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

  • Takako Yanai
  • Satoru Iwasa
  • Hironobu Hashimoto
  • Fumiyoshi Ohyanagi
  • Tomomi Takiguchi
  • Koji Takeda
  • Masahiko Nakao
  • Hiroshi Sakai
  • Toshiaki Nakayama
  • Koichi Minato
  • Takahiro Arai
  • Kenichi Suzuki
  • Yasuhiro Shimada
  • Kengo Nagashima
  • Hiroyuki Terakado
  • Noboru Yamamoto
Original Article

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 H0: 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

Keywords

Olanzapine Chemotherapy-induced nausea and vomiting Prophylaxis Phase II study 

Notes

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.

Compliance with ethical standards

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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Copyright information

© Japan Society of Clinical Oncology 2017

Authors and Affiliations

  • Takako Yanai
    • 1
  • Satoru Iwasa
    • 2
  • Hironobu Hashimoto
    • 1
  • Fumiyoshi Ohyanagi
    • 3
  • Tomomi Takiguchi
    • 4
  • Koji Takeda
    • 5
  • Masahiko Nakao
    • 6
  • Hiroshi Sakai
    • 7
  • Toshiaki Nakayama
    • 8
  • Koichi Minato
    • 9
  • Takahiro Arai
    • 10
  • Kenichi Suzuki
    • 4
  • Yasuhiro Shimada
    • 11
  • Kengo Nagashima
    • 12
  • Hiroyuki Terakado
    • 1
  • Noboru Yamamoto
    • 2
  1. 1.Department of PharmacyNational Cancer Center HospitalTokyoJapan
  2. 2.Department of Experimental TherapeuticsNational Cancer Center HospitalTokyoJapan
  3. 3.Department of Thoracic Medical OncologyCancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
  4. 4.Department of PharmacyCancer Institute Hospital of Japanese Foundation for Cancer ResearchTokyoJapan
  5. 5.Department of Medical OncologyOsaka City General HospitalOsakaJapan
  6. 6.Department of PharmacyOsaka City General HospitalOsakaJapan
  7. 7.Division of Thoracic OncologySaitama Cancer CenterSaitamaJapan
  8. 8.Division of PharmacySaitama Cancer CenterSaitamaJapan
  9. 9.Division of Respiratory MedicineGunma Prefectural Cancer CenterOhtaJapan
  10. 10.Division of PharmacyGunma Prefectural Cancer CenterOhtaJapan
  11. 11.Clinical Oncology DivisionKochi Health Sciences CenterKochiJapan
  12. 12.Department of Global Clinical Research, Graduate School of MedicineChiba UniversityChibaJapan

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