In the United States, approximately 30,000 new cases of pancreatic cancer are diagnosed each year and an almost equal number of deaths are related to this cancer. Different types of chemotherapeutic treatments are used that target different parts of the cancer cell with some success, but there is room for other treatment options. It is known that people with cancer are using high doses of intravenous vitamin C also known as ascorbate, as a cancer treatment and this is occurring frequently. When Vitamin C is given in this manner, it is not taken by mouth; instead, it enters your body through an IV (intravenous) site, or tube that is inserted through a needle into your vein. If you have a port-a-cath in place, the IV will be given using your port. When Vitamin C enters your body through an IV site, it is known that it acts like a drug and not a vitamin. It produces a substance around the cancer cells called hydrogen peroxide. It has been seen in animal research studies that hydrogen peroxide kills the cancer cells while leaving the normal cells unharmed.
Currently the FDA does not approve the use of high-dose intravenous Vitamin C as a cancer treatment. The use of intravenous Vitamin C in this study is experimental. Furthermore, it is important to know that we do not expect the intravenous Vitamin C given in this study to be healing for the treatment of your cancer. Intervention Model: Single Group AssignmentMasking: Open LabelPrimary Purpose: Treatment Translation of in Vitro and in Vivo Ascorbate Research Into a New Treatment Option for Pancreatic Cancer: Phase I/IIa Clinical Trial Drug Information available for: Determine safety of combined gemcitabine chemotherapy with IV ascorbate. [ Time Frame: 12 months ] Assess pharmacokinetic and pharmacodynamic interactions when adding IV AA to front-line gemcitabine chemotherapy in the treatment of locally advanced or metastatic pancreatic cancer not eligible for surgical resection. October 2015 (Final data collection date for primary outcome measure) Experimental: IV doses of Vitamin C
Ages Eligible for Study: 21 Years and older (Adult, Senior) Sexes Eligible for Study: Patients must be 21 years of age or older and have histologically or cytologically diagnosed carcinoma of the pancreas defined as locally advanced or metastatic and if locally advanced, not eligible for surgical resection The patient must screened for eligibility and have care approved by treating oncologist; the oncology care is to be dictated by the oncology team and patient and will include gemcitabine chemotherapy. ECOG Performance Status 0-2 Eastern Cooperative Oncology Group Performance Status Grade 0 = Fully active, able to carry on all pre-disease activities without restriction Grade 1= Restricted in physical strenuous activity but ambulatory and able to carry out work of a light or sedentary nature e.g. light housework, office work Grade 2 = Ambulatory and capable of all self care but unable to carry out any work activities, up and about more than 50% of waking hours
Laboratory: ANC ≥1,500/mm3, Hemoglobin > 8g/dL, platelet ≥ 1000,000/mm3, total bilirubin ≤ 1.5 mg/dL (in the absence of neoplastic involvement), creatinine ≤2.0 mg/dL, transaminase (AST/ALT) ≤2.5X upper limit, urine uric acid < 1,000mg/d, urine pH <6, urine oxalate <60 mg/d. Patients who have no language barrier, are cooperative, and can give informed consent before entering the study after being informed of the medications and procedures to be used in this study may participate. Exclusion Criteria: Glucose-6-phosphate-dehydrogenase (G6PD) deficiency History of oxalate renal calculi; urine oxalate level > 60 mg/d at baseline History of bleeding disorder, iron overload or hemochromatosis Prior chemotherapy or currently receiving chemotherapy or radiation therapy or enrolled in other trials currently or in the preceding 1 month. Patients with evidence of a significant psychiatric disorder by history/examination that would prevent completion of the study will not be allowed to participate.
