Novel amifostine delivery could be ‘tremendous advance’ for pancreatic cancer therapy
Key takeaways:
- Early research showed nasoduodenal tube delivery of amifostine may help protect the duodenum during radiation for pancreatic cancer.
- A phase 1/phase 2 clinical trial will begin later this year.
Fear of nuclear fallout has led to a novel therapeutic approach that could significantly extend the lives of individuals with pancreatic cancer or other gastrointestinal malignancies.
A novel method of amifostine delivery, currently administered via IV to protect healthy tissue during radiation treatment, showed promise protecting the duodenum during high-dose radiation treatment for pancreatic cancer in preclinical models.
Researchers will begin investigating amifostine delivery through a nasoduodenal tube in a clinical trial later this year.
“There are two types of cancer that are very hard to treat. They are glioblastoma and pancreatic cancer,” James M. Tour, PhD, T.T. and W.F. Chao professor of chemistry and professor of materials science and nanoengineering at Rice University, told Healio. “The hope would be that this would be a front-line tool to help knock out pancreatic cancer and give people not just 6 months, but many years.”
Background
Tour and colleagues began their research in this area more than 2 decades ago, as they investigated whether nanoparticles could mitigate the damages of radiation poisoning.
“After the events of 9/11, there was a lot of hysteria and fear that there’d be more terrorist attacks, and that somebody would eventually pop open a [nuclear weapon] in a city,” Tour said. “When plumes of radiation pass over a city, it takes 2 to 3 hours. So, if somebody popped open a nuclear weapon of some sort — they talked a lot about these briefcase bombs — you could never empty a city in time.”
When individuals are exposed to high doses of radiation, the first area to be compromised are stem cells in the intestinal crypts, Tour said.
These stem cells make new cells that coat the villi of the jejunum, which prevent people from developing bacterial infections.
“When you eat, you start getting bacterial infections,” Tour said. “Lab mice die in 2 weeks after whole body radiation. People die in about 1 month. They die of gastrointestinal syndrome — bacteria get through the lining of the intestines.”
Government officials sought research investigating an oral formulation that could protect the public from nuclear radiation.
Tour and colleagues received funding from the Defense Advanced Research Projects Agency (DARPA), as they had been investigating nanoparticles’ ability to protect the small intestine.
For their study, they used oral amifostine as a control, but they found amifostine worked better than the nanoparticles.
Eventually, the government stopped funding the research. However, a colleague suggested amifostine could protect the duodenum, which feeds into the jejunum, allowing oncologists to give higher doses of radiation to target pancreatic cancer.
‘Utterly amazing’
Pancreatic cancer is projected to cause nearly 52,000 deaths in the U.S. in this year, the third most of any cancer type, according to American Cancer Society’s Cancer Statistics 2025 report.
Only 8% of patients diagnosed with pancreatic exocrine tumors survive 5 years.
“When you have a tumor in the head of the pancreas, you can’t do surgery because there’s a main artery that runs right through the head of the pancreas. It’s too dangerous,” Tour said. “If you clip that artery, the patient dies right there on the table. Chemotherapy doesn’t work very well because these tumors have a stroma around them that is very hard to penetrate. You can use radiation, but it doesn’t work very effectively because you can’t use as much radiation as you need to knock out the tumor. You can only shrink it a little bit, because if you used the amount of radiation that you would want to use, you would knock out the duodenum, which is right behind the pancreas. A person can’t live without the duodenum.”
Tour and colleagues started conducting preclinical work. They found mice treated with oral amifostine and simulated radiation had a 100% survival rate after 10 days, compared with 0% for untreated mice.
In a pancreatic cancer model, mice that received oral amifostine and stereotactic body radiotherapy survived three times longer.
“Mice normally have about 160 crypts,” Tour said. “After whole body radiation they would go down to about 15. With amifostine, they would go from like 160 to 145. Most of their crypts were surviving. It was utterly amazing.”
Potential for ‘tremendous advance’
A phase 1/phase 2 clinical trial is scheduled to begin in June, Tour said.
Participants will receive amifostine through a nasoduodenal tube.
“It’s actually considered noninvasive,” Tour said. “They spray a little thing up your nose so it’s not so sensitive. Then it’s a device that goes up your nose, down the back of your throat, into where the stomach empties, and it will spray right into the duodenum. It’s direct. The reason they’re doing that rather than an oral formulation is because you want to limit the variables.”
An oral formulation could be considered in the future if the trial proves successful, but Tour said he does not think individuals with pancreatic cancer would have significant issues with the nasoduodenal tube.
“I’ve had it done for other things,” Tour said of his own personal experience. “It’s a very simple technique.”
Multiple potential patients already have reached out about the trial, Tour said.
“The FDA would consider a 3-month extension on lifetime very good,” he said. “If we could get 6 months, that would be excellent.”
If the trial delivers those results, the treatment could be extended to other gastrointestinal cancers, Tour said.
“The thing about radiation is, it’s not like chemotherapy in the sense that your body gets used to it and then your body no longer responds to it,” Tour said. “Radiation will work time and time again. If you could just continue to protect the duodenum and continue to radiate these patients anytime it cropped back up, this would be a tremendous advance.”
References:
- Molkentine JM, et al. Sci Rep. 2019;doi10.1038/s41598-018-37147-9.
- “Pushing the boundaries of radiation treatment”: Breakthrough in pancreatic cancer therapy advances to clinical trials (press release). Available at: https://news.rice.edu/news/2025/pushing-boundaries-radiation-treatment-breakthrough-pancreatic-cancer-therapy-advances. Published Jan. 30, 2025. Accessed Feb. 5, 2025.
For more information:
James M. Tour, PhD, can be reached at tour@rice.edu.
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