Efficacy of rikkunshito, a Japanese herbal medicine, on nausea, vomiting and anorexia in patients with uterine cervical or corpus cancer treated with cisplatin and paclitaxel –A randomized phase II study

Background

Although antagonists for 5-HT3 and NK-1 receptors and corticosteroids are used for the treatment of chemotherapy-induced nausea and vomiting (CINV), this treatment is still insufficient. Rikkunshito (RKT), a Japanese herbal medicine, is widely prescribed in Japan to treat various gastrointestinal disorders, and has been reported to recover the decreases in food intake and serum ghrelin levels caused by cisplatin (CDDP) in animal models (Gastroenterology 2008;134:2004-13). We thus investigated whether RKT could improve CINV in patients receiving CDDP and paclitaxel (PTX).

Methods

Patients with histologically diagnosed uterine cervical or corpus cancer who were planned to receive CDDP and PTX as first-line chemotherapy were included. Patients were randomly assigned to the RKT group receiving oral administration of RKT 7.5 g/day for 14 days with standard antiemetics (granisetron, aprepitant and dexamethasone), or the control group receiving only standard antiemetics. The primary endpoint was complete control rate (CCR) in the overall phase (0-120 hours after CDDP administration), and secondary endpoints were complete response rate (CRR), total control rate, time to treatment failure, appetite and nausea assessed by VAS, FAACT anorexia and cachexia subscale scores, EORTC-QLQ-C30 scores, grade of appetite/nausea/vomiting by CTCAE v4.0, and serum level of ghrelin. Two-sided P value

Results

Forty patients were enrolled from 4 institutions, and 36 patients (19 in the RKT group, 17 in the control group) were included in efficacy analysis. The primary endpoint CCR in the overall phase was significantly higher in the RKT group than control group (57.9% vs 35.3%, P = 0.175). Furthermore, CCR in the delayed phase (24-120 hours after CDDP administration) and CRR in overall and delayed phases were also significantly higher in the RKT group than control group (63.2% vs 35.3%, P = 0.095; 84.2% vs 52.9%, P = 0.042; 84.2% vs 52.9%, P = 0.042, respectively).

Conclusions

The primary endpoint CCR in the overall phase was achieved, and RKT would improve CINV, especially in the delayed phase.

Clinical trial identification

UMIN000011227

Legal entity responsible for the study

Japanese Organisation for Research and Treatment of Cancer

Funding

The Third-term Comprehensive 10-year Strategy for Cancer Control (H22-General-035) from the Ministry of Health, Labour and Welfare, Japan

Disclosure

All authors have declared no conflicts of interest.