A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer
Kellie L. Bodeker,
Brian J. Smith,
Daniel J. Berg,
Chandrikha Chandrasekharan,
Saima Sharif,
Naomi Fei,
Sandy Vollstedt,
Heather Brown,
Meghan Chandler,
Amanda Lorack,
Stacy McMichael,
Jared Wulfekuhle,
Brett A. Wagner,
Garry R. Buettner,
Bryan G. Allen,
Joseph M. Caster,
Barbara Dion,
Mandana Kamgar,
John M. Buatti,
Joseph J. Cullen
Affiliations
Kellie L. Bodeker
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Brian J. Smith
College of Public Health, The University of Iowa, Iowa City, IA, USA
Daniel J. Berg
Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Chandrikha Chandrasekharan
Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Saima Sharif
Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Naomi Fei
Division of Hematology, Oncology, and Blood & Marrow Transplantation, Department of Internal Medicine, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Sandy Vollstedt
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Heather Brown
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Meghan Chandler
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Amanda Lorack
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Stacy McMichael
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Jared Wulfekuhle
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Brett A. Wagner
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Garry R. Buettner
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Bryan G. Allen
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Joseph M. Caster
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Barbara Dion
Medical College of Wisconsin Division of Hematology and Oncology, Milwaukee, WI, USA
Mandana Kamgar
Medical College of Wisconsin Division of Hematology and Oncology, Milwaukee, WI, USA
John M. Buatti
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA
Joseph J. Cullen
Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA; Department of Surgery, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA; Corresponding author. Department of Radiation Oncology, Roy J. and Lucille A. Carver College of Medicine, The University of Iowa, Iowa City, IA, USA.
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).