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

Authors

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

Publication Date

10-2-2023

Journal

Cancer Research

Abstract

Appendiceal adenocarcinomas (AAs) 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 (IP) delivery of chemotherapy could be an effective treatment strategy. Here, we tested the efficacy of paclitaxel given by IP administration using three orthotopic patient-derived xenograft (PDX) models of AA established in immunodeficient NSG mice. Weekly IP paclitaxel treatment dramatically reduced AA tumor growth in all three PDX models. Comparing the safety and efficacy of intravenous (IV) to IP administration, IP delivery of paclitaxel was more effective with reduced systemic side effects in mice. Given the established safety record of IP paclitaxel in gastric and ovarian cancers, and lack of effective chemotherapeutics for AA, these data showing the activity of IP paclitaxel in orthotopic PDX models of mucinous AA support the evaluation of IP paclitaxel in a prospective clinical trial.

Keywords

Female, Humans, Animals, Mice, Paclitaxel, Prospective Studies, Adenocarcinoma, Mucinous, Adenocarcinoma, Ovarian Neoplasms

Comments

Supplementary Materials

PMID: 37433032