The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?

Mustafa Karaağaç; Yasin Sezgin; Murat Araz; Melek Karakurt Eryılmaz; Muhammet Ali Kaplan; Mehmet Artaç

doi:10.5798/dicletip.706025

The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?

Abstract

Objectives: Pazopanib is an orally administered drug and has approval for the treatment of advanced Soft Tissue Sarcomas (aSTS). The absorption of pazopanib is pH-dependent. Acid-Reducing drugs such as proton pump inhibitors (PPI) may reduce the bioavailability of pazopanib. The primary purpose of this study was to assess whether the use of concomitant PPI and pazopanib had negative effects on survival outcomes. Methods: In this retrospective cross-sectional study, age ≥18 years, having histologically proven STS, receiving pazopanib at least one day, and availability of information about the use of PPI during pazopanib treatment were the inclusion criteria. Patients with adipocytic sarcoma were excluded. Results: A total of 46 eligible patients were assessed in this study. Thirty-one patients used concomitant PPI and pazopanib, 17 of them frequently used PPI, and the others occasionally. Fifteen patients never used concomitant PPI and pazopanib. The median progression-free survival (PFS) was 2.76 months, and the median overall survival (OS) was 7.39 months for patients who never used concomitant PPI and pazopanib. Also, the median PFS was 5.22 months, and the median OS was 14.52 months for patients who used concomitant PPI and pazopanib. In univariate analysis; using concomitant PPI (p=0.049) and primarily uterine located tumors (p=0.038) were significant parameters for PFS. In multivariate logistic regression analysis; both of using concomitant PPI (Wald=6.02; p=0.014) and primarily uterine located tumors (Wald=5.69; p=0.017) retained their association with longer PFS. No parameter was significant for OS. Conclusions: We showed that the use of concomitant PPI and pazopanib was associated with improved PFS. These results may help guide clinicians and researchers for allowing patients co-administrating PPI and pazopanib, especially when treating or investigating patients with dyspeptic symptoms.

Keywords

pazopanib,proton pump inhibitor

References

1. American Cancer Society. Cancer Facts & Figures 2017. Atlanta: American Cancer Society. 2017.
2. Blay J-Y, van Glabbeke M, Verweij J, et al. Advanced soft-tissue sarcoma: a disease that is potentially curable for a subset of patients treated with chemotherapy. Eur J Cancer. 2003; 39: 64-69.
3. Kasper B, Hohenberger P. Pazopanib: a promising new agent in the treatment of soft tissue sarcomas. FuturOncol. 2011; 7: 1373-83.
4. Kasper B, Sleijfer S, Litière S, et al. Long-term responders and survivors on pazopanib for advanced soft tissue sarcomas: Subanalysis of two European Organisation for Research and Treatment of Cancer (EORTC) clinical trials 62043 and 62072. Ann Oncol. 2014; 25: 719- 24.
5. Van Der Graaf WT, Blay JY, Chawla SP, et al. Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial. Lancet. 2012; 379: 1879-86.
6. Hutson TE, Davis ID, Machiels JPH, et al. Efficacy and safety of pazopanib in patients with metastatic renal cell carcinoma. J ClinOncol. 2010; 28: 475-80.
7. Budha NR, Frymoyer A, Smelick GS, et al. Drug absorption interactions between oral targeted anticancer agents and PPIs: Is pH-dependent solubility the achilles heel of targeted therapy. ClinPharmacolTher. 2012; 92: 203-13.
8. Suttle AB, Ball HA, Molimard M, et al. Relationships between pazopanib exposure and clinical safety and efficacy in patients with advanced renal cell carcinoma. Br J Cancer. 2014; 111: 1909-16.

