by Jennifer Brown, University of Iowa

Graphical abstract. Credit: Redox Biology (2024). DOI: 10.1016/j.redox.2024.103375

Results from a randomized, phase 2 clinical trial show that adding high-dose, intravenous (IV) vitamin C to chemotherapy doubles the overall survival of patients with late-stage metastatic pancreatic cancer from eight months to 16 months.

"This is a deadly disease with very poor outcomes for patients. The median survival is eight months with treatment, probably less without treatment, and the five-year survival is tiny," says Joe Cullen, MD, University of Iowa professor of surgery and radiation oncology, and senior author of the study.

"When we started the trial, we thought it would be a success if we got to 12 months survival, but we doubled overall survival to 16 months. The results were so strong in showing the benefit of this therapy for patient survival that we were able to stop the trial early."

The findings, published in Redox Biology, mark another success for high-dose, intravenous vitamin C, which has overcome many hurdles in the almost 20 years UI researchers have persevered to demonstrate its benefit for cancer patients.

"We've had ups and downs, of course, but this is a culmination of a lot of people's hard work," says Cullen, who is also a member of UI Health Care Holden Comprehensive Cancer Center. "It's really a positive thing for patients and for the University of Iowa."

Increased survival, improved quality of life

In the study, 34 patients with stage 4 metastatic pancreatic cancer were randomized to receive either standard chemotherapy (gemcitabine and nab-paclitaxel), or chemotherapy plus infusions of high-dose vitamin C. The results showed that average overall survival was 16 months for the patients receiving the chemotherapy plus vitamin C, compared to eight months for the patients getting just chemotherapy. In addition, progression free survival was extended from four months to six months.

"Not only does it increase overall survival, but the patients seem to feel better with the treatment," Cullen says. "They have fewer side effects, and appear to be able to tolerate more treatment, and we've seen that in other trials, too."

The new study is not the only evidence of the benefit of including IV vitamin C as part of cancer treatment. Earlier this year, the results of another UI phase 2 clinical trial in patients with glioblastoma, a deadly form of brain cancer, were published. That study also showed a significant increase in survival when high-dose, IV vitamin C was added to standard of care chemotherapy and radiation. Cullen was also part of that trial along with his colleague Bryan Allen, MD, Ph.D., UI professor and head of radiation oncology.

A third phase 2 trial in non-small cell lung cancer is still underway, with results expected within the year.

"Our aim is to show that adding high-dose, IV vitamin C, which is very inexpensive and very well tolerated, can improve treatment for these cancers that are among the deadliest affecting the U.S. population," Cullen adds.

A long journey to clinical trials

Cullen, Allen, and their colleagues at UI Health Care have been researching the anti-cancer effect of high-dose, IV vitamin C for decades. Their work revealed a critical difference between vitamin C given intravenously and vitamin C taken orally. Giving vitamin C through an IV produces very high levels in the blood, which cannot be achieved with oral delivery. These high concentrations result in unique chemical reactions within cancer cells that render the cell more vulnerable to chemo- and radiation therapies.

Cullen notes that despite skepticism towards vitamin C as a cancer therapy, the results he and his colleagues have obtained, from basic science findings to understand the biological mechanisms at work, through the various clinical trials, have been highly encouraging and robust.

"Through every step of the process, it continued to improve. We did it in cells, it worked great. We did it in mice, it worked great. Then our phase one trials looked very promising. So, the progression has just been phenomenal, really," Cullen says. "For example, in one of our phase 1 trials for pancreatic cancer, where we combined high-dose, IV vitamin C with radiation, we still have three long-term survivors. They're out nine years at this point, which is far beyond the typical survival range."

In addition to Cullen and Allen, the UI team also included cancer physicians and researchers from the Departments of Surgery, Radiation Oncology, Internal Medicine in the UI Carver College of Medicine, the UI College of Public Health, and the Medical College of Wisconsin in Milwaukee.

More information: Kellie L. Bodeker et al, A randomized trial of pharmacological ascorbate, gemcitabine, and nab-paclitaxel for metastatic pancreatic cancer, Redox Biology (2024). DOI: 10.1016/j.redox.2024.103375

Journal information: Redox Biology 

Provided by University of Iowa