A novel targeted delivery method for amifostine, a radioprotective prodrug, is showing promise in protecting healthy tissues during radiation therapy for pancreatic cancer. Developed by scientists at Rice University, the University of Texas MD Anderson Cancer Center, and Xerient, this approach aims to improve outcomes for patients with this deadly disease, which claims nearly 52,000 lives annually in the United States.
Addressing a Critical Unmet Need
Pancreatic cancer's proximity to critical organs like the small intestine complicates treatment, as high-dose radiation often leads to severe gastrointestinal toxicity. For patients with tumors that are not surgically removable, therapeutic options are limited. This new method seeks to address this challenge by selectively protecting the duodenum, a particularly vulnerable area during radiation therapy.
Amifostine's Repurposing and Targeted Delivery
Amifostine (WR-2721), initially developed at Walter Reed Medical Center, is FDA-approved for intravenous use to protect healthy tissues during radiation therapy. However, its systemic side effects, including nausea and hypotension, have limited its widespread adoption. Researchers have found that targeted oral administration could selectively shield the gastrointestinal tract from radiation while reducing adverse effects. Xerient's new delivery method uses either a nasoduodenal tube or a coated oral tablet to bypass stomach acids and deliver amifostine directly to the duodenum.
Preclinical Evidence of Efficacy
Preclinical studies in mouse models have demonstrated the potential of this approach. Mice treated with oral amifostine and simulated radiotherapy achieved a 100% survival rate after 10 days, while untreated mice did not survive. In a pancreatic tumor model, the combination of amifostine and stereotactic body radiotherapy nearly tripled survival time in mice.
Clinical Trials and Future Directions
With FDA approval, the research team plans to initiate phase 1 and 2 clinical trials to evaluate the safety and efficacy of the nasoduodenal tube delivery method. According to Guy Yachin, co-founder and CEO of Xerient, this system offers advantages such as precise drug delivery, activation, and reduced idle radiation machine time. Xerient is also developing an oral pill for enhanced patient convenience.
The potential applications of this approach extend beyond pancreatic cancer. Amifostine could enable high-dose radiation therapy for other abdominal and pelvic cancers, including hepatobiliary tumors and metastatic abdominal diseases. James Tour from Rice University also noted its potential in protecting astronauts from solar radiation and as an emergency radioprotective measure during nuclear disasters.
Enabling High-Dose Radiation
High-dose radiation has shown promise in improving survival rates for patients with unresectable pancreatic cancer. However, doses above 45 Gy can harm the gastrointestinal tract. By protecting the duodenum, Xerient’s platform allows the safe delivery of higher radiation doses to pancreatic tumors, potentially improving treatment outcomes.
