Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial
Rent the article at a discountRent now
* Final gross prices may vary according to local VAT.Get Access
Treatment for pancreatic cancer with pharmacological ascorbate (ascorbic acid, vitamin C) decreases tumor progression in preclinical models. A phase I clinical trial was performed to establish safety and tolerability of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma.
Nine subjects received twice-weekly intravenous ascorbate (15–125 g) employing Simon’s accelerated titration design to achieve a targeted post-infusion plasma level of ≥350 mg/dL (≥20 mM). Subjects received concurrent gemcitabine. Disease burden, weight, performance status, hematologic and metabolic laboratories, time to progression and overall survival were monitored.
Mean plasma ascorbate trough levels were significantly higher than baseline (1.46 ± 0.02 vs. 0.78 ± 0.09 mg/dL, i.e., 83 vs. 44 μM, p < 0.001). Adverse events attributable to the drug combination were rare and included diarrhea (n = 4) and dry mouth (n = 6). Dose-limiting criteria were not met for this study. Mean survival of subjects completing at least two cycles (8 weeks) of therapy was 13 ± 2 months.
Data suggest pharmacologic ascorbate administered concurrently with gemcitabine is well tolerated. Initial data from this small sampling suggest some efficacy. Further studies powered to determine efficacy should be conducted.
- Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial
Cancer Chemotherapy and Pharmacology
Volume 71, Issue 3 , pp 765-775
- Cover Date
- Print ISSN
- Online ISSN
- Additional Links
- Pancreatic neoplasm
- Ascorbic acid
- Clinical trial
- Phase 1
- Drug toxicity
- Industry Sectors
- Author Affiliations
- 1. Department of Surgery, 1528 JCP—UIHC, The University of Iowa Carver College of Medicine, Iowa City, IA, 52242, USA
- 2. Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
- 3. The Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, USA
- 4. Department of Internal Medicine, The University of Iowa Carver College of Medicine, Iowa City, IA, USA
- 5. Penn State Hershey Cancer Institute, Hersey, PA, USA
- 6. Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, USA
- 7. Integrative Medicine, University of Kansas Medical Center, Kansas City, KS, USA
- 8. Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, USA
- 9. The Veterans’ Affairs Medical Center, Iowa City, IA, USA