Combining a laboratory ultrasound technique called sonoporation with the commercially available chemotherapy compound gemcitabine increases the porosity of pancreatic cells with microbubbles and helps get the drug into cancer cells.1 These initial research findings from a phase 1 clinical trial were presented at the Acoustical Society of America 171st meeting.1
In the phase 1 study of 10 patients undergoing treatment for pancreatic cancer, the new approach nearly doubled median survival time from 7 months to 18 months without increased chemotherapy dosage and with no added toxicity or additional side effects.
“When we compared the amount of treatment our patients were able to undergo, compared to a historical cohort, we saw a significant increase of treatment cycles,” said Spiros Kotopoulis, PhD, a researcher at National Centre for Ultrasound in Gastroenterology at Haukeland University Hospital in Bergen and The Departments of Clinical Science & Medicine at the University of Bergen, Bergen, Norway, where some of his collaborators are also based.
The current 1-year survival rate for all stages of pancreatic cancer is 20% and the 5-year survival rate is 6%, according to the American Cancer Society.
The researchers were careful to use technology and materials already on the market for this study, which will facilitate more rapid clinical translation.
“If this worked, in 20 years, we didn’t want a hospital to have to purchase specialized, expensive, one-use equipment,” said Kotopoulis.
The clinicians began the procedure by administering standard chemotherapy to the patients according to the existing protocol. Once the chemotherapeutic concentration in the blood reached its maximum, the researchers used the ultrasound scanner to induce sonoporation for 31.5 minutes, at 3.5 minute intervals.
When treated with sonoporation, the volunteers were able to undergo 14 (±6) cycles of treatment, versus 8 (±6) with normal chemotherapy.
This ultimately had the effect of stabilizing or decreasing the tumor volumes in 50% of the patients and increasing the median patient survival time from approximately 7 months to 18 months.
The next steps for this research team include a larger phase 1/2 clinical trial with international collaborators. Also, they will work to develop a microbubble compound optimized for targeted drug-delivery at low acoustic intensities. They will also seek to fully understand the mechanisms of sonoporation by using advanced mouse models and bioreactors.
1. Kotopoulis S, Dimcevski G, Gilja O. Ultrasound- and microbubble-enhanced chemotherapy for treating pancreatic cancer: a phase I clinical trial. Presentation at: Acoustical Society of America 171st Meeting; May 23-27, 2016; Salt Lake City, UT. Abstract 3aBA6.