Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.
Ascorbate
Non-small cell
Platinum
Vitamin C
Journal
Redox biology
ISSN: 2213-2317
Titre abrégé: Redox Biol
Pays: Netherlands
ID NLM: 101605639
Informations de publication
Date de publication:
07 2022
07 2022
Historique:
received:
15
02
2022
revised:
05
04
2022
accepted:
17
04
2022
pubmed:
8
5
2022
medline:
9
6
2022
entrez:
7
5
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 35525024
pii: S2213-2317(22)00090-8
doi: 10.1016/j.redox.2022.102318
pmc: PMC9079696
pii:
doi:
Substances chimiques
Platinum
49DFR088MY
Carboplatin
BG3F62OND5
Paclitaxel
P88XT4IS4D
Types de publication
Clinical Trial, Phase II
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
102318Subventions
Organisme : NCI NIH HHS
ID : P30 CA086862
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA078586
Pays : United States
Organisme : NCI NIH HHS
ID : R50 CA243693
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA217797
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES005605
Pays : United States
Informations de copyright
Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.
Références
Lancet Oncol. 2021 Feb;22(2):198-211
pubmed: 33476593
Sci Transl Med. 2020 Feb 26;12(532):
pubmed: 32102933
N Engl J Med. 2002 Jan 10;346(2):92-8
pubmed: 11784875
Nat Med. 2020 May;26(5):650-651
pubmed: 32405061
Biochim Biophys Acta. 2016 Apr;1863(4):727-48
pubmed: 26844773
Nat Rev Clin Oncol. 2018 Apr;15(4):234-248
pubmed: 29405201
Sci Transl Med. 2014 Feb 5;6(222):222ra18
pubmed: 24500406
Proc Natl Acad Sci U S A. 2007 May 22;104(21):8749-54
pubmed: 17502596
Free Radic Res. 2020 Jun;54(6):385-396
pubmed: 32183598
Ann Oncol. 2002 Oct;13(10):1539-49
pubmed: 12377641
Cell Immunol. 2011;266(2):192-9
pubmed: 21074755
N Engl J Med. 2018 Jun 14;378(24):2288-2301
pubmed: 29863955
Cancer Res. 2017 Sep 15;77(18):5054-5067
pubmed: 28765155
Proc Natl Acad Sci U S A. 2020 Jan 21;117(3):1666-1677
pubmed: 31911474
Proc Natl Acad Sci U S A. 2008 Aug 12;105(32):11105-9
pubmed: 18678913
N Engl J Med. 2006 Dec 14;355(24):2542-50
pubmed: 17167137
Stat Med. 2008 Jul 20;27(16):3145-54
pubmed: 17960777
Proc Natl Acad Sci U S A. 2005 Sep 20;102(38):13604-9
pubmed: 16157892
N Engl J Med. 2018 Nov 22;379(21):2040-2051
pubmed: 30280635
Immunobiology. 2014 Jul;219(7):554-64
pubmed: 24698552
N Engl J Med. 1985 Jan 17;312(3):137-41
pubmed: 3880867
Clin Cancer Res. 2019 Nov 15;25(22):6590-6597
pubmed: 31427282
Cancer Cell. 2017 Apr 10;31(4):487-500.e8
pubmed: 28366679
Nutrients. 2014 Jan 03;6(1):249-60
pubmed: 24394537
Ann Oncol. 2005 Jul;16(7):1069-75
pubmed: 15860487
N Engl J Med. 1979 Sep 27;301(13):687-90
pubmed: 384241
Cancer Chemother Pharmacol. 2013 Mar;71(3):765-75
pubmed: 23381814
J Clin Oncol. 2012 Jun 10;30(17):2055-62
pubmed: 22547591
Radiat Res. 2017 Jun;187(6):743-754
pubmed: 28437190
N Engl J Med. 2018 May 31;378(22):2078-2092
pubmed: 29658856