Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma

Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; howeve...

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Main Authors: Sorana G. Pisano, Sarah E. Hoffman, Carlo S. Legasto, Eric M. McLaughlin, Kyle Porter, James L. Chen
Format: Article
Language:English
Published: Wiley 2019-09-01
Series:Clinical and Translational Science
Online Access:https://doi.org/10.1111/cts.12648
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spelling doaj-a29750742cc5482bbaa30047a5d256142020-11-25T01:38:31ZengWileyClinical and Translational Science1752-80541752-80622019-09-0112552953310.1111/cts.12648Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue SarcomaSorana G. Pisano0Sarah E. Hoffman1Carlo S. Legasto2Eric M. McLaughlin3Kyle Porter4James L. Chen5Department of Pharmacy The Ohio State University Columbus Ohio USADepartment of Pharmacy The Ohio State University Columbus Ohio USADepartment of Pharmacy The Ohio State University Columbus Ohio USACenter for Biostatistics The Ohio State University Columbus Ohio USACenter for Biostatistics The Ohio State University Columbus Ohio USACenter for Biostatistics The Ohio State University Columbus Ohio USAPazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.https://doi.org/10.1111/cts.12648
collection DOAJ
language English
format Article
sources DOAJ
author Sorana G. Pisano
Sarah E. Hoffman
Carlo S. Legasto
Eric M. McLaughlin
Kyle Porter
James L. Chen
spellingShingle Sorana G. Pisano
Sarah E. Hoffman
Carlo S. Legasto
Eric M. McLaughlin
Kyle Porter
James L. Chen
Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
Clinical and Translational Science
author_facet Sorana G. Pisano
Sarah E. Hoffman
Carlo S. Legasto
Eric M. McLaughlin
Kyle Porter
James L. Chen
author_sort Sorana G. Pisano
title Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
title_short Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
title_full Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
title_fullStr Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
title_full_unstemmed Effect of Acid‐Suppressive Strategies on Pazopanib Efficacy in Patients With Soft‐Tissue Sarcoma
title_sort effect of acid‐suppressive strategies on pazopanib efficacy in patients with soft‐tissue sarcoma
publisher Wiley
series Clinical and Translational Science
issn 1752-8054
1752-8062
publishDate 2019-09-01
description Pazopanib (PAZ), a tyrosine kinase inhibitor used in the treatment of soft tissue sarcoma (STS), should not be administered with acid‐suppressive medications (ASMs) due to decreased drug solubility. Common practice for patients requiring ASM with PAZ is to separate administration by 12 hours; however, there is little real‐world evidence describing clinical outcomes using this strategy. The aim of this study was to determine whether concomitant ASM impacted efficacy and adverse event rates in patients with STS receiving PAZ. Medical records were retrospectively reviewed for patients with STS who received PAZ from June 2011 to July 2017. Patients were stratified into two groups, PAZ with or without ASM (PAZ + ASM or PAZ only). The primary objective was to determine whether progression‐free survival (PFS) differed between groups. Secondary objectives were to determine overall survival (OS) and occurrence of grade 3/4 toxicities. Ninety‐one patients were included in the study, 42 patients in the PAZ + ASM group and 49 in the PAZ only group. Median PFS was significantly shorter in the PAZ + ASM group than the PAZ only group (5.3 vs. 6.7 months). The PAZ + ASM group also had a 74% higher relative risk of progression or death than the PAZ only group, but there was no difference in OS. Regarding adverse events, the PAZ + ASM group trended toward lower levels of grade 3/4 hypertension (19% vs. 37%). These results suggest that ASM should be avoided in patients with STS receiving PAZ. Larger studies are needed to further elucidate the impact of ASM use with PAZ in clinical practice.
url https://doi.org/10.1111/cts.12648
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