A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer. Redox Biol 2024 Nov;77:103375
Date
10/07/2024Pubmed ID
39369582Pubmed Central ID
PMC11491967DOI
10.1016/j.redox.2024.103375Scopus ID
2-s2.0-85205576035 (requires institutional sign-in at Scopus site) 35 CitationsAbstract
BACKGROUND: Patients with metastatic pancreatic ductal adenocarcinoma (PDAC) have poor 5-year survival. Pharmacological ascorbate (P-AscH-, high dose, intravenous, vitamin C) has shown promise as an adjunct to chemotherapy. We hypothesized adding P-AscH- to gemcitabine and nab-paclitaxel would increase survival in patients with metastatic PDAC.
METHODS: Patients diagnosed with stage IV pancreatic cancer randomized 1:1 to gemcitabine and nab-paclitaxel only (SOC, control) or to SOC with concomitant P-AscH-, 75 g three times weekly (ASC, investigational). The primary outcome was overall survival with secondary objectives of determining progression-free survival and adverse event incidence. Quality of life and patient reported outcomes for common oncologic symptoms were captured as an exploratory objective. Thirty-six participants were randomized; of this 34 received their assigned study treatment. All analyses were based on data frozen on December 11, 2023.
RESULTS: Intravenous P-AscH- increased serum ascorbate levels from micromolar to millimolar levels. P-AscH- added to the gemcitabine + nab-paclitaxel (ASC) increased overall survival to 16 months compared to 8.3 months with gemcitabine + nab-paclitaxel (SOC) (HR = 0.46; 90 % CI 0.23, 0.92; p = 0.030). Median progression free survival was 6.2 (ASC) vs. 3.9 months (SOC) (HR = 0.43; 90 % CI 0.20, 0.92; p = 0.029). Adding P-AscH- did not negatively impact quality of life or increase the frequency or severity of adverse events.
CONCLUSIONS: P-AscH- infusions of 75 g three times weekly in patients with metastatic pancreatic cancer prolongs overall and progression free survival without detriment to quality of life or added toxicity (ClinicalTrials.gov number NCT02905578).
Author List
Bodeker KL, Smith BJ, Berg DJ, Chandrasekharan C, Sharif S, Fei N, Vollstedt S, Brown H, Chandler M, Lorack A, McMichael S, Wulfekuhle J, Wagner BA, Buettner GR, Allen BG, Caster JM, Dion B, Kamgar M, Buatti JM, Cullen JJAuthor
Mandana Kamgar MPH, MD Associate Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdultAged
Albumins
Antineoplastic Combined Chemotherapy Protocols
Ascorbic Acid
Carcinoma, Pancreatic Ductal
Deoxycytidine
Female
Humans
Male
Middle Aged
Neoplasm Metastasis
Paclitaxel
Pancreatic Neoplasms
Quality of Life
