Journal article
Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer
Redox biology, Vol.53, pp.102318-102318
04/20/2022
DOI: 10.1016/j.redox.2022.102318
PMCID: PMC9079696
PMID: 35525024
Abstract
Platinum-based chemotherapy with or without immunotherapy is the mainstay of treatment for advanced stage non-small cell lung cancer (NSCLC) lacking a molecular driver alteration. Pre-clinical studies have reported that pharmacological ascorbate (P-AscH-) enhances NSCLC response to platinum-based therapy. We conducted a phase II clinical trial combining P-AscH- with carboplatin-paclitaxel chemotherapy.
Chemotherapy naïve advanced stage NSCLC patients received 75 g ascorbate twice per week intravenously with carboplatin and paclitaxel every three weeks for four cycles. The primary endpoint was to improve tumor response per Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 compared to the historical control of 20%. The trial was conducted as an optimal Simon's two-stage design. Blood samples were collected for exploratory analyses.
The study enrolled 38 patients and met its primary endpoint with an objective response rate of 34.2% (p = 0.03). All were confirmed partial responses (cPR). The disease control rate was 84.2% (stable disease + cPR). Median progression-free and overall survival were 5.7 months and 12.8 months, respectively. Treatment-related adverse events (TRAE) included one grade 5 (neutropenic fever) and five grade 4 events (cytopenias). Cytokine and chemokine data suggest that the combination elicits an immune response. Immunophenotyping of peripheral blood mononuclear cells demonstrated an increase in effector CD8 T-cells in patients with a progression-free survival (PFS) ≥ 6 months.
The addition of P-AscH- to platinum-based chemotherapy improved tumor response in advanced stage NSCLC. P-AscH- appears to alter the host immune response and needs further investigation as a potential adjuvant to immunotherapy.
•The phase II study evaluated the efficacy and safety of Pharmacological Ascorbate with platinum-based chemotherapy in advanced-stage NSCLC.•Pharmacological Ascorbate improved the response of NSCLC to platinum-doublet chemotherapy.•Cytokine and chemokines data suggest that protocol regimen elicited an immune response with multiple distinct cytokine signatures.•Patients with longer PFS had a greater fold increase in circulating activated effector CD8 T cells.•The combination of ascorbate and chemotherapy was safe and tolerable.
Details
- Title: Subtitle
- Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer
- Creators
- Muhammad Furqan - Department of Internal Medicine, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USATaher Abu-Hejleh - University of IowaLaura M Stephens - Interdisciplinary Graduate Program in Immunology, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USAStacey M Hartwig - University of IowaSarah L Mott - University of IowaCasey F Pulliam - University of IowaMichael Petronek - University of IowaJohn B Henrich - Holden Comprehensive Cancer Center, University of Iowa, 200 Hawkins Dr, Iowa City, IA, 52242, USAMelissa A Fath - University of IowaJon C Houtman - University of IowaSteven M Varga - University of IowaKellie L Bodeker - University of IowaAaron D Bossler - University of IowaAndrew M Bellizzi - University of IowaJian Zhang - University of IowaVarun Monga - University of IowaHariharasudan Mani - University of IowaMarina Ivanovic - University of IowaBrian J Smith - University of IowaMargaret M Byrne - University of IowaWilliam Zeitler - University of IowaBrett A Wagner - University of IowaGarry R Buettner - University of IowaJoseph J Cullen - University of IowaJohn M Buatti - University of IowaDouglas R Spitz - University of IowaBryan G Allen - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Redox biology, Vol.53, pp.102318-102318
- DOI
- 10.1016/j.redox.2022.102318
- PMID
- 35525024
- PMCID
- PMC9079696
- NLM abbreviation
- Redox Biol
- ISSN
- 2213-2317
- eISSN
- 2213-2317
- Publisher
- Elsevier B.V
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health; DOI: 10.13039/100000054, name: National Cancer Institute, award: P01 CA217797, P30 CA086862, R50 CA243693, T32 CA078586; DOI: 10.13039/100011343, name: The University of Iowa Holden Comprehensive Cancer Center
- Language
- English
- Date published
- 04/20/2022
- Academic Unit
- Graduate College Admin and Gen; Microbiology and Immunology; Pathology; Biostatistics; Surgery; Otolaryngology; Hematology, Oncology, and Blood & Marrow Transplantation; Iowa Neuroscience Institute; Radiation Oncology; Fraternal Order of Eagles Diabetes Research Center; Neurosurgery; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984256774102771
Metrics
23 Record Views