CurrentPancreatic cancer research at the University of Iowa Carver College of Medicine: A Phase I Trial of Ascorbic Acid and Gemcitabine for the Treatment of Metastatic Pancreatic Cancer.
Pharmacological Ascorbate for the Control of Metastatic and Node-Positive Pancreatic Cancer (PACMAN): Results from a Phase I Clinical Trial.
Jessemae L. Welsh, Brett Wagner, Pamela Zehr, Daniel Berg, Thorvardur Halfdanarson, Nelson Yee, Kellie Bodeker, Garry R. Buettner, Mark Levine, Joseph J. Cullen
OJECTIVE: Treatment of pancreatic cancer with pharmacological ascorbate (ascorbic acid, Vitamin C) decreases tumor progression in pre-clinical models secondary to dose-dependent increases in hydrogen peroxide (Du, et al. 2010). The aims of our study were to investigate the safety, tolerability and maximum tolerated dose of pharmacological ascorbate combined with gemcitabine in patients with biopsy-proven stage IV pancreatic adenocarcinoma.
METHODS: Ten subjects received twice weekly intravenous ascorbate (15-125 g) in a dose escalation protocol to achieve a targeted post-infusion serum level of ≥ 350 mg/dL. Disease burden was measured by CT and CA 19-9 levels. Weight, performance status, hematologic and metabolic labs, and overall survival were monitored.
RESULTS: Once targeted levels were achieved, ascorbate mean trough levels were significantly higher than baseline (1.62 ± .03 vs. 0.57 ± .06 mg/dL, p < 0.001). Subjects received ascorbate 50-125 g (0.82-1.67 g/kg) twice weekly to maintain serum levels between 350-450 mg/dL (20-25 mM). Adverse events attributable to the drug combination were rare and included diarrhea (n=1) and dry mouth (n=3). Subjects maintained performance status and stable weight with mean weight loss of 1.3 ± 1.7 kg. Current mean survival of subjects who have completed ≥ 2 cycles (8 weeks) of therapy is 10 ± 2.9 months.
CONCLUSION: Our trial suggests that pharmacological ascorbate combined with gemcitabine is safe, well-tolerated, and is associated with few adverse events. Intravenous administration of ascorbate produces serum levels shown to be cytotoxic to pancreatic cancer cells and may lead to overall clinical benefit when combined with gemcitabine.
UI Health Care Article: Together, They’re Fighting to Find a Treatment for Pancreatic Cancer