Phase I Evaluation of Intravenous Ascorbic Acid in Combination with Gemcitabine and Erlotinib in Patients with Metastatic Pancreatic Cancer

• Published in: PloS one Vol. 7; no. 1; p. e29794
• Main Authors: Monti, Daniel A., Mitchell, Edith, Bazzan, Anthony J., Littman, Susan, Zabrecky, George, Yeo, Charles J., Pillai, Madhaven V., Newberg, Andrew B., Deshmukh, Sandeep, Levine, Mark
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.01.2012; Public Library of Science (PLoS)
• Subjects: Acids; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols - adverse effects; Antineoplastic Combined Chemotherapy Protocols - therapeutic use; Ascorbic acid; Ascorbic Acid - administration & dosage; Ascorbic Acid - adverse effects; Cancer; Cancer metastasis; Cancer patients; Cancer therapies; Chemotherapy; Clinical trials; Deoxycytidine - administration & dosage; Deoxycytidine - adverse effects; Deoxycytidine - analogs & derivatives; Design standards; Dosage; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug dosages; Erlotinib; Erlotinib Hydrochloride; Female; Gemcitabine; Humans; Hydrogen peroxide; Infusions, Intravenous; Inhibitor drugs; Integrative medicine; Intravenous administration; Male; Medical treatment; Medicine; Metastases; Metastasis; Middle Aged; Neoplasm Metastasis; Neoplasm Staging; Oncology; Ovarian cancer; Pancreatic cancer; Pancreatic Neoplasms - drug therapy; Pancreatic Neoplasms - pathology; Patients; Plasma; Pulmonary Embolism - chemically induced; Quinazolines - administration & dosage; Quinazolines - adverse effects; Review boards; Safety; Studies; Targeted cancer therapy; Toxicity; Treatment Outcome; Vitamin C; United States > US; Pennsylvania
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0029794

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. 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. 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. Clinicaltrials.gov NCT00954525.