The effect of proton pump inhibitors on survival outcomes in advanced hepatocellular carcinoma treated with sorafenib
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ORIGINAL ARTICLE – CLINICAL ONCOLOGY
The effect of proton pump inhibitors on survival outcomes in advanced hepatocellular carcinoma treated with sorafenib Warit Ruanglertboon1 · Michael J. Sorich1 · Jessica M. Logan2 · Andrew Rowland1 · Ashley M. Hopkins1 Received: 8 May 2020 / Accepted: 14 May 2020 © Springer-Verlag GmbH Germany, part of Springer Nature 2020
Abstract Purpose Sorafenib is an oral tyrosine kinase inhibitor (TKI) and first-line treatment option for advanced hepatocellular carcinoma (HCC). Preliminary evidence indicates proton pump inhibitors (PPI) may affect the absorption of TKIs through decreased gut dissolution. This study aims to evaluate the impact of PPI use on the survival outcomes of advanced HCC patients treated with sorafenib. Methods The study was a secondary analysis of individual-participant data from the phase III clinical trial NCT00699374. Cox proportional hazard analysis was used to evaluate the association between baseline PPI use and survival outcomes. Overall survival (OS) was the primary outcome with progression-free survival (PFS) secondary. Results In a cohort of 542 advanced HCC patients initiating sorafenib treatment, 122 were concomitantly using a PPI at baseline. No significant associations between baseline PPI use and OS were identified on univariable (HR [95% CI]; 1.01 [0.80–1.28], P = 0.93) and adjusted (1.10 [0.82–1.41], P = 0.62) analysis. Furthermore, no significant associations between baseline PPI use and PFS were identified on univariable (0.96 [0.76–1.21], P = 0.73) and adjusted (1.11 [0.86–1.44], P = 0.41) analysis. Conclusion In a large high-quality dataset, PPI use was not observed to compromise the survival outcomes of advanced HCC patients initiated on sorafenib. Keywords Sorafenib · Proton pump inhibitors · Prediction · Survival outcomes
Introduction Sorafenib is an oral tyrosine kinase inhibitor (TKIs) and the current mainstay first-line treatment for advanced hepatocellular carcinoma (HCC) (Likhitsup et al. 2019). Sorafenib acts as a potent inhibitor of vascular endothelial growth factor (VEGFR) subtype 1, 2 and 3, platelet-derived growth factor-beta (PDGFRβ) and fibroblast growth factor receptor 1 (FGFR1) (Wilhelm et al. 2006, 2008). Electronic supplementary material The online version of this article (https://doi.org/10.1007/s00432-020-03261-3) contains supplementary material, which is available to authorized users. * Warit Ruanglertboon [email protected] 1
Department of Clinical Pharmacology, College of Medicine and Public Health, Flinders University, Adelaide, Australia
Mechanisms in Cell Biology and Disease Research Group, Clinical and Health Sciences, Cancer Research Institute, University of South Australia, Adelaide, Australia
2
Recently, clinical studies reported a high degree of interindividual variability in the pharmacokinetic profile of sorafenib (Nexavar: European Public Assessment Reports (EPAR)-Scientific Discussion. 2007). It is suggested that sorafenib has a limited absorption capacity in the gastr
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