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A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy

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Abstract

Purpose

The aim of this phase II study was to evaluate the efficacy and safety of two doses (10 and 5 mg) of olanzapine in combination with standard antiemetic treatment (aprepitant, palonosetron, and dexamethasone) for patients receiving highly emetogenic chemotherapy (HEC).

Methods

A multi-institutional, double-blind, randomized phase II, dose-finding study of olanzapine was performed in patients with a malignant solid tumor who were receiving HEC with cisplatin (≥ 50 mg/m2). Patients were randomly assigned either olanzapine 10 or 5 mg orally on days 1–4, combined with standard antiemetic treatment. The primary endpoint was a complete response (CR; no emesis and no use of rescue medications) in the delayed phase (24–120 h after the start of cisplatin treatment).

Results

153 patients were randomized to the 10 mg group (n = 76) or the 5 mg group (n = 77). The CR rate in the delayed phase was 77.6% (80% CI: 70.3–83.8, P = 0.01) in the 10 mg group and 85.7% (80% CI: 79.2–90.7, P < 0.001) in the 5 mg group (P value for H 0: complete response rate ≤ 65%). The most common adverse event was somnolence, which had an incidence of 53.3 and 45.5% in the 10 and 5 mg olanzapine groups, respectively.

Conclusions

Both doses of 10 and 5 mg olanzapine provided a significant improvement in delayed emesis. A dose of 5 mg olanzapine was determined as the recommended dose for a further phase III study based on higher CR and lower somnolence rates.

Clinical Trial Information

UMIN000014214

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Acknowledgements

The authors thank the patients, clinical investigators, and site personnel who participated in the study. Additional participating institutions and investigators included Shikoku Cancer Center (Daijiro Harada, Yuki Kogure). This work was supported in part by the Foundation for Promotion of Cancer Research in Japan.

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Authors and Affiliations

  1. Department of Pharmacy, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Takako Yanai, Hironobu Hashimoto & Hiroyuki Terakado

  2. Department of Experimental Therapeutics, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan

    Satoru Iwasa & Noboru Yamamoto

  3. Department of Thoracic Medical Oncology, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Fumiyoshi Ohyanagi

  4. Department of Pharmacy, Cancer Institute Hospital of Japanese Foundation for Cancer Research, 3-8-31 Ariake, Koto-ku, Tokyo, 135-8550, Japan

    Tomomi Takiguchi & Kenichi Suzuki

  5. Department of Medical Oncology, Osaka City General Hospital, 2-13-22, Miyakojimahondohri, Miyakojima-ku, Osaka, 534-0021, Japan

    Koji Takeda

  6. Department of Pharmacy, Osaka City General Hospital, 2-13-22, Miyakojimahondohri, Miyakojima-ku, Osaka, 534-0021, Japan

    Masahiko Nakao

  7. Division of Thoracic Oncology, Saitama Cancer Center, 780, Komuro, Ina, Kitaadachi, Saitama, 362-0806, Japan

    Hiroshi Sakai

  8. Division of Pharmacy, Saitama Cancer Center, 780, Komuro, Ina, Kitaadachi, Saitama, 362-0806, Japan

    Toshiaki Nakayama

  9. Division of Respiratory Medicine, Gunma Prefectural Cancer Center, 617-1 Takahayashi-nishi-cho, Ohta, Gunma, 373-0828, Japan

    Koichi Minato

  10. Division of Pharmacy, Gunma Prefectural Cancer Center, 617-1 Takahayashi-nishi-cho, Ohta, Gunma, 373-0828, Japan

    Takahiro Arai

  11. Clinical Oncology Division, Kochi Health Sciences Center, 2125-1, Ike, Kochi, Kochi, 781-8555, Japan

    Yasuhiro Shimada

  12. Department of Global Clinical Research, Graduate School of Medicine, Chiba University, 1-8-1 Inohana Chuo-ku, Chiba, 260-8670, Japan

    Kengo Nagashima

Authors
  1. Takako Yanai
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  2. Satoru Iwasa
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  3. Hironobu Hashimoto
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  4. Fumiyoshi Ohyanagi
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  5. Tomomi Takiguchi
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  7. Masahiko Nakao
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  8. Hiroshi Sakai
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  9. Toshiaki Nakayama
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  10. Koichi Minato
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  11. Takahiro Arai
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  12. Kenichi Suzuki
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  13. Yasuhiro Shimada
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  14. Kengo Nagashima
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  15. Hiroyuki Terakado
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  16. Noboru Yamamoto
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Corresponding author

Correspondence to Noboru Yamamoto.

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Conflict of interest

Satoru Iwasa, Koji Takeda, Yasuhiro Shimada and Noboru Yamamoto have received payment for lectures and research funding from Eli Lilly. All remaining authors have declared no conflicts of interest.

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Yanai, T., Iwasa, S., Hashimoto, H. et al. A double-blind randomized phase II dose-finding study of olanzapine 10 mg or 5 mg for the prophylaxis of emesis induced by highly emetogenic cisplatin-based chemotherapy. Int J Clin Oncol 23, 382–388 (2018). https://doi.org/10.1007/s10147-017-1200-4

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  • DOI: https://doi.org/10.1007/s10147-017-1200-4

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