New Insights on Vitamin C and Cancer
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At the time of the endoscopic ultrasound, the pancreatic duct and biliary tree were not dilated. The biopsy showed poorly differentiated PDA. Cytopathology of the original biopsy was reviewed independently at the University of Alabama and the National Institutes of Health, confirming aggressive poorly differentiated PDA.
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At the initial oncology consultation in May , the patient had a recorded weight of He was not jaundiced. The patient was given a diagnosis of Stage IV poorly differentiated PDA and was offered chemotherapy consisting of gemcitabine and erlotinib. He declined standard of care with a full understanding of the natural course of metastatic PDA, but not wanting to experience the side effects of chemotherapy and reduced quality of life in the expected short remaining lifespan. After consulting with his family, the patient elected to begin escalating doses of PAA through a port-a-cath, with treatment doses ranging from 75 to g per infusion and administered 2—3 times per week, according to accepted dosing and scheduling protocols 14, The patient was prescreened for conditions that might preclude receiving PAA that included G6PD deficiency or abnormal renal function The previously identified liver metastases were also noted overall to have decreased SUV levels.
Finally, the largest liver mass, initially measuring 1. There remained persistent, but smaller low-density lesions throughout the liver without hypermetabolic activity, consistent with residual metastatic disease. In addition, the mass in the head of pancreas was noted to be smaller and with less metabolic activity than observed previously. At the time of this scan, the patient had a stable weight, was pain free, and had an ECOG status of 0. He had an ECOG status of 0 with stable weight and no pain. It was reported that there was continued reduction in the size of the pancreatic head mass with increased necrotic components in the central portion of the tumor consistent with continued regression of malignancy.
The patient, now 2. Follow-up imaging in November Fig. It was found at this imaging that the SUV increased to 10 and progression of disease was questioned, despite the diminishing size. However, compression of the lesion as a cause of increased SUV was suspected. No other abnormalities were identified on the scan. In , the patient had routine follow-up blood work after over doses of PAA, which showed normal CA 19—9 levels, pancreatic enzymes, liver enzymes, and renal function. ECOG status remained 0. No new lesions were identified. A biliary stent was placed in January because of a suspicion of advancing disease after an increase in liver enzymes, but scanning indicated no evidence for biliary dilatation or increase in the pancreatic mass size.
In retrospect, the patient may have had elevated liver enzymes from consuming very high doses of oral vitamin D. In February , 2 weeks after stent placement, the patient presented to the emergency department in septic shock Fig. At this scan, there was no enlargement of the pancreatic head mass or metastatic disease in the liver parenchyma.
He underwent an exploratory laparotomy and was found to have a perforated small bowel segment that required surgical resection. The biliary stent, which had presumably migrated, was found in his cecum. Postoperatively, the patient remained in the ICU in septic shock and in acute respiratory and renal failure. His condition worsened 2 days postoperatively, requiring increasing vasopressors for hemodynamic support, at which point, his wife elected to withdraw support and he died shortly thereafter.
Investigation of new treatment agents that are nontoxic, inexpensive, and show clinical promise are in the best interests of our patients, independent of revenue-generating potential.
a case report
PAA in cancer treatment, with no patentability, is an example. PAA was dismissed as a cancer treatment agent 26 years ago, in retrospect because of a simple pharmacology error Recent in vitro and animal evidences from many laboratories indicate that PAA, but not oral AA, may have selective cancer-killing properties, by acting as a prodrug to generate hydrogen peroxide selectively in extracellular fluid 10,12, For PDA, PAA synergizes with gemcitabine in cell and animal models, and appears to be safe in screened patients 14,16, On the basis of these new clinical observations, we hypothesize that PAA treatment may require a much longer time course than conventional treatment agents.
Also, we suggest that because of the changing appearance of the tumor mass and the procollagen effects of AA 18 , there may be infiltration of the tumor with collagen. These observations could provide insight into the mechanisms of action of PAA in cancer treatment and require further investigation in preclinical and clinical studies.
