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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

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).

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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