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Pancreatic Cancer Case Studies

George P. Kim, MD: Role of Liposomal in Nanoliposomal Irinotecan

George P. Kim, MD
Published Online:Sep 23, 2016
Henry R was diagnosed with adenocarcinoma in the body of the pancreas when he was 64 years old, following rapid weight loss, abdominal pains, and the development of venous thrombosis. 

Metastatic Pancreatic Cancer With George P. Kim, MD, and Eileen M. O'Reilly, MD: Case 2

Metastatic Pancreatic Cancer With George P. Kim, MD, and Eileen M. O'Reilly, MD: Case 1
Metastatic Pancreatic Cancer With George P. Kim, MD, and Eileen M. O'Reilly, MD: Case 2


What role in the mechanism of action might the liposomal component play for nanoliposomal irinotecan?

The mechanism of action has to do with the formulation of the drug. There are 80,000 irinotecan molecules in the liposome and the liposome has a prolonged half-life compared to regular irinotecan, by about four-fold. The half-life can be as long as 25 hours. Or, it can be as long as 70 hours for the SN-38 metabolite, which is the active anti-cancer metabolite. So you have more of the irinotecan circulating throughout the body. It remains in the liposome (95%) and it is circulating throughout the blood, hopefully lodging into tumor vessels and then leaching out the irinotecan which can then work its way through the desmoplastic tumor’s stromal barrier around pancreas cancers and then kill the cancer cells with the SN-38 anti–topoisomerase-1 activity. That is very distinct from irinotecan given by itself which is probably just circulating right by the tumor and not even getting into the tumor matrix or not even getting close to the proximity of the cancer cell. So this sort of formulation is why nal-IRI, or Onivyde, works so well. It may also explain why nab-paclitaxel works well in pancreas cancer. These agents are able to lodge in the tumor and then get access to the tumor cells by affecting the desmoplastic reaction.

Metastatic Pancreatic Cancer: Case 2

Henry R was diagnosed with adenocarcinoma in the body of the pancreas when he was 64 years old, following rapid weight loss, abdominal pains, and the development of venous thrombosis. 

  • At diagnosis, measurable distant lymph node, liver, and lung metastases were observed
  • His CA19-9 level was 2760 U/ml and his concentration of albumin was 28 g/L. His ECOG performance status was 1.

Upfront treatment was administered with nab-paclitaxel and gemcitabine, which lasted for 4months:

  • At the time of progression, pain levels had increased interfering with daily activity and raising the ECOG performance status to a 2.
  • At this point, second-line therapy was initiated with liposomal irinotecan, fluorouracil, and folinic acid.
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