Phase I evaluation of intravenous ascorbic acid in combination with gemcitabine and erlotinib in patients with metastatic pancreatic cancer

Daniel A Monti, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine, Daniel A Monti, Edith Mitchell, Anthony J Bazzan, Susan Littman, George Zabrecky, Charles J Yeo, Madhaven V Pillai, Andrew B Newberg, Sandeep Deshmukh, Mark Levine

Abstract

Background: Preclinical data support further investigation of ascorbic acid in pancreatic cancer. There are currently insufficient safety data in human subjects, particularly when ascorbic acid is combined with chemotherapy.

Methods and findings: 14 subjects with metastatic stage IV pancreatic cancer were recruited to receive an eight week cycle of intravenous ascorbic acid (three infusions per week), using a dose escalation design, along with standard treatment of gemcitabine and erlotinib. Of 14 recruited subjects enrolled, nine completed the study (three in each dosage tier). There were fifteen non-serious adverse events and eight serious adverse events, all likely related to progression of disease or treatment with gemcitabine or erlotinib. Applying RECIST 1.0 criteria, seven of the nine subjects had stable disease while the other two had progressive disease.

Conclusions: These initial safety data do not reveal increased toxicity with the addition of ascorbic acid to gemcitabine and erlotinib in pancreatic cancer patients. This, combined with the observed response to treatment, suggests the need for a phase II study of longer duration.

Trial registration: Clinicaltrials.gov NCT00954525.

Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1. Study CONSORT flow diagram.
Figure 1. Study CONSORT flow diagram.
Figure 2. Peak plasma ascorbic acid concentrations…
Figure 2. Peak plasma ascorbic acid concentrations in millimoles/L after the initial dose and final dose (measurements after the final dose were unavailable for patients 008 and 014).
The green line represents the highest plasma concentration expected with maximally tolerated oral doses of ascorbic acid .
Figure 3. Tumor size initially and after…
Figure 3. Tumor size initially and after 8 weeks of treatment with ascorbic acid, gemcitabine, and erlotinib for each of the patients who completed the study.

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