PMID- 32474662 OWN - NLM STAT- MEDLINE DCOM- 20210512 LR - 20211204 IS - 1432-1041 (Electronic) IS - 0031-6970 (Linking) VI - 76 IP - 9 DP - 2020 Sep TI - Impact of concomitant acid suppressive therapy on pazopanib efficacy and dose reductions in patients with metastatic renal cell carcinoma. PG - 1273-1280 LID - 10.1007/s00228-020-02902-3 [doi] AB - 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. FAU - Van De Sijpe, Greet AU - Van De Sijpe G AUID- ORCID: 0000-0003-1475-6178 AD - Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. greet.vandesijpe@uzleuven.be. AD - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. greet.vandesijpe@uzleuven.be. FAU - Beuselinck, Benoit AU - Beuselinck B AUID- ORCID: 0000-0001-7427-9102 AD - Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. FAU - Van Nieuwenhuyse, Tine AU - Van Nieuwenhuyse T AUID- ORCID: 0000-0002-0898-904X AD - Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. FAU - Poncelet, Roxanne AU - Poncelet R AUID- ORCID: 0000-0002-2093-958X AD - Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. AD - Pharmacy Department, Jessa Hospital, Hasselt, Belgium. FAU - Bechter, Oliver AU - Bechter O AUID- ORCID: 0000-0003-0667-3284 AD - Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium. FAU - Albersen, Maarten AU - Albersen M AUID- ORCID: 0000-0002-6763-6586 AD - Department of Urology, University Hospitals Leuven, Leuven, Belgium. FAU - Roussel, Eduard AU - Roussel E AUID- ORCID: 0000-0002-7835-5536 AD - Department of Urology, University Hospitals Leuven, Leuven, Belgium. FAU - Baldewijns, Marcella AU - Baldewijns M AUID- ORCID: 0000-0002-0882-2944 AD - Department of Pathology, University Hospitals Leuven, Leuven, Belgium. FAU - Tack, Jan AU - Tack J AUID- ORCID: 0000-0002-3206-6704 AD - Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium. AD - Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium. FAU - Spriet, Isabel AU - Spriet I AUID- ORCID: 0000-0001-6342-0676 AD - Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium. AD - Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium. LA - eng PT - Comparative Study PT - Journal Article DEP - 20200530 PL - Germany TA - Eur J Clin Pharmacol JT - European journal of clinical pharmacology JID - 1256165 RN - 0 (Histamine H2 Antagonists) RN - 0 (Indazoles) RN - 0 (Protein Kinase Inhibitors) RN - 0 (Proton Pump Inhibitors) RN - 0 (Pyrimidines) RN - 0 (Sulfonamides) RN - 7RN5DR86CK (pazopanib) SB - IM MH - Aged MH - Carcinoma, Renal Cell/*drug therapy/pathology MH - Cohort Studies MH - Dose-Response Relationship, Drug MH - Female MH - Follow-Up Studies MH - Histamine H2 Antagonists/*administration & dosage/adverse effects MH - Humans MH - Indazoles MH - Kidney Neoplasms/*drug therapy/pathology MH - Male MH - Middle Aged MH - Progression-Free Survival MH - Protein Kinase Inhibitors/administration & dosage/adverse effects MH - Proton Pump Inhibitors/*administration & dosage/adverse effects MH - Pyrimidines/*administration & dosage/adverse effects MH - Retrospective Studies MH - Sulfonamides/*administration & dosage/adverse effects MH - Survival Rate MH - Time Factors MH - Treatment Outcome OTO - NOTNLM OT - Drug-drug interaction OT - Histamine 2 receptor antagonists OT - PPI OT - Pazopanib OT - Proton pump inhibitors OT - Renal cell carcinoma OT - mRCC EDAT- 2020/06/01 06:00 MHDA- 2021/05/13 06:00 CRDT- 2020/06/01 06:00 PHST- 2020/02/06 00:00 [received] PHST- 2020/05/14 00:00 [accepted] PHST- 2020/06/01 06:00 [pubmed] PHST- 2021/05/13 06:00 [medline] PHST- 2020/06/01 06:00 [entrez] AID - 10.1007/s00228-020-02902-3 [pii] AID - 10.1007/s00228-020-02902-3 [doi] PST - ppublish SO - Eur J Clin Pharmacol. 2020 Sep;76(9):1273-1280. doi: 10.1007/s00228-020-02902-3. Epub 2020 May 30.