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Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy

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Summary

Purpose Anorexia induced by cytotoxic chemotherapy on delayed phase is a highly frequent adverse event. We aimed to determine the effects of rikkunshito (RKT) on chemotherapy-induced anorexia (CIA) in patients with lung cancer. Methods This prospective, randomized, cross-over pilot trial included 40 lung cancer patients scheduled to undergo cisplatin-based chemotherapy and randomized to either a group given RKT 7.5 g/day for 14 days (Group A, N = 20) or not (Group B, N = 20), then the treatments were switched. All patients received dexamethasone, palonosetron hydrochloride and aprepitant regardless of group assignment. Rescue drugs were allowed as required. The primary and key secondary endpoints were changes in caloric intake and in plasma acylated ghrelin (AG) levels, respectively. Average daily caloric intake during days 3 to 5 was compared with that on day 1 of each course. Results The primary and key secondary endpoints were analyzed in 31 patients (per protocol population) completing the study. Reduction rate of caloric intake was lower in RKT, than in control courses (18% vs. 25%, P = 0.025). Plasma AG levels significantly declined between days 1 and 3 in RKT (12.3 vs. 7.5 fmol/mL, P < 0.001) and control (10.8 vs. 8.6 fmol/mL, P < 0.001) courses. However, those obviously increased to 8.5 fmol/mL (P = 0.025) by day 5 in RKT course but not in control course (7.7 fmol/mL, P = 0.28). Conclusions Rikkunshito could mitigate CIA and ameliorate plasma AG levels during the delayed phase of CDDP-based chemotherapy in lung cancer patients. Clinical trial registration numbers: UMIN000010748.

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Abbreviations

CDDP:

Cis-dichloro-diamine-platinum

CI:

Cranial irradiation

CIA:

Chemotherapy-induced anorexia

CINV:

Chemotherapy-induced nausea and vomiting

FLIE:

Functional Living Index-Emesis

HEC:

Highly emetogenic chemotherapy

HT3 :

Hydroxytryptamine3

NK-1:

Neurokinin-1

QOL:

Quality of life

RKT:

Rikkunshito

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Acknowledgements

We are grateful to Takeshi Mimura, Hideaki Hanaki, Keizo Misumi, Norifumi Tsubokawa and Daisuke Ueda (Department of Surgical Oncology) for the important contribution of data analyses, to Kanako Amano and Hisako Oka (Department of Nutrition Management) for the data collection of daily caloric intake, and to Hiroshi Sakurashita (Department of Pharmaceutical Services) for the confirmation of proper drug administration.

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Authors and Affiliations

  1. Department of Surgical Oncology, Research Institute for Radiation Biology and Medicine, Hiroshima University, 1-2-3, kasumi, minami-ku, Hiroshima City, 734-8551, Japan

    Tomoharu Yoshiya, Takahiro Mimae, Masaoki Ito, Shinsuke Sasada, Yasuhiro Tsutani, Yoshihiro Miyata & Morihito Okada

  2. The Center for Data Science Education and Research, Shiga University, 1-1-1, banba, Hikone, Shiga, 522-8522, Japan

    Kenichi Satoh

  3. Department of Molecular and Internal Medicine, Hiroshima University, 1-2-3, kasumi, minami-ku, Hiroshima, 734-8551, Japan

    Takeshi Masuda & Noboru Hattori

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  1. Tomoharu Yoshiya
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Correspondence to Morihito Okada.

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All procedures performed in this study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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Yoshiya, T., Mimae, T., Ito, M. et al. Prospective, randomized, cross-over pilot study of the effects of Rikkunshito, a Japanese traditional herbal medicine, on anorexia and plasma-acylated ghrelin levels in lung cancer patients undergoing cisplatin-based chemotherapy. Invest New Drugs 38, 485–492 (2020). https://doi.org/10.1007/s10637-019-00836-x

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