High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial

L John Hoffer, Line Robitaille, Robert Zakarian, David Melnychuk, Petr Kavan, Jason Agulnik, Victor Cohen, David Small, Wilson H Miller Jr, L John Hoffer, Line Robitaille, Robert Zakarian, David Melnychuk, Petr Kavan, Jason Agulnik, Victor Cohen, David Small, Wilson H Miller Jr

Abstract

Background: Biological and some clinical evidence suggest that high-dose intravenous vitamin C (IVC) could increase the effectiveness of cancer chemotherapy. IVC is widely used by integrative and complementary cancer therapists, but rigorous data are lacking as to its safety and which cancers and chemotherapy regimens would be the most promising to investigate in detail.

Methods and findings: We carried out a phase I-II safety, tolerability, pharmacokinetic and efficacy trial of IVC combined with chemotherapy in patients whose treating oncologist judged that standard-of-care or off-label chemotherapy offered less than a 33% likelihood of a meaningful response. We documented adverse events and toxicity associated with IVC infusions, determined pre- and post-chemotherapy vitamin C and oxalic acid pharmacokinetic profiles, and monitored objective clinical responses, mood and quality of life. Fourteen patients were enrolled. IVC was safe and generally well tolerated, although some patients experienced transient adverse events during or after IVC infusions. The pre- and post-chemotherapy pharmacokinetic profiles suggested that tissue uptake of vitamin C increases after chemotherapy, with no increase in urinary oxalic acid excretion. Three patients with different types of cancer experienced unexpected transient stable disease, increased energy and functional improvement.

Conclusions: Despite IVC's biological and clinical plausibility, career cancer investigators currently ignore it while integrative cancer therapists use it widely but without reporting the kind of clinical data that is normally gathered in cancer drug development. The present study neither proves nor disproves IVC's value in cancer therapy, but it provides practical information, and indicates a feasible way to evaluate this plausible but unproven therapy in an academic environment that is currently uninterested in it. If carried out in sufficient numbers, simple studies like this one could identify specific clusters of cancer type, chemotherapy regimen and IVC in which exceptional responses occur frequently enough to justify appropriately focused clinical trials.

Trial registration: ClinicalTrials.gov NCT01050621.

Conflict of interest statement

Competing Interests: Ascorbic acid for injection was an unconditional gift from Alveda Pharma Canada, Ltd. Alveda Pharma Canada had no role in the design, implementation, analysis, interpretation or write-up of this study. This unconditional gift did not, and does not affect our adherence to all PLOS ONE policies on sharing data and materials. There are no relevant declarations relating to employment, consultancy, patents, or any other matter.

Figures

Fig 1. Flow diagram.
Fig 1. Flow diagram.
Fig 2. Mean plasma vitamin C concentrations…
Fig 2. Mean plasma vitamin C concentrations ± SEM (N = 12) during and following infusion of 0.6 g/kg vitamin C, before (■) and after (○) chemotherapy.
AUC (areas under the curve) were not significantly different (p = 0.146, paired t-test).

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