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Effectiveness of aprepitant in addition to ondansetron in the prevention of nausea and vomiting caused by fractionated radiotherapy to the upper abdomen (AVERT)

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Abstract

Purpose

Despite a lower risk of nausea and vomiting in patients receiving radiotherapy to the upper abdomen (UA-RINV) with prophylactic 5-HT3 antagonist therapy, patients can still experience UA-RINV. The aim of this multicenter phase II study was to assess effectiveness, safety, and tolerability of protracted dual NK1-receptor and 5-HT3 antagonist prophylaxis against UA-RINV.

Methods

Patients receiving fractionated radiotherapy with radiosensitizing chemotherapy received oral ondansetron 8 mg po q12 h and aprepitant 125/80/80 mg on a Monday, Wednesday, Friday schedules throughout radiotherapy. The primary outcome was complete response (CR) defined as no vomiting or rescue therapy during the entire observation period of radiotherapy (OP). Nausea, vomiting, and use of rescue medication were recorded in a modified version of the MASCC antiemesis tool completed twice weekly.

Results

Fifty-five patients were enrolled at 5 sites, 52 of whom were evaluable. 57.7% of patients (30/52, 95% CI 43.2–71.3%) achieved CR on study, with 73.1% (38/52, 95% CI 59.0–84.4%) who did not vomit, and 71.2% (37/52, 95% CI 56.9–82.9%) who did not use rescue medication during the OP. Overall, participants vomited or experienced significant nausea (SN) for an average of 6.8% (95% CI 11.4–21.0) and 8.4% (95% CI 4.2–12.7%) of time on study, respectively. Nausea was common with 32 (61.5%) reporting SN at any time during the OP.

Conclusions

UA-RINV remains an important morbidity despite the advent of modern radiotherapy. Aprepitant and ondansetron as dosed in this trial was not superior to standard ondansetron monotherapy.

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Abbreviations

RINV:

Radiation induced nausea and vomiting

OP:

Observation period

RTP:

Radiation therapy period

PK:

Pharmacokinetic

UA:

Upper abdominal

CR:

Complete response

SN:

Significant nausea

AN:

Any nausea

5-HT3:

5-Hydroxytryptamine

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Acknowledgements

We want to remember Dr. Steven Grunberg, who was a key original investigator in the conception and drafting of the protocol for this study before his untimely passing in 2014. His leadership and vision in the field of supportive care in cancer has been an inspiration to all investigators who participated in this study and the broader oncology community.

Support

This project was supported by an industry grant for Merck. The content is solely the responsibility of the authors. ClinicalTrials.gov identifier: NCT00970905.

The following institutions participated in the study:

1. University of Vermont Cancer Center, Burlington, VT

2. Mayo Clinic, Scottsdale, AZ

3. Wake Forest University Baptist Medical Center, NC

4. Dartmouth Hitchcock Medical Center

5. University of Massachusetts Memorial Medical Center

Author information

Authors and Affiliations

  1. University of Vermont Cancer Center, Given Building, E214C, 89 Beaumont Ave, Burlington, VT, 05405, USA

    Steven Ades, K. Wilson & R. Heimann

  2. Mayo Clinic, Scottsdale, AZ, USA

    M. Halyard

  3. Medical Biostatistics, University of Vermont, Burlington, VT, USA

    T. Ashikaga

  4. University of Rochester, Rochester, NY, USA

    S. Kumar

  5. Wake Forest University Baptist Medical Center, Winston-Salem, NC, USA

    W. Blackstock

Authors
  1. Steven Ades
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  2. M. Halyard
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  3. K. Wilson
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  4. T. Ashikaga
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  5. R. Heimann
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  6. S. Kumar
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  7. W. Blackstock
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Corresponding author

Correspondence to Steven Ades.

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Ades, S., Halyard, M., Wilson, K. et al. Effectiveness of aprepitant in addition to ondansetron in the prevention of nausea and vomiting caused by fractionated radiotherapy to the upper abdomen (AVERT). Support Care Cancer 25, 1503–1510 (2017). https://doi.org/10.1007/s00520-016-3540-4

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  • DOI: https://doi.org/10.1007/s00520-016-3540-4

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