ECOG Performance Status of 3-4. Grade 3 = capable of only limited self care, confined to bed or chair more than 50% of waking hours. Grade 4 = completely disabled. Cannot carry on any self care. Totally confined to bed or chair.) Co-morbid condition that would affect survival: end stage congestive heart failure, unstable angina, myocardial infarction within 6 weeks of study, uncontrolled blood sugars ≥ 300 mg/dL, patients with known chronic active hepatitis or cirrhosis. Patients who consume an excess of alcohol or abuse drugs (an excess of alcohol is defined as more than four of any one of the following per day: 30mL distilled spirits, 340mL beer, or 120mL wine) will not be allowed. Patients who smoke tobacco products will not be allowed to participate. Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies. Please refer to this study by its ClinicalTrials.gov identifier: NCT01364805 University of Kansas Medical Center Kansas City, Kansas, United States, 66160 Jeanne Drisko, MD, CNS, FACN, Director Integrative Medicine, University of Kansas Medical Center Research Institute Other Study ID Numbers: Additional relevant MeSH terms: Physiological Effects of Drugs Molecular Mechanisms of Pharmacological ActionVolume 1, January 2016, Pages 10–12 Vitamin C (ascorbic acid, ascorbate) is a basic compound that is of great importance with its role in various enzymatic reactions including the synthesis of collagen, as well as with its redox functions. Vitamin C has become the center of interest in cancer studies, in consequence of the facts that connective tissue changes and vitamin C deficiency were first alleged to be associated with cancer in the 1950s; and that high doses of vitamin C was asserted to be cytotoxic for cancer cells, later on.
The results of the first study carried out in the 1970s were promising; but afterwards, the studies were ascertained to be faulty. Despite the positive results achieved from some laboratory and animal experiments, randomized clinical trials did not verify those findings, and no clear benefit of vitamin C for cancer treatment could be demonstrated. As for studies, where its use in combination with other cancer treatment regimens was assessed, conflicting results were obtained. Although intake of high doses of vitamin C is alleged to be harmless, based on that it is in the group of water soluble vitamins and is not stored in the body, there are many side effects and drug interactions reported in the literature. For now, it is better to abstain from this treatment, until the benefit of the treatment (if any) is clearly demonstrated, considering the potential side effects and interactions.Vitamin C, also known as ascorbic acid and ascorbate, is a basic compound that belongs to the group of water-soluble vitamins.
It has l- and -enantiomer, but d-enantiomer is not available in nature and has no physiological significance; therefore, it always refers to the l-enantiomer of ascorbic acid and ascorbate, unless written otherwise.1 Vitamin C can be produced by most animals and plants from d-glucose and d-galactose, whereas it is not produced in humans due to the lack of l-gulonolactone oxidase enzyme; and therefore, it should be taken externally.2 The World Health Organization (WHO) recommends a daily intake of 45 mg C per day for healthy adults.3The biological importance of vitamin C is that it plays a cofactor role, as a reducing agent, in various enzymatic reactions. Because it has a low redox potential of 280 mV, it has the potential to react with almost all other oxidized free radicals. Therefore, it is used as an antioxidant. Vitamin C is also a compound that plays an important role in collagen synthesis.2 Vitamin C is also responsible in the synthesis of carnitine and various neurotransmitters as well as tyrosine metabolism and microsomal metabolism.4 Because it is available in high concentrations in the immune cells, and is rapidly consumed in the body in case of any infection, it is thought to be associated with the immune system
However, its mechanism has yet to be clearly elucidated.5 Severe vitamin C deficiency leads to gum recession, weakness, lethargy, and scurvy characterized by easy bleeding and bruising. The symptoms of scurvy develop as a result of weakened connective tissue in the body, and vitamin C is given to patients with scurvy for strengthening their connective tissues.6Some alternative medicine proponents assert that high doses of vitamin C can be used in the treatment of cancer. But although promising results have been achieved from some laboratory and animal studies, these assertions have not been supported by clinical studies on humans. In some studies, when it has been combined with other treatment regimens, some effects have been observed but specific contribution of high-dose vitamin C to those results could not be shown.7, 8, 9 and 10For the first time in 1753, citrus fruits were asserted to prevent scurvy; and upon that, the way of the path to the discovery of vitamin C was opened. In 1912, the scientist Casimir Funk coined the term “antiscorbutic vitamin” to refer this compound contained in fruits and vegetables.
