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Background

  • Pancreatic ductal adenocarcinoma (PDAC) is 3% of cancers diagnosed in the United States with 62,210 new cases expected in 2022, but it is the fourth leading cause of cancer-related deaths.
  • Hence, there is a considerable clinical need to develop innovative strategies for effective drug delivery and treatment monitoring, resulting in improved outcomes for patients with PDAC.
  • Sonoporation is a novel method that can enhance the therapeutic efficacy of co-administered chemotherapy by localized contrastenhanced ultrasound imaging (CEUS) of gas-filled microbubbles (ultrasound contrast agent UCA), which temporarily changes the tumor vascular microenvironment by increasing leakage from angiogenic vessels through microstreaming, shockwaves and the activation of various intracellular signaling responses [1].
  • Our Phase I clinical trial of sonoporation in 10 PDAC patients treated with Gemcitabine demonstrated no additional toxicity and an increase in median survival compared to the standard of care treatment (8.9 vs 17.6 months; p = 0.011) [2].
  • Subsequent, animal studies investigated 4 commercial UCAs under 2 different acoustic regimes and established the optimal UCA (Sonazoid; GE Healthcare, Oslo, Norway) as well as acoustic settings for sonoporation of PDAC [3].
  • There are two major chemotherapeutic regimens for the treatment of non-resectable PDAC, a combination of Leucovorin, Fluorouracil, Irinotecan and Oxaliplatin (FOLFIRINOX), considered the first line treatment, or a combination of Gemcitabine with a nanoparticle formulation of Paclitaxel (Nab-Paclitaxel), the second line treatment. These regiments results in a median overall survival of approximately 11 and 8-9 months.
  • The Oncological departments at Jefferson and Haukeland will be responsible for the SoC chemotherapeutic treatment. We will use the hospital’s standard recommended treatment protocols of gemcitabine hydrochloride (Gemkabi®) combined with nanoparticle albumin-bound paclitaxel (Nab-Paclitaxel (Abraxane®)), and FOLFIRINOX.

Publication Date

1-2023

Keywords

pancreatic cancer

Disciplines

Medicine and Health Sciences | Oncology

Comments

Presented at the ASCO Gastrointestinal Cancers Symposium.

Trial in Progress: Sonoporation for Disrupting the Pancreatic Cancer Microenvironment to Enhance Chemotherapy Delivery and Improve Outcomes

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