Ohno, T., Yanai, M., Ando, H., Toyomasu, Y., Ogawa, A., Morita, H., . . . Kuwano, H. (2011). Rikkunshito, a traditional Japanese medicine, suppresses cisplatin-induced anorexia in humans. Clinical and Experimental Gastroenterology, 4, 291–296.

To investigate the effect of Rikkunshito on ghrelin secretion and on cisplatin-induced anorexia in humans

Ten patients were randomly divided into two groups. Both groups received S-1 (80 mg/m²/day orally split into twice-a-day dosing after meals) plus chemotherapy for 21 consecutive days followed by a 14-day rest period. The total daily dose of S-1 was determined based on body surface area (BSA): 80 mg (BSA < 1.25 m²), 100 mg (BSA 1.25–1.5 m²), or 120 mg (BSA > 1.5 m²). Cisplatin 60 mg/m² was administered IV on day 8. All patients were administered 16 mg of dexamethasone and 3 mg of granisetron IV one hour before cisplatin infusion and 8 mg of dexamethasone on days 9 and 10. Group A was started on Rikkunshito for the first course of chemotherapy, followed by a second course of chemotherapy without Rikkunshito. Treatment with Rikkunshito was reversed for group B. During the intervention period, patients took Rikkunshito 7.5 g (2.5 g three times per day by mouth) before each meal on days 1–21. Patients in the control period did not take anything. Blood samples to assess acylated ghrelin levels were collected before and three hours after administration of the cisplatin. Patients were hospitalized after the administration of cisplatin and monitored for five days. The amount of oral intake of each meal was observed and scored, and the average oral intake during five days was calculated.

• The study reported on 10 patients (5 in each arm).
• Mean patient age was 61.8 years, with a range of 50–72 years. (Median age was not calculated in the article.)
• The sample was 80% male and 20% female.
• All patients had gastric cancer: 40% had recurrent disease, 60% had unresectable disease.
• Patients had an Eastern Cooperative Oncology Group performance status score of 0–1 and may have had up to one prior chemotherapy regimen.

• Single site
• Inpatient setting
• Japanese study, suggesting it was done in Japan

• Patients were undergoing active treatment.
• The study has clinical applicability for late effects and survivorship.

A crossover design was used.

Anorexia, nausea, and vomiting were scored according to National Cancer Institute common toxicity criteria.

During the Rikkunshito-on period, there was no significant decrease in the plasma concentration of acylated ghrelin between before and after administration. During the Rikkunshito-off period, the average concentration of plasma-acylated ghrelin three hours after cisplatin administration decreased from preadministration levels but not statistically significantly.

The average oral intake in the Rikkunshito-on period was significantly larger than that in the Rikkunshito-off period (p = 0.0496). The grade of anorexia was significantly lower in the Rikkunshito-on period than in the Rikkunshito-off period (p = 0.0441), and the average oral intake in the Rikkunshito-on period was significantly larger than that in the Rikkunshito-off period. The grade of nausea was not significant; however, the grade in the Rikkunshito-on period tended to be lower. The difference in grade of vomiting was not significant. The time to treatment failure rates during the Rikkunshito-on period were not different. Hypertension, edema, hypokalemia, pseudohyperaldosteronism, hepatic toxicity, and transaminitis have been previously reported but did not appear to be more significant in the Rikkunshito-on or -off period for this study.

Rikkunshito might prevent anorexia induced by cisplatin, and the prophylactic administration of Rikkunshito was felt to be effective in chemotherapy with cisplatin. Patients could continue their treatment on schedule.

• The study had a small sample size, with less than 30 participants.
• The trial was nonrandomized; crossover design may cloud what led to benefit.
• The authors have taken a combination herbal product and assumed that any positive effects in this study are due to ghrelin levels. Previous studies cited by the authors have had mixed results regarding the effect of ghrelin on cachexia and anorexia. The positive effects seen may not be related to effect of Rikkunshito on ghrelin at all but rather due to other effects of one of more of the herbs in Rikkunshito. The presence of multiple herbs in this product may be a confounder.

Rikkunshito may be effective at preventing anorexia induced by cisplatin, but the small sample size makes it unlikely that this data can be generalized. Additional studies are necessary.