Prophylactic efficacy of ninjin’yoeito for oxaliplatin-induced cumulative peripheral neuropathy in patients with colorectal cancer receiving postoperative adjuvant chemotherapy: a randomized, open-label, phase 2 trial (HOPE-2)

Abstract

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.

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Acknowledgements

This study was supported in part by Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (No. 16K09267).

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Contributions

All the authors contributed to this study. YM designed this trial, enrolled the patients, and analyzed the data. YT and HF took care of the patients.

Corresponding author

Correspondence to Yoshiharu Motoo.

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The authors declare no competing interests.

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Motoo, Y., Tomita, Y. & Fujita, H. Prophylactic efficacy of ninjin’yoeito for oxaliplatin-induced cumulative peripheral neuropathy in patients with colorectal cancer receiving postoperative adjuvant chemotherapy: a randomized, open-label, phase 2 trial (HOPE-2). Int J Clin Oncol 25, 1123–1129 (2020). https://doi.org/10.1007/s10147-020-01648-3

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Keywords

  • Oxaliplatin
  • Peripheral neuropathy
  • Ninjin’yoeito
  • Colorectal cancer
  • Kampo