9. Verheijen RB, Swart LE, Beijnen JH, Schellens JHM, Huitema ADR, Steeghs N. Exposure-survival analyses of pazopanib in renal cell carcinoma and soft tissue sarcoma patients: opportunities for dose optimization. Cancer ChemotherPharmacol. 2017; 80: 1171-78.
10. Tan AR, Gibbon DG, Stein MN, et al. Effects of ketoconazole and esomeprazole on the pharmacokinetics of pazopanib in patients with solid tumors. Cancer ChemotherPharmacol. 2013; 71: 1635-43.
11. Smelick GS, Heffron TP, Chu L, et al. Prevalence of acid-reducing agents (ARA) in cancer populations and ARA drug-drug interaction potential for molecular targeted agents in clinical development. Mol Pharm. 2013; 10: 4055-62.
12. Mir O, Touati N, Lia M, et al. Impact of concomitant administration of gastric acid–suppressive agents and pazopanib on outcomes in soft-tissue sarcoma patients treated within the EORTC 62043/62072 trials. Clin Cancer Res. 2019; 25: 1479-85.
13. McAlister RK, Aston J, Pollack M, Du L, Koyama T, Chism DD. Effect of Concomitant pH‐Elevating Medications with Pazopanib on Progression‐Free Survival and Overall Survival in Patients with Metastatic Renal Cell Carcinoma. Oncologist.2018; 23: 686-92.
14. Votrient® [packageinsert]. East Hanover, NJ: Novartis Pharmaceuticals Corporation. 2017.
15. van Leeuwen RWF, Peric R, Hussaarts KGAM, et al. Influence of the Acidic Beverage Cola on the Absorption of Erlotinib in Patients With Non–Small-Cell Lung Cancer. J ClinOncol. 2016; 34: 1309-14.
16. Yin OQP, Gallagher N, Fischer D, et al. Effect of the Proton Pump Inhibitor Esomeprazole on the Oral Absorption and Pharmacokinetics of Nilotinib. J ClinPharmacol. 2010; 50: 960-67.
17. Ter Heine R, Fanggiday JC, Lankheet NAG, et al. Erlotinib and pantoprazole: a relevant interaction or not? Br J ClinPharmacol. 2010; 70: 908-11.
18. Hilton JF, Tu D, Seymour L, Shepherd FA, Bradbury PA. An evaluation of the possible interaction of gastric acid suppressing medication and the EGFR tyrosine kinase inhibitor erlotinib. Lung Cancer. 2013; 82: 136-42.
19. Nakamura T, Matsumine A, Kawai A, et al. The clinical outcome of pazopanib treatment in Japanese patients with relapsed soft tissue sarcoma: A Japanese Musculoskeletal Oncology Group (JMOG) study. Cancer. 2016; 122: 1408-16.
20. Duman BB, Gunaldi M, Ercolak V, et al. Retrospective analysis of 498 primary soft tissue sarcomas in a single Turkish centre. Asian Pac J Cancer Prev. 2012; 13: 4125-28.

Details

Primary Language

English

Subjects

Health Care Administration

Journal Section

Research Article

Authors

Mustafa Karaağaç This is me
Türkiye

Yasin Sezgin This is me
Türkiye

Murat Araz This is me
Türkiye

Melek Karakurt Eryılmaz This is me
Türkiye

Muhammet Ali Kaplan This is me
Türkiye

Mehmet Artaç This is me
Türkiye

Publication Date

March 17, 2020

Submission Date

December 11, 2019

Acceptance Date

January 22, 2020

Published in Issue

Year 2020 Volume: 47 Number: 1

DOI

https://doi.org/10.5798/dicletip.706025

IZ

https://izlik.org/JA48NS83JU

Cite

RIS / Bibtex

APA

Karaağaç, M., Sezgin, Y., Araz, M., Eryılmaz, M. K., Kaplan, M. A., & Artaç, M. (2020). The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided? Dicle Medical Journal, 47(1), 82-88. https://doi.org/10.5798/dicletip.706025

AMA

1.Karaağaç M, Sezgin Y, Araz M, Eryılmaz MK, Kaplan MA, Artaç M. The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided? Dicle Medical Journal. 2020;47(1):82-88. doi:10.5798/dicletip.706025

Chicago

Karaağaç, Mustafa, Yasin Sezgin, Murat Araz, Melek Karakurt Eryılmaz, Muhammet Ali Kaplan, and Mehmet Artaç. 2020. “The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?”. Dicle Medical Journal 47 (1): 82-88. https://doi.org/10.5798/dicletip.706025.

EndNote

Karaağaç M, Sezgin Y, Araz M, Eryılmaz MK, Kaplan MA, Artaç M (March 1, 2020) The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided? Dicle Medical Journal 47 1 82–88.

IEEE

[1]M. Karaağaç, Y. Sezgin, M. Araz, M. K. Eryılmaz, M. A. Kaplan, and M. Artaç, “The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?”, Dicle Medical Journal, vol. 47, no. 1, pp. 82–88, Mar. 2020, doi: 10.5798/dicletip.706025.

ISNAD

Karaağaç, Mustafa - Sezgin, Yasin - Araz, Murat - Eryılmaz, Melek Karakurt - Kaplan, Muhammet Ali - Artaç, Mehmet. “The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?”. Dicle Medical Journal 47/1 (March 1, 2020): 82-88. https://doi.org/10.5798/dicletip.706025.

JAMA

1.Karaağaç M, Sezgin Y, Araz M, Eryılmaz MK, Kaplan MA, Artaç M. The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided? Dicle Medical Journal. 2020;47:82–88.

MLA

Karaağaç, Mustafa, et al. “The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided?”. Dicle Medical Journal, vol. 47, no. 1, Mar. 2020, pp. 82-88, doi:10.5798/dicletip.706025.

Vancouver

1.Mustafa Karaağaç, Yasin Sezgin, Murat Araz, Melek Karakurt Eryılmaz, Muhammet Ali Kaplan, Mehmet Artaç. The Concomitant Use Of Proton Pump Inhibitors And Pazopanib In Patients With Soft-Tissue Sarcoma: Is It Really To Be Avoided? Dicle Medical Journal. 2020 Mar. 1;47(1):82-8. doi:10.5798/dicletip.706025