Cancer Chemotherapy and Pharmacology

, Volume 71, Issue 3, pp 765–775 | Cite as

Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer (PACMAN): results from a phase I clinical trial

  • J. L. Welsh
  • B. A. Wagner
  • T. J. van’t Erve
  • P. S. Zehr
  • D. J. Berg
  • T. R. Halfdanarson
  • N. S. Yee
  • K. L. Bodeker
  • J. Du
  • L. J. RobertsII
  • J. Drisko
  • M. Levine
  • G. R. Buettner
  • J. J. Cullen
Original Article

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.

Keywords

Pancreatic neoplasm Ascorbic acid Clinical trial Phase 1 Gemcitabine Drug toxicity 

Supplementary material

280_2013_2070_MOESM1_ESM.tif (93 kb)
Supplemental Fig. 1. Patient weight changes while receiving ascorbate + gemcitabine therapy. The bar graph demonstrates the mean patient weight at baseline and at removal from the study. Error bars represent the variability in the distribution of patients’ weights. Supplementary material 1 (TIFF 93 kb)
280_2013_2070_MOESM2_ESM.doc (30 kb)
Supplementary material 2 (DOC 29 kb)

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Copyright information

© Springer-Verlag Berlin Heidelberg 2013

Authors and Affiliations

  • J. L. Welsh
    • 1
  • B. A. Wagner
    • 2
  • T. J. van’t Erve
    • 2
  • P. S. Zehr
    • 3
  • D. J. Berg
    • 3
    • 4
  • T. R. Halfdanarson
    • 3
    • 4
  • N. S. Yee
    • 5
  • K. L. Bodeker
    • 2
  • J. Du
    • 2
  • L. J. RobertsII
    • 6
  • J. Drisko
    • 7
  • M. Levine
    • 8
  • G. R. Buettner
    • 2
    • 3
  • J. J. Cullen
    • 1
    • 2
    • 3
    • 9
  1. 1.Department of Surgery, 1528 JCP—UIHCThe University of Iowa Carver College of MedicineIowa CityUSA
  2. 2.Department of Radiation OncologyThe University of Iowa Carver College of MedicineIowa CityUSA
  3. 3.The Holden Comprehensive Cancer CenterThe University of IowaIowa CityUSA
  4. 4.Department of Internal MedicineThe University of Iowa Carver College of MedicineIowa CityUSA
  5. 5.Penn State Hershey Cancer InstituteHerseyUSA
  6. 6.Vanderbilt-Ingram Cancer CenterVanderbilt UniversityNashvilleUSA
  7. 7.Integrative MedicineUniversity of Kansas Medical CenterKansas CityUSA
  8. 8.Molecular and Clinical Nutrition Section, Digestive Diseases Branch, National Institutes of Diabetes and Digestive and Kidney DiseasesNational Institutes of HealthBethesdaUSA
  9. 9.The Veterans’ Affairs Medical CenterIowa CityUSA

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