expert roundtables

Novel Drug Delivery Systems Metastatic Pancreatic Cancer

by Thomas A. Abrams, MD, Alok Khorana, MD, Michael Morse, MD, MHS, FACP

Overview

The incidence of metastatic pancreatic cancer has increased over the past several decades, and it now ranks as the fourth leading cause of cancer death in the United States. Despite the high mortality rate, there is optimism surrounding improved outcomes with newly developed treatment regimens. Our featured experts in the field discuss new treatments with novel drug delivery systems for metastatic pancreatic cancer.

Q:

Have novel drug delivery systems demonstrated the ability to improve drug delivery and treatment outcomes in patients with cancer? 

Alok Khorana, MD

Professor of Medicine
Director, Gastrointestinal Malignancies Program
Cleveland Clinic
Cleveland, OH

Pancreatic cancer has been a struggle to treat because standard cytotoxic regimens have largely proved unsuccessful. The whole era from the late 1990s through 2012 is littered with phase 3 randomized trials of the gemcitabine plus “X” drug (whatever “X” was in each study, specifically speaking). Two recent trials utilizing drug releasing systems led to FDA approvals. Paclitaxel albumin-bound nanoparticles in the gemcitabine + nab-paclitaxel trial in other cancers is one is such study. Recently, the use of nanoliposomal irinotecan in patients in the second-line setting in advanced pancreatic cancer led to overall survival improvement, unlike many randomized trials, and led to the FDA approval of nanoliposomal irinotecan for the second-line treatment of metastatic pancreatic cancer. Therefore, I think there certainly is a case to be made for whatever reason, perhaps it is the desmoplastic reaction around pancreatic cancer, perhaps the mechanism of drug resistance that are already built into pancreatic cancer cells, or perhaps it is the late stage of diagnosis. Whatever the reason is, normal drug mechanisms with novel delivery systems appear to be more necessary in pancreatic cancer than they are in other solid tumors.

“Recently, the use of nanoliposomal irinotecan in patients in the second-line setting in advanced pancreatic cancer led to overall survival improvement, unlike many randomized trials, and led to the FDA approval of nanoliposomal irinotecan for the second-line treatment of metastatic pancreatic cancer.”

Alok Khorana, MD

Thomas A. Abrams, MD

Assistant Professor of Medicine
Harvard Medical School
Senior Physician
Dana-Farber Cancer Institute
Boston, MA

Pancreatic cancer remains a very difficult cancer to treat, but we cannot overlook the improvements we have made in treating patients and the bettering of not only the absolute value of how long patients are living, but also their quality of life is improving for a longer period of time. I think though from a mechanistic standpoint, there certainly are preclinical data to suggest that the liposomal particle has better and increased penetration. That may indeed be a way that it improves upon the standard formulation but without the benefit of a head-to-head clinical trial to really understand whether that is the case, or to prove whether that is true, it is unfortunately a bit of speculation.

Michael Morse, MD, MHS, FACP

Professor of Medicine, Division of Medical Oncology
Professor, Department of Surgery
Duke University Medical Center
Durham, NC

The idea of taking an existing drug and making it better, whether it is liposomal or the macroaggregated albumin type approaches, obviously seems to have some benefits in various malignancies. It is clear that chemotherapy is here to stay, and so finding a better way of delivering it makes a lot of sense. Liposomal technologies have been around for a while. There are a lot of different strategies for allowing them to circulate longer and to allow better penetration, better biodistribution, and so on. It is claimed that the nanoliposomal particles used in this particular strategy are a step up from existing liposomal technologies in a variety of ways, and we do know that there are some ways that it could be better. For example, the amount of irinotecan that you actually have to administer with the nanoliposomal preparation is less. You are giving 70 or 80 mg/m2; whereas, normally we have to give 165 or 180 mg/m2. We are exposing a person to less of the parent drug and less of the active metabolite, whereas the amount accumulating in the tumor is actually higher. SN38 delivery at the tumor level would be greater. I think that is a potential advantage, but we do not have any data that I am aware of directly comparing whether it is safer or more effective than using higher doses of the normal form of irinotecan. It would be nice to see that data one of these days.

“It is clear that chemotherapy is here to stay, and so finding a better way of delivering it makes a lot of sense.”

Michael Morse, MD

References

Au M, Emeto TI, Power J, et al. Emerging therapeutic potential of nanoparticles in pancreatic cancer: a systematic review of clinical trials. Biomedicines. 2016;4(3). pii: E20.

Lamb YN, Scott LJ. Liposomal irinotecan: a review in metastatic pancreatic adenocarcinoma. Drugs. 2017;77(7):785-792.

Papi M, Caputo D, Palmieri V, et al. Clinically approved PEGylated nanoparticles are covered by a protein corona that boosts the uptake by cancer cells. Nanoscale. 2017;9(29):10327-10334.

Zhang H. Onivyde for the therapy of multiple solid tumors. Onco Targets Ther. 2016;9:3001-3007.

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