Multisite Is Superior to Single-Site Intratumoral Chemotherapy to Retard the Outcomes of Pancreatic Ductal Adenocarcinoma in a Murine Model

Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. This study explores the efficacy of multisite intratumoral injections in improving a drug&...

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Bibliographic Details
Published in:Cancers 2023-12, Vol.15 (24), p.5801
Main Authors: Lazarovits, Janette, Epelbaum, Ron, Lachter, Jesse, Amikam, Yaron, Ben Arie, Jacob
Format: Article
Language:English
Subjects:
Adenocarcinoma
Animal models
Animals
Apoptosis
Cancer
Chemotherapy
Clinical outcomes
Comparative analysis
Drug dosages
Gemcitabine
Health aspects
Life span
Lymphocytes
Oncology, Experimental
Oxaliplatin
Pancreatic cancer
Quality of life
Stroma
Toxicity
Tumor microenvironment
Tumors
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Summary:Locally advanced unresectable pancreatic cancer (LAPC) has a dismal prognosis, with intratumoral therapies showing limited benefits. We assume that the dense stroma within these tumors hampers drug dispersion. This study explores the efficacy of multisite intratumoral injections in improving a drug's distribution while minimizing its side effects. In mice with orthotopic LAPC tumors, weekly intratumoral injections of oxaliplatin at four separate sites reduced the tumor growth by 46% compared with saline ( < 0.003). Oxaliplatin exhibited the greatest impact on the tumor microenvironment relative to gemcitabine, Abraxane, or their combination, with increased necrosis, apoptosis, fibroblasts, inflammation, and infiltrating lymphocytes ( < 0.008). When combined with intravenous FOLFIRINOX (FFX), multisite intratumoral oxaliplatin reduced the tumor weight by 35% compared with single-site injection ( = 0.007). No additional visible toxicity was observed even at a 10-fold occurrence of intratumoral treatment. This co-modality treatment significantly improved survival compared with other groups ( = 0.007). Multisite intratumoral therapy in tandem with systemic treatment holds promise for reducing the tumor size and enhancing the overall survival in LAPC.
ISSN:2072-6694
2072-6694
DOI:10.3390/cancers15245801