{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Furqan M"],"funding":["NIEHS NIH HHS","National Cancer Institute","NCI NIH HHS","The University of Iowa Holden Comprehensive Cancer Center","National Institutes of Health"],"pagination":["102318"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9079696"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["53"],"pubmed_abstract":["<h4>Purpose</h4>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.<h4>Experimental design</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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."],"journal":["Redox biology"],"pubmed_title":["Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer."],"pmcid":["PMC9079696"],"funding_grant_id":["T32 CA078586","P30 ES005605","P30 CA086862","R50 CA243693","P01 CA217797"],"pubmed_authors":["Zhang J","Cullen JJ","Fath MA","Byrne MM","Wagner BA","Monga V","Henrich JB","Hartwig SM","Bodeker KL","Houtman JC","Spitz DR","Allen BG","Abu-Hejleh T","Stephens LM","Buatti JM","Bossler AD","Petronek M","Smith BJ","Furqan M","Mott SL","Mani H","Buettner GR","Varga SM","Bellizzi AM","Pulliam CF","Ivanovic M","Zeitler W"],"additional_accession":[]},"is_claimable":false,"name":"Pharmacological ascorbate improves the response to platinum-based chemotherapy in advanced stage non-small cell lung cancer.","description":"<h4>Purpose</h4>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.<h4>Experimental design</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Jul","modification":"2026-05-31T05:05:43.297Z","creation":"2025-02-19T01:55:04.997Z"},"accession":"S-EPMC9079696","cross_references":{"pubmed":["35525024"],"doi":["10.1016/j.redox.2022.102318"]}}