In the study, conducted by a team from the Center Treatment Centers of America led by led by Robert Levin, MD, and Christopher M. Stephenson, DO, used higher doses of the vitamin, administered intravenously, than have been used in previous trials.
Use of vitamin C to treat cancer patients first became popular in the 1970s as a result of the work of Nobel Laureate Linus Pauling. However, studies conducted with orally dosed supplements did not demonstrate any clinical benefit in cancer patients, most likely due to the finding that the levels of orally-administered vitamin C delivered to a patient's blood stream were considerably lower than the levels needed to kill cancer cells in either test tube or animal models.
Recent studies in which vitamin C was administered intravenously (by IV) resulted in higher levels delivered to the patient's bloodstream suggest that vitamin C may, in fact, promote anticancer activity. The CTCA’s recently completed Phase I clinical trial determined the pharmacokinetics, safety and tolerability of IV-administered, high dose vitamin C at levels that could potentially achieve the serum concentrations adequate for anti-cancer activity.
Higher doses achieved
As noted in the study, a previous Phase I IV vitamin C trial stopped dose escalation at approximately 56 g/m2, when peak blood levels approached 26 mM, a level that inhibited tumor growth in mice. However, 30 to 40 mM ascorbic acid in mouse blood only partially inhibited the rate of tumor growth and did not result in tumor regression.
In the recent trial, researchers were seeking to obtain even higher blood concentrations. Their 70 to 80 g/m2 dose delivered blood concentrations of 49 mM. These levels appear to have a greater potential for producing anti-cancer activity in future studies.
"While this may be the baseline for treatment potential," said Dr. Stephenson, "it suggests we are on the right track for future studies and eventual use in fighting cancer."
The use of IV-administered vitamin C in combination with cytotoxic chemotherapy is further encouraged by a recent report showing that vitamin C potentiated the antitumor activity of gemcitabine against seven human and one murine pancreatic cancer cell lines. This observation is of particular interest as two of the human lines were resistant to gemcitabine.
Synergistic antitumor activity occurred in tissue culture and in vivo studies with implanted tumors in mice. In addition, a recently published phase I clinical trial evaluated IV-administered vitamin C combined with gemcitabine and erlotinib in nine patients with stage IV metastatic pancreatic cancer. Pharmacologic levels of vitamin C were potentially achieved in all participants and tumor volumes decreased in eight out of nine patients.
The findings of the CTCA study, coupled with the emerging evidence from the available literature, suggest that the combination of IV-administered vitamin C with gemcitabine to treat pancreatic cancer is therapeutic approach that warrants further evaluation. The CTCA research team is planning to conduct a phase 2 study using the higher dose of 70 to 80 g/m2 to achieve more adequate and longer lasting blood concentrations of vitamin C to better understand the possible outcome of this increased dosage.
Source: Phase I clinical trial to evaluate the safety, tolerability, and pharmacokinetics of high-dose intravenous ascorbic acid in patients with advanced cancer. Stephenson CM, Levin RD, Spector T, Lis CG. Cancer Chemotherapy and Pharmacology. May 2013.