Safety of Endoscopic-Ultrasound-Guided Portal Injection Chemotherapy using Drug-Eluting Microbeads in a Porcine Model

• Douglas O. Faigel

  Division of Gastroenterology and Hepatology

• Vijay P. Singh

  Division of Gastroenterology and Hepatology

• Krutika Patel

  Division of Gastroenterology and Hepatology

• Alaa El Chami

  Division of Gastroenterology and Hepatology

• Catherine C. Raymond

  Center for Procedural Innovation

• Tracy L. Landreth

  Center for Procedural Innovation

• Ronald J. Marler

  Research Laboratories

• Douglas F. Lake

  Mayo Clinic, Scottsdale, Arizona; Arizona State University

• Toufic Kachaamy

  Tempe, Arizona; and Cancer Treatment Centers of America, Phoenix, Arizona, USA

Background and Aims: Patients with diffuse liver metastases have systemic chemotherapy as their only treatment option. We developed Endoscopic Ultrasound (EUS)-guided portal injection chemotherapy (EPIC) to increase drug levels in hepatic tissue as a novel new liver directed therapy.

Methods: Sixteen anesthetized pigs were treated with 50 mg of irinotecan (n=8) or doxorubicin (n=8). Half (n=4) of the animals in each drug group were treated with EPIC-injected microbeads or EUS-guided chemotherapy without beads into the inferior vena cava (control). Animals were observed twice daily for 7 days for signs of clinical toxicities. Tissue samples were harvested for histology and drug levels. Blood counts and chemistries were determined pre-treatment and at 7 days.

Results: No toxicities as evidenced by abnormal animal behavior were observed. No significant changes occurred in blood chemistry or blood counts in the irinotecan groups. For doxorubicin, systemic injection significantly decreased albumin, hemoglobin, and white blood cell count (P<.05), with no changes after EPIC. Hepatic histology showed mild foreign body reactions around the beads. No significant histologic changes were seen in other tissue sites. Neither irinotecan nor SN-38 was detectable at 7 days. For doxorubicin, no drug was detected in the plasma or bone marrow. The mean (SD) doxorubicin hepatic levels were non-significantly increased with EPIC vs control (181 [241] vs 151 [67] ng/g). Cardiac doxorubicin levels were significantly lower with EPIC (15 [4] vs 138 [48] ng/g; P=.02).

Conclusions: EPIC using drug-eluting microbeads was safe in this animal model. For doxorubicin, EPIC may be safer than systemic injection.

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