Before ultrasound exposure, the amount of drug reaching the tumour passively was low and estimated to be below therapeutic levels. In seven out of 10 patients, chemotherapy concentrations within the liver tumour following focussed ultrasound were between two and ten times higher, with an average increase of 3.7 times across all patients.
'Only low levels of chemotherapy entered the tumour passively. The combined thermal and mechanical effects of ultrasound not only significantly enhanced the amount of doxorubicin that enters the tumour, but also greatly improved its distribution, enabling increased intercalation of the drug with the DNA of cancer cells,' said Dr Paul Lyon, lead author of the study.
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'This trial offers strong evidence of the rapidly evolving role of radiology in not only diagnosing disease but also in planning, guiding and monitoring therapy. The treatment was delivered under ultrasound guidance and patients were subsequently followed up by CT, MRI and PET-CT, evidencing local changes in tumours exposed to focussed ultrasound,' commented Professor Fergus Gleeson, radiology lead co-investigator for the trial.
'A key finding of the trial is that the tumour response to the same drug was different in regions treated with ultrasound compared to those treated without, including in tumours that do not conventionally respond to doxorubicin,' added Professor Mark Middleton, principal investigator of the study. 'The ability of ultrasound to increase the dose and distribution of drug within those regions raises the possibility of eliciting a response in several difficult-to-treat solid tumours. This opens the way not only to making more of current drugs but also targeting new agents where they need to be most effective. We can now begin to realize the promise of precision cancer medicine.'
The full paper, '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,' can be read in The Lancet Oncology.
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