Oxaliplatin-induced peripheral neuropathy can be minimized by pressurized regional intravascular delivery in an orthotopic murine pancreatic cancer model
JSN Shankara Narayanan, K Frizzi, S Erdem, P Ray… - Discover Oncology, 2022 - Springer
Discover Oncology, 2022•Springer
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 …
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 …
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.
Springer
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