Epub 2014 May 26.Fritz H1, Flower G2, Weeks L2, Cooley K3, Callachan M1, McGowan J1, Skidmore B1, Kirchner L4, Seely D5.Author information1Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada.2Ottawa Integrative Cancer Centre, Ottawa, Ontario, Canada.3Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada University of Toronto, Toronto, Ontario, Canada.4Carp Ridge Natural Health Clinic, Carp, Ontario, Canada.5Canadian College of Naturopathic Medicine, Toronto, Ontario, Canada Ottawa Integrative Cancer Centre, Ottawa, Ontario, Canada Ottawa Hospital Research Institute, Ottawa, Ontario, Canada dseely@oicc.ca.AbstractBACKGROUND: Intravenous vitamin C (IVC) is a contentious adjunctive cancer therapy, widely used in naturopathic and integrative oncology settings. We conducted a systematic review of human interventional and observational studies assessing IVC for use in cancer patients.METHODS: We searched MEDLINE, EMBASE, The Cochrane Library, CINAHL, and AMED from inception to April 2013 for human studies examining the safety, effectiveness, or pharmacokinetics of IVC use in cancer patients.
RESULTS: Of 897 records, a total of 39 reports of 37 studies were included: 2 randomized controlled trials (RCTs), 15 uncontrolled trials, 6 observational studies, and 14 case reports. IVC dosing ranged from 1 g to more than 200 g ascorbic acid per infusion, typically administered 2 to 3 times weekly. IVC does not appear to increase toxicity or interfere with antitumor effects of gemcitabine/erlotinib therapy or paclitaxel and carboplatin. Based on 1 RCT and data from uncontrolled human trials, IVC may improve time to relapse and possibly enhance reductions in tumor mass and improve survival in combination with chemotherapy. IVC may improve quality of life, physical function, and toxicities associated with chemotherapy, including fatigue, nausea, insomnia, constipation, and depression. Case reports document several instances of tumor regression and long-term disease-free survival associated with use of IVC.CONCLUSION: There is limited high-quality clinical evidence on the safety and effectiveness of IVC.
Go to Patient Version This cancer information summary provides an overview of the use of high-dose vitamin C (also known as ascorbate or L-ascorbic acid) as a treatment for people with cancer. This summary includes a brief history of early clinical trials of high-dose vitamin C; reviews of laboratory, animal, and human studies; and current clinical trials. This summary contains the following key information: Vitamin C is an essential nutrient with redox functions at normal physiologic concentrations. High-dose vitamin C has been studied as a treatment for cancer patients since the 1970s. Laboratory studies have reported that high-dose vitamin C has redox properties and decreased cell proliferation in prostate, pancreatic, hepatocellular, colon, mesothelioma, and neuroblastoma cell lines. Two studies of high-dose vitamin C in cancer patients reported improved quality of life and decreases in cancer-related side effects. Studies of vitamin C combined with other drugs in animal models have shown mixed results.
Intravenous vitamin C has been generally well tolerated in clinical trials. Many of the medical and scientific terms used in this summary are hypertext linked (at first use in each section) to the NCI Dictionary of Cancer Terms, which is oriented toward nonexperts. When a linked term is clicked, a definition will appear in a separate window. Reference citations in some PDQ cancer information summaries may include links to external Web sites that are operated by individuals or organizations for the purpose of marketing or advocating the use of specific treatments or products. These reference citations are included for informational purposes only. Their inclusion should not be viewed as an endorsement of the content of the Web sites, or of any treatment or product, by the PDQ Integrative, Alternative, and Complementary Therapies Editorial Board or the National Cancer Institute.eCollection 2015.Hoffer LJ1, Robitaille L2, Zakarian R3, Melnychuk D4, Kavan P5, Agulnik J6, Cohen V7, Small D6, Miller WH Jr8.Author information1Department of Medicine, Jewish General Hospital, Montreal, Canada.2Lady Davis Institute for Medical Research, Montreal, Canada.3Lady Davis Institute for Medical Research, Montreal, Canada;
Clinical Research Unit, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.4Lady Davis Institute for Medical Research, Montreal, Canada; Department of Oncology, Segal Cancer Centre, Jewish General Hospital, Montreal, Canada.5Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Oncology and Medicine, Segal Cancer Centre, Montreal, Canada.6Lady Davis Institute for Medical Research, Montreal, Canada; Departments of Medicine and Oncology, Peter Brojde Lung Cancer Centre, Jewish General Hospital, Montreal, Canada.7Lady 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.8Lady 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.AbstractBACKGROUND: 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.PMID: 25848948 PMCID: PMC4388666 DOI: 10.1371/journal.pone.0120228 [Indexed for MEDLINE] Free PMC ArticlePublication typesCase ReportsClinical Trial, Phase IClinical Trial, Phase IIMulticenter StudyResearch Support, Non-U.S. Gov'tMeSH termsAgedAntineoplastic Agents/therapeutic use*Antioxidants/administration & dosage*Antioxidants/pharmacokineticsAscorbic Acid/administration & dosage*Ascorbic Acid/pharmacokineticsDrug Therapy, CombinationFemaleHumansInjections, IntravenousMaleMiddle AgedNeoplasms/drug therapy*Quality of Life*Tissue DistributionSubstancesAntineoplastic AgentsAntioxidantsAscorbic AcidSecondary source IDClinicalTrials.gov/NCT01050621Full Text SourcesPublic Library of ScienceEurope PubMed CentralPubMed CentralPubMed Central CanadaMedicalClinicalTrials.govAntioxidants - MedlinePlus Health InformationCancer - MedlinePlus Health