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New ultrasound technique better targets liver tumours

Tuesday July 10th, 2018

A technique to treat liver cancer patients with heat-activated lipid capsules filled with chemotherapy has been found to be successful in phase 1 clinical trials, British researchers report today.

The capsules are directed by ultrasound and when ruptured deliver more chemotherapy directly to the liver tumours, according to researchers from the University of Oxford.

While other clinical trials have combined the chemotherapy-filled lipid capsules with radiofrequency ablation, this study is the first to use ultrasound to remotely trigger drug release from the capsules.

The open-label phase 1 trial was carried out in one UK hospital in the UK, and included 10 patients with incurable tumours in their livers. They had all received standard chemotherapy to help control their tumours, and the trial analysed the safety and feasibility of the new technique.

The findings, published in The Lancet Oncology, show that each patient received a dose of 50mg/m2 of doxorubicin chemotherapy within heat-sensitive lipid capsules is injected into the bloodstream while under general anaesthetic.

Ultrasound focused on the liver tumour, slightly increasing the temperature in that area, and when the capsules reached 39.5°C, the drug was released into the bloodstream inside the tumour. This then creates a high drug concentration gradient, driving more chemotherapy into the tumour.

The researchers measured how much ultrasound exposure was needed to heat the tumour to 39.5°C or higher by temporarily implanting a heat-recording device placed into six patients’ tumours. They also took tumour biopsies from all 10 patients to assess the amount of chemotherapy delivered inside the tumour.

In seven of the patients, chemotherapy concentrations within the liver tumour were two or more times higher after the ultrasound, compared with before ultrasound exposure. The concentration of chemotherapy within the tumour was less than doubled in the other three patients.

On average, the new technique increased the amount of chemotherapy inside the tumour by 3.7 times (from 2.34 µg/g chemotherapy within the tumour before ultrasound exposure, to 8.56 µg/g chemotherapy within the tumour after ultrasound exposure).

Professor Constantin Coussios, University of Oxford, said: “Reaching therapeutic levels of cancer drugs within a tumour, while avoiding side effects for the rest of the body is a challenge for all cancer drugs, including small molecules, antibodies and viruses.

“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 focussed ultrasound. Once inside the tumour, the lipid capsules release the drug, supplying a higher dose of chemotherapy directly to the tumour, which may help to treat tumours more effectively.”

Lyon P, Gray M, Mannaris C et al. Safety and feasibility of ultrasound-triggered targeted drug delivery of doxorubicin from thermosensitive liposomes in liver tumours (TARDOX): a single-centre, open-label, phase 1 trial. The Lancet Oncology 9 July 2018; doi: 10.1016/S1470-2045(18)30332-2

Tags: Cancer | Internal Medicine | UK News

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