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Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study

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Abstract

Purpose

A phase III study adding aprepitant to a 5HT3 receptor antagonist (5HT3-RA) plus dexamethasone in germ cell tumor (GCT) patients treated with 5-day cisplatin combination chemotherapy demonstrated a significant improvement in complete response (CR) (J Clin Onc 30:3998-4003, 2012). Fosaprepitant has demonstrated non-inferiority compared to aprepitant in single-day cisplatin chemotherapy and is approved as a single-dose alternative. This single-arm phase II study is the first clinical trial evaluating fosaprepitant in patients receiving multi-day cisplatin regimen.

Methods

GCT patients receiving a 5-day cisplatin combination chemotherapy were enrolled. Fosaprepitant 150 mg was given IV on days 3 and 5. A 5HT3-RA days 1–5 (days 1, 3, and 5, if palonosetron) plus dexamethasone 20 mg days 1 and 2 and 4 mg po bid days 6, 7, and 8 was administered. Rescue antiemetics were allowed. The primary objective was to determine the CR rate—no emetic episodes or use of rescue medications. Accrual of 64 patients was planned with expected CR > 27 %.

Results

Sixty-five patients were enrolled of whom 54 were eligible for analysis. Median age was 33. Fifty-one patients received bleomycin, etoposide, and cisplatin (BEP) chemotherapy. CR was observed in 13 (24.1 %) patients (95 % Agresti-Coull binomial C.I. 14.5 %, 37.1 %).

Conclusion

The data in this phase II study, in contrast to our prior phase III study, appears to indicate a lower CR rate with the substitution of fosaprepitant for aprepitant. It is unknown whether the substitution of fosaprepitant for aprepitant provides the same benefit in multi-day cisplatin that was achieved with single-day cisplatin.

Trial registration Clinical trial information NCT01736917

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Acknowledgments

All authors had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.

Funding/support

This trial is supported by Merck & Co. Inc.

Author information

Authors and Affiliations

  1. Division of Hematology/Oncology, Melvin & Bren Simon Cancer Center, Indiana University School of Medicine, 535 Barnhill Drive, RT 400, Indianapolis, IN, 46202, USA

    Nabil Adra, Costantine Albany, Mary J. Brames, Somer Case-Eads, Christopher A. Fausel, Nasser H. Hanna & Lawrence H. Einhorn

  2. Department of Biostatistics, Indiana University, Indianapolis, IN, USA

    Cynthia S. Johnson & Ziyue Liu

  3. Hoosier Cancer Research Network, Indianapolis, IN, USA

    Timothy Breen

  4. Methodist Hospital/Nebraska Cancer Specialists, Omaha, NE, USA

    Ralph J. Hauke

  5. Division of Hematology/Oncology, Washington University School of Medicine, St. Louis, MO, USA

    Joel Picus

Authors
  1. Nabil Adra
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  2. Costantine Albany
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  3. Mary J. Brames
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  4. Somer Case-Eads
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  5. Cynthia S. Johnson
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  6. Ziyue Liu
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  7. Christopher A. Fausel
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  8. Timothy Breen
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  9. Nasser H. Hanna
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  10. Ralph J. Hauke
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  11. Joel Picus
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  12. Lawrence H. Einhorn
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Corresponding author

Correspondence to Nabil Adra.

Ethics declarations

This single-arm HCRN phase II study was conducted from 2013 to 2015 after approval by each site’s institutional review board. Informed consent was obtained from all individual participants included in the study.

Conflict of interest

Cynthia S. Johnson’s husband works for Lilly and has Lilly stock in his retirement account. Nasser H. Hanna received grant support from Merck for another study. All other authors declare no competing interests.

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Adra, N., Albany, C., Brames, M.J. et al. Phase II study of fosaprepitant + 5HT3 receptor antagonist + dexamethasone in patients with germ cell tumors undergoing 5-day cisplatin-based chemotherapy: a Hoosier Cancer Research Network study. Support Care Cancer 24, 2837–2842 (2016). https://doi.org/10.1007/s00520-016-3100-y

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  • DOI: https://doi.org/10.1007/s00520-016-3100-y

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