In 1920, the British biochemist Jack Drummond used the term “vitamin C” to refer this compound.11, 12 and 13 For the first time in a study conducted in 1959, it was asserted that cancer could be associated with connective tissue changes, and such a condition could be associated with a deficiency in vitamin C. Upon this assertion, the use of vitamin C in cancer treatment became a topic of conversation.14 High-dose vitamin C began to be tried by the Scottish surgeon Ewan Cameron for the first time in 1970, in his studies on cancer patients. Afterward, the studies attracted greater interest upon the participation of the Nobel Prize winner Linus Pauling. As a result of their studies on patients with advanced cancer, Cameron and Pauling asserted that high-dose ascorbic acid can enhance the body resistance and can be a potential therapy agent for cancer, but those studies were then found to be faulty.15, 16, 17, 18 and 19The general consensus among practitioners is that high-dose intravenous vitamin C (HDIVC) is greater than 10 g/infusion and low-dose intravenous vitamin C (LDIVC) is less than 10 g/infusion.
Although intake of high doses of vitamin C is alleged to be harmless, based on that it is a water soluble vitamin and is not stored in the body, there are many side effects and drug interactions reported in the literature. It has been reported that high-dose vitamin C could increase hemolytic anemia in those who have Glucose-6-phosphate dehydrogenase deficiency; and the risk of renal failure in those who have renal disorders.20 and 21 In addition, because vitamin C may increase the bioavailability of iron, its use in hemochromatosis patients is not recommended.22 Furthermore, vitamin B12 and copper absorption can be reduced, as well.23 Because vitamin C acidifies the urine, it can cause the formation of kidney stones; and on the other hand, a case of hyperoxaluria may emerge due to oxalic acid formed as a result of vitamin C metabolism.24 In a study published in 2000, the tolerable upper limit of vitamin C was determined—for the first time—to be 2 g, and amounts exceeding this limit were reported to have a laxative effect.
Diarrhea is already the most common side effect of high-doses vitamin C.25In the literature, there are studies showing that the use of high-dose vitamin C in combination with certain chemotherapy drugs increases the toxicity. It has been shown that the use of high-dose vitamin C in combination with arsenic trioxide in acute myeloid leukemia, refractory metastatic colon cancer, and metastatic melanoma causes serious side effects and leads to the disease's progression.9, 10 and 26 And in some studies, researchers had to discontinue their studies due to unexpected effects.27 and 28In some laboratory studies, pharmacological doses of vitamin C (0.1–100 mM) were shown to reduce proliferation in cell lines in various types of cancer. The potential mechanism of this effect of vitamin C was investigated in laboratory studies, as well; and high-dose-vitamin C was shown to create cytotoxic effect on cancer cells, by means of chemical reactions that produce hydrogen peroxide.29, 30, 31 and 32 In laboratory studies again, pharmacological doses of ascorbic acid increased the effect of arsenic trioxide in ovarian cancer cells;
gemcitabine in pancreatic cancer cells; and the combination of gemcitabine and epigallocatechin-3-gallate (EGCG) in mesothelioma cells.33, 34 and 35 In a study conducted in 2012, high-dose ascorbate was reported to increase the radiosensitivity of glioblastoma multiforme cells.36 But in some studies, it was reported to reduce the effect of the drug, when used in combination with certain chemotherapy drugs such as doxorubicin, methotrexate, and cisplatin.37The first clinical studies on the effects of high-dose vitamin C were carried out in the 1970s, by Linus Pauling and Ewan Cameron. Dr. Cameron and the chemist Pauling asserted, as a result of their studies, that IV (intravenous) administration of high-dose vitamin C significantly prolongs the survival of advanced-stage cancer patients.15, 16 and 19 However, when their studies were evaluated by the National Cancer Institute later on, they were concluded to be poorly designed and inaccurate. In addition, any of the 3 studies conducted by the Mayo Clinic did not prove the results.17 and 18