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Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin

International Journal of Clinical Oncology volume 21, pages 491–497 (2016)Cite this article

Abstract

Background

Substance P contributes to the hypersensitivity reaction (HSR) to paclitaxel in a rat model. Aprepitant acts as an inhibitor of the binding of substance P to the neurokinin-1 receptor and, consequently, may reduce the frequency of paclitaxel-induced HSR. While aprepitant has a prophylactic effect against vomiting caused by high-dose cisplatin, the benefits of aprepitant have not been clearly demonstrated in patients receiving paclitaxel and carboplatin (TC) combination chemotherapy.

Methods

We conducted a multicenter, placebo-controlled, double-blind, randomized study in Japanese patients with gynecologic cancer who received TC combination chemotherapy. Patients received aprepitant or placebo together with both a 5-HT3 receptor antagonist and dexamethasone prior to chemotherapy. The primary endpoint was the proportion of patients with HSR, and the secondary endpoints were the proportion of patients with “no vomiting”, “no significant nausea”, and complete response, respectively.

Results

Of the 324 randomized patients, 297 (151 in the aprepitant group; 146 in the placebo group) were evaluated. The percentage of patients with HSR (9.2 vs. 7.5 %, respectively; P = 0.339) was not significantly different between the groups. The percentage of “no vomiting” patients (78.2 vs. 54.8 %; P < 0.0001), “no significant nausea” patients (85.4 vs. 74.7 %; P = 0.014), and patients showing complete response (61.6 vs. 47.3 %, P = 0.0073) was significantly higher in the aprepitant group than in the placebo group.

Conclusion

The administration of aprepitant did not have a prophylactic effect on the HSR but was effective in reducing nausea and vomiting in gynecologic cancer patients receiving TC combination chemotherapy.

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Acknowledgments

We thank all of the participating patients, institutions, and the Clinical Research Support Center (CReS Kyushu). We also thank Drs. Ryozo Oishi, Masatoshi Mine, Kazuhiro Nakashima, Soichiro Ushio, and Akiko Kanaya (Department of Pharmacy, Kyushu University Hospital).

Author information

Authors and Affiliations

  1. Department of Obstetrics and Gynecology, Kyushu University Hospital, Fukuoka, Japan

    Hideaki Yahata, Kenzo Sonoda & Kiyoko Kato

  2. Department of Obstetrics and Gynecology, Faculty of Medicine, Kagoshima University Hospital, Kagoshima, Japan

    Hiroaki Kobayashi

  3. Center of Clinical Research, National Kyushu Cancer Center, Fukuoka, Japan

    Mototsugu Shimokawa

  4. Department of Obstetrics and Gynecology, Miyazaki Prefectural Hospital, Miyazaki, Japan

    Tatsuhiro Ohgami

  5. Gynecology Service, National Kyushu Cancer Center, Fukuoka, Japan

    Toshiaki Saito

  6. Department of Obstetrics and Gynecology, Kyushu Hospital, Kitakyushu, Japan

    Shinji Ogawa

  7. Department of Obstetrics and Gynecology, Saiseikai Fukuoka Hospital, Fukuoka, Japan

    Kunihiro Sakai

  8. Department of Obstetrics and Gynecology, Kitakyushu Municipal Medical Center, Kitakyushu, Japan

    Akimasa Ichinoe

  9. Department of Obstetrics and Gynecology, Hamanomachi Hospital, Fukuoka, Japan

    Yousuke Ueoka

  10. Department of Obstetrics and Gynecology, National Kyushu Medical Center, Fukuoka, Japan

    Yasuyuki Hasuo

  11. Department of Obstetrics and Gynecology, Fukuoka Red Cross Hospital, Fukuoka, Japan

    Makoto Nishida

  12. Department of Pharmacy, Kyushu University Hospital, Fukuoka, Japan

    Satohiro Masuda

Authors
  1. Hideaki Yahata
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  2. Hiroaki Kobayashi
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  3. Kenzo Sonoda
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  4. Mototsugu Shimokawa
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  5. Tatsuhiro Ohgami
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  7. Shinji Ogawa
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  8. Kunihiro Sakai
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  9. Akimasa Ichinoe
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  10. Yousuke Ueoka
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  11. Yasuyuki Hasuo
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  12. Makoto Nishida
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  13. Satohiro Masuda
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  14. Kiyoko Kato
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Corresponding author

Correspondence to Hiroaki Kobayashi.

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Funding

This study was supported in part by a grant-in-aid for scientific research from the Japan Society for the Promotion of Science (Numbers 24592520 and 24592519).

Conflict of interest

The authors declare that they have no conflicts of interest.

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Yahata, H., Kobayashi, H., Sonoda, K. et al. Efficacy of aprepitant for the prevention of chemotherapy-induced nausea and vomiting with a moderately emetogenic chemotherapy regimen: a multicenter, placebo-controlled, double-blind, randomized study in patients with gynecologic cancer receiving paclitaxel and carboplatin. Int J Clin Oncol 21, 491–497 (2016). https://doi.org/10.1007/s10147-015-0928-y

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  • DOI: https://doi.org/10.1007/s10147-015-0928-y

Keywords

  • Aprepitant
  • CINV
  • Hypersensitivity reaction
  • Gynecologic cancer
  • MEC regimen