Heat-activated chemo shows promise in liver cancer patients

Heat-sensitive lipid capsules packed with chemotherapy, which can be remotely popped using ultrasound, increased the amount of chemotherapy delivered directly to liver tumors, according to a 10-person study published in The Lancet Oncology.

In the open-label phase 1 trial, researchers tested participants with incurable and non-ablatable primary or secondary tumors at a U.K. hospital. The cohort had previously received traditional chemo to help tame the tumors, while the proof-of-concept trial determined the safety and effectiveness of the new method.

“Reaching therapeutic levels of cancer drugs within a tumor, while avoiding side effects for the rest of the body is a challenge for all cancer drugs, including small molecules, antibodies and viruses,” wrote lead author Paul C. Lyon with the Nuffield Department of Surgical Sciences at John Radcliffe Hospital in Oxford, U.K., and colleagues.

“Our study is the first to trial this new technique in humans, and finds that it is possible to safely trigger and target the delivery of chemotherapy deep within the body using focused ultrasound,” they added. 

Biopsies were taken from patients to determine how much chemotherapy entered the tumor. In seven of the 10 patients, chemo concentrations within the live tumor were two or more times higher after ultrasound. In the three other patients, the chemotherapy concentration was less than double, according to authors.

All patients were monitored for 30 days post-treatment to evaluate unanticipated side effects. Aside from those caused by general anesthetic and chemotherapy, the method produced no additional risks.

“Overall, these findings suggest that target drug delivery to solid tumors triggered non-invasively by therapeutic ultrasound is clinically safe, feasible, and potentially effective,” Lyon et al. wrote.

The authors listed a number of limitations for their study, including its small sample size and biopsies from patients only looked at one area of the tumor. They noted tumors can be varied and biopsies can only estimate the amount of chemo that has entered the tumor as a whole.

In an accompanying editorial, Dieter Haemmerich, with Medical University of South Carolina, said the approach “represents a first important step towards clinical translation of this elegant targeted drug delivery approach,” but argued the “described focused ultrasound plus lyso-thermosensitive liposomal doxorubicin (LTLD) approach might be more widely applicable to other solid tumors because doxorubicin is a wide-spectrum antitumor drug.”