Research Project Abstracts

Intravenous Vitamin C for Non-Hodgkin’s Lymphoma

Principal Investigator: Daniel Monti, MD (Daniel.Monti@jefferson.edu)

There has not been substantive data that treatment with anti-oxidants has a significant clinical impact on cancer illness outcomes.  Vitamin C (ascorbic acid) had seemed to be a contender for cancer treatment in the late 1970’s, but the issue was mostly put to rest when two clinical trials revealed no benefit from large doses of oral Vitamin C.  Recently, however, there has been data to suggest that the issue should be reconsidered for vitamin C administered intravenously (IV), which potentially has an anti-tumour mechanism of action beyond electron donation (“anti-oxidant”).  Vitamin C has little regulatory oversight by the FDA, as it is classified as a nutritional supplement. IV administration of vitamin C among clinics and medical practices is widespread, mostly because of its role as an anti-oxidant and co-factor for several cellular processes.  The Jefferson-Myrna Brind Center of Integrative Medicine (JMBCIM), a Jefferson University Hospital-based clinic, currently has hospital approval to administer IV vitamin C to patients.  The proposed study will only administer IV vitamin C within the dosage confines of current hospital approval.  Human studies have shown that blood levels can be dramatically higher for IV administration (up to seventy fold) and that such high levels appear to be non-toxic.  In the past year, there have been several well-documented case reports that have suggested therapeutic benefit from IV Vitamin C in three cancer types, including non-Hodgkin Lymphoma.  Moreover, recent data from in vitro and in vivo studies suggest a mechanism of action that emerges at high ascorbic acid plasma levels that can only be obtained by intravenous administration. This mechanism is dependent on pro-oxidant actions, as a consequence of ascorbate concentrations achieved only by intravenous administration. Ascorbic acid is always chemically a reducing agent (anti-oxidant), or electron donor. However, at pharmacologic concentrations, ascorbate electron donation sets in motion a series of chemical reactions whose end result is formation of hydrogen peroxide and subsequent pro-oxidant compounds, with selective toxicity to cancer but not normal cells. Thus, while ascorbic acid action is always as an electron donor, its actions at pharmacologic concentrations produce pro-oxidant consequences.

Given this recently elucidated mechanism of action, we will conduct a Phase II pilot study of high dose IV Vitamin C in a small group of patients with treatment refractory non-Hodgkin Lymphoma.  We choose non-Hodgkin Lymphoma that has failed conventional treatment as the tumour type because, 1) these patients do not have other treatment options, 2) the current literature shows that in general, the experimental treatment is relatively non-toxic, and 3) there is anecdotal evidence to suggest that non-Hodgkin lymphoma may be responsive to high plasma levels of Vitamin C.  Up to 20 patients will be enrolled in the protocol. The treatment will be a 90 minute to 180 minute intravenous infusion of pH neutral ascorbic acid, approximately three times per week for a total of 30 infusions. Ascorbic acid will be dosed to reach plasma levels of at least 300 mg/dl by week four (target range will be 300-350 mg/dl).  Ascorbic acid levels in this range and higher generally have not been shown to be toxic in humans.