The role of vitamin C in the treatment of pain: new insights
He presented in March , with a mean expected survival of 4—6 months. The patient felt well and was active. There are early reports of increased physical and psychological well-being with the use of PAA that could be an additional benefit for patients undergoing chemotherapy 15, In January , the patient had increasing liver enzymes believed to be related to disease progression and had biliary stent placement. In retrospect, the increasing liver enzymes may have been related to ingestion of high doses of vitamin D.
He died of a known procedure-related complication that was indirectly related to his underlying diagnosis of PDA, but not from apparent PDA disease progression. Transpapillary or percutaneous placement of biliary stents is a useful adjunct in the management of patients with advanced hepatobiliary malignancies, providing symptom alleviation in the overwhelming majority of patients.
A number of case reports and small series have documented the possibility of stent migration causing bowel perforation, which, under the appropriate circumstances, can be lethal in this patient population 20— Survival of metastatic PDA and regression of metastases are rare 6, This single case report clearly does not prove that long-term PAA is valuable in cancer treatment.
Rather, this case, raising the possibility of efficacy, is a clue to be coupled with others indicating efficacy of PAA in cell and rodent cancer models, including models of pancreatic cancer 10,13 , and synergy in combination with gemcitabine For testing efficacy, prolonged treatment times may be necessary and should be considered in designing treatment trials.
PDA is a human cancer with a poor prognosis. Gemcitabine, a key therapeutic agent for metastatic PDA, and combination treatments have had only a modest impact on extending survival. We believe that a new treatment agent that shows robust laboratory and animal evidence, coupled with minimal patient toxicity, deserves rigorous clinical investigation without concern that clinical trials might not be supported by industry or have potential to generate profits.
Indeed, patients deserve no less. It is our opinion that the current evidence is sufficient to encourage both private and public funding agencies to evaluate support for targeted phase I and II clinical trials of PAA as a complement to standard therapies in the treatment of metastatic PDA. You may be trying to access this site from a secured browser on the server.
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Colleague's Email:. Separate multiple e-mails with a ;. Thought you might appreciate this item s I saw at Anti-Cancer Drugs. Send a copy to your email. Some error has occurred while processing your request. Please try after some time. Back to Top Article Outline. Cancer statistics CA Cancer J Clin ; — Cited Here Current standards and new innovative approaches for treatment of pancreatic cancer.
Eur J Cancer ; — PubMed CrossRef. Phase 2 trial of induction gemcitabine, oxaliplatin, and cetuximab followed by selective capecitabine-based chemoradiation in patients with borderline resectable or unresectable locally advanced pancreatic cancer.
Oncotarget , Jun 9; 8 40 : AC conceived the novel vitamin C-dependent opioid synthesis mechanism and the review topic, and wrote the vitamin C-related sections; CM wrote the general pain-related sections. Oct ; Cochrane Database Syst Rev. Ascorbic acid inhibits antitumor activity of bortezomib in vivo. Vitamin C pharmacokinetics: implications for oral and intravenous use. J Clin Invest 76 : - ,
Figures and Tables. Citations Publications citing this paper. Vitamin C and Cancer Annekathryn Goodman. References Publications referenced by this paper. Mikirova , Ronald E. Endocrine disruption of the epigenome: a breast cancer link.
Kevin C. Microbiome, inflammation, and cancer. Mato , Shelly C Lu. Clinical experience with intravenous administration of ascorbic acid: achievable levels in blood for different states of inflammation and disease in cancer patients Nina A. Mikirova , Joseph J. Increased cancer burden among pesticide applicators and others due to pesticide exposure.
Authors: Gonzalez, Michael J., Miranda-Massari, Jorge R. This concise SpringerBrief on Vitamin C and Cancer presents the latest findings on how vitamin C induces apoptosis. A high concentration of vitamin C allows for ascorbate to generate hydrogen peroxide in tissue that can. Research on vitamin C and its effects on cancer is growing in popularity around the world as positive research continues to accumulate building a stronger case.
Michael C. Parental occupational exposure to pesticides as risk factor for brain tumors in children and young adults: a systematic review and meta-analysis. Pharmacological ascorbate with gemcitabine for the control of metastatic and node-positive pancreatic cancer PACMAN : results from a phase I clinical trial J.
Welsh , B.