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Impact of concomitant acid suppressive therapy on pazopanib efficacy and dose reductions in patients with metastatic renal cell carcinoma

  • Pharmacokinetics and Disposition
  • Published:
European Journal of Clinical Pharmacology Aims and scope Submit manuscript

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.

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Author information

Authors and Affiliations

  1. Pharmacy Department, University Hospitals Leuven, Herestraat 49, 3000, Leuven, Belgium

    Greet Van De Sijpe, Tine Van Nieuwenhuyse, Roxanne Poncelet & Isabel Spriet

  2. Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Leuven, Belgium

    Greet Van De Sijpe & Isabel Spriet

  3. Department of General Medical Oncology, University Hospitals Leuven, Leuven, Belgium

    Benoit Beuselinck & Oliver Bechter

  4. Pharmacy Department, Jessa Hospital, Hasselt, Belgium

    Roxanne Poncelet

  5. Department of Urology, University Hospitals Leuven, Leuven, Belgium

    Maarten Albersen & Eduard Roussel

  6. Department of Pathology, University Hospitals Leuven, Leuven, Belgium

    Marcella Baldewijns

  7. Department of Gastroenterology and Hepatology, University Hospitals Leuven, Leuven, Belgium

    Jan Tack

  8. Translational Research Center for Gastrointestinal Disorders (TARGID), Department of Chronic Diseases and Metabolism (CHROMETA), KU Leuven, Leuven, Belgium

    Jan Tack

Authors
  1. Greet Van De Sijpe
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Contributions

Conceptualization and methodology: Van De Sijpe Greet, Van Nieuwenhuyse Tine, Beuselinck Benoit, and Spriet Isabel; Formal analysis and investigation: Van De Sijpe Greet, Poncelet Roxanne, and Beuselinck Benoit; Writing—original draft preparation: Van De Sijpe Greet; Writing—review and editing: all authors; Supervision: Beuselinck Benoit and Spriet Isabel.

Corresponding author

Correspondence to Greet Van De Sijpe.

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Conflict of interest

Beuselinck Benoit received an unrestricted research grant from Bristol-Myers-Squibb for other research projects and honorarium from Merck, Pfizer, Bristol-Myers-Squibb, Ipsen, and Astra Zeneca. Tack Jan has given scientific advice to Sofar, Takeda, and Truvion, has received research support from Sofar, and has served on the Speaker bureau for Takeda and Truvion. The other authors report no conflict of interest.

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The hospital ethics committee approved this retrospective study.

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Van De Sijpe, G., Beuselinck, B., Van Nieuwenhuyse, T. et al. Impact of concomitant acid suppressive therapy on pazopanib efficacy and dose reductions in patients with metastatic renal cell carcinoma. Eur J Clin Pharmacol 76, 1273–1280 (2020). https://doi.org/10.1007/s00228-020-02902-3

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  • DOI: https://doi.org/10.1007/s00228-020-02902-3

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