周期结束时累积性 PN 的分级。次要终点包括奥沙利铂的相对剂量强度（RDI）、无复发生存率（RFS）和总生存率（OS）。
40 例患者（n=20 例）完成了 8 个化疗周期。在第 8 个化疗周期时，NYT 组（2/20，10.0%）累积性 PN 2 级或更高级别的发生率明显低于对照组（11/20，55.0%，P<0.01）。NYT 组奥沙利铂的 RDI 明显高于对照组（P=0.02）。NYT 组的 RFS 和 OS 优于对照组，但差异无统计学意义。
NYT 可能降低奥沙利铂诱导的累积性 PN 的发生率，并有助于维持 CapeOX 给药方案。
