Redox active iron molecules react with vitamin C and increase cancer cell vulnerability.
High doses of vitamin C increases the sensitivity of cancer cells, and regular infusions with 800 to 1000 times the daily recommended amount was found to be safe to brain and lung cancer patients in clinical trials.
Eleven patients who were enrolled in the brain cancer safety trial received 3 infusions of vitamin C per week for 2 months followed by 2 infusions per week for 7 months, while still receiving standard care chemotherapy and radiation, according to a study published in Cancer Cell.
The goal of each infusion was to raise the concentration of vitamin C in the blood to 20,000 μM, compared with a blood level of approximately 70 μM found in most adults. A high-dose of vitamin C is necessary because it has a half-life of approximately 2 hours in the circulation of humans.
The results of the study showed that the treatment was generally well-tolerated, with only modest adverse events such as frequent trips to the bathroom and dry mouth. Although rare, some patients developed high blood pressure that quickly subsided following infusion.
Although vitamin C—–even at high levels––is not toxic to normal cells, the study found that the abnormally high levels of redox active iron molecules in the tumor tissue react with vitamin C to form hydrogen peroxide and free radicals derived from hydrogen peroxide.
“This paper reveals a metabolic frailty in cancer cells that is based on their product of oxidizing agents that allows us to utilize existing redox active compounds, like vitamin C, to sensitize cancer cells to radiation and chemotherapy,” said co-author Garry Buettner, who was among the first to propose that cancer cells may have a vulnerability to redox active compounds more than 40 years ago.
The free radicals are believed to cause selective DNA damage in cancer cells, resulting in enhanced cancer cell death and sensitization to chemotherapy and radiation in cancer cells.
“This is a significant example of how knowing details of potential mechanisms and the basic science of redox active compounds in cancer versus normal cells can be leveraged clinically in cancer therapy,” said co-senior author Douglas Spitz. “Here, we verified convincingly that increased redox active metal ions in cancer cells were responsible for this differential sensitivity of cancer versus normal cells to very high doses of vitamin C.”
The safety study paved the way for phase 2 clinical trials examining whether high-dose vitamin C is effective at extending overall lifespan and quality of life in patients receiving chemotherapy and radiation.
Currently, the investigators are enrolling patients with stage 4 lung cancer into these phase 2 trials, and will soon begin enrolling patients with glioblastoma. They are hopeful that responses to radiation and chemotherapy can be enhanced in the participants with glioblastoma.
A prior phase 1 trial showed an increase in overall survival of 4 to 6 months in 11 patients with glioblastoma (18 to 22 months), versus the 14 to 16 months of survival that is typically seen with standard treatment.
“The majority of cancer patients we work with are excited to participate in clinical trials that could benefit future patient outcomes down the line,” said co-senior author Bryan Allen. “Results look promising but we’re not going to know if this approach really improves therapy response until we complete these phase 2 trials.”