Oxaliplatin-induced peripheral neuropathy can be minimized by pressurized regional intravascular delivery in an orthotopic murine pancreatic cancer model

Jayanth Surya Narayanan Shankara Narayanan; Katie Frizzi; Suna Erdem; Partha Ray; David Jaroch; Bryan Cox; Steven Katz; Diego Vicente; Rebekah White

doi:10.1007/s12672-022-00483-4

Oxaliplatin-induced peripheral neuropathy can be minimized by pressurized regional intravascular delivery in an orthotopic murine pancreatic cancer model

Discov Oncol. 2022 Apr 6;13(1):21. doi: 10.1007/s12672-022-00483-4.

Authors

Affiliations

¹ Moores Cancer Center, University of California, 3855 Health Sciences Dr, Rm 2336, La Jolla, San Diego, CA, 92037, USA.
² Department of Pathology, University of California, San Diego, CA, USA.
³ TriSalus™ Life Sciences, Inc, Westminster, CO, USA.
⁴ Immuno-Oncology Institute, Roger Williams Medical Center, Providence, RI, USA.
⁵ Uniformed Services University of the Health Sciences, Bethesda, MD, USA.
⁶ Moores Cancer Center, University of California, 3855 Health Sciences Dr, Rm 2336, La Jolla, San Diego, CA, 92037, USA. rewhite@health.ucsd.edu.

Abstract

Purpose: There is a great need to reduce the toxicity of chemotherapy used in the management of pancreatic ductal adenocarcinoma (PDAC). Here we explore if regional pressurized delivery of oxaliplatin can minimize peripheral neuropathy in mice.

Methods: We used an orthotopic PDAC mouse model and delivered a single dose of oxaliplatin through the portal vein using a pressure-enabled system (pancreatic retrograde venous infusion, PRVI). We analyzed the effects of PRVI on tumor burden and peripheral neuropathy using histopathological and functional assays.

Results: Tumor weights in mice treated with 2 mg/kg oxaliplatin using PRVI were significantly lower than in mice treated with the same dose systemically. This resulted in reduced peripheral neuropathy signatures in PRVI mice compared to the 20 mg/kg systemic dose required to achieve similar tumor control.

Conclusion: Regional delivery of highly cytotoxic agents using PRVI can reduce the therapeutic dose of these drugs, thereby lowering toxic side effects.