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.