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Supplementary Figures from Intraperitoneal Paclitaxel Is a Safe and Effective Therapeutic Strategy for Treating Mucinous Appendiceal Adenocarcinoma

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posted on 2023-10-02, 07:20 authored by Ichiaki Ito, Abdelrahman M.G. Yousef, Saikat Chowdhury, Princess N. Dickson, Zahra A. Naini, Michael G. White, Karianne G. Fleten, Kjersti Flatmark, Keith F. Fournier, Natalie W. Fowlkes, John Paul Shen

Figure S1-S8

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National Cancer Institute (NCI)

United States Department of Health and Human Services

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Cancer Prevention and Research Institute of Texas (CPRIT)

Col Daniel Connelly Memorial Fund

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ARTICLE ABSTRACT

Appendiceal adenocarcinomas (AA) are a rare and heterogeneous mix of tumors for which few preclinical models exist. The rarity of AA has made performing prospective clinical trials difficult, which has partly contributed to AA remaining an orphan disease with no chemotherapeutic agents approved by the FDA for its treatment. AA has a unique biology in which it frequently forms diffuse peritoneal metastases but almost never spreads via a hematogenous route and rarely spreads to lymphatics. Given the localization of AA to the peritoneal space, intraperitoneal delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by intraperitoneal administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly intraperitoneal paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous with intraperitoneal administration, intraperitoneal delivery of paclitaxel was more effective, with reduced systemic side effects in mice. Given the established safety record of intraperitoneal paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of intraperitoneal paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of intraperitoneal paclitaxel in a prospective clinical trial. The activity and safety of intraperitoneal paclitaxel in orthotopic PDX models of mucinous appendiceal adenocarcinoma supports the evaluation of intraperitoneal paclitaxel in a prospective clinical trial of this rare tumor type.

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