Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients

K.A. Mapuskar; G. Vasquez Martinez; C.F. Pulliam; M.S. Petronek; E.J. Steinbach; V. Monga; M. Furqan; J.G. Jetton; D.P. Saunders; A. Pearce; S. Davidson; L. Pitre; N.E. Dunlap; R. Fairbanks; C.M. Lee; S.L. Mott; K.L. Bodeker; Huang Cl; J.M. Buatti; C.M. Anderson; R.A. Beardsley; J.T. Holmlund; D. Zepeda-Orozco; D.R. Spitz; B.G. Allen

doi:10.1016/j.redox.2022.102599

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Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients

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Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients

K.A. Mapuskar, G. Vasquez Martinez, C.F. Pulliam, M.S. Petronek, E.J. Steinbach, V. Monga, M. Furqan, J.G. Jetton, D.P. Saunders, A. Pearce, …

Redox biology, Vol.60, pp.102599-102599

01/03/2023

DOI: 10.1016/j.redox.2022.102599

PMCID: PMC9852651

PMID: 36640725

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Abstract

Head and neck squamous cell carcinoma (HNSCC) patients treated with high-dose cisplatin concurrently with radiotherapy (hdCis-RT) commonly suffer kidney injury leading to acute and chronic kidney disease (AKD and CKD, respectively). We conducted a retrospective analysis of renal function and kidney injury-related plasma biomarkers in a subset of HNSCC subjects receiving hdCis-RT in a double-blinded, placebo-controlled clinical trial (NCT02508389) evaluating the superoxide dismutase mimetic, avasopasem manganese (AVA), an investigational new drug. We found that 90 mg AVA treatment prevented a significant reduction in estimated glomerular filtration rate (eGFR) three months as well as six and twelve months after treatment compared to 30 mg AVA and placebo. Moreover, AVA treatment may have allowed renal repair in the first 22 days following cisplatin treatment as evidenced by an increase in epithelial growth factor (EGF), known to aid in renal recovery. An upward trend was also observed in plasma iron homeostasis proteins including total iron (Fe-blood) and iron saturation (Fe-saturation) in the 90 mg AVA group versus placebo. These data support the hypothesis that treatment with 90 mg AVA mitigates cisplatin-induced CKD by inhibiting hdCis-induced renal changes and promoting renal recovery. [Display omitted] •Treatment with avasopasem manganese (GC4419) may mitigate renal function decline in head and neck cancer (HNC) patients treated with high-dose cisplatin administered concurrently with radiotherapy (hdCis-RT).•Treatment with 90 mg avasopasem manganese improved eGFR 3, 6 and 12 months after cisplatin treatment.•Renal recovery biomarker, epithelial growth factor (EGF) was elevated in patients treated with avasopasem as early as day 22 of treatment.

Iron

Acute kidney disease

Avasopasem manganese

Chronic kidney disease

Cisplatin

eGFR

Epithelial growth factor

GC4419

Kidney injury

Radiation

Superoxide dismutase mimetic

Details

Title: Subtitle: Avasopasem manganese (GC4419) protects against cisplatin-induced chronic kidney disease: An exploratory analysis of renal metrics from a randomized phase 2b clinical trial in head and neck cancer patients
Creators: K.A. Mapuskar - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
G. Vasquez Martinez - Nationwide Children's Hospital
C.F. Pulliam - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
M.S. Petronek - University of Iowa
E.J. Steinbach - The University of Iowa Stead Family Department of Pediatrics, Iowa City, IA, USA
V. Monga - University of Iowa Hospitals and Clinics, Department of Internal Medicine, Iowa City, IA, USA
M. Furqan - University of Iowa Hospitals and Clinics, Department of Internal Medicine, Iowa City, IA, USA
J.G. Jetton - Medical College of Wisconsin
D.P. Saunders - NOSM University
A. Pearce - NOSM University
S. Davidson - NOSM University
L. Pitre - NOSM University
N.E. Dunlap - University of Louisville
R. Fairbanks - Cancer Care Northwest
C.M. Lee - Cancer Care Northwest
S.L. Mott - University of Iowa Holden Comprehensive Cancer Center, Iowa City, IA, USA
K.L. Bodeker - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
Huang Cl - University of Iowa Carver College of Medicine, Department of Internal Medicine, Iowa City, IA, USA
J.M. Buatti - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
C.M. Anderson - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
R.A. Beardsley - Galera Therapeutics, Inc., Malvern, PA, USA
J.T. Holmlund - Galera Therapeutics, Inc., Malvern, PA, USA
D. Zepeda-Orozco - Nationwide Children's Hospital
D.R. Spitz - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
B.G. Allen - University of Iowa Hospitals and Clinics, Free Radical and Radiation Biology Program, Department of Radiation Oncology, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Redox biology, Vol.60, pp.102599-102599
DOI: 10.1016/j.redox.2022.102599
PMID: 36640725
PMCID: PMC9852651
NLM abbreviation: Redox Biol
ISSN: 2213-2317
eISSN: 2213-2317
Publisher: Elsevier B.V
Language: English
Date published: 01/03/2023
Academic Unit: Nephrology, Dialysis and Transplantation; Hematology, Oncology, and Blood & Marrow Transplantation; Stead Family Department of Pediatrics; Pathology; Iowa Neuroscience Institute; Biology; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Otolaryngology; Internal Medicine
Record Identifier: 9984359603102771

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