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ARBs for the Treatment of Pancreatic Cancer?

For more than a decade there have been theoretical discussions about the use of drugs commonly used to treat high blood pressure for use in the treatment of cancer – pancreatic cancer (ductal adenocarcinoma of the pancreas). And there have been some prior preliminary research studies.

Now comes a very intriguing and elaborate pre-clinical study involving cells and mice and the blood pressure medicine losartan. This medication is an angiotensin receptor blocker (ARB) which relaxes muscle cells and causes blood vessels to dilate.  Researchers at Massachusetts General Hospital and Harvard Medical School including Jain and colleagues published this study in the October 2013 issue of the journal Nature communications.

The authors find and postulate that losartan appears to be the right ARB to optimally increase vascular perfusion and oxygen delivery in the stroma laden environment of pancreatic adenocarcinomas. As a part of the study losartan was given together with chemotherapy drugs including 5-FU and doxorubicin, and appears to potentiate chemotherapy delivery to the tumor site in pancreatic cancer.

The authors end by postulating that drugs such as losartan (ARBs) might be considered for further evaluation as adjuvant to standard chemotherapy for pancreatic cancer.

This is a highly provocative and promising pre-clinical finding that is deserving of further research.

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Dale O’Brien, MD

Nanoliposomal Topoisomerase I Inhibitor for Advanced Pancreatic Cancer

There is no universally agreed upon second line treatment for metastatic pancreatic cancer (ductal adenocarcinoma of the pancreas). On August 20 2013 in the British Journal of Cancer, the results of an interesting international Phase II clinic trial using nanoliposomal irinotecan for the treatment of earlier pre-treated metastatic pancreatic cancer were published. The researchers included Dr. Margaret Tempero, who is on our Pancreatica Science Board.

The study included 40 patients with metastatic pancreatic cancer who were now considered refractory to earlier treatment with gemcitabine, and who were then given the drug agent PEP02, also known as MM-398 (or Irinotecan Sufosulcrate) as developed by the biotech companies PharmaEngine and Merrimack. This is a nanoliposome, which indicates that the drug molecule is contained in a spherical coating of a lipid or fatty-like substance.

The essential aim of this study was to ascertain the 3-month survival rate in these pancreatic cancer patients with this therapy. The researchers observed 3 patients who demonstrated an objective tumor response.  Over at least two treatment cycles 17 other patients showed evidence of stable disease. 10 patients (of 32) with elevated CA19-9 levels, showed a greater than fifty percent decrease in these levels. The median progression-free duration was 2.4 months. The overall 3-month survival rate was 75%.  And the median overall survival was 5.2 months.

The researchers note that the more common side-effects of this treatment were asthenia, abdominal discomfort, neutropenia and diarrhea.

The authors conclude that at this stage of study the apparent activity of liposomal irinotecan coupled with a relatively tolerable side-effect profile make it a promising candidate for second-line consideration.  Currently Phase III trials are underway.

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Dale O’Brien, MD


EUS for Neuroendocrine Tumors

Depending on who you are and how you count, there are almost twenty kinds of pancreatic cancer. The main two that we generally speak of are ductal adenocarcinoma of the pancreas which arises from the non-hormonal part of the organ and may be responsible for as much as 85% of cases, and pancreatic neuroendocrine tumors (NETS) from the hormonal part of the pancreas – which true incidence is not fully established, but we might say represent about 10% of pancreatic cancer diagnosis.

There are many differences between these two main types of malignancy: natural history, signs and symptoms, treatment, and prognosis. From a functional practical sense, there is also one big difference that we have seen: often adenocarcinoma has presented itself with a diagnosis late but often fairly easily – so that treatment is typically the issue. And neuroendocrine tumors are often elusive in diagnosis with perplexing signs and symptoms  – sometimes for years – so here diagnosis is often the primary issue.

So, it is with interest that we encounter research by Frocione and his Illinois colleagues presented in the June 21st 2013 issue of the World Journal of Gastroenterology that reviews medical literature in terms of the use of the accuracy of the technique of endoscopic ultrasound (EUS) in the diagnosis of pancreatic neuroendocrine tumors.

The researchers reviewed over 2,600 articles in the medical literature, selecting 140 for further scrutiny, and eventually settled on thirteen that met their inclusion criteria. They extracted and pooled data from these studies to ascertain sensitivity, specificity and other parameters for the use of endoscopic ultrasound for pancreatic neuroendocrine diagnosis. They found that the pooled sensitivity of EUS in detecting pancreatic NETs was 87.2 percent; the pooled specificity was 98.0 percent.

The researchers conclude that endoscopic ultrasound appears to be a good way to establish the diagnosis for neuroendocrine tumors. There are limitations to this kind of study, but it is highly interesting and relevant – and certainly worthy of further follow-up and confirmation.

More here


Dale O’Brien, MD

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