Journal of Neuro-Oncology

, Volume 134, Issue 2, pp 325–330 | Cite as

Effect of angiotensin system inhibitors on survival in newly diagnosed glioma patients and recurrent glioblastoma patients receiving chemotherapy and/or bevacizumab

  • Victor A. Levin
  • James Chan
  • Meenal Datta
  • Jennie L. Yee
  • Rakesh K. Jain
Clinical Study

Abstract

Given prior studies that suggest the use of angiotensin system inhibitors (ASIs) is associated with prolonged overall survival (OS) in glioblastoma (GBM) patients, we evaluated the effect of ASIs in glioma patients receiving chemotherapy and/or bevacizumab (BEV). Using retrospective IRB-approved electronic chart review of newly diagnosed WHO grade 2–4 glioma patients from the Kaiser Permanente Tumor Registry of Northern California, we evaluated the impact of ASIs on OS by Cox proportional hazard model analysis for subgroups who received cytotoxic therapy, cytotoxic therapy with BEV, or BEV alone, as well as those with recurrent GBM (rGBM). Of the 1186 glioma patients who received chemotherapy ASI exposure improved OS (HR 0.82; 95% CI 0.71, 0.93; p = 0.003). When stratified by BEV exposure, a sub-analysis revealed further OS advantage for the BEV group (HR 0.75, 95% CI 0.62, 0.90; p = 0.002). In a second cohort of 181 rGBM patients who received BEV in varying dosages, ASI exposure conferred an OS advantage (HR 0.649; 95% CI 0.46, 0.92; p = 0.016). Moreover, patients with ASI exposure who received low-dose BEV treatment (AUCBEV < 3.6 mg wk/kg) had a significantly longer OS (median = 99 weeks; 95% CI 44.3, 205) than those without ASI (median OS = 55.6 weeks; 95% CI 37.7–73.7; p = 0.032). ASI use is associated with longer OS in glioma patients. Further survival advantage with ASI use was observed in rGBM patients receiving low-dose bevacizumab. These data warrant prospective evaluation of adding ASI to low-dose BEV treatment in GBM patients to improve the outcome of standard therapies.

Keywords

Avastin Bevacizumab Drug dose Angiotensin receptor blockers Glioma Glioblastoma Retrospective analysis 

Abbreviations

ACE

Angiotensin converting enzyme

ARB

Angiotensin receptor blocker

AT1

Angiotensin II receptor 1

ASI

Angiotensin system inhibitor

BEV

Bevacizumab

CNS

Central nervous system

GBM

Glioblastoma

nGBM

Newly diagnosed glioblastoma

NSCLC

Non-small-cell lung cancer

OS

Overall survival

PFS

Progression free survival

RCC

Renal cell carcinoma

rGBM

Recurrent glioblastoma

VEGF

Vascular endothelial growth factor

Notes

Acknowledgements

We thank Dr. D. G. Duda for his scientific input. This study was supported, in part, by NIH- P01CA080124 (to R.K.J.) and NIH-F31HL126449 (to M.D.).

Funding

No reagents or funding from these companies were used in these studies.

Compliance with ethical standards

Conflict of interest

V.A.L. received consulting fees from Orbus Therapeutics, Inc., Nativis, Inc., and Bristol-Myers Squibb. R.K.J. received consultant fees from Ophthotech, SPARC, SynDevRx and XTuit. R.K.J owns equity in Enlight, SPARC, SynDevRx and XTuit, and serves on the Board of Directors of XTuit and Boards of Trustees of Tekla Healthcare Investors, Tekla Life Sciences Investors, Tekla Healthcare Opportunities Fund and Tekla World Healthcare Fund. R.K.J only had access to de-identified data.

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Copyright information

© Springer Science+Business Media, LLC 2017

Authors and Affiliations

  • Victor A. Levin
    • 1
    • 2
  • James Chan
    • 3
  • Meenal Datta
    • 5
    • 6
  • Jennie L. Yee
    • 4
  • Rakesh K. Jain
    • 5
  1. 1.Department of Neurosurgery and NeurosciencesKaiser PermanenteRedwood CityUSA
  2. 2.The Universiy of Texas M.D. Anderson Cancer CenterHoustonUSA
  3. 3.Pharmacy Outcomes Research GroupKaiser PermanenteOaklandUSA
  4. 4.Clinic Administered Medications Drug Use ManagementKaiser PermanenteOaklandUSA
  5. 5.Edwin L. Steele Laboratories for Tumor Biology, Department of Radiation OncologyMassachusetts General Hospital and Harvard Medical SchoolBostonUSA
  6. 6.Department of Chemical and Biological EngineeringTufts UniversityMedfordUSA

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