High-dose IV vitamin C doubles pancreatic cancer survival
Key takeaways:
- High-dose IV vitamin C plus standard chemotherapy extended survival for patients with advanced pancreatic cancer.
- The addition of vitamin C did not worsen adverse events.
The addition of high-dose IV vitamin C to standard chemotherapy nearly doubled OS for patients with advanced pancreatic cancer, according to results of a randomized phase 2 trial.
Vitamin C also delayed the impact of adverse events and improved quality of life.
“We were just thrilled to death with the results,” Joseph J. Cullen, MD, FACS, professor of surgery at Carver College of Medicine at University of Iowa, told Healio.
Background
Pancreatic ductal adenocarcinoma (PDAC) causes the third most cancer deaths in the U.S., and mortality has increased 0.5% annually, according to study background.
Only 12% of individuals diagnosed with PDAC survive 5 years, and only 3% of those diagnosed with distant disease live 5 years.
Vitamin C has been investigated as an alternative medicine for decades.
In the 1970s, data emerged showing vitamin C could be beneficial for people with cancer.
Trials in the 1980s did not show a benefit, Cullen said. However, those studies used oral vitamin C.
Mark A. Levine, MD, senior investigator at NIH, evaluated the pharmacokinetics of vitamin C and found giving it via IV increased absorption “almost a thousand-fold,” Cullen said.
Recent phase 1 trials showed 75 g of IV vitamin C could be administered safely with gemcitabine for individuals with stage IV PDAC. They also showed the approach may extend OS.
Methods
Cullen and colleagues assessed the survival benefits of IV vitamin C in a cohort of 36 adults with stage IV PDAC.
Researchers randomly assigned participants to standard-of-care gemcitabine and nab-paclitaxel alone or with IV vitamin C, administered at a dose of 75 g three times weekly.
Of 34 patients who received therapy, 16 (median age, 65 years; range, 56-72; 50% women; 93.8% white) received vitamin C therapy and 18 (median age, 58.5 years; range, 54.5-69; 33.3% women; 94.4% white) received chemotherapy alone.
OS served as the primary endpoint. PFS and safety served as secondary endpoints.
Results
Results showed longer PFS (median, 6.2 months vs. 3.9 months; HR = 0.43; 90% CI, 0.2-0.92) and OS (median, 16 months vs. 8.3 months; HR = 0.46; 90% CI, 0.23-0.92) with the addition of vitamin C. Historically, patients who received the control regimen achieved median OS of 8.5 months.
Participants had adverse events common with gemcitabine and nab-paclitaxel treatment. The vitamin C cohort had a lower rate of serious adverse events (1.2% vs. 1.7%) as well as grade 3 or grade 4 hematologic events (1.1% vs. 1.6%).
Researchers conducted an exploratory analysis on quality of life. Results showed longer time to negative impact from insomnia (6.2 months vs. 3.8 months; P = .047), constipation (6.2 months vs. 3.8 months; P = .032) and financial difficulties (5.4 months vs. 3.8 months; P = .022) in the vitamin C cohort.
“The high-dose vitamin C acts as a pro-oxidant,” Cullen said. “I think of it like pro-rust, just like rust on a car. It causes rust in a tumor. It kills the tumor but, in normal cells, the high dose of vitamin C acts as an antioxidant. What we found in other studies is vitamin C at high doses will reverse the damaging effects of radiation on normal cells.”
Researchers acknowledged study limitations, including the small sample size and lack of diversity in the cohort
Barriers to future research
Cullen and colleagues conducted a prior trial for patients with unresectable pancreatic cancer, and three of the 14 patients survived beyond 9 years.
“It was curative in three patients,” he said.
Those results and this recent study are rationale for a large, multi-institutional phase 3 trial, Cullen said, although he expressed pessimism a drug company would invest in it.
“Drug companies aren’t going to make any money on this,” he said. “It’s cheap. It’s going to be hard for us to try to get a drug company to do a phase 3 trial.”
Cullen and colleagues also are evaluating high-dose vitamin C in patients with lung cancer.
Other researchers have investigated it for individuals with glioblastoma, which have produced some “really nice findings,” Cullen added.
One publication showed vitamin C did not benefit men with end-stage prostate cancer, but no pretrial data supported vitamin C in that disease, Cullen said.
Mechanistically, vitamin C appears to have anticancer effects on tumors with low levels of catalase.
“Catalase converts hydrogen peroxide to water and oxygen,” Cullen said. “If you have low levels of catalase, you can’t convert that hydrogen peroxide, so you get more hydrogen peroxide, which kills the tumor cell. We’ve shown quite nicely in a study about 8 years ago in cells that if you vary the amount of catalase, you vary the amount of vitamin C killing cells. Some of these cancers may have high catalase.”
Another potential reason vitamin C may work better in some tumors is iron metabolism.
“If cells have more iron, they get another chemical reaction where the hydrogen peroxide interacts with the iron and forms this very reactive and damaging radical called hydroxyl radical, which is very toxic,” Cullen said. “It might have to do with levels of iron, but I really think it’s the levels of catalase.”
More research is necessary to examine these mechanisms; however, Cullen said he and colleagues have experienced resistance from the oncology community to vitamin C as treatment.
“One of the biggest barriers we have — and we encountered this when we first started doing the trials here at Iowa — is medical oncologists are ... incredibly resistant because they know the history of vitamin C, and they point to the trials done in the 1980s showing there was no difference,” Cullen said. “Now all the medical oncologists at Iowa want to throw it at every tumor that walks in the door. They see the results. You don’t see that at other places. Unless people have seen the results and have seen the data and have seen our studies, they’re just really reluctant to do it.”
For more information:
Joseph J. Cullen, MD, FACS, can be reached at joseph-cullen@uiowa.edu.
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