Greet Van De Sijpe1,2, Benoit Beuselinck3, Tine Van Nieuwenhuyse4, Roxanne Poncelet4,5, Oliver Bechter3, Maarten Albersen6, Eduard Roussel6, Marcella Baldewijns7, Jan Tack8,9, Isabel Spriet4,10. 1. Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. greet.vandesijpe@uzleuven.be. 2. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. greet.vandesijpe@uzleuven.be. 3. Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. 4. Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. 5. Pharmacy Department, Jessa Hospital, Hasselt, Belgium. 6. Department of Urology, University Hospitals Leuven, Leuven, Belgium. 7. Department of Pathology, University Hospitals Leuven, Leuven, Belgium. 8. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium. 9. Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium. 10. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium.
Abstract
PURPOSE: The aim of this study was to investigate the impact of acid suppressive therapy on clinical efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma (mRCC). METHODS: A single-center retrospective study was carried out. Charts of mRCC patients who received pazopanib as first-line treatment were reviewed and concomitant use of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was studied. Two groups of patients were identified, namely patients receiving PPI/H2RA and patients without acid suppressive therapy. Both groups were compared with regard to progression free survival (PFS), overall survival (OS), tumor response, and time to dose reduction of pazopanib. RESULTS: Ninety-one patients were included. Median PFS was 8 months in the PPI/H2RA group vs. 7 months in the no PPI/H2RA group (hazard ratio (HR) 0.76 (95% confidence interval (CI) 0.42-1.35)), p = 0.35. Median OS was 27 months in the PPI/H2RA group vs. 23 months in the no PPI/H2RA group (HR 0.87 (95% CI 0.46-1.66)), p = 0.68. Mean tumor response was 17% (95% CI 8-25%) in the PPI/H2RA group vs. 11% (95% CI 0-21%) in the no PPI/H2RA group, p = 0.52. Median time to first dose reduction was 9 months in both subgroups (HR 1.25 (95% CI 0.65-2.39)), p = 0.51. Median time to second dose (< 600 mg) reduction was 17 months in the PPI/H2RA group vs. 7 months in the no PPI/H2RA group (HR 0.26 (95% CI 0.07-0.89)), p = 0.03. CONCLUSION: In this limited patient series, no evidence of a negative impact of PPI/H2RA on clinical outcome and time to first dose reduction was observed. These results suggest that PPI/H2RA might be considered, when there is a clinical need, in patients treated with pazopanib for mRCC. However, a prospective study is warranted to confirm these results.
PURPOSE: The aim of this study was to investigate the impact of acid suppressive therapy on clinical efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma (mRCC). METHODS: A single-center retrospective study was carried out. Charts of mRCC patients who received pazopanib as first-line treatment were reviewed and concomitant use of proton pump inhibitors (PPI) and histamine 2 receptor antagonists (H2RA) was studied. Two groups of patients were identified, namely patients receiving PPI/H2RA and patients without acid suppressive therapy. Both groups were compared with regard to progression free survival (PFS), overall survival (OS), tumor response, and time to dose reduction of pazopanib. RESULTS: Ninety-one patients were included. Median PFS was 8 months in the PPI/H2RA group vs. 7 months in the no PPI/H2RA group (hazard ratio (HR) 0.76 (95% confidence interval (CI) 0.42-1.35)), p = 0.35. Median OS was 27 months in the PPI/H2RA group vs. 23 months in the no PPI/H2RA group (HR 0.87 (95% CI 0.46-1.66)), p = 0.68. Mean tumor response was 17% (95% CI 8-25%) in the PPI/H2RA group vs. 11% (95% CI 0-21%) in the no PPI/H2RA group, p = 0.52. Median time to first dose reduction was 9 months in both subgroups (HR 1.25 (95% CI 0.65-2.39)), p = 0.51. Median time to second dose (< 600 mg) reduction was 17 months in the PPI/H2RA group vs. 7 months in the no PPI/H2RA group (HR 0.26 (95% CI 0.07-0.89)), p = 0.03. CONCLUSION: In this limited patient series, no evidence of a negative impact of PPI/H2RA on clinical outcome and time to first dose reduction was observed. These results suggest that PPI/H2RA might be considered, when there is a clinical need, in patients treated with pazopanib for mRCC. However, a prospective study is warranted to confirm these results.
Authors: Stefanie D Krens; Floor J E Lubberman; Marthe van Egmond; Frank G A Jansman; David M Burger; Paul Hamberg; Walter L Vervenne; Hans Gelderblom; Winette T A van der Graaf; Ingrid M E Desar; Carla M L van Herpen; Nielka P van Erp Journal: Int J Cancer Date: 2021-01-19 Impact factor: 7.396