Preclinical Evaluation of Cetuximab and Benzoporphyrin Derivative‐Mediated Intraperitoneal Photodynamic Therapy in a Canine Model,Photochemistry and Photobiology

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Preclinical Evaluation of Cetuximab and Benzoporphyrin Derivative‐Mediated Intraperitoneal Photodynamic Therapy in a Canine Model
Photochemistry and Photobiology ( IF 2.6 ) Pub Date : 2020-04-27 , DOI: 10.1111/php.13247
Gwendolyn Cramer ₁ , Robert Lewis ₂ , Ashley Gymarty ₁ , Sarah Hagan ₁ , Michela Mickler ₁ , Sydney Evans ₁ , Salman R Punekar ₁ , Lee Shuman ₁ , Charles B Simone ₃ , Stephen M Hahn ₄ , Theresa M Busch ₁ , Douglass Fraker ₁ , Keith A Cengel ₁

Affiliation

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.

中文翻译：

犬模型中西妥昔单抗和苯并卟啉衍生物介导的腹腔内光动力疗法的临床前评估

腹膜癌病 (PC) 可作为多种原发性恶性肿瘤的晚期后果发生。仅手术切除、放射或全身干预已证明不足以应对这种侵袭性癌症表现，因为 PC 的生存率仍然很差。光动力疗法 (PDT)，其中光敏药物暴露于光下以产生细胞毒性活性氧物质，可能是 PC 的理想治疗方法，因为它能够将治疗传递到适合腹膜表面肿瘤的深度。此外，表皮生长因子受体 (EGFR) 信号在癌症进展和生存以及 PDT 介导的细胞毒性中起着多种作用，因此 EGFR 抑制剂可能对提高腹腔内 PDT 的治疗指数有价值。本研究在犬模型中检查了苯并卟啉衍生物 (BPD) 介导的腹腔内 PDT 联合 EGFR 抑制剂西妥昔单抗的剂量递增。在存在或不存在小肠切除术 (SBR) 和西妥昔单抗的情况下，我们观察到与接受的光剂量相关的可耐受安全性和毒性特征。此外，我们的研究发现，与其他解剖区域相比，小肠中的 BPD 水平更高，并且在较低光剂量下吻合失败的风险降低，这将有助于为人类类似 PC 治疗的设计提供信息。

更新日期：2020-04-27

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