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Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized, double-blind, placebo-controlled phase III trial

Supportive Care in Cancer volume 22, pages 979–987 (2014)Cite this article

Abstract

Purpose

Aprepitant, an oral neurokinin-1 receptor antagonist, has demonstrated improved control of chemotherapy-induced nausea and vomiting (CINV) in previous studies. This is the first phase III study to evaluate the efficacy and tolerability of aprepitant in patients receiving highly emetogenic chemotherapy (HEC) in Asian countries.

Methods

This multicenter, double-blind, placebo-controlled trial assessed the prevention of CINV during the acute phase (AP), delayed phase (DP), and overall phase (OP). Patients receiving HEC were randomized to either an aprepitant group (day 1, aprepitant 125 mg; days 2–3, aprepitant 80 mg) or a standard therapy group (days 1–3, placebo). Both groups received intravenous granisetron and oral dexamethasone. The primary end point was complete response (CR; no emesis and no use of rescue therapy) during the OP.

Results

Of the 421 randomized patients, 411 (98 %) were assessable for efficacy; 69.6 % (142/204) and 57.0 % (118/207) of patients reported CR during the OP in the aprepitant and standard therapy groups, respectively (P = 0.007). CR rates in the aprepitant group were higher during the DP (74.0 % vs. 59.4 %, P = 0.001) but were similar during the AP (79.4 % vs. 79.3 %, P = 0.942). Toxicity and adverse events were comparable in both groups.

Conclusions

The addition of aprepitant to standard antiemetic treatment regimens for Chinese patients undergoing HEC provided superior CINV prevention and was well tolerated.

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Acknowledgments

This study was presented in part at the 47th Annual Meeting of the American Society of Clinical Oncology, Chicago, IL, 3–7 June 2011 and at the 17th World Conference on Lung Cancer (WCLC), Amsterdam, Holland, 3–7 July 2011. We thank the patients who participated in this study and their families; the medical, nursing, and research staffs at each study center. Writing assistance was provided by Lin Lin, PhD (Shanghai Bioon Info-tech Co. Ltd). This assistance was funded by MSD China. The authors acknowledge Martha C. Vollmer, of Merck, for the editorial assistance.

Funding

This study was sponsored by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Whitehouse Station, NJ, USA.

Disclosure

Li Zhang has received research support from Boehringer Ingelheim, Bayer, Astra Zeneca, Lilly, and Sanofi Aventis. Denesh K. Chitkara and Darcy A. Hille are employees of Merck and may own stock or stock options in the company. All remaining authors have declared no conflicts of interest.

Author information

Affiliations

  1. Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China

    Zhihuang Hu & Li Zhang

  2. State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, 651 Dongfeng Road East, Guangzhou, 510060, People’s Republic of China

    Zhihuang Hu & Li Zhang

  3. The first Department of Internal Medicine, Jilin Province Cancer Hospital, Changchun, People’s Republic of China

    Ying Cheng

  4. Department of Oncology, The Fifth Affiliated Hospital of Sun Yat-sen University, Zhuhai, People’s Republic of China

    Hongyu Zhang

  5. Cancer Institute, Department of Oncology, Shanghai Pulmonary Hospital, Medical School, Tongji University, 507 Zhengmin Road, Shanghai, 200433, People’s Republic of China

    Caicun Zhou

  6. Department of Pulmonary Medicine, Shanghai Chest Hospital, Shanghai Jiaotong University, Shanghai, 200030, People’s Republic of China

    Baohui Han

  7. Department of Chemotherapy, Zhejiang Cancer Hospital, Hangzhou, 310022, People’s Republic of China

    Yiping Zhang

  8. Department of Medical Oncology, Fujian Provincial Cancer Hospital, The Teaching Hospital of Fujian Medical University, Fuzhou, People’s Republic of China

    Cheng Huang

  9. Department of Medical Oncology, Fudan University Shanghai Cancer Center, 270 Dongan Road, Shanghai, 200032, People’s Republic of China

    Jianhua Chang

  10. Department of Chemotherapy, Guangxi Zhuang Autonomous Region Tumor Hospital, Nanning, People’s Republic of China

    Xiangqun Song

  11. Department of Medical Oncology, the Affiliated Hospital of Medical College, Qingdao University, Qingdao, People’s Republic of China

    Jun Liang

  12. Department of Oncology, Southwest Hospital, Third Military Medical University, Chongqing, People’s Republic of China

    Houjie Liang

  13. Department of Pulmonary Medicine, Zhongshan Hospital, Fudan University, 80 Feng Lin Rd, Shanghai, 200032, People’s Republic of China

    Chunxue Bai

  14. Cancer Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, 430030, People’s Republic of China

    Shiying Yu

  15. Department of Medical Oncology, Jiangsu Cancer Hospital, No. 42 Baizi ting, Nanjing, 210009, Jiangsu Province, People’s Republic of China

    Jia Chen

  16. Department of Thoracic Medical Oncology, Beijing Cancer Hospital, Beijing, People’s Republic of China

    Jie Wang

  17. Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University School of Medicine, Hangzhou, Zhejiang, People’s Republic of China

    Hongming Pan

  18. Merck Sharp & Dohme Corp., Whitehouse Station, NJ, USA

    Denesh K. Chitkara & Darcy A. Hille

Authors
  1. Zhihuang Hu
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  2. Ying Cheng
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  3. Hongyu Zhang
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  4. Caicun Zhou
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  5. Baohui Han
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  6. Yiping Zhang
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  7. Cheng Huang
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  8. Jianhua Chang
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  9. Xiangqun Song
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  10. Jun Liang
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  11. Houjie Liang
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  12. Chunxue Bai
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  13. Shiying Yu
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  14. Jia Chen
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  15. Jie Wang
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  16. Hongming Pan
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  17. Denesh K. Chitkara
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  18. Darcy A. Hille
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  19. Li Zhang
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Correspondence to Li Zhang.

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Hu, Z., Cheng, Y., Zhang, H. et al. Aprepitant triple therapy for the prevention of chemotherapy-induced nausea and vomiting following high-dose cisplatin in Chinese patients: a randomized, double-blind, placebo-controlled phase III trial. Support Care Cancer 22, 979–987 (2014). https://doi.org/10.1007/s00520-013-2043-9

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  • DOI: https://doi.org/10.1007/s00520-013-2043-9

Keywords

  • Nausea
  • Emesis
  • Aprepitant
  • Emetogenic chemotherapy
  • Standard antiemetic treatment