Journal article
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, Vol.71(3), pp.765-775
2013
DOI: 10.1007/s00280-013-2070-8
PMCID: PMC3587047
PMID: 23381814
Abstract
Background
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.
Design
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.
Results
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.
Conclusions
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.
Details
- Title: Subtitle
- Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial
- Creators
- J. L WELSH - Department of Surgery, 1528 JCP—UIHC, The University of Iowa Carver College of Medicine, Iowa City, IA 52242, United StatesB. A WAGNER - Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesJ DRISKO - Integrative Medicine, University of Kansas Medical Center, Kansas City, KS, United StatesM LEVINE - Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD, United StatesG. R BUETTNER - Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesJ. J CULLEN - The Veterans' Affairs Medical Center, Iowa City, IA, United StatesT. J VAN'T ERVE - Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesP. S ZEHR - The Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, United StatesD. J BERG - The Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, United StatesT. R HALFDANARSON - The Holden Comprehensive Cancer Center, The University of Iowa, Iowa City, IA, United StatesN. S YEE - Penn State Hershey Cancer Institute, Hersey, PA, United StatesK. L BODEKER - Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesJ DU - Department of Radiation Oncology, The University of Iowa Carver College of Medicine, Iowa City, IA, United StatesL. J ROBERTS - Vanderbilt-Ingram Cancer Center, Vanderbilt University, Nashville, TN, United States
- Resource Type
- Journal article
- Publication Details
- Cancer chemotherapy and pharmacology, Vol.71(3), pp.765-775
- DOI
- 10.1007/s00280-013-2070-8
- PMID
- 23381814
- PMCID
- PMC3587047
- NLM abbreviation
- Cancer Chemother Pharmacol
- ISSN
- 0344-5704
- eISSN
- 1432-0843
- Publisher
- Springer; Heidelberg
- Language
- English
- Date published
- 2013
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Surgery; Radiation Oncology; Internal Medicine
- Record Identifier
- 9984047612602771
Metrics
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