Journal article
A RANDOMIZED TRIAL of PHARMACOLOGICAL ASCORBATE, GEMCITABINE, and nab-PACLITAXEL for METASTATIC PANCREATIC CANCER
Redox biology, Vol.77, 103375
11/2024
DOI: 10.1016/j.redox.2024.103375
PMCID: PMC11491967
PMID: 39369582
Abstract
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).
Details
- Title: Subtitle
- A RANDOMIZED TRIAL of PHARMACOLOGICAL ASCORBATE, GEMCITABINE, and nab-PACLITAXEL for METASTATIC PANCREATIC CANCER
- Creators
- Kellie L. Bodeker - University of IowaBrian J. Smith - University of IowaDaniel J. Berg - University of IowaChandrikha Chandrasekharan - University of IowaSaima Sharif - University of IowaNaomi Fei - University of IowaSandy Vollstedt - University of IowaHeather Brown - University of IowaMeghan Chandler - University of IowaAmanda Lorack - University of IowaStacy McMichael - University of IowaJared Wulfekuhle - University of IowaBrett A. Wagner - University of IowaGarry R. Buettner - University of IowaBryan G. Allen - University of IowaJoseph M. Caster - University of IowaBarbara Dion - Medical College of WisconsinMandana Kamgar - Medical College of WisconsinJohn M. Buatti - University of IowaJoseph J. Cullen - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Redox biology, Vol.77, 103375
- DOI
- 10.1016/j.redox.2024.103375
- PMID
- 39369582
- PMCID
- PMC11491967
- NLM abbreviation
- Redox Biol
- ISSN
- 2213-2317
- eISSN
- 2213-2317
- Publisher
- ELSEVIER
- Grant note
- National Institutes of Health: P01 CA217797 Holden Comprehensive Cancer Center: 1P30CA086862-23
independent monitors J. Wegmann, J. Sieren, J. Geick, A. Farmer, and E. Seig throughout the conduct of this trial. This work was supported by the National Institutes of Health P01 CA217797 as well as the Holden Comprehensive Cancer Center support grant 1P30CA086862-23. The funders did not play a role in the design of the study; the collection, analysis, and interpretation of the data; the writing of the manuscript; and the decision to submit the manuscript for publication.
- Language
- English
- Electronic publication date
- 10/02/2024
- Date published
- 11/2024
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Biostatistics; Surgery; Radiation Oncology; Neurosurgery; Otolaryngology; Holden Comprehensive Cancer Center; Internal Medicine
- Record Identifier
- 9984720060302771
Metrics
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