A Pilot Study of Thermodox and MR-HIFU for Treatment of Relapsed Solid Tumors

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Description

LTLD is a heat-activated formulation of liposomal doxorubicin that releases the drug when exposed to hyperthermic conditions (40-45°C). This novel agent has been well tolerated in adults with similar toxicity profile to doxorubicin. MR-HIFU offers a non-invasive and non-ionizing ability to selective...

LTLD is a heat-activated formulation of liposomal doxorubicin that releases the drug when exposed to hyperthermic conditions (40-45°C). This novel agent has been well tolerated in adults with similar toxicity profile to doxorubicin. MR-HIFU offers a non-invasive and non-ionizing ability to selectively heat large tissue volumes. Thus, MR-HIFU is a promising technology for triggering doxorubicin release from LTLD. LTLD has been evaluated with ultrasound-guided high intensity focused ultrasound and found to be safe and feasible. In this population, patients had a real-time thermometry device implanted intra-tumorally, allowing for only a limited spatial sample of temperature at the target. Without more complete knowledge of temperature distribution in and around the targeted area, the use of ultrasound-guided HIFU for LTLD drug delivery does not provide spatial control over drug release. This may result in areas of over or under treatment within the target, and potentially even off-target drug delivery or overheating. In contrast, our MR-HIFU device provides real-time MR thermometry without additional devices. Building upon recent mathematical as well as pre-clinical work we will use an approach that capitalizes on MR-HIFU features to optimize drug delivery to the targeted tumor. Similar to many original pre-clinical studies and clinical trials with LTLD, our approach involves continuous maintenance of the target at mild hyperthermia with MR-HIFU following LTLD infusion. Following hyperthermia, we will deliver ablation therapy (>55°C) to targeted areas of tumor where feasible and safe. Addition of this ablation therapy after mild-hyperthermia-triggered drug delivery with LTLD has the potential to significantly potentiate chemotherapy with minimal additional adverse effects to improve local control and drug delivery without increasing toxicity, as demonstrated by mathematical modeling as well as pre-clinical studies.

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