title: High-dose intravenous vitamin C combined with cytotoxic chemotherapy in patients with advanced cancer: a phase I-II clinical trial.
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.
  
  
  RESULTS
  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.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01050621.
authors.affiliation: Department of Medicine, Jewish General Hospital, Montreal, Canada.
authors.forename: L John
authors.initials: LJ
authors.lastname: Hoffer
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada.
authors.forename: Line
authors.initials: L
authors.lastname: Robitaille
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Clinical Research Unit, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
authors.forename: Robert
authors.initials: R
authors.lastname: Zakarian
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Department of Oncology, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Melnychuk
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada.
authors.forename: Petr
authors.initials: P
authors.lastname: Kavan
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Medicine and Oncology, Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Canada.
authors.forename: Jason
authors.initials: J
authors.lastname: Agulnik
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada; Departments of Medicine and Oncology, Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Canada.
authors.forename: Victor
authors.initials: V
authors.lastname: Cohen
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Medicine and Oncology, Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Canada.
authors.forename: David
authors.initials: D
authors.lastname: Small
authors.affiliation: Lady Davis Institute for Medical Research, Montreal, Canada; Clinical Research Unit, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada.
authors.forename: Wilson H
authors.initials: WH
authors.lastname: Miller
mesh_terms: D000368:Aged; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000008:administration & dosage* / Q000493:pharmacokinetics; D001205:Ascorbic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000188:drug therapy*; D011788:Quality of Life; D014018:Tissue Distribution
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001205:Ascorbic Acid
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