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A randomized, placebo-controlled pilot trial of aprepitant combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients undergoing cyclophosphamide-based conditioning regimens prior to hematopoietic stem cell transplant (HSCT)

Abstract

The aim of this study was to evaluate the safety and efficacy of aprepitant when used prophylactically to prevent nausea and vomiting during cyclophosphamide-based conditioning regimens. The primary objective of this study was to determine if there was a difference in the number of emesis-free days in patients who received aprepitant as compared to those who received placebo. This prospective, randomized, double blind, placebo-controlled study was performed in 40 adult patients who received a cyclophosphamide-containing HSCT conditioning regimen. Twenty patients were randomized to receive aprepitant, ondansetron, and dexamethasone, and 20 were randomized to receive placebo, ondansetron, and dexamethasone. Complete response (CR) was defined as the absence of emesis and the absence of mild to moderate nausea. The average number of emesis-free days was 14.25 (standard deviation 1.48 days) in the aprepitant group compared to 12.45 days (standard deviation 2.16 days) for patients in the placebo group. Eight patients (40%) in the aprepitant group achieved CR as compared to four patients (20%) in the placebo group. In the setting of cyclophosphamide-containing conditioning regimens, the addition of aprepitant to a standard antiemetic regimen decreased the incidence of emesis as compared to placebo. Aprepitant was well tolerated.

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Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Kelsey Mulverhill.

Ethics declarations

Conflict of interest

Merck & Co., Inc. provided research funding to JB and provided study drug. All remaining authors declare that they have no conflict of interest.

Appendices

Appendix A. Standard antiemetic therapy for study conditioning chemotherapy regimens

Conditioning chemotherapy regimens

Standard antiemetic therapy

BU(16)-CY(120)

 

 Busulfan (BU) PO 16 mg/kg over 4 days

Ondansetron 8 mg PO Q 6 h × 4 days with BU

 Cyclophosphamide (CY) 120 mg/kg over 2 days

Ondansetron 8 mg IV Q 12 h × 5 doses with CY

 6 days total therapy

Dexamethasone 20 mg IV/PO Q 24 h × 2 days before CY

BU(14)-CY(150)

 

 Busulfan PO 14 mg/kg over 3.5 days

Ondansetron 8 mg PO Q 6 h × 4 days with BU

 Cyclophosphamide 150 mg/kg over 3 days

Ondansetron 8 mg IV Q 12 h × 7 doses with CY

 7 days total therapy

Dexamethasone 20 mg IV/PO Q 24 h × 3 days before CY

BU(16)-CY(200)

 

 Busulfan PO 16 mg/kg over 4 days

Ondansetron 8 mg PO Q 6 h × 4 days with BU

 Cyclophosphamide 200 mg/kg over 4 days

Ondansetron 8 mg IV Q 12 h × 9 doses with CY

 8 days total therapy

Dexamethasone 20 mg IV/PO Q 24 h × 4 days before CY

CY-TBI-12

 

 TBI 1200 cGy over 4 days in 8 fractions

Ondansetron 8 mg PO Q 12 h prior to TBI × 4 days

 Cyclophosphamide 120 mg/kg over 2 days

Ondansetron 8 mg IV Q 12 h × 5 doses with CY

 6 days total therapy

Dexamethasone 20 mg IV/PO Q 24 h × 6 days in AM

CY-TBI-14

 

 TBI 1400 cGy over 4 days in 8 fractions

Ondansetron 8 mg PO Q 12 h prior to TBI × 4 days

 Cyclophosphamide 120 mg/kg over 2 days

Ondansetron 8 mg IV Q 12 h × 5 doses with CY

 6 days total therapy

Dexamethasone 20 mg IV/PO Q 24 h × 6 days in AM

Appendix B. Quality of life (QOL)/nausea 100 mm visual analogue scale (VAS) assessment form

QUALITY OF LIFE WITH NAUSEA EVALUATION FORM

Instructions

Below are several questions related to your feelings of well-being. To answer the question make a line/slash mark at the point on the line that best represents how you are feeling at the present time. Please refer to the last 24 hour time period when answering each question.

Example:

1. Do you have nausea?

never nauseated ___|___ nauseated all the time

The place marked above would indicate that you feel nauseated over half of the time.

1. Do you have nausea? never nauseated ____ nauseated all the time

2. Do you vomit?

never vomit ____ vomit all the time

3. Have you had any changes in taste?

no changes in taste ____ many changes in taste

4. How much of an appetite do you have?

no appetite at all ____ more appetite than usual

5. Is the amount you eat sufficient for your needs?

not at all sufficient ____ completely sufficient

****For Data Management Use ONLY****

Date completed     BMT Day     Patient Initials     Patient Number     Protocol

XX-XX-XX          XX              XXX                 XX                     XX

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Bubalo, J., Mulverhill, K., Meyers, G. et al. A randomized, placebo-controlled pilot trial of aprepitant combined with standard antiemetic therapy for the prevention of chemotherapy-induced nausea and vomiting in patients undergoing cyclophosphamide-based conditioning regimens prior to hematopoietic stem cell transplant (HSCT). Bone Marrow Transplant 53, 1010–1018 (2018). https://doi.org/10.1038/s41409-018-0106-8

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