High-dose vitamin C may increase efficacy of cancer therapies – Healio

The addition of high-dose vitamin C to standard chemotherapy or radiation appeared to effective and safe for patients with glioblastoma multiforme and non–small cell lung cancer, according to study results.

Prior studies that assessed use of vitamin C in combination with chemotherapy and radiation yielded conflicting data.

Bryan G. Allen, MD, PhD, assistant professor in the department of radiation oncology at University of Iowa Hospitals and Clinics, and colleagues assessed the efficacy and safety of adding high-dose vitamin C to standard chemotherapy or radiation in two patient populations.

In one dose-escalation analysis, researchers assigned 11 patients with glioblastoma multiforme to vitamin C two to three times weekly in combination with standard of care for approximately 9 months.

Patients initially received low-dose vitamin C at 15 g per infusion. Investigators gradually increased the dose to more than 100 g. Results showed patients who received vitamin C experienced no additional adverse events than those typically observed with chemotherapy and radiation alone.

In a separate analysis, researchers assigned 14 patients with NSCLC to high-dose vitamin C in combination with standard chemotherapy. Results showed 93% of those who received vitamin C responded to treatment — more than double the historical 40% response rate to standard chemotherapy — and more than 30% experienced tumor shrinkage.

HemOnc Today spoke with Allen about the findings and the potential benefits of this treatment strategy.

Question: What prompted your research?

Answer: In the 1970s, studies suggested that vitamin C administered orally and via IV improved outcomes in patients with terminal cancer. However, two randomized trials in the 1980s later showed that oral vitamin C has no benefit compared with placebo. After this, interest in vitamin C waned. Then, in the 2000s, Mark A. Levine, MD, at NIH showed that millimolar concentrations of vitamin C killed cancer cells while normal cells remained unaffected. He collaborated with Garry R. Buettner, PhD, and Joseph Cullen, MD, at University of Iowa, and they found that vitamin C worked in pancreas cancer cells — both in the cell culture model and in the mouse model. They opened a phase 1 clinical trial in stage IV pancreas cancer. Following their example, we adapted it to glioblastoma multiforme and NSCLC. We started with the same process, where we tested the vitamin C in cells first to see if high doses affected cancer cells. We then conducted animal models and went on to conduct these clinical trials.

Q: How
did you and your colleagues conduct the studies?

A: For the glioblastoma study, we conducted a phase 1 clinical trial to confirm that high-dose vitamin C is safe when combined with a standard chemotherapy and radiation regimen. We performed a dose-escalation study because we wanted to be cautious with these large infusions of vitamin C. Therefore, we started with low-dose vitamin C at 15 g per infusion to ensure safety. As we became more comfortable, we gradually increased the dose to more than 100 g of vitamin C. Our phase 2 study looked at whether the combination of vitamin C and chemotherapy was efficacious for patients with NSCLC.

Q: What did the preliminary evidence suggest?

A: In the glioblastoma study, our preliminary evidence in 11 patients showed that vitamin C is safe and well tolerated. Patient outcome data are promising, and this is why we are moving on to a phase 2 trial to see if vitamin C combined with radiation and chemotherapy is efficacious.

In the case of NSCLC, vitamin C appeared safe when combined with high doses of chemotherapy, and the results are promising with regard to having better control than with chemotherapy alone. We still need to complete this phase 2 trial to have a statistical assessment. Therefore, results are promising, but we cannot yet make any statistical claims.

Q: What is the potential explanation for why responses would be better among patients who received vitamin C?

A: In our paper — published in Cancer Cell — we found that cancer cells have increased concentrations of redox active metals, specifically redox active iron, that go through different states that facilitate the oxidation of vitamin C. Once vitamin C is oxidized, it eventually produces hydrogen peroxide. Having this increased free iron in the cancer cell forms more hydrogen peroxide near or in the cancer cell. This stresses the cancer cell, making it more sensitive to radiation and chemotherapy.

Q:
What
is the potential impact of these findings?

A: Compared with the new biological therapies, vitamin C is still relatively cheap. This can enhance the efficacy of standard radiation and chemotherapy for patients with a variety of cancers without dramatically increasing cancer care costs. The impact could be worldwide, especially in countries where they do not have huge medical budgets.

Q: How much more research
is necessary to confirm the potential benefit?

A: With regard to efficacy, we need to complete the phase 2 trial in patients with stage IV NSCLC. We are opening the phase 2 glioblastoma multiforme study to see if the combination regimen is effective. We also hope to open a phase 2 study of patients with locally advanced lung cancer. After these studies are complete, we plan to advance to a phase 3 multicenter trial to see if this combination regimen is more effective than standard regimens.

Q: What advice would you offe
r physicians and their patients about vitamin C consumption?

A: Vitamin C in our studies appears to be safe and well tolerated, and the side effects are minimal. These side effects include dry mouth — due to the high salt load — and transient increases in blood pressure given that we are using between 1 liter and 2 liters of fluid. We always recommend that patients discuss everything with their medical care team before beginning a new therapy. We sometimes see patients who want to take vitamin C alone without radiation or chemotherapy, but in our animal models, we did not see improvements with vitamin C alone. We want to make sure that patients adhere to our protocol and combine vitamin C with their standard cancer treatment regimen.

Q:
Would you
like to mention
anything else?

A: Clinical trials require a true team approach between the patients, physicians and patient support groups. Participation in clinical trials is very important to advance medicine and science. Patients should always ask their health care teams whether they are clinical trial candidates. We are excited about this research, and we hope to keep it moving forward. There have been numerous people coming together to advance this research that started back in the 1970s, but there is still a lot of work to do. – by Jennifer Southall

References:

Schoenfeld JD, et al. Cancer Cell. 2017;doi:1016/j.ccell.2017.02.018.

Cameron E, et al. Proc Natl Acad Sci U S A. 1976;73:3685-3689.

Creagan ET, et al. N Engl J Med. 1979;301:687-690.

Moertel CG, et al. N Engl J Med.1985;312:137-141.

Chen Q, et al. Proc Natl Acad Sci U S A. 2008;105:11105-11109.

Du J, et al. Cancer Res. 2015;75:3314-3326.

Welsh JL, et al. Cancer Chemother Pharmacol. 2013;71:765-775.

For more information:

Bryan G. Allen, MD, PhD, can be reached at University of Iowa Hospitals and Clinics, 200 Hawkins Drive, Iowa City, IA 52242; email: bryan-allen@uiowa.edu.

Disclosure: Allen reports no relevant financial disclosures.

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