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Article

A phase 0 analysis of ixazomib in patients with glioblastoma

  • Authors:
    • Joseph Quillin
    • Rikesh Patel
    • Eric Herzberg
    • Denny Alton
    • Galina Bikzhanova
    • Lisa Geisler
    • Jeffrey Olson
  • View Affiliations / Copyright

    Affiliations: Department of Neurosurgery, Emory University, Atlanta, GA 30322, USA, Winship Cancer Institute, Emory University, Atlanta, GA 30322, USA, Covance Laboratories, Inc., Madison, WI 53704, USA
  • Article Number: 43
    |
    Published online on: August 13, 2020
       https://doi.org/10.3892/mco.2020.2114
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Abstract

Improving overall survival in recurrent glioblastoma remains a challenge, and drugs acting by unique mechanisms are urgently required. Ixazomib is an orally‑administered proteasome inhibitor used in combination with lenalidomide and dexamethasone to treat patients with multiple myeloma who have received at least one prior therapy. However, ixazomib's ability to reach brain tumors has not been studied during its development. The aim of the present study (ClinicalTrials.gov, NCT02630030) was to establish and quantify ixazomib's presence in glioblastoma. The present study investigated 3 patients with recurrent glioblastoma after administration of oral ixazomib citrate (MLN 9708) at a fixed 4.0 mg dose within a 3‑hpreoperative window. A total of 2 blood samples were taken from each patient at the time of incision, tumor sampling and closure. Brain tumor samples were collected during tumor resection. These samples were then used to measure the plasma and brain tumor tissue concentration of the biologically‑active form of ixazomib (MLN 2238). Patient 1 had plasma concentrations of ixazomib averaging 26.2, 21.8 and 15.3 ng/ml at incision, tumor sampling and closure, respectively. The brain tumor tissue concentration was 7.88 ng/g. Patient 2 had the same interval and brain tumor tissue measurements of 19.0, 18.0 and 8.93 ng/ml, and 2.03 ng/g. Patient 3 had plasma concentration interval measurements of 25.6, 36.2 and 28.7 ng/ml. Multiple brain tumor tissue samples were taken in patient 3, with an average tissue ixazomib concentration of 3.37 ng/g. Ixazomib was found at plasma concentrations commensurate with its previously established pharmacokinetic profile without clinically relevant drug‑related adverse events. Ixazomib reaches glioblastoma tissues at measurable concentrations at the time of tumor resection, confirming target tissue delivery. This justifies the phase I study of ixazomib in recurrent glioblastoma currently in development.
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Copy and paste a formatted citation
Spandidos Publications style
Quillin J, Patel R, Herzberg E, Alton D, Bikzhanova G, Geisler L and Olson J: A phase 0 analysis of ixazomib in patients with glioblastoma. Mol Clin Oncol 13: 43, 2020.
APA
Quillin, J., Patel, R., Herzberg, E., Alton, D., Bikzhanova, G., Geisler, L., & Olson, J. (2020). A phase 0 analysis of ixazomib in patients with glioblastoma. Molecular and Clinical Oncology, 13, 43. https://doi.org/10.3892/mco.2020.2114
MLA
Quillin, J., Patel, R., Herzberg, E., Alton, D., Bikzhanova, G., Geisler, L., Olson, J."A phase 0 analysis of ixazomib in patients with glioblastoma". Molecular and Clinical Oncology 13.5 (2020): 43.
Chicago
Quillin, J., Patel, R., Herzberg, E., Alton, D., Bikzhanova, G., Geisler, L., Olson, J."A phase 0 analysis of ixazomib in patients with glioblastoma". Molecular and Clinical Oncology 13, no. 5 (2020): 43. https://doi.org/10.3892/mco.2020.2114
Copy and paste a formatted citation
x
Spandidos Publications style
Quillin J, Patel R, Herzberg E, Alton D, Bikzhanova G, Geisler L and Olson J: A phase 0 analysis of ixazomib in patients with glioblastoma. Mol Clin Oncol 13: 43, 2020.
APA
Quillin, J., Patel, R., Herzberg, E., Alton, D., Bikzhanova, G., Geisler, L., & Olson, J. (2020). A phase 0 analysis of ixazomib in patients with glioblastoma. Molecular and Clinical Oncology, 13, 43. https://doi.org/10.3892/mco.2020.2114
MLA
Quillin, J., Patel, R., Herzberg, E., Alton, D., Bikzhanova, G., Geisler, L., Olson, J."A phase 0 analysis of ixazomib in patients with glioblastoma". Molecular and Clinical Oncology 13.5 (2020): 43.
Chicago
Quillin, J., Patel, R., Herzberg, E., Alton, D., Bikzhanova, G., Geisler, L., Olson, J."A phase 0 analysis of ixazomib in patients with glioblastoma". Molecular and Clinical Oncology 13, no. 5 (2020): 43. https://doi.org/10.3892/mco.2020.2114
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