Purpose

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.

Methods

52 patients with colorectal cancers of pathological stage 3 received postoperative adjuvant chemotherapy with the CapeOX regimen: eight cycles of capecitabine (2400 mg/m²) plus oxaliplatin (130 mg/m²) 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).

Results

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.

Conclusions

NYT may reduce the incidence of oxaliplatin-induced cumulative PN and facilitate maintenance of the CapeOX dosing regimen.

中文翻译：

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ninjin'yoeito 对接受术后辅助化疗的结直肠癌患者奥沙利铂诱导的累积性周围神经病变的预防效果：一项随机、开放标签、2 期试验 (HOPE-2)。

目的

周围神经病变 (PN) 是奥沙利铂的顽固副作用，目前尚无有效的预防措施。Ninjin'yoeito (NYT) 是一种汉方药物，在体外可防止奥沙利铂诱导的神经元细胞损伤，并在体内改善奥沙利铂诱导的 PN。因此，这项随机对照试验旨在阐明 NYT 对奥沙利铂诱导的累积 PN 的预防作用。

方法

52 名病理分期为 3 的结直肠癌患者接受了 CapeOX 方案的术后辅助化疗：卡培他滨 (2400 mg/m ² )加奥沙利铂 (130 mg/m ² ) 8 个周期，间隔 3 周。他们被随机分配到 NYT 给药组和非给药组。在 NYT 组中，从第 1 个周期的第 1 天开始服用 NYT（9.0 g/天）。NYT 在每个周期中每天口服给药。主要终点是八个周期结束时的累积 PN 等级。次要终点包括奥沙利铂的相对剂量强度（RDI）、无复发生存期（RFS）和总生存期（OS）。

结果

40 名患者（ 两组n = 20）完成了 8 个化疗周期。NYT 组第 8 个化疗周期 2 级或以上累积 PN 的发生率（2/20，10.0%）显着低于对照组（11/20，55.0%，P  < 0.01）。NYT 组奥沙利铂的 RDI 显着高于对照组（P  = 0.02）。NYT组的RFS和OS优于对照组，但差异不显着。

结论

NYT 可能会降低奥沙利铂诱导的累积 PN 的发生率，并有助于维持 CapeOX 给药方案。