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Randomized open-label phase II trial of 5-day aprepitant plus ondansetron compared to ondansetron alone in the prevention of chemotherapy-induced nausea-vomiting (CINV) in glioma patients receiving adjuvant temozolomide

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Abstract

Purpose

CINV remains a distressing side effect experienced by glioma patients receiving multi-day temozolomide therapy, in spite of guideline-based antiemetic therapy with selective serotonin-receptor-antagonists. Antiemetic research with aprepitant has routinely excluded glioma patients. In this randomized open-label phase II study, use of a nonstandard 5-day regimen of aprepitant for glioma patients was investigated.

Methods

One hundred thirty-six glioma patients receiving their first cycle of adjuvant temozolomide (150–200 mg/m2/day × 5 days every 28 days) were randomized to Arm-A (ondansetron 8 mg days 1–5 with aprepitant day 1: 125 mg, days 2–5: 80 mg) or Arm-B (ondansetron). Randomization was stratified by tumor grade and number of prior chemotherapy regimens. The primary endpoint was the percentage of patients achieving complete control (CC), defined as no emetic episode or antiemetic rescue medication over the 7-day study period. Secondary endpoints included CINV efficacy in the acute phase (≤ 24 h) and delayed phase (days 2–7), as well as safety and quality of life (QoL).

Results

Patients were 61% male, 97% white, 48% with KPS > 90%, 60% non-smokers, mean age 54, 92% with low alcohol use, and 46% with a CINV history. The CC was 58.6% (Arm-A) and 54.5% (Arm-B). Acute-complete response (CR) rates, defined as CC on day 1 in Arm-A and -B, were 97.1% and 87.9%, respectively (p = 0.056). Treatment-related toxicities were mild or moderate in severity.

Conclusions

Aprepitant plus ondansetron may increase acute-CR, may have benefit regarding CINV’s effect on QoL, and is safe for 5-day temozolomide compared to ondansetron. This study provides no evidence that aprepitant increases CC rate over ondansetron alone.

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Acknowledgements

We would like to acknowledge Wendy R. Gentry for her formatting and development of tables and figures.

Funding

Merck provided aprepitant and funding for this investigator-initiated study.

Author information

Authors and Affiliations

  1. Department of Pharmacy, Duke University Hospital, Durham, USA

    Mallika P. Patel

  2. Department of Neurosurgery, The Preston Robert Tisch Brain Tumor Center, Duke University Medical Center, Durham, NC, USA

    Mallika P. Patel, Sarah Woodring, Dina M. Randazzo, Henry S. Friedman, Annick Desjardins, Eric S. Lipp, Elizabeth Miller, Katherine B. Peters & Mary Lou Affronti

  3. Department of Neurology, Duke University School of Medicine, Durham, NC, USA

    Dina M. Randazzo, Annick Desjardins & Katherine B. Peters

  4. Duke Cancer Center Biostatistics, Durham, NC, USA

    Patrick Healy, James E. Herndon II & Frances McSherry

  5. Department of Biostatistics and Bioinformatics, Duke University School of Medicine, Durham, NC, USA

    James E. Herndon II

  6. Duke Health, Duke University School of Nursing, Durham, NC, 27710, USA

    Mary Lou Affronti

  7. Duke School of Nursing Faculty, Primary Investigator, Department of Neuro-Surgery, The Preston Robert Tisch Brain Tumor Center, 047 Baker House, Trent Drive, DUMC Box 3624, Durham, NC, 27710, USA

    Mary Lou Affronti

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  1. Mallika P. Patel
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Corresponding author

Correspondence to Mary Lou Affronti.

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Ethics approval and informed consent

All study processes involving human subjects were performed in accordance with the ethical standards of the institutional review board of the Duke University Medical Center. All study participants voluntarily provided written informed consent prior to study inclusion.

Conflict of interest

Mary Lou Affronti has been supported by Eisai and Merck for investigator initiated clinical trials, served as an antiemetic expert advisory board member with Eisai for NEPA (2013–2014) and for Merck on an Advisory Expert Input forum (2017). Sarah Woodring, Annick Desjardins, Eric Lipp, and Elizabeth Miller received support from grant by Merck with their involvement during the conduct of the study. All other authors declare no conflict of interest at this time.

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Patel, M.P., Woodring, S., Randazzo, D.M. et al. Randomized open-label phase II trial of 5-day aprepitant plus ondansetron compared to ondansetron alone in the prevention of chemotherapy-induced nausea-vomiting (CINV) in glioma patients receiving adjuvant temozolomide. Support Care Cancer 28, 2229–2238 (2020). https://doi.org/10.1007/s00520-019-05039-x

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