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Preclinical Evaluation of Cetuximab and Benzoporphyrin Derivative‐Mediated Intraperitoneal Photodynamic Therapy in a Canine Model
Author(s) -
Cramer Gwendolyn,
Lewis Robert,
Gymarty Ashley,
Hagan Sarah,
Mickler Michela,
Evans Sydney,
Punekar Salman R.,
Shuman Lee,
Simone Charles B.,
Hahn Stephen M.,
Busch Theresa M.,
Fraker Douglass,
Cengel Keith A.
Publication year - 2020
Publication title -
photochemistry and photobiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.818
H-Index - 131
eISSN - 1751-1097
pISSN - 0031-8655
DOI - 10.1111/php.13247
Subject(s) - cetuximab , photodynamic therapy , medicine , epidermal growth factor receptor , egfr inhibitors , cancer , cytotoxicity , cancer research , oncology , pharmacology , colorectal cancer , chemistry , biochemistry , organic chemistry , in vitro
Peritoneal carcinomatosis (PC) can occur as an advanced consequence of multiple primary malignancies. Surgical resection, radiation or systemic interventions alone have proven inadequate for this aggressive cancer presentation, since PC still has a poor survival profile. Photodynamic therapy (PDT), in which photosensitive drugs are exposed to light to generate cytotoxic reactive oxygen species, may be an ideal treatment for PC because of its ability to deliver treatment to a depth appropriate for peritoneal surface tumors. Additionally, epidermal growth factor receptor (EGFR) signaling plays a variety of roles in cancer progression and survival as well as PDT‐mediated cytotoxicity, so EGFR inhibitors may be valuable in enhancing the therapeutic index of intraperitoneal PDT. This study examines escalating doses of benzoporphyrin derivative (BPD)‐mediated intraperitoneal PDT combined with the EGFR‐inhibitor cetuximab in a canine model. In the presence or absence of small bowel resection (SBR) and cetuximab, we observed a tolerable safety and toxicity profile related to the light dose received. Additionally, our findings that BPD levels are higher in the small bowel compared with other anatomical regions, and that the risk of anastomotic failure decreases at lower light doses will help to inform the design of similar PC treatments in humans.